Sample records for human mirror neuron
-
Rizzolatti, Giacomo; Craighero, Laila
2004-01-01
A category of stimuli of great importance for primates, humans in particular, is that formed by actions done by other individuals. If we want to survive, we must understand the actions of others. Furthermore, without action understanding, social organization is impossible. In the case of humans, there is another faculty that depends on the observation of others' actions: imitation learning. Unlike most species, we are able to learn by imitation, and this faculty is at the basis of human culture. In this review we present data on a neurophysiological mechanism--the mirror-neuron mechanism--that appears to play a fundamental role in both action understanding and imitation. We describe first the functional properties of mirror neurons in monkeys. We review next the characteristics of the mirror-neuron system in humans. We stress, in particular, those properties specific to the human mirror-neuron system that might explain the human capacity to learn by imitation. We conclude by discussing the relationship between the mirror-neuron system and language.
-
Cattaneo, Luigi; Rizzolatti, Giacomo
2009-05-01
Mirror neurons are a class of neurons, originally discovered in the premotor cortex of monkeys, that discharge both when individuals perform a given motor act and when they observe others perform that same motor act. Ample evidence demonstrates the existence of a cortical network with the properties of mirror neurons (mirror system) in humans. The human mirror system is involved in understanding others' actions and their intentions behind them, and it underlies mechanisms of observational learning. Herein, we will discuss the clinical implications of the mirror system.
-
The human mirror neuron system and embodied representations.
Aziz-Zadeh, Lisa; Ivry, Richard B
2009-01-01
Mirror neurons are defined as neurons in the monkey cortex which respond to goal oriented actions, whether the behavior is self-generated or produced by another. Here we briefly review this literature and consider evidence from behavioral, neuropsychological, and brain imaging studies for a similar mirror neuron system in humans. Furthermore, we review functions of this system related to action comprehension and motor imagery, as well as evidence for speculations on the system's ties with conceptual knowledge and language.
-
Why our brains cherish humanity: Mirror neurons and colamus humanitatem
Directory of Open Access Journals (Sweden)
John R. Skoyles
2008-06-01
Full Text Available Commonsense says we are isolated. After all, our bodies are physically separate. But Seneca’s colamus humanitatem, and John Donne’s observation that “no man is an island” suggests we are neither entirely isolated nor separate. A recent discovery in neuroscience—that of mirror neurons—argues that the brain and the mind is neither built nor functions remote from what happens in other individuals. What are mirror neurons? They are brain cells that process both what happens to or is done by an individual, and, as it were, its perceived “refl ection,” when that same thing happens or is done by another individual. Thus, mirror neurons are both activated when an individual does a particular action, and when that individual perceives that same action done by another. The discovery of mirror neurons suggests we need to radically revise our notions of human nature since they offer a means by which we may not be so separated as we think. Humans unlike other apes are adapted to mirror interact nonverbally when together. Notably, our faces have been evolved to display agile and nimble movements. While this is usually explained as enabling nonverbal communication, a better description would be nonverbal commune based upon mirror neurons. I argue we cherish humanity, colamus humanitatem, because mirror neurons and our adapted mirror interpersonal interface blur the physical boundaries that separate us.
-
Mirror neurons: functions, mechanisms and models.
Oztop, Erhan; Kawato, Mitsuo; Arbib, Michael A
2013-04-12
Mirror neurons for manipulation fire both when the animal manipulates an object in a specific way and when it sees another animal (or the experimenter) perform an action that is more or less similar. Such neurons were originally found in macaque monkeys, in the ventral premotor cortex, area F5 and later also in the inferior parietal lobule. Recent neuroimaging data indicate that the adult human brain is endowed with a "mirror neuron system," putatively containing mirror neurons and other neurons, for matching the observation and execution of actions. Mirror neurons may serve action recognition in monkeys as well as humans, whereas their putative role in imitation and language may be realized in human but not in monkey. This article shows the important role of computational models in providing sufficient and causal explanations for the observed phenomena involving mirror systems and the learning processes which form them, and underlines the need for additional circuitry to lift up the monkey mirror neuron circuit to sustain the posited cognitive functions attributed to the human mirror neuron system. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
-
Gender differences in the mu rhythm of the human mirror-neuron system.
Cheng, Yawei; Lee, Po-Lei; Yang, Chia-Yen; Lin, Ching-Po; Hung, Daisy; Decety, Jean
2008-05-07
Psychologically, females are usually thought to be superior in interpersonal sensitivity than males. The human mirror-neuron system is considered to provide the basic mechanism for social cognition. However, whether the human mirror-neuron system exhibits gender differences is not yet clear. We measured the electroencephalographic mu rhythm, as a reliable indicator of the human mirror-neuron system activity, when female (N = 20) and male (N = 20) participants watched either hand actions or a moving dot. The display of the hand actions included androgynous, male, and female characteristics. The results demonstrate that females displayed significantly stronger mu suppression than males when watching hand actions. Instead, mu suppression was similar across genders when participants observed the moving dot and between the perceived sex differences (same-sex vs. opposite-sex). In addition, the mu suppressions during the observation of hand actions positively correlated with the personal distress subscale of the interpersonal reactivity index and negatively correlated with the systemizing quotient. The present findings indirectly lend support to the extreme male brain theory put forward by Baron-Cohen (2005), and may cast some light on the mirror-neuron dysfunction in autism spectrum disorders. The mu rhythm in the human mirror-neuron system can be a potential biomarker of empathic mimicry.
-
A human mirror neuron system for language: Perspectives from signed languages of the deaf.
Knapp, Heather Patterson; Corina, David P
2010-01-01
Language is proposed to have developed atop the human analog of the macaque mirror neuron system for action perception and production [Arbib M.A. 2005. From monkey-like action recognition to human language: An evolutionary framework for neurolinguistics (with commentaries and author's response). Behavioral and Brain Sciences, 28, 105-167; Arbib M.A. (2008). From grasp to language: Embodied concepts and the challenge of abstraction. Journal de Physiologie Paris 102, 4-20]. Signed languages of the deaf are fully-expressive, natural human languages that are perceived visually and produced manually. We suggest that if a unitary mirror neuron system mediates the observation and production of both language and non-linguistic action, three prediction can be made: (1) damage to the human mirror neuron system should non-selectively disrupt both sign language and non-linguistic action processing; (2) within the domain of sign language, a given mirror neuron locus should mediate both perception and production; and (3) the action-based tuning curves of individual mirror neurons should support the highly circumscribed set of motions that form the "vocabulary of action" for signed languages. In this review we evaluate data from the sign language and mirror neuron literatures and find that these predictions are only partially upheld. 2009 Elsevier Inc. All rights reserved.
-
Mirror neurons: from origin to function.
Cook, Richard; Bird, Geoffrey; Catmur, Caroline; Press, Clare; Heyes, Cecilia
2014-04-01
This article argues that mirror neurons originate in sensorimotor associative learning and therefore a new approach is needed to investigate their functions. Mirror neurons were discovered about 20 years ago in the monkey brain, and there is now evidence that they are also present in the human brain. The intriguing feature of many mirror neurons is that they fire not only when the animal is performing an action, such as grasping an object using a power grip, but also when the animal passively observes a similar action performed by another agent. It is widely believed that mirror neurons are a genetic adaptation for action understanding; that they were designed by evolution to fulfill a specific socio-cognitive function. In contrast, we argue that mirror neurons are forged by domain-general processes of associative learning in the course of individual development, and, although they may have psychological functions, they do not necessarily have a specific evolutionary purpose or adaptive function. The evidence supporting this view shows that (1) mirror neurons do not consistently encode action "goals"; (2) the contingency- and context-sensitive nature of associative learning explains the full range of mirror neuron properties; (3) human infants receive enough sensorimotor experience to support associative learning of mirror neurons ("wealth of the stimulus"); and (4) mirror neurons can be changed in radical ways by sensorimotor training. The associative account implies that reliable information about the function of mirror neurons can be obtained only by research based on developmental history, system-level theory, and careful experimentation.
-
Rubia Vila, Francisco José
2011-01-01
Mirror neurons were recently discovered in frontal brain areas of the monkey. They are activated when the animal makes a specific movement, but also when the animal observes the same movement in another animal. Some of them also respond to the emotional expression of other animals of the same species. These mirror neurons have also been found in humans. They respond to or "reflect" actions of other individuals in the brain and are thought to represent the basis for imitation and empathy and hence the neurobiological substrate for "theory of mind", the potential origin of language and the so-called moral instinct.
-
Mirror neurons: Enigma of the metaphysical modular brain.
Acharya, Sourya; Shukla, Samarth
2012-07-01
Mirror neurons are one of the most important discoveries in the last decade of neuroscience. These are a variety of visuospatial neurons which indicate fundamentally about human social interaction. Essentially, mirror neurons respond to actions that we observe in others. The interesting part is that mirror neurons fire in the same way when we actually recreate that action ourselves. Apart from imitation, they are responsible for myriad of other sophisticated human behavior and thought processes. Defects in the mirror neuron system are being linked to disorders like autism. This review is a brief introduction to the neurons that shaped our civilization.
-
Mirror neuron system: basic findings and clinical applications.
Iacoboni, Marco; Mazziotta, John C
2007-09-01
In primates, ventral premotor and rostral inferior parietal neurons fire during the execution of hand and mouth actions. Some cells (called mirror neurons) also fire when hand and mouth actions are just observed. Mirror neurons provide a simple neural mechanism for understanding the actions of others. In humans, posterior inferior frontal and rostral inferior parietal areas have mirror properties. These human areas are relevant to imitative learning and social behavior. Indeed, the socially isolating condition of autism is associated with a deficit in mirror neuron areas. Strategies inspired by mirror neuron research recently have been used in the treatment of autism and in motor rehabilitation after stroke.
-
Where do mirror neurons come from?
Heyes, Cecilia
2010-03-01
Debates about the evolution of the 'mirror neuron system' imply that it is an adaptation for action understanding. Alternatively, mirror neurons may be a byproduct of associative learning. Here I argue that the adaptation and associative hypotheses both offer plausible accounts of the origin of mirror neurons, but the associative hypothesis has three advantages. First, it provides a straightforward, testable explanation for the differences between monkeys and humans that have led some researchers to question the existence of a mirror neuron system. Second, it is consistent with emerging evidence that mirror neurons contribute to a range of social cognitive functions, but do not play a dominant, specialised role in action understanding. Finally, the associative hypothesis is supported by recent data showing that, even in adulthood, the mirror neuron system can be transformed by sensorimotor learning. The associative account implies that mirror neurons come from sensorimotor experience, and that much of this experience is obtained through interaction with others. Therefore, if the associative account is correct, the mirror neuron system is a product, as well as a process, of social interaction. (c) 2009 Elsevier Ltd. All rights reserved.
-
Mirror neurons and imitation: a computationally guided review.
Oztop, Erhan; Kawato, Mitsuo; Arbib, Michael
2006-04-01
Neurophysiology reveals the properties of individual mirror neurons in the macaque while brain imaging reveals the presence of 'mirror systems' (not individual neurons) in the human. Current conceptual models attribute high level functions such as action understanding, imitation, and language to mirror neurons. However, only the first of these three functions is well-developed in monkeys. We thus distinguish current opinions (conceptual models) on mirror neuron function from more detailed computational models. We assess the strengths and weaknesses of current computational models in addressing the data and speculations on mirror neurons (macaque) and mirror systems (human). In particular, our mirror neuron system (MNS), mental state inference (MSI) and modular selection and identification for control (MOSAIC) models are analyzed in more detail. Conceptual models often overlook the computational requirements for posited functions, while too many computational models adopt the erroneous hypothesis that mirror neurons are interchangeable with imitation ability. Our meta-analysis underlines the gap between conceptual and computational models and points out the research effort required from both sides to reduce this gap.
-
Mirror neurons: Enigma of the metaphysical modular brain
Acharya, Sourya; Shukla, Samarth
2012-01-01
Mirror neurons are one of the most important discoveries in the last decade of neuroscience. These are a variety of visuospatial neurons which indicate fundamentally about human social interaction. Essentially, mirror neurons respond to actions that we observe in others. The interesting part is that mirror neurons fire in the same way when we actually recreate that action ourselves. Apart from imitation, they are responsible for myriad of other sophisticated human behavior and thought process...
-
Mirror neurons: From origin to function
Cook, R; Bird, G; Catmur, C; Press, C; Heyes, C
2014-01-01
This article argues that mirror neurons originate in sensorimotor associative learning and therefore a new approach is needed to investigate their functions. Mirror neurons were discovered about 20 years ago in the monkey brain, and there is now evidence that they are also present in the human brain. The intriguing feature of many mirror neurons is that they fire not only when the animal is performing an action, such as grasping an object using a power grip, but also when the animal passively...
-
What do mirror neurons mirror?
Uithol, S.; Rooij, I.J.E.I. van; Bekkering, H.; Haselager, W.F.G.
2011-01-01
Single cell recordings in monkeys provide strong evidence for an important role of the motor system in action understanding. This evidence is backed up by data from studies of the (human) mirror neuron system using neuroimaging or TMS techniques, and behavioral experiments. Although the data
-
Reflections on mirror neurons and speech perception
Lotto, Andrew J.; Hickok, Gregory S.; Holt, Lori L.
2010-01-01
The discovery of mirror neurons, a class of neurons that respond when a monkey performs an action and also when the monkey observes others producing the same action, has promoted a renaissance for the Motor Theory (MT) of speech perception. This is because mirror neurons seem to accomplish the same kind of one to one mapping between perception and action that MT theorizes to be the basis of human speech communication. However, this seeming correspondence is superficial, and there are theoretical and empirical reasons to temper enthusiasm about the explanatory role mirror neurons might have for speech perception. In fact, rather than providing support for MT, mirror neurons are actually inconsistent with the central tenets of MT. PMID:19223222
-
Mirror Neurons and Mirror-Touch Synesthesia.
Linkovski, Omer; Katzin, Naama; Salti, Moti
2016-05-30
Since mirror neurons were introduced to the neuroscientific community more than 20 years ago, they have become an elegant and intuitive account for different cognitive mechanisms (e.g., empathy, goal understanding) and conditions (e.g., autism spectrum disorders). Recently, mirror neurons were suggested to be the mechanism underlying a specific type of synesthesia. Mirror-touch synesthesia is a phenomenon in which individuals experience somatosensory sensations when seeing someone else being touched. Appealing as it is, careful delineation is required when applying this mechanism. Using the mirror-touch synesthesia case, we put forward theoretical and methodological issues that should be addressed before relying on the mirror-neurons account. © The Author(s) 2016.
-
The mirror neuron system : New frontiers
Keysers, Christian; Fadiga, Luciano
2008-01-01
Since the discovery of mirror neurons, much effort has been invested into Studying their location and properties in the human brain. Here we review these original findings and introduce the Main topics of this special issue of Social Neuroscience. What does the mirror system code? How is the mirror
-
Rogalsky, Corianne; Love, Tracy; Driscoll, David; Anderson, Steven W.; Hickok, Gregory
2013-01-01
The discovery of mirror neurons in macaque has led to a resurrection of motor theories of speech perception. Although the majority of lesion and functional imaging studies have associated perception with the temporal lobes, it has also been proposed that the ‘human mirror system’, which prominently includes Broca’s area, is the neurophysiological substrate of speech perception. Although numerous studies have demonstrated a tight link between sensory and motor speech processes, few have directly assessed the critical prediction of mirror neuron theories of speech perception, namely that damage to the human mirror system should cause severe deficits in speech perception. The present study measured speech perception abilities of patients with lesions involving motor regions in the left posterior frontal lobe and/or inferior parietal lobule (i.e., the proposed human ‘mirror system’). Performance was at or near ceiling in patients with fronto-parietal lesions. It is only when the lesion encroaches on auditory regions in the temporal lobe that perceptual deficits are evident. This suggests that ‘mirror system’ damage does not disrupt speech perception, but rather that auditory systems are the primary substrate for speech perception. PMID:21207313
-
The mirror neuron system: new frontiers.
Keysers, Christian; Fadiga, Luciano
2008-01-01
Since the discovery of mirror neurons, much effort has been invested into studying their location and properties in the human brain. Here we review these original findings and introduce the main topics of this special issue of Social Neuroscience. What does the mirror system code? How is the mirror system embedded into the mosaic of circuits that compose our brain? How does the mirror system contribute to communication, language and social interaction? Can the principle of mirror neurons be extended to emotions, sensations and thoughts? Papers using a wide range of methods, including single cell recordings, fMRI, TMS, EEG and psychophysics, collected in this special issue, start to give us some impressive answers.
-
Heyes, Cecilia
2010-06-01
Mirror neurons have been hailed as the key to understanding social cognition. I argue that three currents of thought-relating to evolution, atomism and telepathy-have magnified the perceived importance of mirror neurons. When they are understood to be a product of associative learning, rather than an adaptation for social cognition, mirror neurons are no longer mesmerising, but they continue to raise important questions about both the psychology of science and the neural bases of social cognition. Copyright 2010 Elsevier Inc. All rights reserved.
-
Programmed to Learn? The Ontogeny of Mirror Neurons
Del Giudice, Marco; Manera, Valeria; Keysers, Christian
2009-01-01
Mirror neurons are increasingly recognized as a crucial substrate for many developmental processes, including imitation and social learning. Although there has been considerable progress in describing their function and localization in the primate and adult human brain, we still know little about their ontogeny. The idea that mirror neurons result…
-
Burgess, Jed D.; Arnold, Sara L.; Fitzgibbon, Bernadette M.; Fitzgerald, Paul B.; Enticott, Peter G.
2013-01-01
Mirror neurons are a class of motor neuron that are active during both the performance and observation of behavior, and have been implicated in interpersonal understanding. There is evidence to suggest that the mirror response is modulated by the perspective from which an action is presented (e.g., egocentric or allocentric). Most human research, however, has only examined this when presenting intransitive actions. Twenty-three healthy adult participants completed a transcranial magnetic stimulation experiment that assessed corticospinal excitability whilst viewing transitive hand gestures from both egocentric (i.e., self) and allocentric (i.e., other) viewpoints. Although action observation was associated with increases in corticospinal excitability (reflecting putative human mirror neuron activity), there was no effect of visual perspective. These findings are discussed in the context of contemporary theories of mirror neuron ontogeny, including models concerning associative learning and evolutionary adaptation. PMID:24137125
-
Burgess, Jed D; Arnold, Sara L; Fitzgibbon, Bernadette M; Fitzgerald, Paul B; Enticott, Peter G
2013-01-01
Mirror neurons are a class of motor neuron that are active during both the performance and observation of behavior, and have been implicated in interpersonal understanding. There is evidence to suggest that the mirror response is modulated by the perspective from which an action is presented (e.g., egocentric or allocentric). Most human research, however, has only examined this when presenting intransitive actions. Twenty-three healthy adult participants completed a transcranial magnetic stimulation experiment that assessed corticospinal excitability whilst viewing transitive hand gestures from both egocentric (i.e., self) and allocentric (i.e., other) viewpoints. Although action observation was associated with increases in corticospinal excitability (reflecting putative human mirror neuron activity), there was no effect of visual perspective. These findings are discussed in the context of contemporary theories of mirror neuron ontogeny, including models concerning associative learning and evolutionary adaptation.
-
Sensorimotor learning and the ontogeny of the mirror neuron system.
Catmur, Caroline
2013-04-12
Mirror neurons, which have now been found in the human and songbird as well as the macaque, respond to both the observation and the performance of the same action. It has been suggested that their matching response properties have evolved as an adaptation for action understanding; alternatively, these properties may arise through sensorimotor experience. Here I review mirror neuron response characteristics from the perspective of ontogeny; I discuss the limited evidence for mirror neurons in early development; and I describe the growing body of evidence suggesting that mirror neuron responses can be modified through experience, and that sensorimotor experience is the critical type of experience for producing mirror neuron responses. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
-
Directory of Open Access Journals (Sweden)
Jed Donald Burgess
2013-10-01
Full Text Available Mirror neurons are a class of motor neuron that are active during both the performance and observation of behavior, and have been implicated in interpersonal understanding There is evidence to suggest that the mirror response is modulated by the perspective from which an action is presented (e.g., egocentric or allocentric. Most human research, however, has only examined this when presenting intransitive actions. Twenty-three healthy adult participants completed a transcranial magnetic stimulation (TMS experiment that assessed corticospinal excitability whilst viewing transitive hand gestures from both egocentric (i.e., self and allocentric (i.e., other viewpoints. Although action observation was associated with increases in corticospinal excitability (reflecting putative human mirror neuron activity, there was no effect of visual perspective. These findings are discussed in the context of contemporary theories of mirror neuron ontogeny, including models concerning associative learning and evolutionary adaptation.
-
The mirror neuron system and the consequences of its dysfunction.
Iacoboni, Marco; Dapretto, Mirella
2006-12-01
The discovery of premotor and parietal cells known as mirror neurons in the macaque brain that fire not only when the animal is in action, but also when it observes others carrying out the same actions provides a plausible neurophysiological mechanism for a variety of important social behaviours, from imitation to empathy. Recent data also show that dysfunction of the mirror neuron system in humans might be a core deficit in autism, a socially isolating condition. Here, we review the neurophysiology of the mirror neuron system and its role in social cognition and discuss the clinical implications of mirror neuron dysfunction.
-
Sensorimotor learning and the ontogeny of the mirror neuron system
Catmur, C
2013-01-01
Mirror neurons, which have now been found in the human and songbird as well as the macaque, respond to both the observation and the performance of the same action. It has been suggested that their matching response properties have evolved as an adaptation for action understanding; alternatively, these properties may arise through sensorimotor experience. Here I review mirror neuron response characteristics from the perspective of ontogeny; I discuss the limited evidence for mirror neurons in ...
-
Unbroken Mirror Neurons in Autism Spectrum Disorders
Fan, Yang-Teng; Decety, Jean; Yang, Chia-Yen; Liu, Ji-Lin; Cheng, Yawei
2010-01-01
Background: The "broken mirror" theory of autism, which proposes that a dysfunction of the human mirror neuron system (MNS) is responsible for the core social and cognitive deficits in individuals with autism spectrum disorders (ASD), has received considerable attention despite weak empirical evidence. Methods: In this electroencephalographic…
-
[Mirror neurons: from anatomy to pathophysiological and therapeutic implications].
Mathon, B
2013-04-01
Mirror neurons are a special class of neurons discovered in the 1990s. They respond when we perform an action and also when we see someone else perform that action. They play a role in the pathophysiology of some neuropsychiatric diseases. Mirror neurons have been identified in humans: in Broca's area and the inferior parietal cortex. Their responses are qualitative and selective depending on the observed action. Emotions (including disgust) and empathy seem to operate according to a mirror mechanism. Indeed, the mirror system allows us to encode the sensory experience and to simulate the emotional state of others. This results in our improved identification of the emotions in others. Additionally, mirror neurons can encode an observed action in motor stimuli and allow its reproduction; thus, they are involved in imitation and learning. Current studies are assessing the role of mirror neurons in the pathopysiology of social-behavior disorders, including autism and schizophrenia. Understanding this mirror system will allow us to develop psychotherapy practices based on empathic resonance between the patient and the therapist. Also, some authors report that a passive rehabilitation technique, based on stimulation of the mirror-neuron system, has a beneficial effect in the treatment of patients with post-stroke motor deficits. Mirror neurons are an anatomical entity that enables improved understanding of behavior and emotions, and serves as a base for developing new cognitive therapies. Additional studies are needed to clarify the exact role of this neuronal system in social cognition and its role in the development of some neuropsychiatric diseases. Copyright © 2013 Elsevier Masson SAS. All rights reserved.
-
Mirror neurons and language in schizophrenia
Bendová, Marie
2016-01-01
Mirror neurons are a specific kind of visuomotor neurons that are involved in action execution and also in action perception. The mirror mechanism is linked to a variety of complex psychological functions such as social-cognitive functions and language. People with schizophrenia have often difficulties both in mirror neuron system and in language skills. In the first part of our research we studied the connectivity of mirror neuron areas (such as IFG, STG, PMC, SMC and so on) by fMRI in resti...
-
New Reflections on Mirror Neuron Research, the Tower of Babel, and Intercultural Education
Westbrook, Timothy Paul
2015-01-01
Studies of the human mirror neuron system demonstrate how mental mimicking of one's social environment affects learning. The mirror neuron system also has implications for intercultural encounters. This article explores the common ground between the mirror neuron system and theological principles from the Tower of Babel narrative and applies them…
-
The infant mirror neuron system studied with high density EEG.
Nyström, Pär
2008-01-01
The mirror neuron system has been suggested to play a role in many social capabilities such as action understanding, imitation, language and empathy. These are all capabilities that develop during infancy and childhood, but the human mirror neuron system has been poorly studied using neurophysiological measures. This study measured the brain activity of 6-month-old infants and adults using a high-density EEG net with the aim of identifying mirror neuron activity. The subjects viewed both goal-directed movements and non-goal-directed movements. An independent component analysis was used to extract the sources of cognitive processes. The desynchronization of the mu rhythm in adults has been shown to be a marker for activation of the mirror neuron system and was used as a criterion to categorize independent components between subjects. The results showed significant mu desynchronization in the adult group and significantly higher ERP activation in both adults and 6-month-olds for the goal-directed action observation condition. This study demonstrate that infants as young as 6 months display mirror neuron activity and is the first to present a direct ERP measure of the mirror neuron system in infants.
-
A Human Mirror Neuron System for Language: Perspectives from Signed Languages of the Deaf
Knapp, Heather Patterson; Corina, David P.
2010-01-01
Language is proposed to have developed atop the human analog of the macaque mirror neuron system for action perception and production [Arbib M.A. 2005. From monkey-like action recognition to human language: An evolutionary framework for neurolinguistics (with commentaries and author's response). "Behavioral and Brain Sciences, 28", 105-167; Arbib…
-
Review Essay: Mirror Neurons in the Discourse of Social Sciences
Directory of Open Access Journals (Sweden)
Henning Pätzold
2010-08-01
Full Text Available Since their discovery in the mid-1990s, mirror neurons have been the subject of continuous discussions in neurosciences as well as in the social sciences. The interest of scientists outside the life sciences in mirror neurons is primarily based on the fact that mirror neurons not only have epistemological meaning, but also seem to play an important role in processes of social insights and emotions, like empathy. With her book, Nadia ZABOURA provides a new contribution from a social and cultural sciences point of view, which critically reflects the discussion on mirror neurons and its consequences on the social sciences and humanities. Starting off from philosophical approaches to the mind-matter-dualism and the question of intersubjectivity, she explores the meaning of mirror neurons for the debate on empathy and communication. By discussing concepts of philosophy and communication sciences as well as current knowledge on mirror neurons, she concludes that they do not provide a stable basis for any material reductionism, which would explain phenomena like intersubjectivity only by recordable neuronal processes. The book refers to a variety of related theories (ranging from DESCARTES through to MEAD and TOMASELLO; these references are inspiring, yet they stay cursory for the most part. All in all the book offers avenues for further inquiry on the issues in focus, and can rather be taken as "tour of suggestions" through the topical field of mirror neurons and the related research. URN: urn:nbn:de:0114-fqs1003245
-
Hearing sounds, understanding actions: action representation in mirror neurons.
Kohler, Evelyne; Keysers, Christian; Umiltà, M Alessandra; Fogassi, Leonardo; Gallese, Vittorio; Rizzolatti, Giacomo
2002-08-02
Many object-related actions can be recognized by their sound. We found neurons in monkey premotor cortex that discharge when the animal performs a specific action and when it hears the related sound. Most of the neurons also discharge when the monkey observes the same action. These audiovisual mirror neurons code actions independently of whether these actions are performed, heard, or seen. This discovery in the monkey homolog of Broca's area might shed light on the origin of language: audiovisual mirror neurons code abstract contents-the meaning of actions-and have the auditory access typical of human language to these contents.
-
Why our brains cherish humanity: Mirror neurons and colamus humanitatem
Skoyles, John R.
2008-01-01
Commonsense says we are isolated. After all, our bodies are physically separate. But Seneca’s colamus humanitatem, and John Donne’s observation that “no man is an island” suggests we are neither entirely isolated nor separate. A recent discovery in neuroscience-that of mirror neurons-argues that the brain and the mind is neither built nor functions remote from what happens in other individuals. What are mirror neurons? They are brain cells that process both what happens to or is done by an in...
-
Eisen, Andrew; Lemon, Roger; Kiernan, Matthew C; Hornberger, Michael; Turner, Martin R
2015-07-01
There is growing evidence that mirror neurons, initially discovered over two decades ago in the monkey, are present in the human brain. In the monkey, mirror neurons characteristically fire not only when it is performing an action, such as grasping an object, but also when observing a similar action performed by another agent (human or monkey). In this review we discuss the origin, cortical distribution and possible functions of mirror neurons as a background to exploring their potential relevance in amyotrophic lateral sclerosis (ALS). We have recently proposed that ALS (and the related condition of frontotemporal dementia) may be viewed as a failure of interlinked functional complexes having their origins in key evolutionary adaptations. This can include loss of the direct projections from the corticospinal tract, and this is at least part of the explanation for impaired motor control in ALS. Since, in the monkey, corticospinal neurons also show mirror properties, ALS in humans might also affect the mirror neuron system. We speculate that a defective mirror neuron system might contribute to other ALS deficits affecting motor imagery, gesture, language and empathy. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
-
Sign language processing and the mirror neuron system.
Corina, David P; Knapp, Heather
2006-05-01
In this paper we review evidence for frontal and parietal lobe involvement in sign language comprehension and production, and evaluate the extent to which these data can be interpreted within the context of a mirror neuron system for human action observation and execution. We present data from three literatures--aphasia, cortical stimulation, and functional neuroimaging. Generally, we find support for the idea that sign language comprehension and production can be viewed in the context of a broadly-construed frontal-parietal human action observation/execution system. However, sign language data cannot be fully accounted for under a strict interpretation of the mirror neuron system. Additionally, we raise a number of issues concerning the lack of specificity in current accounts of the human action observation/execution system.
-
Eisen, Andrew; Lemon, Roger; Kiernan, Matthew C.; Hornberger, Michael; Turner, Martin R.
2015-01-01
There is growing evidence that mirror neurons, initially discovered over two decades ago in the monkey, are present in the human brain. In the monkey, mirror neurons characteristically fire not only when it is performing an action, such as grasping an object, but also when observing a similar action performed by another agent (human or monkey). In this review we discuss the origin, cortical distribution and possible functions of mirror neurons as a background to exploring their potential rele...
-
Burgess, Jed D.; Arnold, Sara L.; Fitzgibbon, Bernadette M.; Fitzgerald, Paul B.; Enticott, Peter G.
2013-01-01
Mirror neurons are a class of motor neuron that are active during both the performance and observation of behavior, and have been implicated in interpersonal understanding There is evidence to suggest that the mirror response is modulated by the perspective from which an action is presented (e.g., egocentric or allocentric). Most human research, however, has only examined this when presenting intransitive actions. Twenty-three healthy adult participants completed a transcranial magnetic stimu...
-
Is the human mirror neuron system plastic? Evidence from a transcranial magnetic stimulation study.
Mehta, Urvakhsh Meherwan; Waghmare, Avinash V; Thirthalli, Jagadisha; Venkatasubramanian, Ganesan; Gangadhar, Bangalore N
2015-10-01
Virtual lesions in the mirror neuron network using inhibitory low-frequency (1Hz) transcranial magnetic stimulation (TMS) have been employed to understand its spatio-functional properties. However, no studies have examined the influence of neuro-enhancement by using excitatory high-frequency (20Hz) repetitive transcranial magnetic stimulation (HF-rTMS) on these networks. We used three forms of TMS stimulation (HF-rTMS, single and paired pulse) to investigate whether the mirror neuron system facilitates the motor system during goal-directed action observation relative to inanimate motion (motor resonance), a marker of putative mirror neuron activity. 31 healthy individuals were randomized to receive single-sessions of true or sham HF-rTMS delivered to the left inferior frontal gyrus - a component of the human mirror system. Motor resonance was assessed before and after HF-rTMS using three TMS cortical reactivity paradigms: (a) 120% of resting motor threshold (RMT), (b) stimulus intensity set to evoke motor evoked potential of 1-millivolt amplitude (SI1mV) and (c) a short latency paired pulse paradigm. Two-way RMANOVA showed a significant group (true versus sham) X occasion (pre- and post-HF-rTMS motor resonance) interaction effect for SI1mV [F(df)=6.26 (1, 29), p=0.018] and 120% RMT stimuli [F(df)=7.01 (1, 29), p=0.013] indicating greater enhancement of motor resonance in the true HF-rTMS group than the sham-group. This suggests that HF-rTMS could adaptively modulate properties of the mirror neuron system. This neuro-enhancement effect is a preliminary step that can open translational avenues for novel brain stimulation therapeutics targeting social-cognition deficits in schizophrenia and autism. Copyright © 2015 Elsevier B.V. All rights reserved.
-
The neuroscience of observing consciousness & mirror neurons in therapeutic hypnosis.
Rossi, Ernest L; Rossi, Kathryn L
2006-04-01
Neuroscience documents the activity of "mirror neurons" in the human brain as a mechanism whereby we experience empathy and recognize the intentions of others by observing their behavior and automatically matching their brain activity. This neural basis of empathy finds support in research on dysfunctions in the mirror systems of humans with autism and fMRI research on normal subjects designed to assess intentionality, emotions, and complex cognition. Such empathy research now appears to be consistent with the historical and research literature on hypnotic induction, rapport, and many of the classical phenomena of suggestion. A preliminary outline of how mirror neurons may function as a rapport zone mediating between observing consciousness, the gene expression/protein synthesis cycle, and brain plasticity in therapeutic hypnosis and psychosomatic medicine is proposed. Brain plasticity is generalized in the theory, research, and practice of utilizing mirror neurons as an explanatory framework in developing and training new skill sets for facilitating an activity-dependent approach to creative problem solving, mind-body healing, and rehabilitation with therapeutic hypnosis.
-
On whether mirror neurons play a significant role in processing affective prosody.
Ramachandra, Vijayachandra
2009-02-01
Several behavioral and neuroimaging studies have indicated that both right and left cortical structures and a few subcortical ones are involved in processing affective prosody. Recent investigations have shown that the mirror neuron system plays a crucial role in several higher-level functions such as empathy, theory of mind, language, etc., but no studies so far link the mirror neuron system with affective prosody. In this paper is a speculation that the mirror neuron system, which serves as a common neural substrate for different higher-level functions, may play a significant role in processing affective prosody via its connections with the limbic lobe. Actual research must apply electrophysiological and neuroimaging techniques to assess whether the mirror neuron systems underly affective prosody in humans.
-
The mirror system in human and nonhuman primates.
Orban, Guy A
2014-04-01
The description of the mirror neuron system provided by Cook et al. is incomplete for the macaque, and incorrect for humans. This is relevant to exaptation versus associative learning as the underlying mechanism generating mirror neurons, and to the sensorimotor learning as evidence for the authors' viewpoint. The proposed additional testing of the mirror system in rodents is unrealistic.
-
Le Bel, Ronald M.; Pineda, Jaime A.; Sharma, Anu
2009-01-01
The mirror neuron system (MNS) is a trimodal system composed of neuronal populations that respond to motor, visual, and auditory stimulation, such as when an action is performed, observed, heard or read about. In humans, the MNS has been identified using neuroimaging techniques (such as fMRI and mu suppression in the EEG). It reflects an…
-
Mirror Neurons in Humans: Consisting or Confounding Evidence?
Turella, Luca; Pierno, Andrea C.; Tubaldi, Federico; Castiello, Umberto
2009-01-01
The widely known discovery of mirror neurons in macaques shows that premotor and parietal cortical areas are not only involved in executing one's own movement, but are also active when observing the action of others. The goal of this essay is to critically evaluate the substance of functional magnetic resonance imaging (fMRI) and positron emission…
-
Mirror neurons and the social nature of language: the neural exploitation hypothesis.
Gallese, Vittorio
2008-01-01
This paper discusses the relevance of the discovery of mirror neurons in monkeys and of the mirror neuron system in humans to a neuroscientific account of primates' social cognition and its evolution. It is proposed that mirror neurons and the functional mechanism they underpin, embodied simulation, can ground within a unitary neurophysiological explanatory framework important aspects of human social cognition. In particular, the main focus is on language, here conceived according to a neurophenomenological perspective, grounding meaning on the social experience of action. A neurophysiological hypothesis--the "neural exploitation hypothesis"--is introduced to explain how key aspects of human social cognition are underpinned by brain mechanisms originally evolved for sensorimotor integration. It is proposed that these mechanisms were later on adapted as new neurofunctional architecture for thought and language, while retaining their original functions as well. By neural exploitation, social cognition and language can be linked to the experiential domain of action.
-
Exploring associations between gaze patterns and putative human mirror neuron system activity.
Donaldson, Peter H; Gurvich, Caroline; Fielding, Joanne; Enticott, Peter G
2015-01-01
The human mirror neuron system (MNS) is hypothesized to be crucial to social cognition. Given that key MNS-input regions such as the superior temporal sulcus are involved in biological motion processing, and mirror neuron activity in monkeys has been shown to vary with visual attention, aberrant MNS function may be partly attributable to atypical visual input. To examine the relationship between gaze pattern and interpersonal motor resonance (IMR; an index of putative MNS activity), healthy right-handed participants aged 18-40 (n = 26) viewed videos of transitive grasping actions or static hands, whilst the left primary motor cortex received transcranial magnetic stimulation. Motor-evoked potentials recorded in contralateral hand muscles were used to determine IMR. Participants also underwent eyetracking analysis to assess gaze patterns whilst viewing the same videos. No relationship was observed between predictive gaze and IMR. However, IMR was positively associated with fixation counts in areas of biological motion in the videos, and negatively associated with object areas. These findings are discussed with reference to visual influences on the MNS, and the possibility that MNS atypicalities might be influenced by visual processes such as aberrant gaze pattern.
-
Exploring associations between gaze patterns and putative human mirror neuron system activity
Directory of Open Access Journals (Sweden)
Peter Hugh Donaldson
2015-07-01
Full Text Available The human mirror neuron system (MNS is hypothesised to be crucial to social cognition. Given that key MNS-input regions such as the superior temporal sulcus are involved in biological motion processing, and mirror neuron activity in monkeys has been shown to vary with visual attention, aberrant MNS function may be partly attributable to atypical visual input. To examine the relationship between gaze pattern and interpersonal motor resonance (IMR; an index of putative MNS activity, healthy right-handed participants aged 18-40 (n = 26 viewed videos of transitive grasping actions or static hands, whilst the left primary motor cortex received transcranial magnetic stimulation (TMS. Motor-evoked potentials (MEPs recorded in contralateral hand muscles were used to determine IMR. Participants also underwent eyetracking analysis to assess gaze patterns whilst viewing the same videos. No relationship was observed between predictive gaze (PG and IMR. However, IMR was positively associated with fixation counts in areas of biological motion in the videos, and negatively associated with object areas. These findings are discussed with reference to visual influences on the MNS, and the possibility that MNS atypicalities might be influenced by visual processes such as aberrant gaze pattern.
-
Mirror Neurons, Embodied Cognitive Agents and Imitation Learning
Wiedermann, Jiří
2003-01-01
Mirror neurons are a relatively recent discovery; it has been conjectured that these neurons play an important role in imitation learning and other cognitive phenomena. We will study a possible place and role of mirror neurons in the neural architecture of embodied cognitive agents. We will formulate and investigate the hypothesis that mirror neurons serve as a mechanism which coordinates the multimodal (i.e., motor, perceptional and proprioceptive) information and completes it so that the ag...
-
Programmed to learn? The ontogeny of mirror neurons
Del Giudice, Marco; Manera, Valeria; Keysers, Christian
Mirror neurons are increasingly recognized as a crucial substrate for many developmental processes, including imitation and social learning. Although there has been considerable progress in describing their function and localization in the primate and adult human brain, we still know little about
-
Observing complex action sequences: The role of the fronto-parietal mirror neuron system.
Molnar-Szakacs, Istvan; Kaplan, Jonas; Greenfield, Patricia M; Iacoboni, Marco
2006-11-15
A fronto-parietal mirror neuron network in the human brain supports the ability to represent and understand observed actions allowing us to successfully interact with others and our environment. Using functional magnetic resonance imaging (fMRI), we wanted to investigate the response of this network in adults during observation of hierarchically organized action sequences of varying complexity that emerge at different developmental stages. We hypothesized that fronto-parietal systems may play a role in coding the hierarchical structure of object-directed actions. The observation of all action sequences recruited a common bilateral network including the fronto-parietal mirror neuron system and occipito-temporal visual motion areas. Activity in mirror neuron areas varied according to the motoric complexity of the observed actions, but not according to the developmental sequence of action structures, possibly due to the fact that our subjects were all adults. These results suggest that the mirror neuron system provides a fairly accurate simulation process of observed actions, mimicking internally the level of motoric complexity. We also discuss the results in terms of the links between mirror neurons, language development and evolution.
-
Connecting mirror neurons and forward models.
Miall, R C
2003-12-02
Two recent developments in motor neuroscience are promising the extension of theoretical concepts from motor control towards cognitive processes, including human social interactions and understanding the intentions of others. The first of these is the discovery of what are now called mirror neurons, which code for both observed and executed actions. The second is the concept of internal models, and in particular recent proposals that forward and inverse models operate in paired modules. These two ideas will be briefly introduced, and a recent suggestion linking between the two processes of mirroring and modelling will be described which may underlie our abilities for imitating actions, for cooperation between two actors, and possibly for communication via gesture and language.
-
The Mirror Neuron System and Action Recognition
Buccino, Giovanni; Binkofski, Ferdinand; Riggio, Lucia
2004-01-01
Mirror neurons, first described in the rostral part of monkey ventral premotor cortex (area F5), discharge both when the animal performs a goal-directed hand action and when it observes another individual performing the same or a similar action. More recently, in the same area mirror neurons responding to the observation of mouth actions have been…
-
Mirror neuron framework yields representations for robot interaction
Barakova, E.I.; Lourens, T.
2009-01-01
Common coding is a functional principle that underlies the mirror neuron paradigm. It insures actual parity between perception and action, since the perceived and performed actions are equivalently and simultaneously represented within the mirror neuron system. Based on the parity of this
-
Action observation: Inferring intentions without mirror neurons
DEFF Research Database (Denmark)
Frith, Christopher; Kilner, James M
2008-01-01
A recent study has shown, using fMRI, that the mirror neuron system does not mediate action understanding when the observed action is novel or when it is hard to understand.......A recent study has shown, using fMRI, that the mirror neuron system does not mediate action understanding when the observed action is novel or when it is hard to understand....
-
On Empathy: The Mirror Neuron System and Art Education
Jeffers, Carol S.
2009-01-01
This paper re/considers empathy and its implications for learning in the art classroom, particularly in light of relevant neuroscientific investigations of the mirror neuron system recently discovered in the human brain. These investigations reinterpret the meaning of perception, resonance, and connection, and point to the fundamental importance…
-
Mirror neurons, birdsong, and human language: a hypothesis.
Levy, Florence
2011-01-01
THE MIRROR SYSTEM HYPOTHESIS AND INVESTIGATIONS OF BIRDSONG ARE REVIEWED IN RELATION TO THE SIGNIFICANCE FOR THE DEVELOPMENT OF HUMAN SYMBOLIC AND LANGUAGE CAPACITY, IN TERMS OF THREE FUNDAMENTAL FORMS OF COGNITIVE REFERENCE: iconic, indexical, and symbolic. Mirror systems are initially iconic but can progress to indexical reference when produced without the need for concurrent stimuli. Developmental stages in birdsong are also explored with reference to juvenile subsong vs complex stereotyped adult syllables, as an analogy with human language development. While birdsong remains at an indexical reference stage, human language benefits from the capacity for symbolic reference. During a pre-linguistic "babbling" stage, recognition of native phonemic categories is established, allowing further development of subsequent prefrontal and linguistic circuits for sequential language capacity.
-
The function of mirror neurons in the learning process
Directory of Open Access Journals (Sweden)
Mara Daniel
2017-01-01
Full Text Available In the last years, Neurosciences have developed very much, being elaborated many important theories scientific research in the field. The main goal of neuroscience is to understand how groups of neurons interact to create the behavior. Neuroscientists studying the action of molecules, genes and cells. It also explores the complex interactions involved in motion perception, thoughts, emotions and learning. Brick fundamental nervous system is the nerve cell, neuron. Neurons exchange information by sending electrical signals and chemical through connections called synapses. Discovered by a group of Italian researchers from the University of Parma, neurons - mirror are a special class of nerve cells played an important role in the direct knowledge, automatic and unconscious environment. These cortical neurons are activated not only when an action is fulfilled, but when we see how the same action is performed by someone else, they represent neural mechanism by which the actions, intentions and emotions of others can be understood automatically. In childhood neurons - mirror are extremely important. Thanks to them we learned a lot in the early years: smile, to ask for help and, in fact, all the behaviors and family and group norms. People learn by what they see and sense the others. Neurons - mirror are important to understanding the actions and intentions of other people and learn new skills through mirror image. They are involved in planning and controlling actions, abstract thinking and memory. If a child observes an action, neurons - mirror is activated and forming new neural pathways as if even he takes that action. Efficient activity of mirror neurons leads to good development in all areas at a higher emotional intelligence and the ability to empathize with others.
-
Modeling the Development of Goal-Specificity in Mirror Neurons.
Thill, Serge; Svensson, Henrik; Ziemke, Tom
2011-12-01
Neurophysiological studies have shown that parietal mirror neurons encode not only actions but also the goal of these actions. Although some mirror neurons will fire whenever a certain action is perceived (goal-independently), most will only fire if the motion is perceived as part of an action with a specific goal. This result is important for the action-understanding hypothesis as it provides a potential neurological basis for such a cognitive ability. It is also relevant for the design of artificial cognitive systems, in particular robotic systems that rely on computational models of the mirror system in their interaction with other agents. Yet, to date, no computational model has explicitly addressed the mechanisms that give rise to both goal-specific and goal-independent parietal mirror neurons. In the present paper, we present a computational model based on a self-organizing map, which receives artificial inputs representing information about both the observed or executed actions and the context in which they were executed. We show that the map develops a biologically plausible organization in which goal-specific mirror neurons emerge. We further show that the fundamental cause for both the appearance and the number of goal-specific neurons can be found in geometric relationships between the different inputs to the map. The results are important to the action-understanding hypothesis as they provide a mechanism for the emergence of goal-specific parietal mirror neurons and lead to a number of predictions: (1) Learning of new goals may mostly reassign existing goal-specific neurons rather than recruit new ones; (2) input differences between executed and observed actions can explain observed corresponding differences in the number of goal-specific neurons; and (3) the percentage of goal-specific neurons may differ between motion primitives.
-
The mirror neuron system and the strange case of Broca's area.
Cerri, Gabriella; Cabinio, Monia; Blasi, Valeria; Borroni, Paola; Iadanza, Antonella; Fava, Enrica; Fornia, Luca; Ferpozzi, Valentina; Riva, Marco; Casarotti, Alessandra; Martinelli Boneschi, Filippo; Falini, Andrea; Bello, Lorenzo
2015-03-01
Mirror neurons, originally described in the monkey premotor area F5, are embedded in a frontoparietal network for action execution and observation. A similar Mirror Neuron System (MNS) exists in humans, including precentral gyrus, inferior parietal lobule, and superior temporal sulcus. Controversial is the inclusion of Broca's area, as homologous to F5, a relevant issue in light of the mirror hypothesis of language evolution, which postulates a key role of Broca's area in action/speech perception/production. We assess "mirror" properties of this area by combining neuroimaging and intraoperative neurophysiological techniques. Our results show that Broca's area is minimally involved in action observation and has no motor output on hand or phonoarticulatory muscles, challenging its inclusion in the MNS. The presence of these functions in premotor BA6 makes this area the likely homologue of F5 suggesting that the MNS may be involved in the representation of articulatory rather than semantic components of speech. © 2014 Wiley Periodicals, Inc.
-
Mirror neurons and the understanding of behavioural symptoms in psychiatric disorders.
Buccino, Giovanni; Amore, Mario
2008-05-01
Recent findings show that we can understand other people's actions, intentions and emotions through a mirror mechanism as if we performed the same actions and felt the same intentions or emotions (embodied simulation). The present paper reviews experimental evidence that this mechanism may be broken in some psychiatric disorders. A mirror neuron system has been described in both monkeys and humans that allows one to map an observed action on a correspondent motor representation in the observer's brain. This mechanism has been involved in many higher motor functions ranging from action understanding to imitation and intention coding. A mirror mechanism has also been invoked in empathy, through an embodied simulation. A dysfunction of the mirror neuron system may be at the root of the inability to empathize in patients with autism and may play a role in some negative and positive symptoms found in patients with schizophrenia. This opens up new perspectives in the interpretation of psychotic symptoms and possibly in developing therapeutic strategies.
-
Le Bel, Ronald M; Pineda, Jaime A; Sharma, Anu
2009-01-01
The mirror neuron system (MNS) is a trimodal system composed of neuronal populations that respond to motor, visual, and auditory stimulation, such as when an action is performed, observed, heard or read about. In humans, the MNS has been identified using neuroimaging techniques (such as fMRI and mu suppression in the EEG). It reflects an integration of motor-auditory-visual information processing related to aspects of language learning including action understanding and recognition. Such integration may also form the basis for language-related constructs such as theory of mind. In this article, we review the MNS system as it relates to the cognitive development of language in typically developing children and in children at-risk for communication disorders, such as children with autism spectrum disorder (ASD) or hearing impairment. Studying MNS development in these children may help illuminate an important role of the MNS in children with communication disorders. Studies with deaf children are especially important because they offer potential insights into how the MNS is reorganized when one modality, such as audition, is deprived during early cognitive development, and this may have long-term consequences on language maturation and theory of mind abilities. Readers will be able to (1) understand the concept of mirror neurons, (2) identify cortical areas associated with the MNS in animal and human studies, (3) discuss the use of mu suppression in the EEG for measuring the MNS in humans, and (4) discuss MNS dysfunction in children with (ASD).
-
Oberman, Lindsay M; Hubbard, Edward M; McCleery, Joseph P
2014-04-01
Cook et al. argue that mirror neurons originate from associative learning processes, without evolutionary influence from social-cognitive mechanisms. We disagree with this claim and present arguments based upon cross-species comparisons, EEG findings, and developmental neuroscience that the evolution of mirror neurons is most likely driven simultaneously and interactively by evolutionarily adaptive psychological mechanisms and lower-level biological mechanisms that support them.
-
Imitation, mirror neurons and autism
Williams, Justin H.G.; Whiten, Andrew; Suddendorf, Thomas; Perrett, David I.
2001-01-01
Various deficits in the cognitive functioning of people with autism have been documented in recent years but these provide only partial explanations for the condition. We focus instead on an imitative disturbance involving difficulties both in copying actions and in inhibiting more stereotyped mimicking, such as echolalia. A candidate for the neural basis of this disturbance may be found in a recently discovered class of neurons in frontal cortex, 'mirror neurons' (MNs). These neurons show ac...
-
Mirror neurons, birdsong and human language: a hypothesis
Directory of Open Access Journals (Sweden)
Florence eLevy
2012-01-01
Full Text Available AbstractThe Mirror System Hypothesis (MSH and investigations of birdsong are reviewed in relation to the significance for the development of human symbolic and language capacity, in terms of three fundamental forms of cognitive reference: iconic, indexical, and symbolic. Mirror systems are initially iconic but can progress to indexal reference when produced without the need for concurrent stimuli. Developmental stages in birdsong are also explored with reference to juvenile subsong vs complex stereotyped adult syllables, as an analogy with human language development. While birdsong remains at an indexal reference stage, human language benefits from the capacity for symbolic reference. During a pre-linguistic ‘babbling’ stage, recognition of native phonemic categories is established, allowing further development of a subsequent prefrontal and linguistic circuits for sequential language capacity.
-
Mirror neurons, birdsong and human language: a hypothesis
Florence eLevy
2012-01-01
AbstractThe Mirror System Hypothesis (MSH) and investigations of birdsong are reviewed in relation to the significance for the development of human symbolic and language capacity, in terms of three fundamental forms of cognitive reference: iconic, indexical, and symbolic. Mirror systems are initially iconic but can progress to indexal reference when produced without the need for concurrent stimuli. Developmental stages in birdsong are also explored with reference to juvenile subsong vs comple...
-
Social interaction in robotic agents emulating the mirror neuron function
Barakova, E.I.; Mira, J.; Álvarez, J.R.
2007-01-01
Emergent interactions that are expressed by the movements of two agents are discussed in this paper. The common coding principle is used to show how the mirror neuron system may facilitate interaction behaviour. Synchronization between neuron groups in different structures of the mirror neuron
-
Mirror Neurons from Associative Learning
Catmur, Caroline; Press, Clare; Heyes, Cecilia
2016-01-01
Mirror neurons fire both when executing actions and observing others perform similar actions. Their sensorimotor matching properties have generally been considered a genetic adaptation for social cognition; however, in the present chapter we argue that the evidence in favor of this account is not compelling. Instead we present evidence supporting an alternative account: that mirror neurons’ matching properties arise from associative learning during individual development. Notably, this proces...
-
Mirror Neurons, the Development of Empathy, and Digital Story Telling
Hess, Mary
2012-01-01
This article explores the intersection of work in media education, religious education, concerns about digital cultures' impact on human relationality, and the possible role that mirror neurons might play in the development of empathy. Digital story telling--particularly as embodied in the work of the Center for Digital Storytelling…
-
[Empathy and mirror neurons. A view on contemporary neuropsychological empathy research].
Häusser, Leonard F
2012-01-01
Neurons firing both to specific actions performed by self and matching actions performed by others are classified as mirror neurons. Since its discovery in 1991, this phenomenon has been surveyed in the field of motor and sensorimotor function and incipiently in the field of language and emotions. The research group of Giacomo Rizzolatti assumes that mirror neurons form the biological basis of compassion and thereby of affective empathic experience. The research regarding mirror neurons is yet in early stages and further research is required to specify mirror neuron systems. In view of empathy it is the insula which is of central importance for the recognition of disgust. The discovery of mirror neurons allows a comprehension of empathy as an immediate and compassionate partaking of a response, enabling an understanding of the other persons feeling. At the same time, the resonating affect remains allocated to the other person, distinguishing this comprehensive process from a mere emotional contagion. At present, the phenomenon of mirror neurons is gaining clinical relevance in the field of autism spectrum disorders and apoplexia. One's own ability for empathy as well as promoting empathetic abilities of others is of central importance for the clinical praxis, in particular concerning the treatment of children and adolescents.
-
Sensorimotor learning configures the human mirror system.
Catmur, Caroline; Walsh, Vincent; Heyes, Cecilia
2007-09-04
Cells in the "mirror system" fire not only when an individual performs an action but also when one observes the same action performed by another agent [1-4]. The mirror system, found in premotor and parietal cortices of human and monkey brains, is thought to provide the foundation for social understanding and to enable the development of theory of mind and language [5-9]. However, it is unclear how mirror neurons acquire their mirror properties -- how they derive the information necessary to match observed with executed actions [10]. We address this by showing that it is possible to manipulate the selectivity of the human mirror system, and thereby make it operate as a countermirror system, by giving participants training to perform one action while observing another. Before this training, participants showed event-related muscle-specific responses to transcranial magnetic stimulation over motor cortex during observation of little- and index-finger movements [11-13]. After training, this normal mirror effect was reversed. These results indicate that the mirror properties of the mirror system are neither wholly innate [14] nor fixed once acquired; instead they develop through sensorimotor learning [15, 16]. Our findings indicate that the human mirror system is, to some extent, both a product and a process of social interaction.
-
Extending the mirror neuron system model, II: what did I just do? A new role for mirror neurons.
Bonaiuto, James; Arbib, Michael A
2010-04-01
A mirror system is active both when an animal executes a class of actions (self-actions) and when it sees another execute an action of that class. Much attention has been given to the possible roles of mirror systems in responding to the actions of others but there has been little attention paid to their role in self-actions. In the companion article (Bonaiuto et al. Biol Cybern 96:9-38, 2007) we presented MNS2, an extension of the Mirror Neuron System model of the monkey mirror system trained to recognize the external appearance of its own actions as a basis for recognizing the actions of other animals when they perform similar actions. Here we further extend the study of the mirror system by introducing the novel hypotheses that a mirror system may additionally help in monitoring the success of a self-action and may also be activated by recognition of one's own apparent actions as well as efference copy from one's intended actions. The framework for this computational demonstration is a model of action sequencing, called augmented competitive queuing, in which action choice is based on the desirability of executable actions. We show how this "what did I just do?" function of mirror neurons can contribute to the learning of both executability and desirability which in certain cases supports rapid reorganization of motor programs in the face of disruptions.
-
Out of time: a possible link between mirror neurons, autism and electromagnetic radiation.
Thornton, Ian M
2006-01-01
Recent evidence suggests a link between autism and the human mirror neuron system. In this paper, I argue that temporal disruption from the environment may play an important role in the observed mirror neuron dysfunction, leading in turn to the pattern of deficits associated with autism. I suggest that the developing nervous system of an infant may be particularly prone to temporal noise that can interfere with the initial calibration of brain networks such as the mirror neuron system. The most likely source of temporal noise in the environment is artificially generated electromagnetic radiation. To date, there has been little evidence that electromagnetic radiation poses a direct biological hazard. It is clear, however, that time-varying electromagnetic waves have the potential to temporally modulate the nervous system, particularly when populations of neurons are required to act together. This modulation may be completely harmless for the fully developed nervous system of an adult. For an infant, this same temporal disruption might act to severely delay or disrupt vital calibration processes.
-
The Mirror Neuron System: Grasping Others' Actions from Birth?
Lepage, Jean-Francois; Theoret, Hugo
2007-01-01
In the adult human brain, the presence of a system matching the observation and the execution of actions is well established. This mechanism is thought to rely primarily on the contribution of so-called "mirror neurons", cells that are active when a specific gesture is executed as well as when it is seen or heard. Despite the wealth of evidence…
-
Swinnen, S. P.; Alaerts, K.
2015-03-01
The review paper by D'Ausilio and coauthors [3] is very timely and addresses one of the long-standing issues with respect to the coding features of mirror neurons. Through the history of mirror neuron research, there has been some controversy with respect to the level of granularity of the mirror neuron system, as studied in animal and human systems. While some researchers have suggested that abstract (high level) features of movement are coded, others have claimed evidence for more muscle specific (low level) coding properties (for an example, see [1,2]). D'Ausilio et al. [3] take a strong position in their review, suggesting a convergence between basic mechanisms of movement control and the mirror neuron system. Their suggestion is inspired by Bernstein's influential work on the so-called degrees of freedom problem. Even though a goal can in principle be reached in an infinite number of ways, consistent and stereotypical patterns of kinematics and muscle activation are often observed [4]. This has led to the notion of movement synergies as the basic building blocks for movement control. Even though it is essentially possible to contract isolated muscles or even motor units, Bernstein suggested that control of complex movement relies on movement synergies or coordinative structures, referring to a group of muscles that behave as a functional unit. This reduces the computational demands of the central nervous system considerably by assigning more responsibility to the lower levels of the movement control system. Bernstein's approach has inspired the dynamical systems perspective that has focused on a better understanding of complex biological systems such as interlimb coordination in humans [8]. For example, the upper limbs behave as a coordinative structure whereby simultaneous activation of the homologous muscle groups constitutes the default or preferred coordination mode that has to be defied when alternative patterns of coordination need to be performed or
-
The origin and function of mirror neurons: the missing link.
Lingnau, Angelika; Caramazza, Alfonso
2014-04-01
We argue, by analogy to the neural organization of the object recognition system, that demonstration of modulation of mirror neurons by associative learning does not imply absence of genetic adaptation. Innate connectivity defines the types of processes mirror neurons can participate in while allowing for extensive local plasticity. However, the proper function of these neurons remains to be worked out.
-
The role of mirror neurons in language acquisition and evolution.
Behme, Christina
2014-04-01
I argue that Cook et al.'s attack of the genetic hypothesis of mirror neurons misses its target because the authors miss the point that genetics may specify how neurons may learn, not what they learn. Paying more attention to recent work linking mirror neurons to language acquisition and evolution would strengthen Cook et al.'s arguments against a rigid genetic hypothesis.
-
Yuan, Ti-Fei; Chen, Wei; Shan, Chunlei; Rocha, Nuno; Arias-Carrión, Oscar; Paes, Flávia; de Sá, Alberto Souza; Machado, Sergio
2015-01-01
The activity dependent brain repair mechanism has been widely adopted in many types of neurorehabilitation. The activity leads to target specific and non-specific beneficial effects in different brain regions, such as the releasing of neurotrophic factors, modulation of the cytokines and generation of new neurons in adult hood. However physical exercise program clinically are limited to some of the patients with preserved motor functions; while many patients suffered from paralysis cannot make such efforts. Here the authors proposed the employment of mirror neurons system in promoting brain rehabilitation by "observation based stimulation". Mirror neuron system has been considered as an important basis for action understanding and learning by mimicking others. During the action observation, mirror neuron system mediated the direct activation of the same group of motor neurons that are responsible for the observed action. The effect is clear, direct, specific and evolutionarily conserved. Moreover, recent evidences hinted for the beneficial effects on stroke patients after mirror neuron system activation therapy. Finally some music-relevant therapies were proposed to be related with mirror neuron system.
-
Using Mu Rhythm Desynchronization to Measure Mirror Neuron Activity in Infants
Nystrom, Par; Ljunghammar, Therese; Rosander, Kerstin; von Hofsten, Claes
2011-01-01
The Mirror Neuron System hypothesis stating that observed actions are projected onto the observer's own action system assigns an important role to development, because only actions mastered by the observer can be mirrored. The purpose of the present study was to investigate whether there is evidence of a functioning mirror neuron system (MNS) in…
-
Mirror neurons encode the subjective value of an observed action
Caggiano, Vittorio; Fogassi, Leonardo; Rizzolatti, Giacomo; Casile, Antonino; Giese, Martin A.; Thier, Peter
2012-01-01
Objects grasped by an agent have a value not only for the acting agent, but also for an individual observing the grasping act. The value that the observer attributes to the object that is grasped can be pivotal for selecting a possible behavioral response. Mirror neurons in area F5 of the monkey premotor cortex have been suggested to play a crucial role in the understanding of action goals. However, it has not been addressed if these neurons are also involved in representing the value of the grasped object. Here we report that observation-related neuronal responses of F5 mirror neurons are indeed modulated by the value that the monkey associates with the grasped object. These findings suggest that during action observation F5 mirror neurons have access to key information needed to shape the behavioral responses of the observer. PMID:22753471
-
Associative learning is necessary but not sufficient for mirror neuron development
Bonaiuto, James
2014-01-01
Existing computational models of the mirror system demonstrate the additional circuitry needed for mirror neurons to display the range of properties that they exhibit. Such models emphasize the need for existing connectivity to form visuomotor associations, processing to reduce the space of possible inputs, and demonstrate the role neurons with mirror properties might play in monitoring one's own actions.
-
Associative learning is necessary but not sufficient for mirror neuron development.
Bonaiuto, James
2014-04-01
Existing computational models of the mirror system demonstrate the additional circuitry needed for mirror neurons to display the range of properties that they exhibit. Such models emphasize the need for existing connectivity to form visuomotor associations, processing to reduce the space of possible inputs, and demonstrate the role neurons with mirror properties might play in monitoring one's own actions.
-
Fitzgibbon, Bernadette M; Kirkovski, Melissa; Fornito, Alex; Paton, Bryan; Fitzgerald, Paul B; Enticott, Peter G
2016-04-01
Recent neuroimaging studies have demonstrated that activation of the putative human mirror neuron system (MNS) can be elicited via visuomotor training. This is generally interpreted as supporting an associative learning account of the mirror neuron system (MNS) that argues against the ontogeny of the MNS to be an evolutionary adaptation for social cognition. The current study assessed whether a central component of social cognition, emotion processing, would influence the MNS activity to trained visuomotor associations, which could support a broader role of the MNS in social cognition. Using functional magnetic resonance imaging (fMRI), we assessed repetition suppression to the presentation of stimulus pairs involving a simple hand action and a geometric shape that was either congruent or incongruent with earlier association training. Each pair was preceded by an image of positive, negative, or neutral emotionality. In support of an associative learning account of the MNS, repetition suppression was greater for trained pairs compared with untrained pairs in several regions, primarily supplementary motor area (SMA) and right inferior frontal gyrus (rIFG). This response, however, was not modulated by the valence of the emotional images. These findings argue against a fundamental role of emotion processing in the mirror neuron response, and are inconsistent with theoretical accounts linking mirror neurons to social cognition. Copyright © 2016 Elsevier Ltd. All rights reserved.
-
Heyes, Cecilia
2014-01-01
Fifty years ago, Niko Tinbergen defined the scope of behavioural biology with his four problems: causation, ontogeny, survival value and evolution. About 20 years ago, there was another highly significant development in behavioural biology—the discovery of mirror neurons (MNs). Here, I use Tinbergen's original four problems (rather than the list that appears in textbooks) to highlight the differences between two prominent accounts of MNs, the genetic and associative accounts; to suggest that the latter provides the defeasible ‘best explanation’ for current data on the causation and ontogeny of MNs; and to argue that functional analysis, of the kind that Tinbergen identified somewhat misleadingly with studies of ‘survival value’, should be a high priority for future research. In this kind of functional analysis, system-level theories would assign MNs a small, but potentially important, role in the achievement of action understanding—or another social cognitive function—by a production line of interacting component processes. These theories would be tested by experimental intervention in human and non-human animal samples with carefully documented and controlled developmental histories. PMID:24778376
-
Heyes, Cecilia
2014-01-01
Fifty years ago, Niko Tinbergen defined the scope of behavioural biology with his four problems: causation, ontogeny, survival value and evolution. About 20 years ago, there was another highly significant development in behavioural biology-the discovery of mirror neurons (MNs). Here, I use Tinbergen's original four problems (rather than the list that appears in textbooks) to highlight the differences between two prominent accounts of MNs, the genetic and associative accounts; to suggest that the latter provides the defeasible 'best explanation' for current data on the causation and ontogeny of MNs; and to argue that functional analysis, of the kind that Tinbergen identified somewhat misleadingly with studies of 'survival value', should be a high priority for future research. In this kind of functional analysis, system-level theories would assign MNs a small, but potentially important, role in the achievement of action understanding-or another social cognitive function-by a production line of interacting component processes. These theories would be tested by experimental intervention in human and non-human animal samples with carefully documented and controlled developmental histories.
-
Corina, David P; Knapp, Heather Patterson
2008-12-01
In the quest to further understand the neural underpinning of human communication, researchers have turned to studies of naturally occurring signed languages used in Deaf communities. The comparison of the commonalities and differences between spoken and signed languages provides an opportunity to determine core neural systems responsible for linguistic communication independent of the modality in which a language is expressed. The present article examines such studies, and in addition asks what we can learn about human languages by contrasting formal visual-gestural linguistic systems (signed languages) with more general human action perception. To understand visual language perception, it is important to distinguish the demands of general human motion processing from the highly task-dependent demands associated with extracting linguistic meaning from arbitrary, conventionalized gestures. This endeavor is particularly important because theorists have suggested close homologies between perception and production of actions and functions of human language and social communication. We review recent behavioral, functional imaging, and neuropsychological studies that explore dissociations between the processing of human actions and signed languages. These data suggest incomplete overlap between the mirror-neuron systems proposed to mediate human action and language.
-
Action observation and mirror neuron network: a tool for motor stroke rehabilitation.
Sale, P; Franceschini, M
2012-06-01
Mirror neurons are a specific class of neurons that are activated and discharge both during observation of the same or similar motor act performed by another individual and during the execution of a motor act. Different studies based on non invasive neuroelectrophysiological assessment or functional brain imaging techniques have demonstrated the presence of the mirror neuron and their mechanism in humans. Various authors have demonstrated that in the human these networks are activated when individuals learn motor actions via execution (as in traditional motor learning), imitation, observation (as in observational learning) and motor imagery. Activation of these brain areas (inferior parietal lobe and the ventral premotor cortex, as well as the caudal part of the inferior frontal gyrus [IFG]) following observation or motor imagery may thereby facilitate subsequent movement execution by directly matching the observed or imagined action to the internal simulation of that action. It is therefore believed that this multi-sensory action-observation system enables individuals to (re) learn impaired motor functions through the activation of these internal action-related representations. In humans, the mirror mechanism is also located in various brain segment: in Broca's area, which is involved in language processing and speech production and not only in centres that mediate voluntary movement, but also in cortical areas that mediate visceromotor emotion-related behaviours. On basis of this finding, during the last 10 years various studies were carry out regarding the clinical use of action observation for motor rehabilitation of sub-acute and chronic stroke patients.
-
From quantum entanglement to mirror neuron
International Nuclear Information System (INIS)
Zak, Michail
2007-01-01
It is proposed that two fundamental phenomena: quantum entanglement in physics, and mirror neuron in biopsychology, can be described by using the same mathematical formalism, namely, the feedback from the Liouville equation to equation of motion
-
Do mirror neurons explain misattribution of emotions in music?
Gridley, Mark C; Hoff, Robert
2006-04-01
It is speculated that certain listeners' misattribution of anger in the music of avant garde jazz saxophonists could be explained by the activity of mirror neurons. There is a neurological basis for the human tendency to imitate what is perceived in another person. This may lead to an inference that whatever comparable activity would be required to achieve a similar condition in the imitator is the condition being experienced by the person being imitated.
-
From music making to speaking: Engaging the mirror neuron system in autism
Wan, Catherine Y.; Demaine, Krystal; Zipse, Lauryn; Norton, Andrea; Schlaug, Gottfried
2010-01-01
Individuals with autism show impairments in emotional tuning, social interactions and communication. These are functions that have been attributed to the putative human mirror neuron system (MNS), which contains neurons that respond to the actions of self and others. It has been proposed that a dysfunction of that system underlies some of the characteristics of autism. Here, we review behavioral and imaging studies that implicate the MNS (or a brain network with similar functions) in sensory-...
-
Fogassi, Leonardo; Ferrari, Pier Francesco
2011-01-01
Mirror neurons are a class of visuomotor neurons, discovered in the monkey premotor cortex and in an anatomically connected area of the inferior parietal lobule, that activate both during action execution and action observation. They constitute a circuit dedicated to match actions made by others with the internal motor representations of the observer. It has been proposed that this matching system enables individuals to understand others' behavior and motor intentions. Here we will describe the main features of mirror neurons in monkeys. Then we will present evidence of the presence of a mirror system in humans and of its involvement in several social-cognitive functions, such as imitation, intention, and emotion understanding. This system may have several implications at a cognitive level and could be linked to specific social deficits in humans such as autism. Recent investigations addressed the issue of the plasticity of the mirror neuron system in both monkeys and humans, suggesting also their possible use in rehabilitation. WIREs Cogn Sci 2011 2 22-38 DOI: 10.1002/wcs.89 For further resources related to this article, please visit the WIREs website. Copyright © 2010 John Wiley & Sons, Ltd.
-
Mirror neurons and their clinical relevance.
Rizzolatti, Giacomo; Fabbri-Destro, Maddalena; Cattaneo, Luigi
2009-01-01
One of the most exciting events in neurosciences over the past few years has been the discovery of a mechanism that unifies action perception and action execution. The essence of this 'mirror' mechanism is as follows: whenever individuals observe an action being done by someone else, a set of neurons that code for that action is activated in the observers' motor system. Since the observers are aware of the outcome of their motor acts, they also understand what the other individual is doing without the need for intermediate cognitive mediation. In this Review, after discussing the most pertinent data concerning the mirror mechanism, we examine the clinical relevance of this mechanism. We first discuss the relationship between mirror mechanism impairment and some core symptoms of autism. We then outline the theoretical principles of neurorehabilitation strategies based on the mirror mechanism. We conclude by examining the relationship between the mirror mechanism and some features of the environmental dependency syndromes.
-
Studying the Behaviour of Model of Mirror Neuron System in Case of Autism
Directory of Open Access Journals (Sweden)
Shikha Anirban
2012-04-01
Full Text Available Several experiment done by the researchers conducted that autism is caused by the dysfunctional mirror neuron system and the dysfunctions of mirror neuron system is proportional to the symptom severity of autism. In the present work those experiments were studied as well as studying a model of mirror neuron system called MNS2 developed by a research group. This research examined the behavior of the model in case of autism and compared the result with those studies conducting dysfunctions of mirror neuron system in autism. To perform this, a neural network employing the model was developed which recognized the three types of grasping (faster, normal and slower. The network was implemented with back propagation through time learning algorithm. The whole grasping process was divided into 30 time steps and different hand and object states at each time step was used as the input of the network. Normally the network successfully recognized all of the three types of grasps. The network required more times as the number of inactive neurons increased. And in case of maximum inactive neurons of the mirror neuron system the network became unable to recognize the types of grasp. As the time to recognize the types of grasp is proportional to the number of inactive neurons, the experiment result supports the hypothesis that dysfunctions of MNS is proportional to the symptom severity of autism. Keywords— Autism, MNS, mirror neuron, neural network, BPTT
-
[Infantile autism and mirror neurons].
Cornelio-Nieto, J O
2009-02-27
Infantile autism is a disorder that is characterised by alterations affecting reciprocal social interactions, abnormal verbal and non-verbal communication, poor imaginative activity and a restricted repertoire of activities and interests. The causes of autism remain unknown, but there are a number of different approaches that attempt to explain the neurobiological causes of the syndrome. A recent theory that has been considered is that of a dysfunction in the mirror neuron system (MNS). The MNS is a neuronal complex, originally described in monkeys and also found in humans, that is related with our movements and which offers specific responses to the movements and intended movements of other subjects. This system is believed to underlie processes of imitation and our capacity to learn by imitation. It is also thought to play a role in language acquisition, in expressing the emotions, in understanding what is happening to others and in empathy. Because these functions are altered in children with autism, it has been suggested that there is some dysfunction present in the MNS of those with autism. Dysfunction of the MNS could account for the symptoms that are observed in children with autism.
-
Walk like me, talk like me. The connection between mirror neurons and autism spectrum disorder.
Saffin, Jillian M; Tohid, Hassaan
2016-04-01
Understanding social cognition has become a hallmark in deciphering autism spectrum disorder. Neurobiological theories are taking precedence in causation studies as researchers look to abnormalities in brain development as the cause of deficits in social behavior, cognitive processes, and language. Following their discovery in the 1990s, mirror neurons have become a dominant theory for that the mirror neuron system may play a critical role in the pathophysiology of various symptoms of autism. Over the decades, the theory has evolved from the suggestion of a broken mirror neuron system to impairments in mirror neuron circuitry. The mirror neuron system has not gained total support due to inconsistent findings; a comprehensive analysis of the growing body of research could shed light on the benefits, or the disadvantage of continuing to study mirror neurons and their connection to autism.
-
Directory of Open Access Journals (Sweden)
Pineda Jaime A
2008-10-01
Full Text Available Abstract A core assumption of how humans understand and infer the intentions and beliefs of others is the existence of a functional self-other distinction. At least two neural systems have been proposed to manage such a critical distinction. One system, part of the classic motor system, is specialized for the preparation and execution of motor actions that are self realized and voluntary, while the other appears primarily involved in capturing and understanding the actions of non-self or others. The latter system, of which the mirror neuron system is part, is the canonical action 'resonance' system in the brain that has evolved to share many of the same circuits involved in motor control. Mirroring or 'shared circuit systems' are assumed to be involved in resonating, imitating, and/or simulating the actions of others. A number of researchers have proposed that shared representations of motor actions may form a foundational cornerstone for higher order social processes, such as motor learning, action understanding, imitation, perspective taking, understanding facial emotions, and empathy. However, mirroring systems that evolve from the classic motor system present at least three problems: a development, a correspondence, and a control problem. Developmentally, the question is how does a mirroring system arise? How do humans acquire the ability to simulate through mapping observed onto executed actions? Are mirror neurons innate and therefore genetically programmed? To what extent is learning necessary? In terms of the correspondence problem, the question is how does the observer agent know what the observed agent's resonance activation pattern is? How does the matching of motor activation patterns occur? Finally, in terms of the control problem, the issue is how to efficiently control a mirroring system when it is turned on automatically through observation? Or, as others have stated the problem more succinctly: "Why don't we imitate all the time
-
Pineda, Jaime A
2008-01-01
A core assumption of how humans understand and infer the intentions and beliefs of others is the existence of a functional self-other distinction. At least two neural systems have been proposed to manage such a critical distinction. One system, part of the classic motor system, is specialized for the preparation and execution of motor actions that are self realized and voluntary, while the other appears primarily involved in capturing and understanding the actions of non-self or others. The latter system, of which the mirror neuron system is part, is the canonical action 'resonance' system in the brain that has evolved to share many of the same circuits involved in motor control. Mirroring or 'shared circuit systems' are assumed to be involved in resonating, imitating, and/or simulating the actions of others. A number of researchers have proposed that shared representations of motor actions may form a foundational cornerstone for higher order social processes, such as motor learning, action understanding, imitation, perspective taking, understanding facial emotions, and empathy. However, mirroring systems that evolve from the classic motor system present at least three problems: a development, a correspondence, and a control problem. Developmentally, the question is how does a mirroring system arise? How do humans acquire the ability to simulate through mapping observed onto executed actions? Are mirror neurons innate and therefore genetically programmed? To what extent is learning necessary? In terms of the correspondence problem, the question is how does the observer agent know what the observed agent's resonance activation pattern is? How does the matching of motor activation patterns occur? Finally, in terms of the control problem, the issue is how to efficiently control a mirroring system when it is turned on automatically through observation? Or, as others have stated the problem more succinctly: "Why don't we imitate all the time?" In this review, we argue
-
Kalinowski, Joseph; Saltuklaroglu, Tim
2003-04-01
'Choral speech', 'unison speech', or 'imitation speech' has long been known to immediately induce reflexive, spontaneous, and natural sounding fluency, even the most severe cases of stuttering. Unlike typical post-therapeutic speech, a hallmark characteristic of choral speech is the sense of 'invulnerability' to stuttering, regardless of phonetic context, situational environment, or audience size. We suggest that choral speech immediately inhibits stuttering by engaging mirror systems of neurons, innate primitive neuronal substrates that dominate the initial phases of language development due to their predisposition to reflexively imitate gestural action sequences in a fluent manner. Since mirror systems are primordial in nature, they take precedence over the much later developing stuttering pathology. We suggest that stuttering may best be ameliorated by reengaging mirror neurons via choral speech or one of its derivatives (using digital signal processing technology) to provide gestural mirrors, that are nature's way of immediately overriding the central stuttering block. Copyright 2003 Elsevier Science Ltd.
-
Antunes, Gabriela; Faria da Silva, Samuel F; Simoes de Souza, Fabio M
2018-06-01
Mirror neurons fire action potentials both when the agent performs a certain behavior and watches someone performing a similar action. Here, we present an original mirror neuron model based on the spike-timing-dependent plasticity (STDP) between two morpho-electrical models of neocortical pyramidal neurons. Both neurons fired spontaneously with basal firing rate that follows a Poisson distribution, and the STDP between them was modeled by the triplet algorithm. Our simulation results demonstrated that STDP is sufficient for the rise of mirror neuron function between the pairs of neocortical neurons. This is a proof of concept that pairs of neocortical neurons associating sensory inputs to motor outputs could operate like mirror neurons. In addition, we used the mirror neuron model to investigate whether channelopathies associated with autism spectrum disorder could impair the modeled mirror function. Our simulation results showed that impaired hyperpolarization-activated cationic currents (Ih) affected the mirror function between the pairs of neocortical neurons coupled by STDP.
-
Confounding the origin and function of mirror neurons.
Rizzolatti, Giacomo
2014-04-01
Cook et al. argue that mirror neurons originate in sensorimotor associative learning and that their function is determined by their origin. Both these claims are hard to accept. It is here suggested that a major role in the origin of the mirror mechanism is played by top-down connections rather than by associative learning.
-
Dapretto, Mirella; Davies, Mari S; Pfeifer, Jennifer H; Scott, Ashley A; Sigman, Marian; Bookheimer, Susan Y; Iacoboni, Marco
2005-01-01
To examine mirror neuron abnormalities in autism, high-functioning children with autism and matched controls underwent fMRI while imitating and observing emotional expressions. Although both groups performed the tasks equally well, children with autism showed no mirror neuron activity in the inferior frontal gyrus (pars opercularis). Notably, activity in this area was inversely related to symptom severity in the social domain, suggesting that a dysfunctional ‘mirror neuron system’ may underli...
-
View-Invariant Visuomotor Processing in Computational Mirror Neuron System for Humanoid
Dawood, Farhan; Loo, Chu Kiong
2016-01-01
Mirror neurons are visuo-motor neurons found in primates and thought to be significant for imitation learning. The proposition that mirror neurons result from associative learning while the neonate observes his own actions has received noteworthy empirical support. Self-exploration is regarded as a procedure by which infants become perceptually observant to their own body and engage in a perceptual communication with themselves. We assume that crude sense of self is the prerequisite for social interaction. However, the contribution of mirror neurons in encoding the perspective from which the motor acts of others are seen have not been addressed in relation to humanoid robots. In this paper we present a computational model for development of mirror neuron system for humanoid based on the hypothesis that infants acquire MNS by sensorimotor associative learning through self-exploration capable of sustaining early imitation skills. The purpose of our proposed model is to take into account the view-dependency of neurons as a probable outcome of the associative connectivity between motor and visual information. In our experiment, a humanoid robot stands in front of a mirror (represented through self-image using camera) in order to obtain the associative relationship between his own motor generated actions and his own visual body-image. In the learning process the network first forms mapping from each motor representation onto visual representation from the self-exploratory perspective. Afterwards, the representation of the motor commands is learned to be associated with all possible visual perspectives. The complete architecture was evaluated by simulation experiments performed on DARwIn-OP humanoid robot. PMID:26998923
-
View-Invariant Visuomotor Processing in Computational Mirror Neuron System for Humanoid.
Dawood, Farhan; Loo, Chu Kiong
2016-01-01
Mirror neurons are visuo-motor neurons found in primates and thought to be significant for imitation learning. The proposition that mirror neurons result from associative learning while the neonate observes his own actions has received noteworthy empirical support. Self-exploration is regarded as a procedure by which infants become perceptually observant to their own body and engage in a perceptual communication with themselves. We assume that crude sense of self is the prerequisite for social interaction. However, the contribution of mirror neurons in encoding the perspective from which the motor acts of others are seen have not been addressed in relation to humanoid robots. In this paper we present a computational model for development of mirror neuron system for humanoid based on the hypothesis that infants acquire MNS by sensorimotor associative learning through self-exploration capable of sustaining early imitation skills. The purpose of our proposed model is to take into account the view-dependency of neurons as a probable outcome of the associative connectivity between motor and visual information. In our experiment, a humanoid robot stands in front of a mirror (represented through self-image using camera) in order to obtain the associative relationship between his own motor generated actions and his own visual body-image. In the learning process the network first forms mapping from each motor representation onto visual representation from the self-exploratory perspective. Afterwards, the representation of the motor commands is learned to be associated with all possible visual perspectives. The complete architecture was evaluated by simulation experiments performed on DARwIn-OP humanoid robot.
-
View-Invariant Visuomotor Processing in Computational Mirror Neuron System for Humanoid.
Directory of Open Access Journals (Sweden)
Farhan Dawood
Full Text Available Mirror neurons are visuo-motor neurons found in primates and thought to be significant for imitation learning. The proposition that mirror neurons result from associative learning while the neonate observes his own actions has received noteworthy empirical support. Self-exploration is regarded as a procedure by which infants become perceptually observant to their own body and engage in a perceptual communication with themselves. We assume that crude sense of self is the prerequisite for social interaction. However, the contribution of mirror neurons in encoding the perspective from which the motor acts of others are seen have not been addressed in relation to humanoid robots. In this paper we present a computational model for development of mirror neuron system for humanoid based on the hypothesis that infants acquire MNS by sensorimotor associative learning through self-exploration capable of sustaining early imitation skills. The purpose of our proposed model is to take into account the view-dependency of neurons as a probable outcome of the associative connectivity between motor and visual information. In our experiment, a humanoid robot stands in front of a mirror (represented through self-image using camera in order to obtain the associative relationship between his own motor generated actions and his own visual body-image. In the learning process the network first forms mapping from each motor representation onto visual representation from the self-exploratory perspective. Afterwards, the representation of the motor commands is learned to be associated with all possible visual perspectives. The complete architecture was evaluated by simulation experiments performed on DARwIn-OP humanoid robot.
-
Dapretto, Mirella; Davies, Mari S; Pfeifer, Jennifer H; Scott, Ashley A; Sigman, Marian; Bookheimer, Susan Y; Iacoboni, Marco
2006-01-01
To examine mirror neuron abnormalities in autism, high-functioning children with autism and matched controls underwent fMRI while imitating and observing emotional expressions. Although both groups performed the tasks equally well, children with autism showed no mirror neuron activity in the inferior frontal gyrus (pars opercularis). Notably, activity in this area was inversely related to symptom severity in the social domain, suggesting that a dysfunctional 'mirror neuron system' may underlie the social deficits observed in autism.
-
Imitation, mirror neurons and autism.
Williams, J H; Whiten, A; Suddendorf, T; Perrett, D I
2001-06-01
Various deficits in the cognitive functioning of people with autism have been documented in recent years but these provide only partial explanations for the condition. We focus instead on an imitative disturbance involving difficulties both in copying actions and in inhibiting more stereotyped mimicking, such as echolalia. A candidate for the neural basis of this disturbance may be found in a recently discovered class of neurons in frontal cortex, 'mirror neurons' (MNs). These neurons show activity in relation both to specific actions performed by self and matching actions performed by others, providing a potential bridge between minds. MN systems exist in primates without imitative and 'theory of mind' abilities and we suggest that in order for them to have become utilized to perform social cognitive functions, sophisticated cortical neuronal systems have evolved in which MNs function as key elements. Early developmental failures of MN systems are likely to result in a consequent cascade of developmental impairments characterised by the clinical syndrome of autism.
-
Ho, S Shaun; Macdonald, Adam; Swain, James E
2014-04-01
Mirror neuron-based associative learning may be understood according to associative learning theories, in addition to sensorimotor learning theories. This is important for a comprehensive understanding of the role of mirror neurons and related hormone modulators, such as oxytocin, in complex social interactions such as among parent-infant dyads and in examples of mirror neuron function that involve abnormal motor systems such as depression.
-
Possible Links among Mirror Neurons and Genes Related to Autism
MOCHIZUKI, Mai; 望月，麻衣
2016-01-01
Autism includes many neurodevelopmental disorders and defi cits in communication. Althoughresearchers have considered various origins, the onset mechanism is still not clear. The aim ofthis article is to provide some clues for interaction of autism with mirror neuronal and geneticfactors. First, the impact of neural brain cells considered to infl uence autism will be discussedwith reference to mirror neurons. Then, the discussion will move to genes related to autism.Consequently, it is argued...
-
Studying the Behaviour of Model of Mirror Neuron System in Case of Autism
Anirban, Shikha; Hanif Ali, Mohammad
2012-01-01
Several experiment done by the researchers conducted that autism is caused by the dysfunctional mirror neuron system and the dysfunctions of mirror neuron system is proportional to the symptom severity of autism. In the present work those experiments were studied as well as studying a model of mirror neuron system called MNS2 developed by a research group. This research examined the behavior of the model in case of autism and compared the result with those studies conducting dysfunctions of m...
-
Auditory-vocal mirroring in songbirds.
Mooney, Richard
2014-01-01
Mirror neurons are theorized to serve as a neural substrate for spoken language in humans, but the existence and functions of auditory-vocal mirror neurons in the human brain remain largely matters of speculation. Songbirds resemble humans in their capacity for vocal learning and depend on their learned songs to facilitate courtship and individual recognition. Recent neurophysiological studies have detected putative auditory-vocal mirror neurons in a sensorimotor region of the songbird's brain that plays an important role in expressive and receptive aspects of vocal communication. This review discusses the auditory and motor-related properties of these cells, considers their potential role on song learning and communication in relation to classical studies of birdsong, and points to the circuit and developmental mechanisms that may give rise to auditory-vocal mirroring in the songbird's brain.
-
Mirror neuron dysfunction in autism spectrum disorders.
Perkins, Tom; Stokes, Mark; McGillivray, Jane; Bittar, Richard
2010-10-01
Autism spectrum disorders (ASDs) are developmental conditions characterized by deficits in social interaction, verbal and nonverbal communication and obsessive/stereotyped patterns of behaviour. Although there is no reliable neurophysiological marker associated with ASDs, dysfunction of the parieto-frontal mirror neuron system has been suggested as a disturbance linked to the disorder. Mirror neurons (MNs) are visuomotor neurons which discharge both when performing and observing a goal directed action. Research suggests MNs may have a role in imitation, empathy, theory of mind and language. Although the research base is small, evidence from functional MRI, transcranial magnetic stimulation, and an electroencephalographic component called the mu rhythm suggests MNs are dysfunctional in subjects with ASD. These deficits are more pronounced when ASD subjects complete tasks with social relevance, or that are emotional in nature. Promising research has identified that interventions targeting MN related functions such as imitation can improve social functioning in ASDs. Boosting the function of MNs may improve the prognosis of ASDs, and contribute to diagnostic clarity. Copyright 2010 Elsevier Ltd. All rights reserved.
-
Hebbian learning and predictive mirror neurons for actions, sensations and emotions.
Keysers, Christian; Gazzola, Valeria
2014-01-01
Spike-timing-dependent plasticity is considered the neurophysiological basis of Hebbian learning and has been shown to be sensitive to both contingency and contiguity between pre- and postsynaptic activity. Here, we will examine how applying this Hebbian learning rule to a system of interconnected neurons in the presence of direct or indirect re-afference (e.g. seeing/hearing one's own actions) predicts the emergence of mirror neurons with predictive properties. In this framework, we analyse how mirror neurons become a dynamic system that performs active inferences about the actions of others and allows joint actions despite sensorimotor delays. We explore how this system performs a projection of the self onto others, with egocentric biases to contribute to mind-reading. Finally, we argue that Hebbian learning predicts mirror-like neurons for sensations and emotions and review evidence for the presence of such vicarious activations outside the motor system.
-
[The mirror neuron system in motor and sensory rehabilitation].
Oouchida, Yutaka; Izumi, Shinichi
2014-06-01
The discovery of the mirror neuron system has dramatically changed the study of motor control in neuroscience. The mirror neuron system provides a conceptual framework covering the aspects of motor as well as sensory functions in motor control. Previous studies of motor control can be classified as studies of motor or sensory functions, and these two classes of studies appear to have advanced independently. In rehabilitation requiring motor learning, such as relearning movement after limb paresis, however, sensory information of feedback for motor output as well as motor command are essential. During rehabilitation from chronic pain, motor exercise is one of the most effective treatments for pain caused by dysfunction in the sensory system. In rehabilitation where total intervention unifying the motor and sensory aspects of motor control is important, learning through imitation, which is associated with the mirror neuron system can be effective and suitable. In this paper, we introduce the clinical applications of imitated movement in rehabilitation from motor impairment after brain damage and phantom limb pain after limb amputation.
-
Timecourse of mirror and counter-mirror effects measured with transcranial magnetic stimulation.
Cavallo, Andrea; Heyes, Cecilia; Becchio, Cristina; Bird, Geoffrey; Catmur, Caroline
2014-08-01
The human mirror system has been the subject of much research over the past two decades, but little is known about the timecourse of mirror responses. In addition, it is unclear whether mirror and counter-mirror effects follow the same timecourse. We used single-pulse transcranial magnetic stimulation to investigate the timecourse of mirror and counter-mirror responses in the human brain. Experiment 1 demonstrated that mirror responses can be measured from around 200 ms after observed action onset. Experiment 2 demonstrated significant effects of counter-mirror sensorimotor training at all timepoints at which a mirror response was found in Experiment 1 (i.e. from 200 ms onward), indicating that mirror and counter-mirror responses follow the same timecourse. By suggesting similarly direct routes for mirror and counter-mirror responses, these results support the associative account of mirror neuron origins whereby mirror responses arise as a result of correlated sensorimotor experience during development. More generally, they contribute to theorizing regarding mirror neuron function by providing some constraints on how quickly mirror responses can influence social cognition. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.
-
Keysers, Christian; Perrett, David I; Gazzola, Valeria
2014-04-01
Hebbian Learning should not be reduced to contiguity, as it detects contingency and causality. Hebbian Learning accounts of mirror neurons make predictions that differ from associative learning: Through Hebbian Learning, mirror neurons become dynamic networks that calculate predictions and prediction errors and relate to ideomotor theories. The social force of imitation is important for mirror neuron emergence and suggests canalization.
-
Auditory–vocal mirroring in songbirds
Mooney, Richard
2014-01-01
Mirror neurons are theorized to serve as a neural substrate for spoken language in humans, but the existence and functions of auditory–vocal mirror neurons in the human brain remain largely matters of speculation. Songbirds resemble humans in their capacity for vocal learning and depend on their learned songs to facilitate courtship and individual recognition. Recent neurophysiological studies have detected putative auditory–vocal mirror neurons in a sensorimotor region of the songbird's brain that plays an important role in expressive and receptive aspects of vocal communication. This review discusses the auditory and motor-related properties of these cells, considers their potential role on song learning and communication in relation to classical studies of birdsong, and points to the circuit and developmental mechanisms that may give rise to auditory–vocal mirroring in the songbird's brain. PMID:24778375
-
Mirror neuron activity associated with social impairments but not age in autism spectrum disorder.
Enticott, Peter G; Kennedy, Hayley A; Rinehart, Nicole J; Tonge, Bruce J; Bradshaw, John L; Taffe, John R; Daskalakis, Zafiris J; Fitzgerald, Paul B
2012-03-01
The neurobiology of autism spectrum disorder (ASD) is not particularly well understood, and biomedical treatment approaches are therefore extremely limited. A prominent explanatory model suggests that social-relating symptoms may arise from dysfunction within the mirror neuron system, while a recent neuroimaging study suggests that these impairments in ASD might reduce with age. Participants with autism spectrum disorder (i.e., DSM-IV autistic disorder or Asperger's disorder) (n = 34) and matched control subjects (n = 36) completed a transcranial magnetic stimulation study in which corticospinal excitability was assessed during the observation of hand gestures. Regression analyses revealed that the ASD group presented with significantly reduced corticospinal excitability during the observation of a transitive hand gesture (relative to observation of a static hand) (p mirror neuron system activity within ventral premotor cortex/inferior frontal gyrus. Among the ASD group, there was also a negative association between putative mirror neuron activity and self-reported social-relating impairments, but there was no indication that mirror neuron impairments in ASD decrease with age. These data provide general support for the mirror neuron hypothesis of autism; researchers now must clarify the precise functional significance of mirror neurons to truly understand their role in the neuropathophysiology of ASD and to determine whether they should be used as targets for the treatment of ASD.
-
Keysers, C.; Perrett, D.I.; Gazzola, V.
2014-01-01
Hebbian Learning should not be reduced to contiguity, as it detects contingency and causality. Hebbian Learning accounts of mirror neurons make predictions that differ from associative learning: Through Hebbian Learning, mirror neurons become dynamic networks that calculate predictions and prediction errors and relate to ideomotor theories. The social force of imitation is important for mirror neuron emergence and suggests canalization. Publisher PDF Peer reviewed
-
Language comprehension warps the mirror neuron system
Directory of Open Access Journals (Sweden)
Noah eZarr
2013-12-01
Full Text Available Is the mirror neuron system (MNS used in language understanding? According to embodied accounts of language comprehension, understanding sentences describing actions makes use of neural mechanisms of action control, including the MNS. Consequently, repeatedly comprehending sentences describing similar actions should induce adaptation of the MNS thereby warping its use in other cognitive processes such as action recognition and prediction. To test this prediction, participants read blocks of multiple sentences where each sentence in the block described transfer of objects in a direction away or toward the reader. Following each block, adaptation was measured by having participants predict the end-point of videotaped actions. The adapting sentences disrupted prediction of actions in the same direction, but a only for videos of biological motion, and b only when the effector implied by the language (e.g., the hand matched the videos. These findings are signatures of the mirror neuron system.
-
van Gog, Tamara; Paas, Fred; Marcus, Nadine; Ayres, Paul; Sweller, John
2009-01-01
Learning by observing and imitating others has long been recognized as constituting a powerful learning strategy for humans. Recent findings from neuroscience research, more specifically on the mirror neuron system, begin to provide insight into the neural bases of learning by observation and imitation. These findings are discussed here, along…
-
Williams, Justin H G
2008-04-01
Mirror neuron system dysfunction may underlie a self-other matching impairment, which has previously been suggested to account for autism. Embodied Cognition Theory, which proposes that action provides a foundation for cognition has lent further credence to these ideas. The hypotheses of a self-other matching deficit and impaired mirror neuron function in autism have now been well supported by studies employing a range of methodologies. However, underlying mechanisms require further exploration to explain how mirror neurons may be involved in attentional and mentalizing processes. Impairments in self-other matching and mirror neuron function are not necessarily inextricably linked and it seems possible that different sub-populations of mirror neurons, located in several regions, contribute differentially to social cognitive functions. It is hypothesized that mirror neuron coding for action-direction may be required for developing attentional sensitivity to self-directed actions, and consequently for person-oriented, stimulus-driven attention. Mirror neuron networks may vary for different types of social learning such as "automatic" imitation and imitation learning. Imitation learning may be more reliant on self-other comparison processes (based on mirror neurons) that identify differences as well as similarities between actions. Differential connectivity with the amygdala-orbitofrontal system may also be important. This could have implications for developing "theory of mind," with intentional self-other comparison being relevant to meta-representational abilities, and "automatic" imitation being more relevant to empathy. While it seems clear that autism is associated with impaired development of embodied aspects of cognition, the ways that mirror neurons contribute to these brain-behavior links are likely to be complex.
-
Ho, S. Shaun; MacDonald, Adam; Swain, James E.
2014-01-01
Mirror neuron–based associative learning may be understood according to associative learning theories, in addition to sensorimotor learning theories. This is important for a comprehensive understanding of the role of mirror neurons and related hormone modulators, such as oxytocin, in complex social interactions such as among parent–infant dyads and in examples of mirror neuron function that involve abnormal motor systems such as depression.
-
Spatio-temporal dynamics of the mirror neuron system during social intentions.
Cacioppo, Stephanie; Bolmont, Mylene; Monteleone, George
2017-10-27
Previous research has shown that specific goals and intentions influence a person's allocation of social attention. From a neural viewpoint, a growing body of evidence suggests that the inferior fronto-parietal network, including the mirror neuron system, plays a role in the planning and the understanding of motor intentions. However, it is unclear whether and when the mirror neuron system plays a role in social intentions. Combining a behavioral task with electrical neuroimaging in 22 healthy male participants, the current study investigates whether the temporal brain dynamic of the mirror neuron system differs during two types of social intentions i.e., lust vs. romantic intentions. Our results showed that 62% of the stimuli evoking lustful intentions also evoked romantic intentions, and both intentions were sustained by similar activations of the inferior frontal gyrus and the inferior parietal lobule/angular gyrus for the first 432 ms after stimulus onset. Intentions to not love or not lust, on the other hand, were characterized by earlier differential activations of the inferior fronto-parietal network i.e., as early as 244 ms after stimulus onset. These results suggest that the mirror neuron system may not only code for the motor correlates of intentions, but also for the social meaning of intentions and its valence at both early/automatic and later/more elaborative stages of information processing.
-
Coupling Perception with Actions via Mirror Neurons
Czech Academy of Sciences Publication Activity Database
Wiedermann, Jiří
č. 55 (2003), s. 11-12 ISSN 0926-4981 R&D Projects: GA ČR GA201/02/1456 Institutional research plan: AV0Z1030915 Keywords : mirror neurons * cognitive agents * neural nets Subject RIV: BA - General Mathematics http://www.ercim.eu/publication/Ercim_News/enw55/wiedermann.html
-
Oh, Hyuk; Gentili, Rodolphe J; Reggia, James A; Contreras-Vidal, José L
2011-01-01
It has been suggested that the human mirror neuron system can facilitate learning by imitation through coupling of observation and action execution. During imitation of observed actions, the functional relationship between and within the inferior frontal cortex, the posterior parietal cortex, and the superior temporal sulcus can be modeled within the internal model framework. The proposed biologically plausible mirror neuron system model extends currently available models by explicitly modeling the intraparietal sulcus and the superior parietal lobule in implementing the function of a frame of reference transformation during imitation. Moreover, the model posits the ventral premotor cortex as performing an inverse computation. The simulations reveal that: i) the transformation system can learn and represent the changes in extrinsic to intrinsic coordinates when an imitator observes a demonstrator; ii) the inverse model of the imitator's frontal mirror neuron system can be trained to provide the motor plans for the imitated actions.
-
Oh, Hyuk; Gentili, Rodolphe J.; Reggia, James A.; Contreras-Vidal, José L.
2014-01-01
It has been suggested that the human mirror neuron system can facilitate learning by imitation through coupling of observation and action execution. During imitation of observed actions, the functional relationship between and within the inferior frontal cortex, the posterior parietal cortex, and the superior temporal sulcus can be modeled within the internal model framework. The proposed biologically plausible mirror neuron system model extends currently available models by explicitly modeling the intraparietal sulcus and the superior parietal lobule in implementing the function of a frame of reference transformation during imitation. Moreover, the model posits the ventral premotor cortex as performing an inverse computation. The simulations reveal that: i) the transformation system can learn and represent the changes in extrinsic to intrinsic coordinates when an imitator observes a demonstrator; ii) the inverse model of the imitator’s frontal mirror neuron system can be trained to provide the motor plans for the imitated actions. PMID:22255261
-
Keysers, C.; Perrett, David I; Gazzola, Valeria
Hebbian Learning should not be reduced to contiguity, as it detects contingency and causality. Hebbian Learning accounts of mirror neurons make predictions that differ from associative learning: Through Hebbian Learning, mirror neurons become dynamic networks that calculate predictions and
-
Lateralization of the human mirror neuron system.
Aziz-Zadeh, Lisa; Koski, Lisa; Zaidel, Eran; Mazziotta, John; Iacoboni, Marco
2006-03-15
A cortical network consisting of the inferior frontal, rostral inferior parietal, and posterior superior temporal cortices has been implicated in representing actions in the primate brain and is critical to imitation in humans. This neural circuitry may be an evolutionary precursor of neural systems associated with language. However, language is predominantly lateralized to the left hemisphere, whereas the degree of lateralization of the imitation circuitry in humans is unclear. We conducted a functional magnetic resonance imaging study of imitation of finger movements with lateralized stimuli and responses. During imitation, activity in the inferior frontal and rostral inferior parietal cortex, although fairly bilateral, was stronger in the hemisphere ipsilateral to the visual stimulus and response hand. This ipsilateral pattern is at variance with the typical contralateral activity of primary visual and motor areas. Reliably increased signal in the right superior temporal sulcus (STS) was observed for both left-sided and right-sided imitation tasks, although subthreshold activity was also observed in the left STS. Overall, the data indicate that visual and motor components of the human mirror system are not left-lateralized. The left hemisphere superiority for language, then, must be have been favored by other types of language precursors, perhaps auditory or multimodal action representations.
-
Brain regions with mirror properties: a meta-analysis of 125 human fMRI studies.
Molenberghs, Pascal; Cunnington, Ross; Mattingley, Jason B
2012-01-01
Mirror neurons in macaque area F5 fire when an animal performs an action, such as a mouth or limb movement, and also when the animal passively observes an identical or similar action performed by another individual. Brain-imaging studies in humans conducted over the last 20 years have repeatedly attempted to reveal analogous brain regions with mirror properties in humans, with broad and often speculative claims about their functional significance across a range of cognitive domains, from language to social cognition. Despite such concerted efforts, the likely neural substrates of these mirror regions have remained controversial, and indeed the very existence of a distinct subcategory of human neurons with mirroring properties has been questioned. Here we used activation likelihood estimation (ALE), to provide a quantitative index of the consistency of patterns of fMRI activity measured in human studies of action observation and action execution. From an initial sample of more than 300 published works, data from 125 papers met our strict inclusion and exclusion criteria. The analysis revealed 14 separate clusters in which activation has been consistently attributed to brain regions with mirror properties, encompassing 9 different Brodmann areas. These clusters were located in areas purported to show mirroring properties in the macaque, such as the inferior parietal lobule, inferior frontal gyrus and the adjacent ventral premotor cortex, but surprisingly also in regions such as the primary visual cortex, cerebellum and parts of the limbic system. Our findings suggest a core network of human brain regions that possess mirror properties associated with action observation and execution, with additional areas recruited during tasks that engage non-motor functions, such as auditory, somatosensory and affective components. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.
-
Dysfunction of the Human Mirror Neuron System in Ideomotor Apraxia: Evidence from Mu Suppression.
Frenkel-Toledo, Silvi; Liebermann, Dario G; Bentin, Shlomo; Soroker, Nachum
2016-06-01
Stroke patients with ideomotor apraxia (IMA) have difficulties controlling voluntary motor actions, as clearly seen when asked to imitate simple gestures performed by the examiner. Despite extensive research, the neurophysiological mechanisms underlying failure to imitate gestures in IMA remain controversial. The aim of the current study was to explore the relationship between imitation failure in IMA and mirror neuron system (MNS) functioning. Mirror neurons were found to play a crucial role in movement imitation and in imitation-based motor learning. Their recruitment during movement observation and execution is signaled in EEG recordings by suppression of the lower (8-10 Hz) mu range. We examined the modulation of EEG in this range in stroke patients with left (n = 21) and right (n = 15) hemisphere damage during observation of video clips showing different manual movements. IMA severity was assessed by the DeRenzi standardized diagnostic test. Results showed that failure to imitate observed manual movements correlated with diminished mu suppression in patients with damage to the right inferior parietal lobule and in patients with damage to the right inferior frontal gyrus pars opercularis-areas where major components of the human MNS are assumed to reside. Voxel-based lesion symptom mapping revealed a significant impact on imitation capacity for the left inferior and superior parietal lobules and the left post central gyrus. Both left and right hemisphere damages were associated with imitation failure typical of IMA, yet a clear demonstration of relationship to the MNS was obtained only in the right hemisphere damage group. Suppression of the 8-10 Hz range was stronger in central compared with occipital sites, pointing to a dominant implication of mu rather than alpha rhythms. However, the suppression correlated with De Renzi's apraxia test scores not only in central but also in occipital sites, suggesting a multifactorial mechanism for IMA, with a possible
-
Autoradiographic assessment of [3H]proline uptake by neurons of epileptogenic mirror focus
International Nuclear Information System (INIS)
Khudoerkov, R.M.
1985-01-01
Epileptogenic mirror focus was produced in the left parietal area of the rat brain by cobalt implantation into the contralateral hemisphere. On the 14th day after cobalt implantation [ 3 H]proline was injected into both experimental and control rats (without cobalt). The incorporation of [ 3 H]proline in neurons of layers III and V of the parietal brain cortex and neurons of the nucleus lateralis thalami was investigated by the autoradiography technique. A statistically reliable increase in [ 3 H]proline uptake was observed in neurons of layer III (31%) and in neurons of layer V (41%) of the epileptogenic mirror focus. The other neuronal types revealed no reliable changes. The morphological and functional aspects of the altered protein metabolism during epileptogenesis are discussed. (author)
-
The mirror mechanism: recent findings and perspectives
Rizzolatti, Giacomo; Fogassi, Leonardo
2014-01-01
Mirror neurons are a specific type of visuomotor neuron that discharge both when a monkey executes a motor act and when it observes a similar motor act performed by another individual. In this article, we review first the basic properties of these neurons. We then describe visual features recently investigated which indicate that, besides encoding the goal of motor acts, mirror neurons are modulated by location in space of the observed motor acts, by the perspective from which the others’ motor acts are seen, and by the value associated with the object on which others’ motor acts are performed. In the last part of this article, we discuss the role of the mirror mechanism in planning actions and in understanding the intention underlying the others’ motor acts. We also review some human studies suggesting that motor intention in humans may rely, as in the monkey, on the mirror mechanism. PMID:24778385
-
Mirror neurons and motor intentionality.
Rizzolatti, Giacomo; Sinigaglia, Corrado
2007-01-01
Our social life rests to a large extent on our ability to understand the intentions of others. What are the bases of this ability? A very influential view is that we understand the intentions of others because we are able to represent them as having mental states. Without this meta-representational (mind-reading) ability their behavior would be meaningless to us. Over the past few years this view has been challenged by neurophysiological findings and, in particular, by the discovery of mirror neurons. The functional properties of these neurons indicate that intentional understanding is based primarily on a mechanism that directly matches the sensory representation of the observed actions with one's own motor representation of those same actions. These findings reveal how deeply motor and intentional components of action are intertwined, suggesting that both can be fully comprehended only starting from a motor approach to intentionality.
-
Responses of mirror neurons in area F5 to hand and tool grasping observation
Rochat, Magali J.; Caruana, Fausto; Jezzini, Ahmad; Escola, Ludovic; Intskirveli, Irakli; Grammont, Franck; Gallese, Vittorio; Rizzolatti, Giacomo
2010-01-01
Mirror neurons are a distinct class of neurons that discharge both during the execution of a motor act and during observation of the same or similar motor act performed by another individual. However, the extent to which mirror neurons coding a motor act with a specific goal (e.g., grasping) might also respond to the observation of a motor act having the same goal, but achieved with artificial effectors, is not yet established. In the present study, we addressed this issue by recording mirror neurons from the ventral premotor cortex (area F5) of two monkeys trained to grasp objects with pliers. Neuron activity was recorded during the observation and execution of grasping performed with the hand, with pliers and during observation of an experimenter spearing food with a stick. The results showed that virtually all neurons responding to the observation of hand grasping also responded to the observation of grasping with pliers and, many of them to the observation of spearing with a stick. However, the intensity and pattern of the response differed among conditions. Hand grasping observation determined the earliest and the strongest discharge, while pliers grasping and spearing observation triggered weaker responses at longer latencies. We conclude that F5 grasping mirror neurons respond to the observation of a family of stimuli leading to the same goal. However, the response pattern depends upon the similarity between the observed motor act and the one executed by the hand, the natural motor template. PMID:20577726
-
Hanuschkin, A.; Ganguli, S.; Hahnloser, R. H. R.
2013-01-01
Mirror neurons are neurons whose responses to the observation of a motor act resemble responses measured during production of that act. Computationally, mirror neurons have been viewed as evidence for the existence of internal inverse models. Such models, rooted within control theory, map-desired sensory targets onto the motor commands required to generate those targets. To jointly explore both the formation of mirrored responses and their functional contribution to inverse models, we develop...
-
Leaping from brain to mind: a critique of mirror neuron explanations of countertransference.
Vivona, Jeanine M
2009-06-01
In the current vigorous debate over the value of neuroscience to psychoanalysis, the epistemological status of the links between the data of brain research and the constructs of interest to psychoanalysts has rarely been examined. An inspection of recent discussions of mirror neuron research, particularly regarding countertransference, reveals gaps between psychoanalytic processes and the available brain activation data, and allows the evaluation of evidence for three implicit assumptions frequently made to bridge these gaps: (1) there is a straightforward correspondence between observed brain activity and mental activity; (2) similarity of localized brain activity across individuals signifies a shared interpersonal experience; (3) an automatic brain mechanism enables direct interpersonal sharing of experiences in the absence of inference and language. Examination of mirror neuron research findings reveals that these assumptions are either untested or questionable. Moreover, within neuroscience there are competing interpretations of mirror neuron findings, with diverse implications for psychoanalysis. The present state of mirror neuron research may offer us new hypotheses or metaphors, but does not provide empirical validation of the proposed models. More generally, as we attempt to learn from research findings generated outside psychoanalysis, we must strive to think scientifically, by minding the difference between data and interpretation.
-
de Zubicaray, Greig; Postle, Natasha; McMahon, Katie; Meredith, Matthew; Ashton, Roderick
2010-01-01
Previous neuroimaging research has attempted to demonstrate a preferential involvement of the human mirror neuron system (MNS) in the comprehension of effector-related action word (verb) meanings. These studies have assumed that Broca's area (or Brodmann's area 44) is the homologue of a monkey premotor area (F5) containing mouth and hand mirror…
-
Neural mechanisms of vocal imitation: The role of sleep replay in shaping mirror neurons.
Giret, Nicolas; Edeline, Jean-Marc; Del Negro, Catherine
2017-06-01
Learning by imitation involves not only perceiving another individual's action to copy it, but also the formation of a memory trace in order to gradually establish a correspondence between the sensory and motor codes, which represent this action through sensorimotor experience. Memory and sensorimotor processes are closely intertwined. Mirror neurons, which fire both when the same action is performed or perceived, have received considerable attention in the context of imitation. An influential view of memory processes considers that the consolidation of newly acquired information or skills involves an active offline reprocessing of memories during sleep within the neuronal networks that were initially used for encoding. Here, we review the recent advances in the field of mirror neurons and offline processes in the songbird. We further propose a theoretical framework that could establish the neurobiological foundations of sensorimotor learning by imitation. We propose that the reactivation of neuronal assemblies during offline periods contributes to the integration of sensory feedback information and the establishment of sensorimotor mirroring activity at the neuronal level. Copyright © 2017 Elsevier Ltd. All rights reserved.
-
Mirror Me: Imitative Responses in Adults with Autism
Schunke, Odette; Schöttle, Daniel; Vettorazzi, Eik; Brandt, Valerie; Kahl, Ursula; Bäumer, Tobias; Ganos, Christos; David, Nicole; Peiker, Ina; Engel, Andreas K; Brass, Marcel; Münchau, Alexander
2016-01-01
Dysfunctions of the human mirror neuron system have been postulated to underlie some deficits in autism spectrum disorders including poor imitative performance and impaired social skills. Using three reaction time experiments addressing mirror neuron system functions under simple and complex conditions, we examined 20 adult autism spectrum…
-
Fründt, Odette; Schulz, Robert; Schöttle, Daniel; Cheng, Bastian; Thomalla, Götz; Braaß, Hanna; Ganos, Christos; David, Nicole; Peiker, Ina; Engel, Andreas K.; Bäumer, Tobias; Münchau, Alexander
2018-01-01
Mirror neuron system (MNS) dysfunctions might underlie deficits in autism spectrum disorders (ASD). Diffusion tensor imaging based probabilistic tractography was conducted in 15 adult ASD patients and 13 matched, healthy controls. Fractional anisotropy (FA) was quantified to assess group differences in tract-related white matter microstructure of…
-
Mirror neurons, language, and embodied cognition.
Perlovsky, Leonid I; Ilin, Roman
2013-05-01
Basic mechanisms of the mind, cognition, language, its semantic and emotional mechanisms are modeled using dynamic logic (DL). This cognitively and mathematically motivated model leads to a dual-model hypothesis of language and cognition. The paper emphasizes that abstract cognition cannot evolve without language. The developed model is consistent with a joint emergence of language and cognition from a mirror neuron system. The dual language-cognition model leads to the dual mental hierarchy. The nature of cognition embodiment in the hierarchy is analyzed. Future theoretical and experimental research is discussed. Published by Elsevier Ltd.
-
EEG evidence for mirror neuron dysfunction in autism spectrum disorders.
Oberman, Lindsay M; Hubbard, Edward M; McCleery, Joseph P; Altschuler, Eric L; Ramachandran, Vilayanur S; Pineda, Jaime A
2005-07-01
Autism spectrum disorders (ASD) are largely characterized by deficits in imitation, pragmatic language, theory of mind, and empathy. Previous research has suggested that a dysfunctional mirror neuron system may explain the pathology observed in ASD. Because EEG oscillations in the mu frequency (8-13 Hz) over sensorimotor cortex are thought to reflect mirror neuron activity, one method for testing the integrity of this system is to measure mu responsiveness to actual and observed movement. It has been established that mu power is reduced (mu suppression) in typically developing individuals both when they perform actions and when they observe others performing actions, reflecting an observation/execution system which may play a critical role in the ability to understand and imitate others' behaviors. This study investigated whether individuals with ASD show a dysfunction in this system, given their behavioral impairments in understanding and responding appropriately to others' behaviors. Mu wave suppression was measured in ten high-functioning individuals with ASD and ten age- and gender-matched control subjects while watching videos of (1) a moving hand, (2) a bouncing ball, and (3) visual noise, or (4) moving their own hand. Control subjects showed significant mu suppression to both self and observed hand movement. The ASD group showed significant mu suppression to self-performed hand movements but not to observed hand movements. These results support the hypothesis of a dysfunctional mirror neuron system in high-functioning individuals with ASD.
-
Mirror Neurons, Embodied Cognitive Agents and Imitation Learning
Czech Academy of Sciences Publication Activity Database
Wiedermann, Jiří
2003-01-01
Roč. 22, č. 6 (2003), s. 545-559 ISSN 1335-9150 R&D Projects: GA ČR GA201/02/1456 Institutional research plan: CEZ:AV0Z1030915 Keywords : complete agents * mirror neurons * embodied cognition * imitation learning * sensorimotor control Subject RIV: BA - General Mathematics Impact factor: 0.254, year: 2003 http://www.cai.sk/ojs/index.php/cai/article/view/468
-
Music and mirror neurons: from motion to 'e'motion.
Molnar-Szakacs, Istvan; Overy, Katie
2006-12-01
The ability to create and enjoy music is a universal human trait and plays an important role in the daily life of most cultures. Music has a unique ability to trigger memories, awaken emotions and to intensify our social experiences. We do not need to be trained in music performance or appreciation to be able to reap its benefits-already as infants, we relate to it spontaneously and effortlessly. There has been a recent surge in neuroimaging investigations of the neural basis of musical experience, but the way in which the abstract shapes and patterns of musical sound can have such profound meaning to us remains elusive. Here we review recent neuroimaging evidence and suggest that music, like language, involves an intimate coupling between the perception and production of hierarchically organized sequential information, the structure of which has the ability to communicate meaning and emotion. We propose that these aspects of musical experience may be mediated by the human mirror neuron system.
-
Acting together in and beyond the mirror neuron system
Kokal, Idil; Gazzola, Valeria; Keysers, Christian
2009-01-01
Moving a set dinner table often takes two people, and doing so without spilling the glasses requires the close coordination of the two agents' actions. It has been argued that the mirror neuron system may be the key neural locus of such coordination. Instead, here we show that such coordination
-
EEG study of the mirror neuron system in children with high functioning autism.
Raymaekers, Ruth; Wiersema, Jan Roelf; Roeyers, Herbert
2009-12-22
Individuals with Autism Spectrum Disorder (ASD) are characterised by an impaired imitation, thought to be critical for early affective, social and communicative development. One neurological system proposed to underlie this function is the mirror neuron system (MNS) and previous research has suggested a dysfunctional MNS in ASD. The EEG mu frequency, more precisely the reduction of the mu power, is considered to be an index for mirror neuron functioning. In this work, EEG registrations are used to evaluate the mirror neuron functioning of twenty children with high functioning autism (HFA) between 8 and 13 years. Their mu suppression to self-executed and observed movement is compared to typically developing peers and related to age, intelligence and symptom severity. Both groups show significant mu suppression to both self and observed hand movements. No group differences are found in either condition. These results do not support the hypothesis that HFA is associated with a dysfunctional MNS. The discrepancy with previous research is discussed in light of the heterogeneity of the ASD population.
-
Universal Connection through Art: Role of Mirror Neurons in Art Production and Reception.
Piechowski-Jozwiak, Bartlomiej; Boller, François; Bogousslavsky, Julien
2017-05-05
Art is defined as expression or application of human creative skill and imagination producing works to be appreciated primarily for their aesthetic value or emotional power. This definition encompasses two very important elements-the creation and reception of art-and by doing so it establishes a link, a dialogue between the artist and spectator. From the evolutionary biological perspective, activities need to have an immediate or remote effect on the population through improving survival, gene selection, and environmental adjustment, and this includes art. It may serve as a universal means of communication bypassing time, cultural, ethnic, and social differences. The neurological mechanisms of both art production and appreciation are researched by neuroscientists and discussed both in terms of healthy brain biology and complex neuronal networking perspectives. In this paper, we describe folk art and the issue of symbolic archetypes in psychoanalytic thought as well as offer neuronal mechanisms for art by emphasizing mirror/neurons and the role they play in it.
-
FMRI evidence of 'mirror' responses to geometric shapes.
Press, Clare; Catmur, Caroline; Cook, Richard; Widmann, Hannah; Heyes, Cecilia; Bird, Geoffrey
2012-01-01
Mirror neurons may be a genetic adaptation for social interaction. Alternatively, the associative hypothesis proposes that the development of mirror neurons is driven by sensorimotor learning, and that, given suitable experience, mirror neurons will respond to any stimulus. This hypothesis was tested using fMRI adaptation to index populations of cells with mirror properties. After sensorimotor training, where geometric shapes were paired with hand actions, BOLD response was measured while human participants experienced runs of events in which shape observation alternated with action execution or observation. Adaptation from shapes to action execution, and critically, observation, occurred in ventral premotor cortex (PMv) and inferior parietal lobule (IPL). Adaptation from shapes to execution indicates that neuronal populations responding to the shapes had motor properties, while adaptation to observation demonstrates that these populations had mirror properties. These results indicate that sensorimotor training induced populations of cells with mirror properties in PMv and IPL to respond to the observation of arbitrary shapes. They suggest that the mirror system has not been shaped by evolution to respond in a mirror fashion to biological actions; instead, its development is mediated by stimulus-general processes of learning within a system adapted for visuomotor control.
-
Deciphering mirror neurons: rational decision versus associative learning.
Khalil, Elias L
2014-04-01
The rational-decision approach is superior to the associative-learning approach of Cook et al. at explaining why mirror neurons fire or do not fire - even when the stimulus is the same. The rational-decision approach is superior because it starts with the analysis of the intention of the organism, that is, with the identification of the specific objective or goal that the organism is trying to maximize.
-
Hebbian learning and predictive mirror neurons for actions, sensations and emotions
Keysers, C.; Gazzola, Valeria
2014-01-01
Spike-timing-dependent plasticity is considered the neurophysiological basis of Hebbian learning and has been shown to be sensitive to both contingency and contiguity between pre- and postsynaptic activity. Here, we will examine how applying this Hebbian learning rule to a system of interconnected neurons in the presence of direct or indirect re-afference (e.g. seeing/hearing one's own actions) predicts the emergence of mirror neurons with predictive properties. In this framework, we analyse ...
-
FMRI evidence of 'mirror' responses to geometric shapes.
Directory of Open Access Journals (Sweden)
Clare Press
Full Text Available Mirror neurons may be a genetic adaptation for social interaction. Alternatively, the associative hypothesis proposes that the development of mirror neurons is driven by sensorimotor learning, and that, given suitable experience, mirror neurons will respond to any stimulus. This hypothesis was tested using fMRI adaptation to index populations of cells with mirror properties. After sensorimotor training, where geometric shapes were paired with hand actions, BOLD response was measured while human participants experienced runs of events in which shape observation alternated with action execution or observation. Adaptation from shapes to action execution, and critically, observation, occurred in ventral premotor cortex (PMv and inferior parietal lobule (IPL. Adaptation from shapes to execution indicates that neuronal populations responding to the shapes had motor properties, while adaptation to observation demonstrates that these populations had mirror properties. These results indicate that sensorimotor training induced populations of cells with mirror properties in PMv and IPL to respond to the observation of arbitrary shapes. They suggest that the mirror system has not been shaped by evolution to respond in a mirror fashion to biological actions; instead, its development is mediated by stimulus-general processes of learning within a system adapted for visuomotor control.
-
Directory of Open Access Journals (Sweden)
Alexander eHanuschkin
2013-06-01
Full Text Available Mirror neurons are neurons whose responses to the observation of a motor act resemble responses measured during production of that act. Computationally, mirror neurons have been viewed as evidence for the existence of internal inverse models. Such models, rooted within control theory, map desired sensory targets onto the motor commands required to generate those targets. To jointly explore both the formation of mirrored responses and their functional contribution to inverse models, we develop a correlation-based theory of interactions between a sensory and a motor area. We show that a simple eligibility-weighted Hebbian learning rule, operating within a sensorimotor loop during motor explorations and stabilized by heterosynaptic competition, naturally gives rise to mirror neurons as well as control theoretic inverse models encoded in the synaptic weights from sensory to motor neurons. Crucially, we find that the correlational structure or stereotypy of the neural code underlying motor explorations determines the nature of the learned inverse model: Random motor codes lead to causal inverses that map sensory activity patterns to their motor causes; such inverses are maximally useful, they allow for imitating arbitrary sensory target sequences. By contrast, stereotyped motor codes lead to less useful predictive inverses that map sensory activity to future motor actions.Our theory generalizes previous work on inverse models by showing that such models can be learned in a simple Hebbian framework without the need for error signals or backpropagation, and it makes new conceptual connections between the causal nature of inverse models, the statistical structure of motor variability, and the time-lag between sensory and motor responses of mirror neurons. Applied to bird song learning, our theory can account for puzzling aspects of the song system, including necessity of sensorimotor gating and selectivity of auditory responses to bird’s own song
-
Hanuschkin, A; Ganguli, S; Hahnloser, R H R
2013-01-01
Mirror neurons are neurons whose responses to the observation of a motor act resemble responses measured during production of that act. Computationally, mirror neurons have been viewed as evidence for the existence of internal inverse models. Such models, rooted within control theory, map-desired sensory targets onto the motor commands required to generate those targets. To jointly explore both the formation of mirrored responses and their functional contribution to inverse models, we develop a correlation-based theory of interactions between a sensory and a motor area. We show that a simple eligibility-weighted Hebbian learning rule, operating within a sensorimotor loop during motor explorations and stabilized by heterosynaptic competition, naturally gives rise to mirror neurons as well as control theoretic inverse models encoded in the synaptic weights from sensory to motor neurons. Crucially, we find that the correlational structure or stereotypy of the neural code underlying motor explorations determines the nature of the learned inverse model: random motor codes lead to causal inverses that map sensory activity patterns to their motor causes; such inverses are maximally useful, by allowing the imitation of arbitrary sensory target sequences. By contrast, stereotyped motor codes lead to less useful predictive inverses that map sensory activity to future motor actions. Our theory generalizes previous work on inverse models by showing that such models can be learned in a simple Hebbian framework without the need for error signals or backpropagation, and it makes new conceptual connections between the causal nature of inverse models, the statistical structure of motor variability, and the time-lag between sensory and motor responses of mirror neurons. Applied to bird song learning, our theory can account for puzzling aspects of the song system, including necessity of sensorimotor gating and selectivity of auditory responses to bird's own song (BOS) stimuli.
-
Neonatal imitation and an epigenetic account of mirror neuron development.
Simpson, Elizabeth A; Fox, Nathan A; Tramacere, Antonella; Ferrari, Pier F
2014-04-01
Neonatal imitation should not exclusively be considered at the population-level; instead, we propose that inconsistent findings regarding its occurrence result from important individual differences in imitative responses. We also highlight what we consider to be a false dichotomy of genetic versus learning accounts of the development of mirror neurons, and instead suggest a more parsimonious epigenetic perspective.
-
Imagining and Imaging the Social Brain: The Case of Mirror Neurons.
Lanzoni, Susan
In a contemporary setting in which all things "neuro" have great cultural sway, an analysis of the ways in which neuroscience is indebted to the methods and findings of the social sciences has received less attention. Indeed, in the new specialization of social neuroscience, neuroscientists now collaborate with contemporary psychologists and invoke historical psychological theories to help theorize empathy and social understanding. This article examines the overlap between psychological frameworks of social emotion and neuroscience in the case of mirror neurons, discovered in the 1990s. Some neuroscientists purport that mirror neurons underlie the social behaviours of imitation and empathy, and have found support for this view of theories of simulation and embodied cognition. They have also invoked pragmatic and phenomenological approaches to mind and behaviour dating back to the early 20 th century. Neuroscientists have thus imported, adapted, and interpreted psychological models to help define social understanding, empathy, and imitation in many imaging studies.
-
Differential Patterns of Dysconnectivity in Mirror Neuron and Mentalizing Networks in Schizophrenia
Schilbach, Leonhard; Derntl, Birgit; Aleman, Andre; Caspers, Svenja; Clos, Mareike; Diederen, Kelly M J; Gruber, Oliver; Kogler, Lydia; Liemburg, Edith J; Sommer, Iris E; Müller, Veronika I; Cieslik, Edna C; Eickhoff, Simon B
Impairments of social cognition are well documented in patients with schizophrenia (SCZ), but the neural basis remains poorly understood. In light of evidence that suggests that the "mirror neuron system" (MNS) and the "mentalizing network" (MENT) are key substrates of intersubjectivity and joint
-
Mirror neurons and the action theory of language origins
Steels, Luc
2000-01-01
The research reported here attempts to understand how language may have originated from sensori-motor competences. Recently the observation of mirror neurons has lead to the suggestion that there is not only a rich representation of motor action but also that this representation is used for multiple purposes: action execution, action planning, action imaging, and action recognition. Of particular importance is the observation that one agent can recognise an action plan of another one and t...
-
Facial expressions : What the mirror neuron system can and cannot tell us
van der Gaag, Christiaan; Minderaa, Ruud B.; Keysers, Christian
2007-01-01
Facial expressions contain both motor and emotional components. The inferior frontal gyrus (IFG) and posterior parietal cortex have been considered to compose a mirror neuron system (MNS) for the motor components of facial expressions, while the amygdala and insula may represent an "additional" MNS
-
Imitation, empathy, and mirror neurons.
Iacoboni, Marco
2009-01-01
There is a convergence between cognitive models of imitation, constructs derived from social psychology studies on mimicry and empathy, and recent empirical findings from the neurosciences. The ideomotor framework of human actions assumes a common representational format for action and perception that facilitates imitation. Furthermore, the associative sequence learning model of imitation proposes that experience-based Hebbian learning forms links between sensory processing of the actions of others and motor plans. Social psychology studies have demonstrated that imitation and mimicry are pervasive, automatic, and facilitate empathy. Neuroscience investigations have demonstrated physiological mechanisms of mirroring at single-cell and neural-system levels that support the cognitive and social psychology constructs. Why were these neural mechanisms selected, and what is their adaptive advantage? Neural mirroring solves the "problem of other minds" (how we can access and understand the minds of others) and makes intersubjectivity possible, thus facilitating social behavior.
-
Tactile interactions activate mirror system regions in the human brain.
McKyton, Ayelet
2011-12-07
Communicating with others is essential for the development of a society. Although types of communications, such as language and visual gestures, were thoroughly investigated in the past, little research has been done to investigate interactions through touch. To study this we used functional magnetic resonance imaging. Twelve participants were scanned with their eyes covered while stroking four kinds of items, representing different somatosensory stimuli: a human hand, a realistic rubber hand, an object, and a simple texture. Although the human and the rubber hands had the same overall shape, in three regions there was significantly more blood oxygen level dependent activation when touching the real hand: the anterior medial prefrontal cortex, the ventral premotor cortex, and the posterior superior temporal cortex. The last two regions are part of the mirror network and are known to be activated through visual interactions such as gestures. Interestingly, in this study, these areas were activated through a somatosensory interaction. A control experiment was performed to eliminate confounds of temperature, texture, and imagery, suggesting that the activation in these areas was correlated with the touch of a human hand. These results reveal the neuronal network working behind human tactile interactions, and highlight the participation of the mirror system in such functions.
-
Morphological differences in the mirror neuron system in Williams Syndrome
Ng, Rowena; Brown, Timothy T.; Erhart, Matthew; Järvinen, Anna M.; Korenberg, Julie R.; Bellugi, Ursula; Halgren, Eric
2015-01-01
Williams syndrome (WS) is a genetic condition characterized by an overly gregarious personality, including high empathetic concern for others. Although seemingly disparate from the profile of autism spectrum disorder (ASD), both are associated with deficits in social communication/cognition. Notably, the mirror neuron system (MNS) has been implicated in social dysfunction for ASD; yet, the integrity of this network and its association with social functioning in WS remains unknown. Magnetic re...
-
Van Gog, Tamara; Paas, Fred; Marcus, Nadine; Ayres, Paul; Sweller, John
2009-01-01
Van Gog, T., Paas, F., Marcus, N., Ayres, P., & Sweller, J. (2009). The mirror-neuron system and observational learning: Implications for the effectiveness of dynamic visualizations. Educational Psychology Review, 21, 21-30.
-
Mirror neuron system based therapy for emotional disorders.
Yuan, Ti-Fei; Hoff, Robert
2008-11-01
Mirror neuron system (MNS) represents one of the most important discoveries in the area of neuropsychology of past decades. More than 500 papers have been published in this area (PubMed), and the major functions of MNS include action understanding, imitation, empathy, all of which are critical for an individual to be social. Recent studies suggested that MNS can modulate emotion states possibly through the empathy mechanism. Here we propose that MNS-based therapies provide a non-invasive approach in treatments to emotional disorders that were observed in autism patients, post-stroke patients with depression as well as other mood dysregulation conditions.
-
From music making to speaking: engaging the mirror neuron system in autism.
Wan, Catherine Y; Demaine, Krystal; Zipse, Lauryn; Norton, Andrea; Schlaug, Gottfried
2010-05-31
Individuals with autism show impairments in emotional tuning, social interactions and communication. These are functions that have been attributed to the putative human mirror neuron system (MNS), which contains neurons that respond to the actions of self and others. It has been proposed that a dysfunction of that system underlies some of the characteristics of autism. Here, we review behavioral and imaging studies that implicate the MNS (or a brain network with similar functions) in sensory-motor integration and speech representation, and review data supporting the hypothesis that MNS activity could be abnormal in autism. In addition, we propose that an intervention designed to engage brain regions that overlap with the MNS may have significant clinical potential. We argue that this engagement could be achieved through forms of music making. Music making with others (e.g., playing instruments or singing) is a multi-modal activity that has been shown to engage brain regions that largely overlap with the human MNS. Furthermore, many children with autism thoroughly enjoy participating in musical activities. Such activities may enhance their ability to focus and interact with others, thereby fostering the development of communication and social skills. Thus, interventions incorporating methods of music making may offer a promising approach for facilitating expressive language in otherwise nonverbal children with autism. Copyright (c) 2010 Elsevier Inc. All rights reserved.
-
Hamilton, Antonia F. de C.; Brindley, Rachel M.; Frith, Uta
2007-01-01
The motor mirror neuron system supports imitation and goal understanding in typical adults. Recently, it has been proposed that a deficit in this mirror neuron system might contribute to poor imitation performance in children with autistic spectrum disorders (ASD) and might be a cause of poor social abilities in these children. We aimed to test…
-
Aversive learning shapes neuronal orientation tuning in human visual cortex.
McTeague, Lisa M; Gruss, L Forest; Keil, Andreas
2015-07-28
The responses of sensory cortical neurons are shaped by experience. As a result perceptual biases evolve, selectively facilitating the detection and identification of sensory events that are relevant for adaptive behaviour. Here we examine the involvement of human visual cortex in the formation of learned perceptual biases. We use classical aversive conditioning to associate one out of a series of oriented gratings with a noxious sound stimulus. After as few as two grating-sound pairings, visual cortical responses to the sound-paired grating show selective amplification. Furthermore, as learning progresses, responses to the orientations with greatest similarity to the sound-paired grating are increasingly suppressed, suggesting inhibitory interactions between orientation-selective neuronal populations. Changes in cortical connectivity between occipital and fronto-temporal regions mirror the changes in visuo-cortical response amplitudes. These findings suggest that short-term behaviourally driven retuning of human visual cortical neurons involves distal top-down projections as well as local inhibitory interactions.
-
The mirror system and its role in social cognition.
Rizzolatti, Giacomo; Fabbri-Destro, Maddalena
2008-04-01
Experiments in monkeys have shown that coding the goal of the motor acts is a fundamental property of the cortical motor system. In area F5, goal-coding motor neurons are also activated by observing motor acts done by others (the 'classical' mirror mechanism); in area F2 and area F1, some motor neurons are activated by the mere observation of goal-directed movements of a cursor displayed on a computer screen (a 'mirror-like' mechanism). Experiments in humans and monkeys have shown that the mirror mechanism enables the observer to understand the intention behind an observed motor act, in addition to the goal of it. Growing evidence shows that a deficit in the mirror mechanism underlies some aspects of autism.
-
Directory of Open Access Journals (Sweden)
Gaussier Philippe
2011-12-01
Full Text Available Mirror neurons have often been considered as the explanation of how primates can imitate. In this paper, we show that a simple neural network architecture that learns visuo-motor associations can be enough to let low level imitation emerge without a priori mirror neurons. Adding sequence learning mechanisms and action inhibition allows to perform deferred imitation of gestures demonstrated visually or by body manipulation. With the building of a cognitive map giving the capability of learning plans, we can study in our model the emergence of both low level and high level resonances highlighted by Rizzolatti et al.
-
Reflecting on the mirror neuron system in autism: a systematic review of current theories.
Hamilton, Antonia F de C
2013-01-01
There is much interest in the claim that dysfunction of the mirror neuron system in individuals with autism spectrum condition causes difficulties in social interaction and communication. This paper systematically reviews all published studies using neuroscience methods (EEG/MEG/TMS/eyetracking/EMG/fMRI) to examine the integrity of the mirror system in autism. 25 suitable papers are reviewed. The review shows that current data are very mixed and that studies using weakly localised measures of the integrity of the mirror system are hard to interpret. The only well localised measure of mirror system function is fMRI. In fMRI studies, those using emotional stimuli have reported group differences, but studies using non-emotional hand action stimuli do not. Overall, there is little evidence for a global dysfunction of the mirror system in autism. Current data can be better understood under an alternative model in which social top-down response modulation is abnormal in autism. The implications of this model and future research directions are discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.
-
Can syntax appear in a mirror (system)?
Tettamanti, Marco; Moro, Andrea
2012-07-01
Converging evidence indicates that the processing of some aspects related to the phonetic and the semantic components of language is tightly associated with both the perceptual and the motor neural systems. It has been suggested that mirror neurons contribute to language understanding by virtue of a neurophysiological response matching perceptual linguistic information onto corresponding motor plans. This proposal has sometimes been extended to advocate that the language competence as a whole, including syntax, may be ascribed to this kind of perceptuo-motor mappings. This position paper examines what kinds of empirical and theoretical challenges such general mirror neuron language accounts need to face in order to proof their validity--challenges that we think have not been adequately addressed yet. We highlight that the most important limitation is constituted by the fact that some core defining properties of human language, at the phonetic, semantic, and especially at the syntactic level, are not transparent to the bodily senses and thus they cannot be the direct source of mirror neuron perceptuo-motor matching. Copyright © 2011 Elsevier Srl. All rights reserved.
-
Kemmerer, David; Gonzalez-Castillo, Javier
2010-01-01
Verbs have two separate levels of meaning. One level reflects the uniqueness of every verb and is called the "root". The other level consists of a more austere representation that is shared by all the verbs in a given class and is called the "event structure template". We explore the following hypotheses about how, with specific reference to the motor features of action verbs, these two distinct levels of semantic representation might correspond to two distinct levels of the mirror neuron system. Hypothesis 1: Root-level motor features of verb meaning are partially subserved by somatotopically mapped mirror neurons in the left primary motor and/or premotor cortices. Hypothesis 2: Template-level motor features of verb meaning are partially subserved by representationally more schematic mirror neurons in Brodmann area 44 of the left inferior frontal gyrus. Evidence has been accumulating in support of the general neuroanatomical claims made by these two hypotheses-namely, that each level of verb meaning is associated with the designated cortical areas. However, as yet no studies have satisfied all the criteria necessary to support the more specific neurobiological claims made by the two hypotheses-namely, that each level of verb meaning is associated with mirror neurons in the pertinent brain regions. This would require demonstrating that within those regions the same neuronal populations are engaged during (a) the linguistic processing of particular motor features of verb meaning, (b) the execution of actions with the corresponding motor features, and (c) the observation of actions with the corresponding motor features. 2008 Elsevier Inc. All rights reserved.
-
Weisstanner, Christian; Saxer, Stefanie; Wiest, Roland; Kaelin-Lang, Alain; Newman, Christopher J; Steinlin, Maja; Grunt, Sebastian
2017-03-21
To investigate the neuronal activation pattern underlying the effects of mirror illusion in children/adolescents with normal motor development and in children/adolescents with hemiparesis and preserved contralateral corticospinal organisation. The type of cortical reorganisation was classified according to results of transcranial magnetic stimulation. Only subjects with congenital lesions and physiological contralateral cortical reorganisation were included. Functional magnetic resonance imaging was performed to investigate neuronal activation patterns with and without a mirror box. Each test consisted of a unimanual and a bimanual motor task. Seven children/adolescents with congenital hemiparesis (10-20 years old, three boys and four girls) and seven healthy subjects (8-17 years old, four boys and three girls) participated in this study. In the bimanual experiment, children with hemiparesis showed a significant effect of the mirror illusion (phemiparesis leads to activation of brain areas involved in visual conflict detection and cognitive control to resolve this conflict. This effect is observed only in bimanual training. We consider that for mirror therapy in children and adolescents with hemiparesis a bimanual approach is more suitable than a unimanual approach.
-
Why is your spouse so predictable? Connecting mirror neuron system and self-expansion model of love.
Ortigue, Stephanie; Bianchi-Demicheli, Francesco
2008-12-01
The simulation theory assumes we understand actions and intentions of others through a direct matching process. This matching process activates a complex brain network involving the mirror neuron system (MNS), which is self-related and active when one does something or observes someone else acting. Because social psychology admits that mutual intention's understanding grows in close relationship as love grows, we hypothesize that mirror mechanisms take place in love relationships. The similarities between the mirror matching process and the mutual intention's understanding that occurs when two persons are in love suggest that exposure to love might affect functional and neural mechanisms, thus facilitating the understanding of the beloved's intentions. Congruent with our hypothesis, our preliminary results from 38 subjects strongly suggest a significant facilitation effect of love on understanding the intentions of the beloved (as opposed to control stimuli). Based on these phenomenological, and neurofunctional findings we suggest that the mirror mechanisms are involved in the facilitation effects of love for understanding intentions, and might further be extended to any types of love (e.g., passionate love, maternal love). Love experiences are important not only to the beloved himself, but also to any societal, cultural, and institutional patterns that relate to love. Yet, concerning its subjective character, love experiences are difficult to access. The modern procedures and techniques of socio-cognitive neuroscience make it possible to understand love and self-related experiences not only by the analysis of subjective self-reported questionnaires, but also by approaching the automatic (non-conscious) mirror experiences of love in healthy subjects, and neurological patients with a brain damage within the mirror neuron system. Although the psychology of love is now well admitted, the systematic study of the automatic facilitation effect of love through mirror
-
Mirror Neuron System and Mentalizing System connect during online social interaction.
Sperduti, Marco; Guionnet, Sophie; Fossati, Philippe; Nadel, Jacqueline
2014-08-01
Two sets of brain areas are repeatedly reported in neuroimaging studies on social cognition: the Mirror Neuron System and the Mentalizing System. The Mirror System is involved in goal understanding and has been associated with several emotional and cognitive functions central to social interaction, ranging from empathy to gestural communication and imitation. The Mentalizing System is recruited in tasks requiring cognitive processes such as self-reference and understanding of other's intentions. Although theoretical accounts for an interaction between the two systems have been proposed, little is known about their synergy during social exchanges. In order to explore this question, we have recorded brain activity by means of functional MRI during live social exchanges based on reciprocal imitation of hand gestures. Here, we investigate, using the method of psychophysiological interaction, the changes in functional connectivity of the Mirror System due to the conditions of interest (being imitated, imitating) compared with passive observation of hand gestures. We report a strong coupling between the Mirror System and the Mentalizing System during the imitative exchanges. Our findings suggest a complementary role of the two networks during social encounters. The Mirror System would engage in the preparation of own actions and the simulation of other's actions, while the Mentalizing System would engage in the anticipation of the other's intention and thus would participate to the co-regulation of reciprocal actions. Beyond a specific effect of imitation, the design used offers the opportunity to tackle the role of role-switching in an interpersonal account of social cognition.
-
Mirror and (absence of) counter-mirror responses to action sounds measured with TMS.
Ticini, Luca F; Schütz-Bosbach, Simone; Waszak, Florian
2017-11-01
To what extent is the mirror neuron mechanism malleable to experience? The answer to this question can help characterising its ontogeny and its role in social cognition. Some suggest that it develops through sensorimotor associations congruent with our own actions. Others argue for its extreme volatility that will encode any sensorimotor association in the environment. Here, we added to this debate by exploring the effects of short goal-directed 'mirror' and 'counter-mirror' trainings (a 'mirror' training is defined as the first type of training encountered by the participants) on human auditory mirror motor-evoked potentials (MEPs). We recorded MEPs in response to two tones void of previous motor meaning, before and after mirror and counter-mirror trainings in which participants generated two tones of different pitch by performing free-choice button presses. The results showed that mirror MEPs, once established, were protected against an equivalent counter-mirror experience: they became manifest very rapidly and the same number of training trials that lead to the initial association did not suffice to reverse the MEP pattern. This steadiness of the association argues that, by serving direct-matching purposes, the mirror mechanism is a good solution for social cognition. © The Author (2017). Published by Oxford University Press.
-
Autism and the mirror neuron system: Insights from learning and teaching
Vivanti, G; Rogers, SJ
2014-01-01
Individuals with autism have difficulties in social learning domains which typically involve mirror neuron system (MNS) activation. However, the precise role of the MNS in the development of autism and its relevance to treatment remain unclear. In this paper, we argue that three distinct aspects of social learning are critical for advancing knowledge in this area: (i) the mechanisms that allow for the implicit mapping of and learning from others' behaviour, (ii) the motivation to attend to an...
-
Empathy and the somatotopic auditory mirror system in humans
Gazzola, Valeria; Aziz-Zadeh, Lisa; Keysers, Christian
2006-01-01
How do we understand the actions of other individuals if we can only hear them? Auditory mirror neurons respond both while monkeys perform hand or mouth actions and while they listen to sounds of similar actions [1, 2]. This system might be critical for auditory action understanding and language
-
Language comprehension warps the mirror neuron system.
Zarr, Noah; Ferguson, Ryan; Glenberg, Arthur M
2013-01-01
Is the mirror neuron system (MNS) used in language understanding? According to embodied accounts of language comprehension, understanding sentences describing actions makes use of neural mechanisms of action control, including the MNS. Consequently, repeatedly comprehending sentences describing similar actions should induce adaptation of the MNS thereby warping its use in other cognitive processes such as action recognition and prediction. To test this prediction, participants read blocks of multiple sentences where each sentence in the block described transfer of objects in a direction away or toward the reader. Following each block, adaptation was measured by having participants predict the end-point of videotaped actions. The adapting sentences disrupted prediction of actions in the same direction, but (a) only for videos of biological motion, and (b) only when the effector implied by the language (e.g., the hand) matched the videos. These findings are signatures of the MNS.
-
Agnati, Luigi Francesco; Guidolin, Diego; Cortelli, Pietro; Genedani, Susanna; Cela-Conde, Camilo; Fuxe, Kjell
2012-10-02
Humans share the common intuition of a self that has access to an inner 'theater of mind' (Baars, 2003). The problem is how this internal theater is formed. Moving from Cook's view (Cook, 2008), we propose that the 'sentience' present in single excitable cells is integrated into units of neurons and glial cells transiently assembled into "functional modules" (FMs) organized as systems of encased networks (from cell networks to molecular networks). In line with Hebb's proposal of 'cell assemblies', FMs can be linked to form higher-order mosaics by means of reverberating circuits. Brain-level subjective awareness results from the binding phenomenon that coordinates several FM mosaics. Thus, consciousness may be thought as the global result of integrative processes taking place at different levels of miniaturization in plastic mosaics. On the basis of these neurobiological data and speculations and of the evidence of 'mirror neurons' the 'Hall of Mirrors' is proposed as a significant metaphor of consciousness. This article is part of a Special Issue entitled: Brain Integration. Copyright © 2011 Elsevier B.V. All rights reserved.
-
Hobson, Hannah M; Bishop, Dorothy V M
2017-03-01
Mu suppression studies have been widely used to infer the activity of the human mirror neuron system (MNS) in a number of processes, ranging from action understanding, language, empathy and the development of autism spectrum disorders (ASDs). Although mu suppression is enjoying a resurgence of interest, it has a long history. This review aimed to revisit mu's past, and examine its recent use to investigate MNS involvement in language, social processes and ASDs. Mu suppression studies have largely failed to produce robust evidence for the role of the MNS in these domains. Several key potential shortcomings with the use and interpretation of mu suppression, documented in the older literature and highlighted by more recent reports, are explored here.
-
Brang, David; Ramachandran, V S
2010-05-01
Autism is a disorder characterized by social withdrawal, impoverished language and empathy, and a profound inability to adopt another's viewpoint - a failure to construct a "theory of mind" for interpreting another person's thoughts and intentions. We previously showed that these symptoms might be explained, in part, by a paucity of mirror neurons. Prompted by an MRI report of an individual with autism, we now suggest that there may be, in addition, a congenital aplasia/dysplasia of the olfactory bulbs with consequent reduction of vasopressin and oxytocin receptor binding. There may also be sub-clinical temporal lobe epilepsy affecting the recently discovered third visual system that is rich in "empathy" related mirror neurons (MNS) and projects (via the TOP junction - just below the inferior parietal lobule) to limbic structures that regulate autonomic outflow. This causes deranged autonomic feedback, resulting in additional deficiencies in MNS with loss of emotional empathy and introspection.
-
Wolf, N S; Gales, M; Shane, E; Shane, M
2000-01-01
In summary, we are impressed with the existence of a mirror neuron system in the prefrontal cortex that serves as part of a complex neural network, including afferent and efferent connections to the limbic system, in particular the amygdala, in addition to the premotor and motor cortex. We think it is possible to arrive at an integration that postulates the mirror neuron system and its many types of associated multimodal neurons as contributing significantly to implicit procedural learning, a process that underlies a range of complex nonconscious, unconscious, preconscious and conscious cognitive activities, from playing musical instruments to character formation and traumatic configurations. This type of brain circuitry may establish an external coherence with developmental systems self psychology which implies that positive new experience is meliorative and that the intentional revival of old-old traumatic relational configurations might enhance maladaptive procedural patterns that would lead to the opposite of the intended beneficial change. When analysts revive traumatic transference patterns for the purpose of clarification and interpretation, they may fail to appreciate that such traumatic transference patterns make interpretation ineffective because, as we have stated above, the patient lacks self-reflection under such traumatic conditions. The continued plasticity and immediacy of the mirror neuron system can contribute to positive new experiences that promote the formation of new, adaptive, implicit-procedural patterns. Perhaps this broadened repertoire in the patient of ways of understanding interrelational events through the psychoanalytic process allows the less adaptive patterns ultimately to become vestigial and the newer, more adaptive patterns to emerge as dominant. Finally, as we have stated, we believe that the intentional transferential revival of trauma (i.e., the old-old relational configuration) may not contribute to therapeutic benefit. In
-
Directory of Open Access Journals (Sweden)
Sajad Parsaei
2017-09-01
Conclusion: The results of this study showed that mirror neurons within the premotor cortex are an important neural mechanism in the brain activity pattern, which causes the effectiveness of imagery in the improvement of motor skills.
-
Atypical activation of the mirror neuron system during perception of hand motion in autism.
Martineau, Joëlle; Andersson, Frédéric; Barthélémy, Catherine; Cottier, Jean-Philippe; Destrieux, Christophe
2010-03-12
Disorders in the autism spectrum are characterized by deficits in social and communication skills such as imitation, pragmatic language, theory of mind, and empathy. The discovery of the "mirror neuron system" (MNS) in macaque monkeys may provide a basis from which to explain some of the behavioral dysfunctions seen in individuals with autism spectrum disorders (ASD).We studied seven right-handed high-functioning male autistic and eight normal subjects (TD group) using functional magnetic resonance imaging during observation and execution of hand movements compared to a control condition (rest). The between group comparison of the contrast [observation versus rest] provided evidence of a bilateral greater activation of inferior frontal gyrus during observation of human motion than during rest for the ASD group than for the TD group. This hyperactivation of the pars opercularis (belonging to the MNS) during observation of human motion in autistic subjects provides strong support for the hypothesis of atypical activity of the MNS that may be at the core of the social deficits in autism. Copyright 2010 Elsevier B.V. All rights reserved.
-
Altschuler, Eric Lewin
2008-01-01
Autism is a severe disease with no known cause and no cure or treatment. Recently, ourselves and subsequently others found that so-called "mirror neurons" - neurons that respond not only when a person moves, but upon observation of movement in another - are dysfunctional in autistic children. Here I suggest an easy, simple, inexpensive and fun method to improve mirror neuron functioning in autistic children, increase appreciation in autistic children for the theory of mind and thinking of others, and most importantly hopefully to improve real world functioning: play with virtual online pets that are the "embodiment" of a stuffed animal the child has. Adoption and then care and play with online pets forces, in a fun way, one to think about the world through the eyes and needs of the pet. A simple method to test this play with online virtual pet therapy is described.
-
Directory of Open Access Journals (Sweden)
Abdul chalik meidian
2014-03-01
Full Text Available Stroke is an interruption of blood vasculature system in the brain that causes suddenly neurological dysfunction, resulted in clinically brain tissue damage in a relatively long time period, decreased physical mobility and functional ability impaired of upper limb. The purpose of this study is to know an increasing in upper limb functional ability among stroke patients after mirror neuron system exercise and constraint induced movement therapy exercise and to know the comparison of both exercise. This study uses an experimental research with pre-test and post-test control group design. Number of samples of the first group is 13 patients given mirror neuron system exercise for 30-60 minutes , while the second group 13 patients were given constraint induced movement therapy exercise for 30-60 minutes. The research was conducted in 2 month period time. Each patient is taught a variety of upper limb functional ability in accordance with the operational concept guidance and patients were asked to repeat the exercise independently at home as directed. Measuring test of upper limb functional ability is using the wolf motor function test instruments. The result is an increase the upper limb functional ability of 21.7% in the mirror neuron system exercise group and proved a significant difference (p<0.05 and an increase in the upper limb functional ability of 17.1% in the constraint induced movement therapy exercise group and proved a significant difference (p<0.05 while the difference of increasing of upper limb functional ability of the two groups showed no significant difference (p>0,05. It was concluded that the mirror neuron system exercise is similar with constraint induced movement therapy exercise in increasing the upper limb functional ability among stroke patients.
-
Mirror neuron system as the joint from action to language.
Chen, Wei; Yuan, Ti-Fei
2008-08-01
Mirror neuron system (MNS) represents one of the most important discoveries of cognitive neuroscience in the past decade, and it has been found to involve in multiple aspects of brain functions including action understanding, imitation, language understanding, empathy, action prediction and speech evolution. This manuscript reviewed the function of MNS in action understanding as well as language evolution, and specifically assessed its roles as the bridge from body language to fluent speeches. Then we discussed the speech defects of autism patients due to the disruption of MNS. Finally, given that MNS is plastic in adult brain, we proposed MNS targeted therapy provides an efficient rehabilitation approach for brain damages conditions as well as autism patients.
-
Mirror-Like Mechanisms and Music
Directory of Open Access Journals (Sweden)
Alessandro D'Ausilio
2009-01-01
Full Text Available The neural processes underlying sensory-motor integration have always attracted strong interest. The classic view is that action and perception are two extremes of mental operations. In the past 2 decades, though, a large number of discoveries have indeed refuted such an interpretation in favor of a more integrated view. Specifically, the discovery of mirror neurons in monkey premotor cortex is a rather strong demonstration that sensory and motor processes share the same neural substrates. In fact, these cells show complex sensory-motor properties, such that observed, heard, or executed goal-directed actions could equally activate these neurons. On the other hand, the neuroscience of music has similarly emerged as an active and productive field of research. In fact, music-related behaviors are a useful model of action-perception mechanisms and how they develop through training. More recently, these two lines of research have begun to intersect into a novel branch of research. As a consequence, it has been proposed recently that mirror-like mechanisms might be at the basis of human music perception-production abilities. The scope of the present short review is to set the scientific background for mirror-like mechanisms in music by examining recent published data.
-
Lotem, Arnon; Kolodny, Oren
2014-04-01
An associative learning account of mirror neurons should not preclude genetic evolution of its underlying mechanisms. On the contrary, an associative learning framework for cognitive development should seek heritable variation in the learning rules and in the data-acquisition mechanisms that construct associative networks, demonstrating how small genetic modifications of associative elements can give rise to the evolution of complex cognition.
-
Keysers, Christian; Paracampo, Riccardo; Gazzola, V.
2018-01-01
We review neuromodulation and lesion studies that address how activations in the mirror neuron system contribute to our perception of observed actions. Past reviews showed disruptions of this parieto-premotor network impair imitation and goal and kinematic processing. Recent studies bring five new
-
Cortical Motor Organization, Mirror Neurons, and Embodied Language: An Evolutionary Perspective
Directory of Open Access Journals (Sweden)
Leonardo Fogassi
2012-11-01
Full Text Available The recent conceptual achievement that the cortical motor system plays a crucial role not only in motor control but also in higher cognitive functions has given a new perspective also on the involvement of motor cortex in language perception and production. In particular, there is evidence that the matching mechanism based on mirror neurons can be involved in both pho-nological recognition and retrieval of meaning, especially for action word categories, thus suggesting a contribution of an action–perception mechanism to the automatic comprehension of semantics. Furthermore, a compari-son of the anatomo-functional properties of the frontal motor cortex among different primates and their communicative modalities indicates that the combination of the voluntary control of the gestural communication systems and of the vocal apparatus has been the critical factor in the transition from a gestural-based communication into a predominantly speech-based system. Finally, considering that the monkey and human premotor-parietal motor system, plus the prefrontal cortex, are involved in the sequential motor organization of actions and in the hierarchical combination of motor elements, we propose that elements of such motor organization have been exploited in other domains, including some aspects of the syntactic structure of language.
-
Mirror neuron system involvement in empathy: a critical look at the evidence.
Baird, Amee D; Scheffer, Ingrid E; Wilson, Sarah J
2011-01-01
It has been proposed that the human mirror neuron system (MNS) plays an integral role in mediating empathy. In this review, we critically examine evidence from three bodies of research that have been cited as supporting this notion: (1) behavioral studies that have examined the relationship between imitation and empathy, (2) findings from functional neuroimaging studies that report a positive correlation between MNS activation and self-report on an empathy questionnaire, and (3) observations of impaired imitation and empathy in autism spectrum disorders (ASD). In addition, we briefly review lesion studies of the neural correlates of imitation and empathy. Current evidence suggests that the MNS is broadly involved in empathy, but at this stage there has been limited consideration of its various forms, including motor, emotional, and cognitive empathy. There are also various forms of imitation, encompassing emotional and non-emotional, automatic, and voluntary actions. We propose that the relationship between imitation and empathy may vary depending on the specific type of each of these abilities. Furthermore, these abilities may be mediated by partially distinct neural networks, which involve the MNS to a variable degree.
-
Mirror neurons: action observation treatment as a tool in stroke rehabilitation.
Franceschini, M; Agosti, M; Cantagallo, A; Sale, P; Mancuso, M; Buccino, G
2010-12-01
The observation of actions performed by others activate in an observer the same neural structures (including mirror neurons) as when he/she actually performs the same actions. The aim of the present study was to assess whether action observation treatment may improve upper limb motor impairment in chronic stroke patients. This was an observational study. Patients were recruited by three Italian Centres for Neurorehabilitation between 2006 and 2008. Twenty-eight chronic stroke patients with upper limb impairment have undergone for four weeks, five days a week, a rehabilitation treatment based on observation of video-clips presenting hand daily actions, followed by the imitation of those same actions with the affected limb. Functional evaluation by means of Modified Barthel Index (MBI), Frenchay Arm Test (FAT) and Fugl Meyer (FM) was carried out twice before treatment (BT1 and BT2), at an interval of 15 days, then after treatment (AT1) and finally at a two-month follow-up (AT2). Wilcoxon Signed Rank test was applied to test differences between scores obtained from functional scales before and after treatment (BT1 vs. BT2; BT2 vs. AT1; AT1 vs. AT2). In all scales, scores did not differ when comparing BT1 with BT2. Scores improved significantly in all scales at AT1 as compared to BT2 (MBI, P=0.026; FAT, P=0.005; FM, P=0.001). This improvement was still present at the two-month follow-up as testified by no score difference between AT1 and AT2. Action Observation Treatment may become a useful strategy in the rehabilitation of stroke patients. The present preliminary study suggests that stimulation of neural structures (including mirror neurons), activated when the patients actually perform the same actions as those observed could constitute a good alternative rehabilitative approach in chronic stroke patients.
-
DEFF Research Database (Denmark)
Wegener, Charlotte; Wegener, Gregers
2016-01-01
and metaphorical value of mirroring for creativity theory across two different research fields — neuroscience and learning. We engage in a mutual (possibly creative) exploration of mirroring from ‘mirror neurons’ to mirroring in social learning theory. One of the most fascinating aspects of mirroring...... as a neurobiological and as a learning phenomenon is that it points to the embodied and unconscious aspects of social interaction. Thus, mirroring should not be reduced to the non-creative, mechanical repetition of the original, outstanding creativity. To mirror is a human capability built into our capacity to create......Most definitions of creativity emphasise originality. The creative product is recognised as distinct from other products and the creative person as someone who stands out from the crowd. What tend to be overlooked are acts of mirroring as a crucial element of the creative process. The human ability...
-
Glutamate neurons are intermixed with midbrain dopamine neurons in nonhuman primates and humans
Root, David H.; Wang, Hui-Ling; Liu, Bing; Barker, David J.; Mód, László; Szocsics, Péter; Silva, Afonso C.; Maglóczky, Zsófia; Morales, Marisela
2016-01-01
The rodent ventral tegmental area (VTA) and substantia nigra pars compacta (SNC) contain dopamine neurons intermixed with glutamate neurons (expressing vesicular glutamate transporter 2; VGluT2), which play roles in reward and aversion. However, identifying the neuronal compositions of the VTA and SNC in higher mammals has remained challenging. Here, we revealed VGluT2 neurons within the VTA and SNC of nonhuman primates and humans by simultaneous detection of VGluT2 mRNA and tyrosine hydroxylase (TH; for identification of dopamine neurons). We found that several VTA subdivisions share similar cellular compositions in nonhuman primates and humans; their rostral linear nuclei have a high prevalence of VGluT2 neurons lacking TH; their paranigral and parabrachial pigmented nuclei have mostly TH neurons, and their parabrachial pigmented nuclei have dual VGluT2-TH neurons. Within nonhuman primates and humans SNC, the vast majority of neurons are TH neurons but VGluT2 neurons were detected in the pars lateralis subdivision. The demonstration that midbrain dopamine neurons are intermixed with glutamate or glutamate-dopamine neurons from rodents to humans offers new opportunities for translational studies towards analyzing the roles that each of these neurons play in human behavior and in midbrain-associated illnesses such as addiction, depression, schizophrenia, and Parkinson’s disease. PMID:27477243
-
Arévalo, Analia L; Baldo, Juliana V; Dronkers, Nina F
2012-02-01
Recent work has been mixed with respect to the notion of embodied semantics, which suggests that processing linguistic stimuli referring to motor-related concepts recruits the same sensorimotor regions of cortex involved in the execution and observation of motor acts or the objects associated with those acts. In this study, we asked whether lesions to key sensorimotor regions would preferentially impact the comprehension of stimuli associated with the use of the hand, mouth or foot. Twenty-seven patients with left-hemisphere strokes and 10 age- and education-matched controls were presented with pictures and words representing objects and actions typically associated with the use of the hand, mouth, foot or no body part at all (i.e., neutral). Picture/sound pairs were presented simultaneously, and participants were required to press a space bar only when the item pairs matched (i.e., congruent trials). We conducted two different analyses: 1) we compared task performance of patients with and without lesions in several key areas previously implicated in the putative human mirror neuron system (i.e., Brodmann areas 4/6, 1/2/3, 21 and 44/45), and 2) we conducted Voxel-based Lesion-Symptom Mapping analyses (VLSM; Bates et al., 2003) to identify additional regions associated with the processing of effector-related versus neutral stimuli. Processing of effector-related stimuli was associated with several regions across the left hemisphere, and not solely with premotor/motor or somatosensory regions. We also did not find support for a somatotopically-organized distribution of effector-specific regions. We suggest that, rather than following the strict interpretation of homuncular somatotopy for embodied semantics, these findings support theories proposing the presence of a greater motor-language network which is associated with, but not restricted to, the network responsible for action execution and observation. Copyright © 2010 Elsevier Srl. All rights reserved.
-
Poupětová, Veronika
2017-01-01
Mirror neurons are very specific nerve cells that are both motor and sensory in nature. Mirror neurons are a relatively new discovery first identified by a team of neurophysiologists at the University of Parma. These neurons were first observed in primates, and then later in humans in several regions of the cerebral cortex. A large amount of research on mirror neurons have shown that they play an important role in imitation, language acquisition and empathy. The theoretical part of this work ...
-
Autism, emotion recognition and the mirror neuron system: the case of music.
Molnar-Szakacs, Istvan; Wang, Martha J; Laugeson, Elizabeth A; Overy, Katie; Wu, Wai-Ling; Piggot, Judith
2009-11-16
Understanding emotions is fundamental to our ability to navigate and thrive in a complex world of human social interaction. Individuals with Autism Spectrum Disorders (ASD) are known to experience difficulties with the communication and understanding of emotion, such as the nonverbal expression of emotion and the interpretation of emotions of others from facial expressions and body language. These deficits often lead to loneliness and isolation from peers, and social withdrawal from the environment in general. In the case of music however, there is evidence to suggest that individuals with ASD do not have difficulties recognizing simple emotions. In addition, individuals with ASD have been found to show normal and even superior abilities with specific aspects of music processing, and often show strong preferences towards music. It is possible these varying abilities with different types of expressive communication may be related to a neural system referred to as the mirror neuron system (MNS), which has been proposed as deficient in individuals with autism. Music's power to stimulate emotions and intensify our social experiences might activate the MNS in individuals with ASD, and thus provide a neural foundation for music as an effective therapeutic tool. In this review, we present literature on the ontogeny of emotion processing in typical development and in individuals with ASD, with a focus on the case of music.
-
Zhu, Huaping; Sun, Yaoru; Zeng, Jinhua; Sun, Hongyu
2011-05-01
Previous studies have suggested that the dysfunction of the human mirror neuron system (hMNS) plays an important role in the autism spectrum disorder (ASD). In this work, we propose a novel training program from our interdisciplinary research to improve mirror neuron functions of autistic individuals by using a BCI system with virtual reality technology. It is a promising approach for the autism to learn and develop social communications in a VR environment. A test method for this hypothesis is also provided. Copyright © 2011 Elsevier Ltd. All rights reserved.
-
Neuronal medium that supports basic synaptic functions and activity of human neurons in vitro.
Bardy, Cedric; van den Hurk, Mark; Eames, Tameji; Marchand, Cynthia; Hernandez, Ruben V; Kellogg, Mariko; Gorris, Mark; Galet, Ben; Palomares, Vanessa; Brown, Joshua; Bang, Anne G; Mertens, Jerome; Böhnke, Lena; Boyer, Leah; Simon, Suzanne; Gage, Fred H
2015-05-19
Human cell reprogramming technologies offer access to live human neurons from patients and provide a new alternative for modeling neurological disorders in vitro. Neural electrical activity is the essence of nervous system function in vivo. Therefore, we examined neuronal activity in media widely used to culture neurons. We found that classic basal media, as well as serum, impair action potential generation and synaptic communication. To overcome this problem, we designed a new neuronal medium (BrainPhys basal + serum-free supplements) in which we adjusted the concentrations of inorganic salts, neuroactive amino acids, and energetic substrates. We then tested that this medium adequately supports neuronal activity and survival of human neurons in culture. Long-term exposure to this physiological medium also improved the proportion of neurons that were synaptically active. The medium was designed to culture human neurons but also proved adequate for rodent neurons. The improvement in BrainPhys basal medium to support neurophysiological activity is an important step toward reducing the gap between brain physiological conditions in vivo and neuronal models in vitro.
-
DEFF Research Database (Denmark)
Hou, Jiancheng; Rajmohan, Ravi; Fang, Dan
2017-01-01
Mirror neurons (MNs) activate when performing an action and when an observer witnesses the same action performed by another individual. Functional magnetic resonance imaging (fMRI) and presentation of motion captured piano performances were used to identify differences in MN activation...... pronounced in the “Enjoyment” mode. Our findings suggest that activation of MNs is not only initiated by the imagined action of an observed movement, but such activation is modulated by the level of musical expertise and knowledge of associated motor movements that the observer brings to the viewing...
-
Embodiment in Communication--Aphasia, Apraxia and the Possible Role of Mirroring and Imitation
Ahlsen, Elisabeth
2008-01-01
The role of embodiment in communication is attracting an increased interest. This interest is to some extent caused by hypotheses and findings concerning mirror neurons in macaques, that is, neurons that are activated by production as well as perception of, for example, a certain movement of action. Mirror neurons seem to provide a fairly simple…
-
Associative (not Hebbian) learning and the mirror neuron system.
Cooper, Richard P; Cook, Richard; Dickinson, Anthony; Heyes, Cecilia M
2013-04-12
The associative sequence learning (ASL) hypothesis suggests that sensorimotor experience plays an inductive role in the development of the mirror neuron system, and that it can play this crucial role because its effects are mediated by learning that is sensitive to both contingency and contiguity. The Hebbian hypothesis proposes that sensorimotor experience plays a facilitative role, and that its effects are mediated by learning that is sensitive only to contiguity. We tested the associative and Hebbian accounts by computational modelling of automatic imitation data indicating that MNS responsivity is reduced more by contingent and signalled than by non-contingent sensorimotor training (Cook et al. [7]). Supporting the associative account, we found that the reduction in automatic imitation could be reproduced by an existing interactive activation model of imitative compatibility when augmented with Rescorla-Wagner learning, but not with Hebbian or quasi-Hebbian learning. The work argues for an associative, but against a Hebbian, account of the effect of sensorimotor training on automatic imitation. We argue, by extension, that associative learning is potentially sufficient for MNS development. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
-
Qualitative analysis neurons in the adult human dentate nucleus
Directory of Open Access Journals (Sweden)
Marić Dušica
2012-01-01
Full Text Available Although many relevant findings regarding to the morphology and cytoarchitectural development of the dentate nucleus have been presented so far, very little qualitative information has been collected on neuronal morphology in the adult human dentate nucleus. The neurons were labelled by Golgi staining from thirty human cerebella, obtained from medico-legal forensic autopsies of adult human bodies and free of significant brain pathology. The human dentate neurons were qualitatively analyzed and these cells were classified into two main classes: the small and the large multipolar neurons. Considering the shape of the cell body, number of the primary dendrites, shape of the dendritic tree and their position within the dentate nucleus, three subclasses of the large multipolar neurons have been recognized. The classification of neurons from the human dentate nucleus has been qualitatively confirmed in fetuses and premature infants. This study represents the first qualitative analysis and classification of the large multipolar neurons in the dentate nucleus of the adult human.
-
Mehta, Urvakhsh Meherwan; Thirthalli, Jagadisha; Basavaraju, Rakshathi; Gangadhar, Bangalore N; Pascual-Leone, Alvaro
2014-09-01
The "mirror-neuron system" has been proposed to be a neurophysiological substrate for social cognition (SC) ability. We used transcranial magnetic stimulation (TMS) paradigms to compare putative mirror neuron activity (MNA) in 3 groups: antipsychotic-naive, medicated schizophrenia patients, and healthy comparison subjects. We also explored the association between MNA and SC ability in patients. Fifty-four consenting right-handed schizophrenia patients (33 antipsychotic naive) and 45 matched healthy comparison subjects completed a TMS experiment to assess putative premotor MNA. We used 4 TMS paradigms of eliciting motor-evoked potentials (MEP) in the right first dorsal interosseous (FDI) muscle. These were applied while the subjects observed a goal-directed action involving the FDI (actual action and its video) and a static image. The difference in the amplitude of the MEP while they observed the static image and the action provided a measure of MNA. Subjects also underwent SC assessments (theory of mind [ToM], emotion processing, and social perception). Two-way repeated measures ANOVA revealed significant group × occasion interaction effect in 3 TMS paradigms, indicating deficient motor facilitation during action observation relative to rest state in antipsychotic-naive schizophrenia patients as compared with the other two groups. Among patients, there were significant direct correlations between measures of MNA and ToM performance. Antipsychotic-naive schizophrenia patients have poorer MNA than medicated patients and healthy controls. Measures of putative MNA had significant and consistent associations with ToM abilities. These findings suggest a possibility of deficient mirror neuron system underlying SC deficits in schizophrenia. © The Author 2013. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.
-
Atypical cross talk between mentalizing and mirror neuron networks in autism spectrum disorder.
Fishman, Inna; Keown, Christopher L; Lincoln, Alan J; Pineda, Jaime A; Müller, Ralph-Axel
2014-07-01
Converging evidence indicates that brain abnormalities in autism spectrum disorder (ASD) involve atypical network connectivity, but it is unclear whether altered connectivity is especially prominent in brain networks that participate in social cognition. To investigate whether adolescents with ASD show altered functional connectivity in 2 brain networks putatively impaired in ASD and involved in social processing, theory of mind (ToM) and mirror neuron system (MNS). Cross-sectional study using resting-state functional magnetic resonance imaging involving 25 adolescents with ASD between the ages of 11 and 18 years and 25 typically developing adolescents matched for age, handedness, and nonverbal IQ. Statistical parametric maps testing the degree of whole-brain functional connectivity and social functioning measures. Relative to typically developing controls, participants with ASD showed a mixed pattern of both over- and underconnectivity in the ToM network, which was associated with greater social impairment. Increased connectivity in the ASD group was detected primarily between the regions of the MNS and ToM, and was correlated with sociocommunicative measures, suggesting that excessive ToM-MNS cross talk might be associated with social impairment. In a secondary analysis comparing a subset of the 15 participants with ASD with the most severe symptomology and a tightly matched subset of 15 typically developing controls, participants with ASD showed exclusive overconnectivity effects in both ToM and MNS networks, which were also associated with greater social dysfunction. Adolescents with ASD showed atypically increased functional connectivity involving the mentalizing and mirror neuron systems, largely reflecting greater cross talk between the 2. This finding is consistent with emerging evidence of reduced network segregation in ASD and challenges the prevailing theory of general long-distance underconnectivity in ASD. This excess ToM-MNS connectivity may reflect
-
Electrophysiological properties of neurons derived from human stem cells and iNeurons in vitro.
Halliwell, Robert F
2017-06-01
Functional studies of neurons have traditionally used nervous system tissues from a variety of non-human vertebrate and invertebrate species, even when the focus of much of this research has been directed at understanding human brain function. Over the last decade, the identification and isolation of human stem cells from embryonic, tissue (or adult) and induced pluripotent stem cells (iPSCs) has revolutionized the availability of human neurons for experimental studies in vitro. In addition, the direct conversion of terminally differentiated fibroblasts into Induced neurons (iN) has generated great excitement because of the likely value of such human stem cell derived neurons (hSCNs) and iN cells in drug discovery, neuropharmacology, neurotoxicology and regenerative medicine. This review addresses the current state of our knowledge of functional receptors and ion channels expressed in neurons derived from human stem cells and iNeurons and identifies gaps and questions that might be investigated in future studies; it focusses almost exclusively on what is known about the electrophysiological properties of neurons derived from human stem cells and iN cells in vitro with an emphasis on voltage and ligand gated ion channels, since these mediate synaptic signalling in the nervous system and they are at the heart of neuropharmacology. Copyright © 2016 Elsevier Ltd. All rights reserved.
-
Berry, Bonnie J; Smith, Alec S T; Long, Christopher J; Martin, Candace C; Hickman, James J
2018-05-22
Alzheimer's disease (AD) is characterized by slow, progressive neurodegeneration leading to severe neurological impairment, but current drug development efforts are limited by the lack of robust, human-based disease models. Amyloid-β (Aβ) is known to play an integral role in AD progression as it has been shown to interfere with neurological function. However, studies into AD pathology commonly apply Aβ to neurons for short durations at nonphysiological concentrations to induce an exaggerated dysfunctional phenotype. Such methods are unlikely to elucidate early stage disease dysfunction, when treatment is still possible, since damage to neurons by these high concentrations is extensive. In this study, we investigated chronic, pathologically relevant Aβ oligomer concentrations to induce an electrophysiological phenotype that is more representative of early AD progression compared to an acute high-dose application in human cortical neurons. The high, acute oligomer dose resulted in severe neuronal toxicity as well as upregulation of tau and phosphorylated tau. Chronic, low-dose treatment produced significant functional impairment without increased cell death or accumulation of tau protein. This in vitro phenotype more closely mirrors the status of early stage neural decline in AD pathology and could provide a valuable tool to further understanding of early stage AD pathophysiology and for screening potential therapeutic compounds.
-
Mirror system based therapy for autism spectrum disorders
Institute of Scientific and Technical Information of China (English)
Wei CHEN; Jing ZHANG; Jun DING
2008-01-01
This paper reviews the present theories and empirical research of autisms' cognitive research and mir-ror systems and introduces a new hypothesis about the causes of autism spectrum disorders (ASD): autistic mir-ror neuron dysfunction hypothesis. ASD subjects show obvious lack of the activation of the mirror system during the task of observation or emotional cognition. It is sig-nificant to investigate the mirror system for revealing the causes of autism and it is also helpful for developing new ways to diagnose or treat this disorder.
-
Mirror neuron system and observational learning: behavioral and neurophysiological evidence.
Lago-Rodriguez, Angel; Lopez-Alonso, Virginia; Fernández-del-Olmo, Miguel
2013-07-01
Three experiments were performed to study observational learning using behavioral, perceptual, and neurophysiological data. Experiment 1 investigated whether observing an execution model, during physical practice of a transitive task that only presented one execution strategy, led to performance improvements compared with physical practice alone. Experiment 2 investigated whether performing an observational learning protocol improves subjects' action perception. In experiment 3 we evaluated whether the type of practice performed determined the activation of the Mirror Neuron System during action observation. Results showed that, compared with physical practice, observing an execution model during a task that only showed one execution strategy does not provide behavioral benefits. However, an observational learning protocol allows subjects to predict more precisely the outcome of the learned task. Finally, intersperse observation of an execution model with physical practice results in changes of primary motor cortex activity during the observation of the motor pattern previously practiced, whereas modulations in the connectivity between primary and non primary motor areas (PMv-M1; PPC-M1) were not affected by the practice protocol performed by the observer. Copyright © 2013 Elsevier B.V. All rights reserved.
-
Choline acetyltransferase-containing neurons in the human parietal neocortex
Directory of Open Access Journals (Sweden)
V Benagiano
2009-06-01
Full Text Available A number of immunocytochemical studies have indicated the presence of cholinergic neurons in the cerebral cortex of various species of mammals. Whether such cholinergic neurons in the human cerebral cortex are exclusively of subcortical origin is still debated. In this immunocytochemical study, the existence of cortical cholinergic neurons was investigated on surgical samples of human parietal association neocortex using a highly specific monoclonal antibody against choline acetyltransferase (ChAT, the acetylcholine biosynthesising enzyme. ChAT immunoreactivity was detected in a subpopulation of neurons located in layers II and III. These were small or medium-sized pyramidal neurons which showed cytoplasmic immunoreactivity in the perikarya and processes, often in close association to blood microvessels. This study, providing demonstration of ChAT neurons in the human parietal neocortex, strongly supports the existence of intrinsic cholinergic innervation of the human neocortex. It is likely that these neurons contribute to the cholinergic innervation of the intracortical microvessels.
-
Soudobé trendy v oblasti zrcadlových neuronů
ŠLAJSOVÁ, Kristýna
2014-01-01
This bachelor thesis will discuss the extensive area of mirror neurons. Conception of the thesis is rather theoretical; the thesis is led like a survey study and also contains a research from a variety of foreign languages sources. The thesis provides an insight into the solid subject of mirror neurons and their psychological aspects. These aspects deal with the theory of the mirror neurons in a context of a mother child relations, language and speech, cultural differences, emotions and imita...
-
Is human imitation based on a mirror-neuron system? Some behavioural evidence
Wohlschläger, A.; Bekkering, H.
2002-01-01
Recently, a population of neurones was discovered in the monkey's (Macaca nemestrina) ventrolateral part of the pre-motor cortex (area F5). It is specialised for recognising object-oriented actions, regardless of whether these actions are performed or observed by the monkey. The latter observation
-
Is human imitation based on a mirror-neurone system? Some behavioural evidence
Wohlschlager, A; Bekkering, H; Wohlschläger, A
Recently, a population of neurones was discovered in the monkey's (Macaca nemestrina) ventrolateral part of the pre-motor cortex (area F5). It is specialised for recognising object-oriented actions, regardless of whether these actions are performed or observed by the monkey. The latter observation
-
Afferent neuronal control of type-I gonadotropin releasing hormone (GnRH neurons in the human
Directory of Open Access Journals (Sweden)
Erik eHrabovszky
2013-09-01
Full Text Available Understanding the regulation of the human menstrual cycle represents an important ultimate challenge of reproductive neuroendocrine research. However, direct translation of information from laboratory animal experiments to the human is often complicated by strikingly different and unique reproductive strategies and central regulatory mechanisms that can be present in even closely related animal species. In all mammals studied so far, type-I gonadotropin releasing hormone (GnRH synthesizing neurons form the final common output way from the hypothalamus in the neuroendocrine control of the adenohypophysis. Under various physiological and pathological conditions, hormonal and metabolic signals either regulate GnRH neurons directly or act on upstream neuronal circuitries to influence the pattern of pulsatile GnRH secretion into the hypophysial portal circulation. Neuronal afferents to GnRH cells convey important metabolic-, stress-, sex steroid-, lactational- and circadian signals to the reproductive axis, among other effects. This article gives an overview of the available neuroanatomical literature that described the afferent regulation of human GnRH neurons by peptidergic, monoaminergic and amino acidergic neuronal systems. Recent studies of human genetics provided evidence that central peptidergic signaling by kisspeptins and neurokinin B play particularly important roles in puberty onset and later, in the sex steroid-dependent feedback regulation of GnRH neurons. This review article places special emphasis on the topographic distribution, sexual dimorphism, aging-dependent neuroanatomical changes and plastic connectivity to GnRH neurons of the critically important human hypothalamic kisspeptin and neurokinin B systems.
-
Grasping the intentions of others with one's own mirror neuron system.
Directory of Open Access Journals (Sweden)
Marco Iacoboni
2005-03-01
Full Text Available Understanding the intentions of others while watching their actions is a fundamental building block of social behavior. The neural and functional mechanisms underlying this ability are still poorly understood. To investigate these mechanisms we used functional magnetic resonance imaging. Twenty-three subjects watched three kinds of stimuli: grasping hand actions without a context, context only (scenes containing objects, and grasping hand actions performed in two different contexts. In the latter condition the context suggested the intention associated with the grasping action (either drinking or cleaning. Actions embedded in contexts, compared with the other two conditions, yielded a significant signal increase in the posterior part of the inferior frontal gyrus and the adjacent sector of the ventral premotor cortex where hand actions are represented. Thus, premotor mirror neuron areas-areas active during the execution and the observation of an action-previously thought to be involved only in action recognition are actually also involved in understanding the intentions of others. To ascribe an intention is to infer a forthcoming new goal, and this is an operation that the motor system does automatically.
-
Graphene foam as a biocompatible scaffold for culturing human neurons
Mattei, Cristiana; Nasr, Babak; Hudson, Emma J.; Alshawaf, Abdullah J.; Chana, Gursharan; Everall, Ian P.; Dottori, Mirella; Skafidas, Efstratios
2018-01-01
In this study, we explore the use of electrically active graphene foam as a scaffold for the culture of human-derived neurons. Human embryonic stem cell (hESC)-derived cortical neurons fated as either glutamatergic or GABAergic neuronal phenotypes were cultured on graphene foam. We show that graphene foam is biocompatible for the culture of human neurons, capable of supporting cell viability and differentiation of hESC-derived cortical neurons. Based on the findings, we propose that graphene foam represents a suitable scaffold for engineering neuronal tissue and warrants further investigation as a model for understanding neuronal maturation, function and circuit formation. PMID:29657752
-
Neuronal medium that supports basic synaptic functions and activity of human neurons in vitro
Bardy, C.; Hurk, M. van den; Eames, T.; Marchand, C.; Hernandez, R.V.; Kellogg, M.; Gorris, M.A.J.; Galet, B.; Palomares, V.; Brown, J.; Bang, A.G.; Mertens, J.; Bohnke, L.; Boyer, L.; Simon, S.; Gage, F.H.
2015-01-01
Human cell reprogramming technologies offer access to live human neurons from patients and provide a new alternative for modeling neurological disorders in vitro. Neural electrical activity is the essence of nervous system function in vivo. Therefore, we examined neuronal activity in media widely
-
Neurite outgrowth in human iPSC-derived neurons
Data on morphology of rat and human neurons in cell cultureThis dataset is associated with the following publication:Druwe, I., T. Freudenrich , K. Wallace , T. Shafer , and W. Mundy. Comparison of Human Induced PluripotentStem Cell-Derived Neurons and Rat Primary CorticalNeurons as In Vitro Models of Neurite Outgrowth. Applied In vitro Toxicology. Mary Ann Liebert, Inc., Larchmont, NY, USA, 2(1): 26-36, (2016).
-
Parkin Mutations Reduce the Complexity of Neuronal Processes in iPSC-derived Human Neurons
Ren, Yong; Jiang, Houbo; Hu, Zhixing; Fan, Kevin; Wang, Jun; Janoschka, Stephen; Wang, Xiaomin; Ge, Shaoyu; Feng, Jian
2015-01-01
Parkinson’s disease (PD) is characterized by the degeneration of nigral dopaminergic (DA) neurons and non-DA neurons in many parts of the brain. Mutations of parkin, an E3 ubiquitin ligase that strongly binds to microtubules, are the most frequent cause of recessively inherited Parkinson’s disease. The lack of robust PD phenotype in parkin knockout mice suggests a unique vulnerability of human neurons to parkin mutations. Here, we show that the complexity of neuronal processes as measured by total neurite length, number of terminals, number of branch points and Sholl analysis, was greatly reduced in induced pluripotent stem cell (iPSC)-derived TH+ or TH− neurons from PD patients with parkin mutations. Consistent with these, microtubule stability was significantly decreased by parkin mutations in iPSC-derived neurons. Overexpression of parkin, but not its PD-linked mutant nor GFP, restored the complexity of neuronal processes and the stability of microtubules. Consistent with these, the microtubule-depolymerizing agent colchicine mimicked the effect of parkin mutations by decreasing neurite length and complexity in control neurons while the microtubule-stabilizing drug taxol mimicked the effect of parkin overexpression by enhancing the morphology of parkin-deficient neurons. The results suggest that parkin maintains the morphological complexity of human neurons by stabilizing microtubules. PMID:25332110
-
Novel transcriptional networks regulated by CLOCK in human neurons.
Fontenot, Miles R; Berto, Stefano; Liu, Yuxiang; Werthmann, Gordon; Douglas, Connor; Usui, Noriyoshi; Gleason, Kelly; Tamminga, Carol A; Takahashi, Joseph S; Konopka, Genevieve
2017-11-01
The molecular mechanisms underlying human brain evolution are not fully understood; however, previous work suggested that expression of the transcription factor CLOCK in the human cortex might be relevant to human cognition and disease. In this study, we investigated this novel transcriptional role for CLOCK in human neurons by performing chromatin immunoprecipitation sequencing for endogenous CLOCK in adult neocortices and RNA sequencing following CLOCK knockdown in differentiated human neurons in vitro. These data suggested that CLOCK regulates the expression of genes involved in neuronal migration, and a functional assay showed that CLOCK knockdown increased neuronal migratory distance. Furthermore, dysregulation of CLOCK disrupts coexpressed networks of genes implicated in neuropsychiatric disorders, and the expression of these networks is driven by hub genes with human-specific patterns of expression. These data support a role for CLOCK-regulated transcriptional cascades involved in human brain evolution and function. © 2017 Fontenot et al.; Published by Cold Spring Harbor Laboratory Press.
-
Characterization of Induced Pluripotent Stem Cell-derived Human Serotonergic Neurons
Directory of Open Access Journals (Sweden)
Lining Cao
2017-05-01
Full Text Available In the brain, the serotonergic neurons located in the raphe nucleus are the unique resource of the neurotransmitter serotonin, which plays a pivotal role in the regulation of brain development and functions. Dysfunction of the serotonin system is present in many psychiatric disorders. Lack of in vitro functional human model limits the understanding of human central serotonergic system and its related diseases and clinical applications. Previously, we have developed a method generating human serotonergic neurons from induced pluripotent stem cells (iPSCs. In this study, we analyzed the features of these human iPSCs-derived serotonergic neurons both in vitro and in vivo. We found that these human serotonergic neurons are sensitive to the selective neurotoxin 5, 7-Dihydroxytryptamine (5,7-DHT in vitro. After being transplanted into newborn mice, the cells not only expressed their typical molecular markers, but also showed the migration and projection to the host’s cerebellum, hindbrain and spinal cord. The data demonstrate that these human iPSCs-derived neurons exhibit the typical features as the serotonergic neurons in the brain, which provides a solid foundation for studying on human serotonin system and its related disorders.
-
Neurons in primary motor cortex engaged during action observation.
Dushanova, Juliana; Donoghue, John
2010-01-01
Neurons in higher cortical areas appear to become active during action observation, either by mirroring observed actions (termed mirror neurons) or by eliciting mental rehearsal of observed motor acts. We report the existence of neurons in the primary motor cortex (M1), an area that is generally considered to initiate and guide movement performance, responding to viewed actions. Multielectrode recordings in monkeys performing or observing a well-learned step-tracking task showed that approximately half of the M1 neurons that were active when monkeys performed the task were also active when they observed the action being performed by a human. These 'view' neurons were spatially intermingled with 'do' neurons, which are active only during movement performance. Simultaneously recorded 'view' neurons comprised two groups: approximately 38% retained the same preferred direction (PD) and timing during performance and viewing, and the remainder (62%) changed their PDs and time lag during viewing as compared with performance. Nevertheless, population activity during viewing was sufficient to predict the direction and trajectory of viewed movements as action unfolded, although less accurately than during performance. 'View' neurons became less active and contained poorer representations of action when only subcomponents of the task were being viewed. M1 'view' neurons thus appear to reflect aspects of a learned movement when observed in others, and form part of a broadly engaged set of cortical areas routinely responding to learned behaviors. These findings suggest that viewing a learned action elicits replay of aspects of M1 activity needed to perform the observed action, and could additionally reflect processing related to understanding, learning or mentally rehearsing action.
-
Autism and the mirror neuron system: insights from learning and teaching.
Vivanti, Giacomo; Rogers, Sally J
2014-01-01
Individuals with autism have difficulties in social learning domains which typically involve mirror neuron system (MNS) activation. However, the precise role of the MNS in the development of autism and its relevance to treatment remain unclear. In this paper, we argue that three distinct aspects of social learning are critical for advancing knowledge in this area: (i) the mechanisms that allow for the implicit mapping of and learning from others' behaviour, (ii) the motivation to attend to and model conspecifics and (iii) the flexible and selective use of social learning. These factors are key targets of the Early Start Denver Model, an autism treatment approach which emphasizes social imitation, dyadic engagement, verbal and non-verbal communication and affect sharing. Analysis of the developmental processes and treatment-related changes in these different aspects of social learning in autism can shed light on the nature of the neuropsychological mechanisms underlying social learning and positive treatment outcomes in autism. This knowledge in turn may assist in developing more successful pedagogic approaches to autism spectrum disorder. Thus, intervention research can inform the debate on relations among neuropsychology of social learning, the role of the MNS, and educational practice in autism.
-
Autism and the mirror neuron system: insights from learning and teaching
Vivanti, Giacomo; Rogers, Sally J.
2014-01-01
Individuals with autism have difficulties in social learning domains which typically involve mirror neuron system (MNS) activation. However, the precise role of the MNS in the development of autism and its relevance to treatment remain unclear. In this paper, we argue that three distinct aspects of social learning are critical for advancing knowledge in this area: (i) the mechanisms that allow for the implicit mapping of and learning from others' behaviour, (ii) the motivation to attend to and model conspecifics and (iii) the flexible and selective use of social learning. These factors are key targets of the Early Start Denver Model, an autism treatment approach which emphasizes social imitation, dyadic engagement, verbal and non-verbal communication and affect sharing. Analysis of the developmental processes and treatment-related changes in these different aspects of social learning in autism can shed light on the nature of the neuropsychological mechanisms underlying social learning and positive treatment outcomes in autism. This knowledge in turn may assist in developing more successful pedagogic approaches to autism spectrum disorder. Thus, intervention research can inform the debate on relations among neuropsychology of social learning, the role of the MNS, and educational practice in autism. PMID:24778379
-
Aldana, Blanca I; Zhang, Yu; Lihme, Maria Fog; Bak, Lasse K; Nielsen, Jørgen E; Holst, Bjørn; Hyttel, Poul; Freude, Kristine K; Waagepetersen, Helle S
2017-06-01
Alterations in the cellular metabolic machinery of the brain are associated with neurodegenerative disorders such as Alzheimer's disease. Novel human cellular disease models are essential in order to study underlying disease mechanisms. In the present study, we characterized major metabolic pathways in neurons derived from human induced pluripotent stem cells (hiPSC). With this aim, cultures of hiPSC-derived neurons were incubated with [U- 13 C]glucose, [U- 13 C]glutamate or [U- 13 C]glutamine. Isotopic labeling in metabolites was determined using gas chromatography coupled to mass spectrometry, and cellular amino acid content was quantified by high-performance liquid chromatography. Additionally, we evaluated mitochondrial function using real-time assessment of oxygen consumption via the Seahorse XF e 96 Analyzer. Moreover, in order to validate the hiPSC-derived neurons as a model system, a metabolic profiling was performed in parallel in primary neuronal cultures of mouse cerebral cortex and cerebellum. These serve as well-established models of GABAergic and glutamatergic neurons, respectively. The hiPSC-derived neurons were previously characterized as being forebrain-specific cortical glutamatergic neurons. However, a comparable preparation of predominantly mouse cortical glutamatergic neurons is not available. We found a higher glycolytic capacity in hiPSC-derived neurons compared to mouse neurons and a substantial oxidative metabolism through the mitochondrial tricarboxylic acid (TCA) cycle. This finding is supported by the extracellular acidification and oxygen consumption rates measured in the cultured human neurons. [U- 13 C]Glutamate and [U- 13 C]glutamine were found to be efficient energy substrates for the neuronal cultures originating from both mice and humans. Interestingly, isotopic labeling in metabolites from [U- 13 C]glutamate was higher than that from [U- 13 C]glutamine. Although the metabolic profile of hiPSC-derived neurons in vitro was
-
Mirror Neurons and the Evolution of Language
Corballis, Michael C.
2010-01-01
The mirror system provided a natural platform for the subsequent evolution of language. In nonhuman primates, the system provides for the understanding of biological action, and possibly for imitation, both prerequisites for language. I argue that language evolved from manual gestures, initially as a system of pantomime, but with gestures…
-
Mirrored STDP Implements Autoencoder Learning in a Network of Spiking Neurons.
Burbank, Kendra S
2015-12-01
The autoencoder algorithm is a simple but powerful unsupervised method for training neural networks. Autoencoder networks can learn sparse distributed codes similar to those seen in cortical sensory areas such as visual area V1, but they can also be stacked to learn increasingly abstract representations. Several computational neuroscience models of sensory areas, including Olshausen & Field's Sparse Coding algorithm, can be seen as autoencoder variants, and autoencoders have seen extensive use in the machine learning community. Despite their power and versatility, autoencoders have been difficult to implement in a biologically realistic fashion. The challenges include their need to calculate differences between two neuronal activities and their requirement for learning rules which lead to identical changes at feedforward and feedback connections. Here, we study a biologically realistic network of integrate-and-fire neurons with anatomical connectivity and synaptic plasticity that closely matches that observed in cortical sensory areas. Our choice of synaptic plasticity rules is inspired by recent experimental and theoretical results suggesting that learning at feedback connections may have a different form from learning at feedforward connections, and our results depend critically on this novel choice of plasticity rules. Specifically, we propose that plasticity rules at feedforward versus feedback connections are temporally opposed versions of spike-timing dependent plasticity (STDP), leading to a symmetric combined rule we call Mirrored STDP (mSTDP). We show that with mSTDP, our network follows a learning rule that approximately minimizes an autoencoder loss function. When trained with whitened natural image patches, the learned synaptic weights resemble the receptive fields seen in V1. Our results use realistic synaptic plasticity rules to show that the powerful autoencoder learning algorithm could be within the reach of real biological networks.
-
Anatomical differences in the mirror neuron system and social cognition network in autism.
Hadjikhani, Nouchine; Joseph, Robert M; Snyder, Josh; Tager-Flusberg, Helen
2006-09-01
Autism spectrum disorder (ASD) is a neurodevelopmental disorder associated with impaired social and emotional skills, the anatomical substrate of which is still unknown. In this study, we compared a group of 14 high-functioning ASD adults with a group of controls matched for sex, age, intelligence quotient, and handedness. We used an automated technique of analysis that accurately measures the thickness of the cerebral cortex and generates cross-subject statistics in a coordinate system based on cortical anatomy. We found local decreases of gray matter in the ASD group in areas belonging to the mirror neuron system (MNS), argued to be the basis of empathic behavior. Cortical thinning of the MNS was correlated with ASD symptom severity. Cortical thinning was also observed in areas involved in emotion recognition and social cognition. These findings suggest that the social and emotional deficits characteristic of autism may reflect abnormal thinning of the MNS and the broader network of cortical areas subserving social cognition.
-
Directory of Open Access Journals (Sweden)
Stefania La Porta
2016-05-01
His research has been forming the basis of the theoretical and methodological focus of music therapy to psychodynamic. The ability to reproduce the relational process characterized by affective attunements in a rehabilitation setting - music therapy where there are dis-evolution, as in the case of patients with Alzheimer's disease, you can reactivate capacity affective and relational residual strengthening in the subject 'personal and social identity mortified by the disease. Role within that path is done by a very peculiar type of neurons, mirror neurons, the subject of study in recent years by the neurosciences, whose characteristic would be to get excited is when a person performs a certain action, both when it is another to do it before his eyes.
-
Brain mechanisms underlying human communication
Noordzij, M.L.; Newman-Norlund, S.E.; Ruiter, J.P.A. de; Hagoort, P.; Levinson, S.C.; Toni, I.
2009-01-01
Human communication has been described as involving the coding-decoding of a conventional symbol system, which could be supported by parts of the human motor system (i.e. the "mirror neurons system"). However, this view does not explain how these conventions could develop in the first place. Here we
-
Morphological differences in the mirror neuron system in Williams syndrome.
Ng, Rowena; Brown, Timothy T; Erhart, Matthew; Järvinen, Anna M; Korenberg, Julie R; Bellugi, Ursula; Halgren, Eric
2016-01-01
Williams syndrome (WS) is a genetic condition characterized by an overly gregarious personality, including high empathetic concern for others. Although seemingly disparate from the profile of autism spectrum disorder (ASD), both are associated with deficits in social communication/cognition. Notably, the mirror neuron system (MNS) has been implicated in social dysfunction for ASD; yet, the integrity of this network and its association with social functioning in WS remains unknown. Magnetic resonance imaging (MRI) methods were used to examine the structural integrity of the MNS of adults with WS versus typically developing (TD) individuals. The Social Responsiveness Scale (SRS), a tool typically used to screen for social features of ASD, was also employed to assess the relationships between social functioning with the MNS morphology in WS participants. WS individuals showed reduced cortical surface area of MNS substrates yet relatively preserved cortical thickness as compared to TD adults. Increased cortical thickness of the inferior parietal lobule (IPL) was associated with increased deficits in social communication, social awareness, social cognition, and autistic mannerisms. However, social motivation was not related to anatomical features of the MNS. Our findings indicate that social deficits typical to both ASD and WS may be attributed to an aberrant MNS, whereas the unusual social drive marked in WS is subserved by substrates distinct from this network.
-
Brain mechanisms underlying human communication
Noordzij, Matthijs Leendert; Newman-Norlund, Sarah E.; de Ruiter, Jan Peter; Hagoort, Peter; Levinson, Stephen C.; Toni, Ivan
2009-01-01
Human communication has been described as involving the coding-decoding of a conventional symbol system, which could be supported by parts of the human motor system (i.e. the “mirror neurons system”). However, this view does not explain how these conventions could develop in the first place. Here we
-
Generation of neuropeptidergic hypothalamic neurons from human pluripotent stem cells.
Merkle, Florian T; Maroof, Asif; Wataya, Takafumi; Sasai, Yoshiki; Studer, Lorenz; Eggan, Kevin; Schier, Alexander F
2015-02-15
Hypothalamic neurons orchestrate many essential physiological and behavioral processes via secreted neuropeptides, and are relevant to human diseases such as obesity, narcolepsy and infertility. We report the differentiation of human pluripotent stem cells into many of the major types of neuropeptidergic hypothalamic neurons, including those producing pro-opiolemelanocortin, agouti-related peptide, hypocretin/orexin, melanin-concentrating hormone, oxytocin, arginine vasopressin, corticotropin-releasing hormone (CRH) or thyrotropin-releasing hormone. Hypothalamic neurons can be generated using a 'self-patterning' strategy that yields a broad array of cell types, or via a more reproducible directed differentiation approach. Stem cell-derived human hypothalamic neurons share characteristic morphological properties and gene expression patterns with their counterparts in vivo, and are able to integrate into the mouse brain. These neurons could form the basis of cellular models, chemical screens or cellular therapies to study and treat common human diseases. © 2015. Published by The Company of Biologists Ltd.
-
Mirroring Facial Expressions and Emotions in Dyadic Conversations
DEFF Research Database (Denmark)
Navarretta, Costanza
2016-01-01
This paper presents an investigation of mirroring facial expressions and the emotions which they convey in dyadic naturally occurring first encounters. Mirroring facial expressions are a common phenomenon in face-to-face interactions, and they are due to the mirror neuron system which has been...... and overlapping facial expressions are very frequent. In this study, we want to determine whether the overlapping facial expressions are mirrored or are otherwise correlated in the encounters, and to what extent mirroring facial expressions convey the same emotion. The results of our study show that the majority...... of smiles and laughs, and one fifth of the occurrences of raised eyebrows are mirrored in the data. Moreover some facial traits in co-occurring expressions co-occur more often than it would be expected by chance. Finally, amusement, and to a lesser extent friendliness, are often emotions shared by both...
-
Spider Silk as Guiding Biomaterial for Human Model Neurons
Directory of Open Access Journals (Sweden)
Frank Roloff
2014-01-01
Full Text Available Over the last years, a number of therapeutic strategies have emerged to promote axonal regeneration. An attractive strategy is the implantation of biodegradable and nonimmunogenic artificial scaffolds into injured peripheral nerves. In previous studies, transplantation of decellularized veins filled with spider silk for bridging critical size nerve defects resulted in axonal regeneration and remyelination by invading endogenous Schwann cells. Detailed interaction of elongating neurons and the spider silk as guidance material is unknown. To visualize direct cellular interactions between spider silk and neurons in vitro, we developed an in vitro crossed silk fiber array. Here, we describe in detail for the first time that human (NT2 model neurons attach to silk scaffolds. Extending neurites can bridge gaps between single silk fibers and elongate afterwards on the neighboring fiber. Culturing human neurons on the silk arrays led to an increasing migration and adhesion of neuronal cell bodies to the spider silk fibers. Within three to four weeks, clustered somata and extending neurites formed ganglion-like cell structures. Microscopic imaging of human neurons on the crossed fiber arrays in vitro will allow for a more efficient development of methods to maximize cell adhesion and neurite growth on spider silk prior to transplantation studies.
-
Neurons from the adult human dentate nucleus: neural networks in the neuron classification.
Grbatinić, Ivan; Marić, Dušica L; Milošević, Nebojša T
2015-04-07
Topological (central vs. border neuron type) and morphological classification of adult human dentate nucleus neurons according to their quantified histomorphological properties using neural networks on real and virtual neuron samples. In the real sample 53.1% and 14.1% of central and border neurons, respectively, are classified correctly with total of 32.8% of misclassified neurons. The most important result present 62.2% of misclassified neurons in border neurons group which is even greater than number of correctly classified neurons (37.8%) in that group, showing obvious failure of network to classify neurons correctly based on computational parameters used in our study. On the virtual sample 97.3% of misclassified neurons in border neurons group which is much greater than number of correctly classified neurons (2.7%) in that group, again confirms obvious failure of network to classify neurons correctly. Statistical analysis shows that there is no statistically significant difference in between central and border neurons for each measured parameter (p>0.05). Total of 96.74% neurons are morphologically classified correctly by neural networks and each one belongs to one of the four histomorphological types: (a) neurons with small soma and short dendrites, (b) neurons with small soma and long dendrites, (c) neuron with large soma and short dendrites, (d) neurons with large soma and long dendrites. Statistical analysis supports these results (pneurons can be classified in four neuron types according to their quantitative histomorphological properties. These neuron types consist of two neuron sets, small and large ones with respect to their perykarions with subtypes differing in dendrite length i.e. neurons with short vs. long dendrites. Besides confirmation of neuron classification on small and large ones, already shown in literature, we found two new subtypes i.e. neurons with small soma and long dendrites and with large soma and short dendrites. These neurons are
-
Directory of Open Access Journals (Sweden)
Anna Pohl
2017-12-01
Full Text Available BackgroundAffective dysfunctions are common in patients with Parkinson’s disease, but the underlying neurobiological deviations have rarely been examined. Parkinson’s disease is characterized by a loss of dopamine neurons in the substantia nigra resulting in impairment of motor and non-motor basal ganglia-cortical loops. Concerning emotional deficits, some studies provide evidence for altered brain processing in limbic- and lateral-orbitofrontal gating loops. In a second line of evidence, human premotor and inferior parietal homologs of mirror neuron areas were involved in processing and understanding of emotional facial expressions. We examined deviations in brain activation during processing of facial expressions in patients and related these to emotion recognition accuracy.Methods13 patients and 13 healthy controls underwent an emotion recognition task and a functional magnetic resonance imaging (fMRI measurement. In the Emotion Hexagon test, participants were presented with blends of two emotions and had to indicate which emotion best described the presented picture. Blended pictures with three levels of difficulty were included. During fMRI scanning, participants observed video clips depicting emotional, non-emotional, and neutral facial expressions or were asked to produce these facial expressions themselves.ResultsPatients performed slightly worse in the emotion recognition task, but only when judging the most ambiguous facial expressions. Both groups activated inferior frontal and anterior inferior parietal homologs of mirror neuron areas during observation and execution of the emotional facial expressions. During observation, responses in the pars opercularis of the right inferior frontal gyrus, in the bilateral inferior parietal lobule and in the bilateral supplementary motor cortex were decreased in patients. Furthermore, in patients, activation of the right anterior inferior parietal lobule was positively related to accuracy in
-
Populations of subplate and interstitial neurons in fetal and adult human telencephalon.
Judaš, Miloš; Sedmak, Goran; Pletikos, Mihovil; Jovanov-Milošević, Nataša
2010-10-01
In the adult human telencephalon, subcortical (gyral) white matter contains a special population of interstitial neurons considered to be surviving descendants of fetal subplate neurons [Kostovic & Rakic (1980) Cytology and the time of origin of interstitial neurons in the white matter in infant and adult human and monkey telencephalon. J Neurocytol9, 219]. We designate this population of cells as superficial (gyral) interstitial neurons and describe their morphology and distribution in the postnatal and adult human cerebrum. Human fetal subplate neurons cannot be regarded as interstitial, because the subplate zone is an essential part of the fetal cortex, the major site of synaptogenesis and the 'waiting' compartment for growing cortical afferents, and contains both projection neurons and interneurons with distinct input-output connectivity. However, although the subplate zone is a transient fetal structure, many subplate neurons survive postnatally as superficial (gyral) interstitial neurons. The fetal white matter is represented by the intermediate zone and well-defined deep periventricular tracts of growing axons, such as the corpus callosum, anterior commissure, internal and external capsule, and the fountainhead of the corona radiata. These tracts gradually occupy the territory of transient fetal subventricular and ventricular zones.The human fetal white matter also contains distinct populations of deep fetal interstitial neurons, which, by virtue of their location, morphology, molecular phenotypes and advanced level of dendritic maturation, remain distinct from subplate neurons and neurons in adjacent structures (e.g. basal ganglia, basal forebrain). We describe the morphological, histochemical (nicotinamide-adenine dinucleotide phosphate-diaphorase) and immunocytochemical (neuron-specific nuclear protein, microtubule-associated protein-2, calbindin, calretinin, neuropeptide Y) features of both deep fetal interstitial neurons and deep (periventricular
-
Generation of Spinal Motor Neurons from Human Pluripotent Stem Cells.
Santos, David P; Kiskinis, Evangelos
2017-01-01
Human embryonic stem cells (ESCs) are characterized by their unique ability to self-renew indefinitely, as well as to differentiate into any cell type of the human body. Induced pluripotent stem cells (iPSCs) share these salient characteristics with ESCs and can easily be generated from any given individual by reprogramming somatic cell types such as fibroblasts or blood cells. The spinal motor neuron (MN) is a specialized neuronal subtype that synapses with muscle to control movement. Here, we present a method to generate functional, postmitotic, spinal motor neurons through the directed differentiation of ESCs and iPSCs by the use of small molecules. These cells can be utilized to study the development and function of human motor neurons in healthy and disease states.
-
Neurons in the human amygdala selective for perceived emotion
Wang, Shuo; Tudusciuc, Oana; Mamelak, Adam N.; Ross, Ian B.; Adolphs, Ralph; Rutishauser, Ueli
2014-01-01
The human amygdala plays a key role in recognizing facial emotions and neurons in the monkey and human amygdala respond to the emotional expression of faces. However, it remains unknown whether these responses are driven primarily by properties of the stimulus or by the perceptual judgments of the perceiver. We investigated these questions by recording from over 200 single neurons in the amygdalae of 7 neurosurgical patients with implanted depth electrodes. We presented degraded fear and happy faces and asked subjects to discriminate their emotion by button press. During trials where subjects responded correctly, we found neurons that distinguished fear vs. happy emotions as expressed by the displayed faces. During incorrect trials, these neurons indicated the patients’ subjective judgment. Additional analysis revealed that, on average, all neuronal responses were modulated most by increases or decreases in response to happy faces, and driven predominantly by judgments about the eye region of the face stimuli. Following the same analyses, we showed that hippocampal neurons, unlike amygdala neurons, only encoded emotions but not subjective judgment. Our results suggest that the amygdala specifically encodes the subjective judgment of emotional faces, but that it plays less of a role in simply encoding aspects of the image array. The conscious percept of the emotion shown in a face may thus arise from interactions between the amygdala and its connections within a distributed cortical network, a scheme also consistent with the long response latencies observed in human amygdala recordings. PMID:24982200
-
Directory of Open Access Journals (Sweden)
Robert Krencik
2017-12-01
Full Text Available Summary: Human astrocytes network with neurons in dynamic ways that are still poorly defined. Our ability to model this relationship is hampered by the lack of relevant and convenient tools to recapitulate this complex interaction. To address this barrier, we have devised efficient coculture systems utilizing 3D organoid-like spheres, termed asteroids, containing pre-differentiated human pluripotent stem cell (hPSC-derived astrocytes (hAstros combined with neurons generated from hPSC-derived neural stem cells (hNeurons or directly induced via Neurogenin 2 overexpression (iNeurons. Our systematic methods rapidly produce structurally complex hAstros and synapses in high-density coculture with iNeurons in precise numbers, allowing for improved studies of neural circuit function, disease modeling, and drug screening. We conclude that these bioengineered neural circuit model systems are reliable and scalable tools to accurately study aspects of human astrocyte-neuron functional properties while being easily accessible for cell-type-specific manipulations and observations. : In this article, Krencik and colleagues show that high-density cocultures of pre-differentiated human astrocytes with induced neurons, from pluripotent stem cells, elicit mature characteristics by 3â5Â weeks. This provides a faster and more defined alternative method to organoid cultures for investigating human neural circuit function. Keywords: human pluripotent stem cells, neurons, astrocytes, synapses, coculture, three-dimensional spheres, organoids, disease modeling
-
Voltage-gated Na+ currents in human dorsal root ganglion neurons
Zhang, Xiulin; Priest, Birgit T; Belfer, Inna; Gold, Michael S
2017-01-01
Available evidence indicates voltage-gated Na+ channels (VGSCs) in peripheral sensory neurons are essential for the pain and hypersensitivity associated with tissue injury. However, our understanding of the biophysical and pharmacological properties of the channels in sensory neurons is largely based on the study of heterologous systems or rodent tissue, despite evidence that both expression systems and species differences influence these properties. Therefore, we sought to determine the extent to which the biophysical and pharmacological properties of VGSCs were comparable in rat and human sensory neurons. Whole cell patch clamp techniques were used to study Na+ currents in acutely dissociated neurons from human and rat. Our results indicate that while the two major current types, generally referred to as tetrodotoxin (TTX)-sensitive and TTX-resistant were qualitatively similar in neurons from rats and humans, there were several differences that have important implications for drug development as well as our understanding of pain mechanisms. DOI: http://dx.doi.org/10.7554/eLife.23235.001 PMID:28508747
-
Self-contained induction of neurons from human embryonic stem cells.
Directory of Open Access Journals (Sweden)
Tsuyoshi Okuno
Full Text Available BACKGROUND: Neurons and glial cells can be efficiently induced from mouse embryonic stem (ES cells in a conditioned medium collected from rat primary-cultured astrocytes (P-ACM. However, the use of rodent primary cells for clinical applications may be hampered by limited supply and risk of contamination with xeno-proteins. METHODOLOGY/PRINCIPAL FINDINGS: We have developed an alternative method for unimpeded production of human neurons under xeno-free conditions. Initially, neural stem cells in sphere-like clusters were induced from human ES (hES cells after being cultured in P-ACM under free-floating conditions. The resultant neural stem cells could circumferentially proliferate under subsequent adhesive culture, and selectively differentiate into neurons or astrocytes by changing the medium to P-ACM or G5, respectively. These hES cell-derived neurons and astrocytes could procure functions similar to those of primary cells. Interestingly, a conditioned medium obtained from the hES cell-derived astrocytes (ES-ACM could successfully be used to substitute P-ACM for induction of neurons. Neurons made by this method could survive in mice brain after xeno-transplantation. CONCLUSION/SIGNIFICANCE: By inducing astrocytes from hES cells in a chemically defined medium, we could produce human neurons without the use of P-ACM. This self-serving method provides an unlimited source of human neural cells and may facilitate clinical applications of hES cells for neurological diseases.
-
The function of mirror neurons in the learning process
Mara Daniel
2017-01-01
In the last years, Neurosciences have developed very much, being elaborated many important theories scientific research in the field. The main goal of neuroscience is to understand how groups of neurons interact to create the behavior. Neuroscientists studying the action of molecules, genes and cells. It also explores the complex interactions involved in motion perception, thoughts, emotions and learning. Brick fundamental nervous system is the nerve cell, neuron. Neurons exchange information...
-
Visualization of migration of human cortical neurons generated from induced pluripotent stem cells.
Bamba, Yohei; Kanemura, Yonehiro; Okano, Hideyuki; Yamasaki, Mami
2017-09-01
Neuronal migration is considered a key process in human brain development. However, direct observation of migrating human cortical neurons in the fetal brain is accompanied by ethical concerns and is a major obstacle in investigating human cortical neuronal migration. We established a novel system that enables direct visualization of migrating cortical neurons generated from human induced pluripotent stem cells (hiPSCs). We observed the migration of cortical neurons generated from hiPSCs derived from a control and from a patient with lissencephaly. Our system needs no viable brain tissue, which is usually used in slice culture. Migratory behavior of human cortical neuron can be observed more easily and more vividly by its fluorescence and glial scaffold than that by earlier methods. Our in vitro experimental system provides a new platform for investigating development of the human central nervous system and brain malformation. Copyright © 2017 Elsevier B.V. All rights reserved.
-
Neuropeptide co-expression in hypothalamic kisspeptin neurons of laboratory animals and the human
Directory of Open Access Journals (Sweden)
Katalin eSkrapits
2015-02-01
Full Text Available Hypothalamic peptidergic neurons using kisspeptin (KP and its co-transmitters for communication are critically involved in the regulation of mammalian reproduction and puberty. This article provides an overview of neuropeptides present in KP neurons, with a focus on the human species. Immunohistochemical studies reveal that large subsets of human KP neurons synthesize neurokinin B, as also shown in laboratory species. In contrast, dynorphin described in KP neurons of rodents and sheep is found rarely in KP cells of human males and postmenopausal females. Similarly, galanin is detectable in mouse, but not human, KP cells, whereas substance P, cocaine- and amphetamine-regulated transcript and proenkephalin-derived opioids are expressed in varying subsets of KP neurons in humans, but not reported in ARC of other species. Human KP neurons do not contain neurotensin, cholecystokinin, proopiomelanocortin-derivatives, agouti-related protein, neuropeptide Y, somatostatin or tyrosine hydroxylase (dopamine. These data identify the possible co-transmitters of human KP cells. Neurochemical properties distinct from those of laboratory species indicate that humans use considerably different neurotransmitter mechanisms to regulate fertility.
-
Directory of Open Access Journals (Sweden)
Hilmar Heister
2015-01-01
Full Text Available In the two essays “The Philosophers and the Animals” and “The Poets and the Animals” (in The Lives of Animals, 1999 J.M. Coetzee lets Elizabeth Costello urge us to use our sympathetic imagination in order to access the experience of others—in particular, animals—and engage with them empathetically. Coetzee’s fiction illustrates how the use of the sympathetic imagination might evoke empathy in the reader. Narrative structure and the character’s mode of introspection engage the reader’s empathy through an ambivalent process of distancing and approximation, as Fritz Breithaupt puts forward in his narrative theory of empathy (Kulturen der Empathie, 2009. The sympathetic imagination and the complementary notion of embodiment feature prominently in Coetzee’s fictional discourse and resonate with neuroscience’s research on mirror neurons and their relation to empathy.
-
Physiological characterisation of human iPS-derived dopaminergic neurons.
Directory of Open Access Journals (Sweden)
Elizabeth M Hartfield
Full Text Available Human induced pluripotent stem cells (hiPSCs offer the potential to study otherwise inaccessible cell types. Critical to this is the directed differentiation of hiPSCs into functional cell lineages. This is of particular relevance to research into neurological disease, such as Parkinson's disease (PD, in which midbrain dopaminergic neurons degenerate during disease progression but are unobtainable until post-mortem. Here we report a detailed study into the physiological maturation over time of human dopaminergic neurons in vitro. We first generated and differentiated hiPSC lines into midbrain dopaminergic neurons and performed a comprehensive characterisation to confirm dopaminergic functionality by demonstrating dopamine synthesis, release, and re-uptake. The neuronal cultures include cells positive for both tyrosine hydroxylase (TH and G protein-activated inward rectifier potassium channel 2 (Kir3.2, henceforth referred to as GIRK2, representative of the A9 population of substantia nigra pars compacta (SNc neurons vulnerable in PD. We observed for the first time the maturation of the slow autonomous pace-making (<10 Hz and spontaneous synaptic activity typical of mature SNc dopaminergic neurons using a combination of calcium imaging and electrophysiology. hiPSC-derived neurons exhibited inositol tri-phosphate (IP3 receptor-dependent release of intracellular calcium from the endoplasmic reticulum in neuronal processes as calcium waves propagating from apical and distal dendrites, and in the soma. Finally, neurons were susceptible to the dopamine neuron-specific toxin 1-methyl-4-phenylpyridinium (MPP+ which reduced mitochondrial membrane potential and altered mitochondrial morphology. Mature hiPSC-derived dopaminergic neurons provide a neurophysiologically-defined model of previously inaccessible vulnerable SNc dopaminergic neurons to bridge the gap between clinical PD and animal models.
-
Specific responses of human hippocampal neurons are associated with better memory.
Suthana, Nanthia A; Parikshak, Neelroop N; Ekstrom, Arne D; Ison, Matias J; Knowlton, Barbara J; Bookheimer, Susan Y; Fried, Itzhak
2015-08-18
A population of human hippocampal neurons has shown responses to individual concepts (e.g., Jennifer Aniston) that generalize to different instances of the concept. However, recordings from the rodent hippocampus suggest an important function of these neurons is their ability to discriminate overlapping representations, or pattern separate, a process that may facilitate discrimination of similar events for successful memory. In the current study, we explored whether human hippocampal neurons can also demonstrate the ability to discriminate between overlapping representations and whether this selectivity could be directly related to memory performance. We show that among medial temporal lobe (MTL) neurons, certain populations of neurons are selective for a previously studied (target) image in that they show a significant decrease in firing rate to very similar (lure) images. We found that a greater proportion of these neurons can be found in the hippocampus compared with other MTL regions, and that memory for individual items is correlated to the degree of selectivity of hippocampal neurons responsive to those items. Moreover, a greater proportion of hippocampal neurons showed selective firing for target images in good compared with poor performers, with overall memory performance correlated with hippocampal selectivity. In contrast, selectivity in other MTL regions was not associated with memory performance. These findings show that a substantial proportion of human hippocampal neurons encode specific memories that support the discrimination of overlapping representations. These results also provide previously unidentified evidence consistent with a unique role of the human hippocampus in orthogonalization of representations in declarative memory.
-
The role of shared neural activations, mirror neurons, and morality in empathy--a critical comment.
Lamm, Claus; Majdandžić, Jasminka
2015-01-01
In the last decade, the phenomenon of empathy has received widespread attention by the field of social neuroscience. This has provided fresh insights for theoretical models of empathy, and substantially influenced the academic and public conceptions about this complex social skill. The present paper highlights three key issues which are often linked to empathy, but which at the same time might obscure our understanding of it. These issues are: (1) shared neural activations and whether these can be interpreted as evidence for simulation accounts of empathy; (2) the causal link of empathy to our presumed mirror neuron system; and (3) the question whether increasing empathy will result in better moral decisions and behaviors. The aim of our review is to provide the basis for critically evaluating our current understanding of empathy, and its public reception, and to inspire new research directions. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.
-
Object words modulate the activity of the mirror neuron system during action imitation.
Wu, Haiyan; Tang, Honghong; Ge, Yue; Yang, Suyong; Mai, Xiaoqin; Luo, Yue-Jia; Liu, Chao
2017-11-01
Although research has demonstrated that the mirror neuron system (MNS) plays a crucial role in both action imitation and action-related semantic processing, whether action-related words can inversely modulate the MNS activity remains unclear. Here, three types of task-irrelevant words (body parts, verbs, and manufactured objects) were presented to examine the modulation effect of these words on the MNS activity during action observation and imitation. Twenty-two participants were recruited for the fMRI scanning and remaining data from 19 subjects were reported here. Brain activity results showed that word types elicited different modulation effects over nodes of the MNS (i.e., the right inferior frontal gyrus, premotor cortex, inferior parietal lobule, and STS), especially during the imitation stage. Compared with other word conditions, action imitation following manufactured objects words induced stronger activation in these brain regions during the imitation stage. These results were consistent in both task-dependent and -independent ROI analysis. Our findings thus provide evidence for the unique effect of object words on the MNS during imitation of action, which may also confirm the key role of goal inference in action imitation.
-
Optogenetic control of human neurons in organotypic brain cultures
DEFF Research Database (Denmark)
Andersson, My; Avaliani, Natalia; Svensson, Andreas
2016-01-01
Optogenetics is one of the most powerful tools in neuroscience, allowing for selective control of specific neuronal populations in the brain of experimental animals, including mammals. We report, for the first time, the application of optogenetic tools to human brain tissue providing a proof......-of-concept for the use of optogenetics in neuromodulation of human cortical and hippocampal neurons as a possible tool to explore network mechanisms and develop future therapeutic strategies....
-
Mirroring "meaningful" actions: sensorimotor learning modulates imitation of goal-directed actions.
Catmur, Caroline; Heyes, Cecilia
2017-06-19
Imitation is important in the development of social and technological skills throughout the lifespan. Experiments investigating the acquisition and modulation of imitation (and of its proposed neural substrate, the mirror neuron system) have produced evidence that the capacity for imitation depends on associative learning in which connections are formed between sensory and motor representations of actions. However, evidence that the development of imitation depends on associative learning has been found only for non-goal-directed actions. One reason for the lack of research on goal-directed actions is that imitation of such actions is commonly confounded with the tendency to respond in a spatially compatible manner. However, since the most prominent account of mirror neuron function, and hence of imitation, suggests that these cells encode goal-directed actions, it is important to establish whether sensorimotor learning can also modulate imitation of goal-directed actions. Experiment 1 demonstrated that imitation of goal-directed grasping can be measured while controlling for spatial compatibility, and Experiment 2 showed that this imitation effect can be modulated by sensorimotor training. Together these data support the hypothesis that the capacity for behavioural imitation, and the properties of the mirror neuron system, are constructed in the course of development through associative learning.
-
Kim, Eosu; Jung, Young-Chul; Ku, Jeonghun; Kim, Jae-Jin; Lee, Hyeongrae; Kim, So Young; Kim, Sun I; Cho, Hyun-Sang
2009-11-13
Social cognition entails both cognitive and affective processing, and impairments in both have accounted for residual symptoms of bipolar disorder (BD). However, there has been a lack of studies identifying neural substrates responsible for social cognitive difficulties in BD patients. Fourteen euthymic BD patients and 14 healthy normal controls underwent functional MRI while performing a virtual reality social cognition task, which incorporated both cognitive and emotional dimensions, simulating real-world social situations. During the scanning, subjects tried to guess (attribute) possible reasons for expressed emotion of virtual humans (avatars) while viewing their facial expressions, just after observing their verbal and nonverbal (facial) expressions which were emotionally valenced (happy, angry and neutral). BD patients compared to normal controls showed delayed reaction times in emotional conditions, with comparable response accuracy. Healthy normal controls activated the right anterior cingulate cortex, inferior frontal, and insular cortex in emotional conditions contrasted with neutral control conditions, that is, the regions that have been related to empathic processes during viewing others' emotional expression. Relative to normal controls, BD patients showed reduced activations in the 'mirror neuron system', including the right inferior frontal cortex, premotor cortex, and insula, mainly in angry or happy condition. These results may suggest that, even during euthymic state, BD patients have difficulties in recruiting brain regions for the utilization of emotional cues as a means for understanding others. Clinical attention should be paid to emotion-related residual symptoms to help improve social outcomes in these patients.
-
Si vis me flere. Emotions in the mirror
Directory of Open Access Journals (Sweden)
Clelia Falletti
2011-11-01
Full Text Available This paper addresses the issue of the actor's work with the aidof elements from neurosciences and philosophy. It presents texts by Horace in which he gives indications to actors and speakers. Suchassumptions are elaborated with texts by Diderot and Copeau in orderto raise comprehensions about the emotions and more rational tasks of the actor's work. It presents the concept of mirror mechanism to showhow mirror neurons in the brain are responsible for chain actions in the nervous system. It compares those mechanisms with the actor'swork.
-
Precise auditory-vocal mirroring in neurons for learned vocal communication.
Prather, J F; Peters, S; Nowicki, S; Mooney, R
2008-01-17
Brain mechanisms for communication must establish a correspondence between sensory and motor codes used to represent the signal. One idea is that this correspondence is established at the level of single neurons that are active when the individual performs a particular gesture or observes a similar gesture performed by another individual. Although neurons that display a precise auditory-vocal correspondence could facilitate vocal communication, they have yet to be identified. Here we report that a certain class of neurons in the swamp sparrow forebrain displays a precise auditory-vocal correspondence. We show that these neurons respond in a temporally precise fashion to auditory presentation of certain note sequences in this songbird's repertoire and to similar note sequences in other birds' songs. These neurons display nearly identical patterns of activity when the bird sings the same sequence, and disrupting auditory feedback does not alter this singing-related activity, indicating it is motor in nature. Furthermore, these neurons innervate striatal structures important for song learning, raising the possibility that singing-related activity in these cells is compared to auditory feedback to guide vocal learning.
-
Han, Chongyang; Estacion, Mark; Huang, Jianying; Vasylyev, Dymtro; Zhao, Peng; Dib-Hajj, Sulayman D.
2015-01-01
Although species-specific differences in ion channel properties are well-documented, little has been known about the properties of the human Nav1.8 channel, an important contributor to pain signaling. Here we show, using techniques that include voltage clamp, current clamp, and dynamic clamp in dorsal root ganglion (DRG) neurons, that human Nav1.8 channels display slower inactivation kinetics and produce larger persistent current and ramp current than previously reported in other species. DRG neurons expressing human Nav1.8 channels unexpectedly produce significantly longer-lasting action potentials, including action potentials with half-widths in some cells >10 ms, and increased firing frequency compared with the narrower and usually single action potentials generated by DRG neurons expressing rat Nav1.8 channels. We also show that native human DRG neurons recapitulate these properties of Nav1.8 current and the long-lasting action potentials. Together, our results demonstrate strikingly distinct properties of human Nav1.8, which contribute to the firing properties of human DRG neurons. PMID:25787950
-
Generation of neuropeptidergic hypothalamic neurons from human pluripotent stem cells
Merkle, Florian T.; Maroof, Asif; Wataya, Takafumi; Sasai, Yoshiki; Studer, Lorenz; Eggan, Kevin; Schier, Alexander F.
2015-01-01
Hypothalamic neurons orchestrate many essential physiological and behavioral processes via secreted neuropeptides, and are relevant to human diseases such as obesity, narcolepsy and infertility. We report the differentiation of human pluripotent stem cells into many of the major types of neuropeptidergic hypothalamic neurons, including those producing pro-opiolemelanocortin, agouti-related peptide, hypocretin/orexin, melanin-concentrating hormone, oxytocin, arginine vasopressin, corticotropin...
-
The mirror mechanism and mu rhythm in social development.
Vanderwert, Ross E; Fox, Nathan A; Ferrari, Pier F
2013-04-12
Since the discovery of mirror neurons (MNs) in the monkey there has been a renewed interest in motor theories of cognitive and social development in humans by providing a potential neural mechanism underlying an action observation/execution matching system. It has been proposed that this system plays a fundamental role in the development of complex social and cognitive behaviors such as imitation and action recognition. In this review we discuss what is known about MNs from the work using single-cell recordings in the adult monkey, the evidence for the putative MN system in humans, and the extent to which research using electroencephalography (EEG) methods has contributed to our understanding of the development of these motor systems and their role in the social behaviors postulated by the MN hypothesis. We conclude with directions for future research that will improve our understanding of the putative human MN system and the functional role of MNs in social development. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
-
Yamazaki, Yumiko; Yokochi, Hiroko; Tanaka, Michio; Okanoya, Kazuo; Iriki, Atsushi
2010-01-01
The anterior portion of the inferior parietal cortex possesses comprehensive representations of actions embedded in behavioural contexts. Mirror neurons, which respond to both self-executed and observed actions, exist in this brain region in addition to those originally found in the premotor cortex. We found that parietal mirror neurons responded differentially to identical actions embedded in different contexts. Another type of parietal mirror neuron represents an inverse and complementary property of responding equally to dissimilar actions made by itself and others for an identical purpose. Here, we propose a hypothesis that these sets of inferior parietal neurons constitute a neural basis for encoding the semantic equivalence of various actions across different agents and contexts. The neurons have mirror neuron properties, and they encoded generalization of agents, differentiation of outcomes, and categorization of actions that led to common functions. By integrating the activities of these mirror neurons with various codings, we further suggest that in the ancestral primates' brains, these various representations of meaningful action led to the gradual establishment of equivalence relations among the different types of actions, by sharing common action semantics. Such differential codings of the components of actions might represent precursors to the parts of protolanguage, such as gestural communication, which are shared among various members of a society. Finally, we suggest that the inferior parietal cortex serves as an interface between this action semantics system and other higher semantic systems, through common structures of action representation that mimic language syntax.
-
Quantitative analysis of intraneuronal transport in human iPS neurons
Directory of Open Access Journals (Sweden)
Haruko Nakamura
2015-08-01
Full Text Available Induced pluripotent stem (iPS cells are promising tools to investigate disease mechanism and develop new drugs. Intraneuronal transport, which is fundamental for neuronal survival and function, is vulnerable to various pharmacological and chemical agents and is disrupted in some neurodegenerative disorders. We applied a quantification method for axonal transport by counting CM-DiI–labeled particles traveling along the neurite, which allowed us to monitor and quantitate, for the first time, intraneuronal transport in human neurons differentiated from iPS cells (iCell neurons. We evaluated the acute effects of several anti-neoplastic agents that have been previously shown to affect intraneuronal transport. Vincristine, paclitaxel and oxaliplatin decreased the number of moving particle along neurites. Cisplatin, however, produced no effect on intraneuronal transport, which is in contrast to our previous report indicating that it inhibits transport in chick dorsal root ganglion neurons. Our system may be a useful method for assessing intraneuronal transport and neurotoxicity in human iPS neurons.
-
Spindle neurons of the human anterior cingulate cortex
Nimchinsky, E. A.; Vogt, B. A.; Morrison, J. H.; Hof, P. R.; Bloom, F. E. (Principal Investigator)
1995-01-01
The human anterior cingulate cortex is distinguished by the presence of an unusual cell type, a large spindle neuron in layer Vb. This cell has been noted numerous times in the historical literature but has not been studied with modern neuroanatomic techniques. For instance, details regarding the neuronal class to which these cells belong and regarding their precise distribution along both ventrodorsal and anteroposterior axes of the cingulate gyrus are still lacking. In the present study, morphological features and the anatomic distribution of this cell type were studied using computer-assisted mapping and immunocytochemical techniques. Spindle neurons are restricted to the subfields of the anterior cingulate cortex (Brodmann's area 24), exhibiting a greater density in anterior portions of this area than in posterior portions, and tapering off in the transition zone between anterior and posterior cingulate cortex. Furthermore, a majority of the spindle cells at any level is located in subarea 24b on the gyral surface. Immunocytochemical analysis revealed that the neurofilament protein triple was present in a large percentage of these neurons and that they did not contain calcium-binding proteins. Injections of the carbocyanine dye DiI into the cingulum bundle revealed that these cells are projection neurons. Finally, spindle cells were consistently affected in Alzheimer's disease cases, with an overall loss of about 60%. Taken together, these observations indicate that the spindle cells of the human cingulate cortex represent a morphological subpopulation of pyramidal neurons whose restricted distribution may be associated with functionally distinct areas.
-
Exploring the role of neural mirroring in children with autism spectrum disorder.
Ruysschaert, Lieselot; Warreyn, Petra; Wiersema, Jan R; Oostra, Ann; Roeyers, Herbert
2014-04-01
Investigating the underlying neural mechanisms of autism spectrum disorder (ASD) has recently been influenced by the discovery of mirror neurons. These neurons, active during both observation and execution of actions, are thought to play a crucial role in imitation and other social-communicative skills that are often impaired in ASD. In the current electroencephalographic study, we investigated mu suppression, indicating neural mirroring in children with ASD between the ages of 24 and 48 months and age-matched typically developing children, during observation of goal-directed actions and non-goal-directed mimicked hand movements, as well as during action execution. Results revealed no significant group differences with significant central mu suppression in the ASD children and control children during both execution and observation of goal-directed actions and during observation of hand movements. Furthermore, no significant correlations between mu suppression on one hand and quality of imitation, age, and social communication questionnaire scores on the other hand were found. These findings challenge the "broken mirror" hypothesis of ASD, suggesting that impaired neural mirroring is not a distinctive feature of ASD. © 2014 International Society for Autism Research, Wiley Periodicals, Inc.
-
Human neuronal cell protein responses to Nipah virus infection
Directory of Open Access Journals (Sweden)
Hassan Sharifah
2007-06-01
Full Text Available Abstract Background Nipah virus (NiV, a recently discovered zoonotic virus infects and replicates in several human cell types. Its replication in human neuronal cells, however, is less efficient in comparison to other fully susceptible cells. In the present study, the SK-N-MC human neuronal cell protein response to NiV infection is examined using proteomic approaches. Results Method for separation of the NiV-infected human neuronal cell proteins using two-dimensional polyacrylamide gel electrophoresis (2D-PAGE was established. At least 800 protein spots were resolved of which seven were unique, six were significantly up-regulated and eight were significantly down-regulated. Six of these altered proteins were identified using mass spectrometry (MS and confirmed using MS/MS. The heterogenous nuclear ribonucleoprotein (hnRNP F, guanine nucleotide binding protein (G protein, voltage-dependent anion channel 2 (VDAC2 and cytochrome bc1 were present in abundance in the NiV-infected SK-N-MC cells in contrast to hnRNPs H and H2 that were significantly down-regulated. Conclusion Several human neuronal cell proteins that are differentially expressed following NiV infection are identified. The proteins are associated with various cellular functions and their abundance reflects their significance in the cytopathologic responses to the infection and the regulation of NiV replication. The potential importance of the ratio of hnRNP F, and hnRNPs H and H2 in regulation of NiV replication, the association of the mitochondrial protein with the cytopathologic responses to the infection and induction of apoptosis are highlighted.
-
Long-term Culture of Human iPS Cell-derived Telencephalic Neuron Aggregates on Collagen Gel.
Oyama, Hiroshi; Takahashi, Koji; Tanaka, Yoshikazu; Takemoto, Hiroshi; Haga, Hisashi
2018-01-01
It takes several months to form the 3-dimensional morphology of the human embryonic brain. Therefore, establishing a long-term culture method for neuronal tissues derived from human induced pluripotent stem (iPS) cells is very important for studying human brain development. However, it is difficult to keep primary neurons alive for more than 3 weeks in culture. Moreover, long-term adherent culture to maintain the morphology of telencephalic neuron aggregates induced from human iPS cells is also difficult. Although collagen gel has been widely used to support long-term culture of cells, it is not clear whether human iPS cell-derived neuron aggregates can be cultured for long periods on this substrate. In the present study, we differentiated human iPS cells to telencephalic neuron aggregates and examined long-term culture of these aggregates on collagen gel. The results indicated that these aggregates could be cultured for over 3 months by adhering tightly onto collagen gel. Furthermore, telencephalic neuronal precursors within these aggregates matured over time and formed layered structures. Thus, long-term culture of telencephalic neuron aggregates derived from human iPS cells on collagen gel would be useful for studying human cerebral cortex development.Key words: Induced pluripotent stem cell, forebrain neuron, collagen gel, long-term culture.
-
Mirror neurons and embodied simulation in the development of archetypes and self-agency.
Knox, Jean
2009-06-01
In this paper I explore the role of mirror neurons and motor intentionality in the development of self-agency. I suggest that this will also give us a firmer basis for an emergent view of archetypes, as key components in the development trajectory of self-agency, from its foundation in bodily action to its mature expression in mentalization and a conscious awareness of intentionality. I offer some ideas about the implications of these issues of self-agency for our clinical work with patients whose developmental trajectory of self-agency has been partially inhibited, so that their communications have a coercive effect. I discuss the possibility that this kind of clinical phenomenon may relate to Gallese and Lakoff's hypothesis that abstract thought and imagination are forms of simulated action, and that the same sensory-motor circuits that control action also control imagination, concept formation and understanding, but with a crucial development, that of an inhibition of the connections between secondary pre-motor cortical areas and the primary motor cortex. I shall speculate that in the earlier developmental stages of self-agency, the separation of secondary from primary motor areas is not complete, so that imagination and thought are not entirely independent of physical action.
-
Directed neuronal differentiation of human embryonic stem cells
Directory of Open Access Journals (Sweden)
Noggle Scott A
2003-10-01
Full Text Available Abstract Background We have developed a culture system for the efficient and directed differentiation of human embryonic stem cells (HESCs to neural precursors and neurons. HESC were maintained by manual passaging and were differentiated to a morphologically distinct OCT-4+/SSEA-4- monolayer cell type prior to the derivation of embryoid bodies. Embryoid bodies were grown in suspension in serum free conditions, in the presence of 50% conditioned medium from the human hepatocarcinoma cell line HepG2 (MedII. Results A neural precursor population was observed within HESC derived serum free embryoid bodies cultured in MedII conditioned medium, around 7–10 days after derivation. The neural precursors were organized into rosettes comprised of a central cavity surrounded by ring of cells, 4 to 8 cells in width. The central cells within rosettes were proliferating, as indicated by the presence of condensed mitotic chromosomes and by phosphoHistone H3 immunostaining. When plated and maintained in adherent culture, the rosettes of neural precursors were surrounded by large interwoven networks of neurites. Immunostaining demonstrated the expression of nestin in rosettes and associated non-neuronal cell types, and a radial expression of Map-2 in rosettes. Differentiated neurons expressed the markers Map-2 and Neurofilament H, and a subpopulation of the neurons expressed tyrosine hydroxylase, a marker for dopaminergic neurons. Conclusion This novel directed differentiation approach led to the efficient derivation of neuronal cultures from HESCs, including the differentiation of tyrosine hydroxylase expressing neurons. HESC were morphologically differentiated to a monolayer OCT-4+ cell type, which was used to derive embryoid bodies directly into serum free conditions. Exposure to the MedII conditioned medium enhanced the derivation of neural precursors, the first example of the effect of this conditioned medium on HESC.
-
Ketamine Causes Mitochondrial Dysfunction in Human Induced Pluripotent Stem Cell-Derived Neurons
Ito, Hiroyuki; Uchida, Tokujiro; Makita, Koshi
2015-01-01
Purpose Ketamine toxicity has been demonstrated in nonhuman mammalian neurons. To study the toxic effect of ketamine on human neurons, an experimental model of cultured neurons from human induced pluripotent stem cells (iPSCs) was examined, and the mechanism of its toxicity was investigated. Methods Human iPSC-derived dopaminergic neurons were treated with 0, 20, 100 or 500 μM ketamine for 6 and 24 h. Ketamine toxicity was evaluated by quantification of caspase 3/7 activity, reactive oxygen species (ROS) production, mitochondrial membrane potential, ATP concentration, neurotransmitter reuptake activity and NADH/NAD+ ratio. Mitochondrial morphological change was analyzed by transmission electron microscopy and confocal microscopy. Results Twenty-four-hour exposure of iPSC-derived neurons to 500 μM ketamine resulted in a 40% increase in caspase 3/7 activity (P ketamine (100 μM) decreased the ATP level (22%, P ketamine concentration, which suggests that mitochondrial dysfunction preceded ROS generation and caspase activation. Conclusions We established an in vitro model for assessing the neurotoxicity of ketamine in iPSC-derived neurons. The present data indicate that the initial mitochondrial dysfunction and autophagy may be related to its inhibitory effect on the mitochondrial electron transport system, which underlies ketamine-induced neural toxicity. Higher ketamine concentration can induce ROS generation and apoptosis in human neurons. PMID:26020236
-
Morphometric characteristics of the neurons of the human subiculum proper
Directory of Open Access Journals (Sweden)
Živanović-Mačužić Ivana
2012-01-01
Full Text Available The human subiculum is a significant part of the hippocampal formation positioned between the hippocampus proper and the entorhinal and other cortices. It plays an important role in spatial navigation, memory processing and control of the response to stress. The aim of our study was identification of the morphometric characteristics of the neurons of the human subiculum proper: the maximum length and width of cell body and total dendritic length and volume of cell body. Comparing the measured parameters of different types of subicular neurons (bipolar, multipolar, pyramidal neurons with triangular-shaped soma and neurons with oval-shaped soma, we can conclude that bipolar neurons have the lowest values of the measured parameters: the maximum length of their cell body is 14.1 ± 0.2 µm, the maximum width is 13.9 ± 0.5 µm, and total dendritic length is 14597 ± 3.1 µm. The lowest volume value was observed in bipolar neurons; the polymorphic layer is 1152.99 ± 662.69 µm3. The pyramidal neurons of the pyramidal layer have the highest value for the maximal length of the cell body (44.43 ± 7.94 µm, maximum width (23.64 ± 1.89 µm, total dendritic length (1830 ± 466.3 µm and volume (11768.65±4004.9 µm3 These characteristics of the pyramidal neurons indicate their importance, because the axons of these neurons make up the greatest part of the fornix, along with the axons of neurons of the CA1 hippocampal field.
-
Han, Chongyang; Estacion, Mark; Huang, Jianying; Vasylyev, Dymtro; Zhao, Peng; Dib-Hajj, Sulayman D; Waxman, Stephen G
2015-05-01
Although species-specific differences in ion channel properties are well-documented, little has been known about the properties of the human Nav1.8 channel, an important contributor to pain signaling. Here we show, using techniques that include voltage clamp, current clamp, and dynamic clamp in dorsal root ganglion (DRG) neurons, that human Na(v)1.8 channels display slower inactivation kinetics and produce larger persistent current and ramp current than previously reported in other species. DRG neurons expressing human Na(v)1.8 channels unexpectedly produce significantly longer-lasting action potentials, including action potentials with half-widths in some cells >10 ms, and increased firing frequency compared with the narrower and usually single action potentials generated by DRG neurons expressing rat Na(v)1.8 channels. We also show that native human DRG neurons recapitulate these properties of Na(v)1.8 current and the long-lasting action potentials. Together, our results demonstrate strikingly distinct properties of human Na(v)1.8, which contribute to the firing properties of human DRG neurons.
-
Optical coherence tomography visualizes neurons in human entorhinal cortex
Magnain, Caroline; Augustinack, Jean C.; Konukoglu, Ender; Frosch, Matthew P.; Sakadžić, Sava; Varjabedian, Ani; Garcia, Nathalie; Wedeen, Van J.; Boas, David A.; Fischl, Bruce
2015-01-01
Abstract. The cytoarchitecture of the human brain is of great interest in diverse fields: neuroanatomy, neurology, neuroscience, and neuropathology. Traditional histology is a method that has been historically used to assess cell and fiber content in the ex vivo human brain. However, this technique suffers from significant distortions. We used a previously demonstrated optical coherence microscopy technique to image individual neurons in several square millimeters of en-face tissue blocks from layer II of the human entorhinal cortex, over 50 μm in depth. The same slices were then sectioned and stained for Nissl substance. We registered the optical coherence tomography (OCT) images with the corresponding Nissl stained slices using a nonlinear transformation. The neurons were then segmented in both images and we quantified the overlap. We show that OCT images contain information about neurons that is comparable to what can be obtained from Nissl staining, and thus can be used to assess the cytoarchitecture of the ex vivo human brain with minimal distortion. With the future integration of a vibratome into the OCT imaging rig, this technique can be scaled up to obtain undistorted volumetric data of centimeter cube tissue blocks in the near term, and entire human hemispheres in the future. PMID:25741528
-
Hughes, Mark A; Brennan, Paul M; Bunting, Andrew S; Cameron, Katherine; Murray, Alan F; Shipston, Mike J
2014-05-01
Interfacing neurons with silicon semiconductors is a challenge being tackled through various bioengineering approaches. Such constructs inform our understanding of neuronal coding and learning and ultimately guide us toward creating intelligent neuroprostheses. A fundamental prerequisite is to dictate the spatial organization of neuronal cells. We sought to pattern neurons using photolithographically defined arrays of polymer parylene-C, activated with fetal calf serum. We used a purified human neuronal cell line [Lund human mesencephalic (LUHMES)] to establish whether neurons remain viable when isolated on-chip or whether they require a supporting cell substrate. When cultured in isolation, LUHMES neurons failed to pattern and did not show any morphological signs of differentiation. We therefore sought a cell type with which to prepattern parylene regions, hypothesizing that this cellular template would enable secondary neuronal adhesion and network formation. From a range of cell lines tested, human embryonal kidney (HEK) 293 cells patterned with highest accuracy. LUHMES neurons adhered to pre-established HEK 293 cell clusters and this coculture environment promoted morphological differentiation of neurons. Neurites extended between islands of adherent cell somata, creating an orthogonally arranged neuronal network. HEK 293 cells appear to fulfill a role analogous to glia, dictating cell adhesion, and generating an environment conducive to neuronal survival. We next replaced HEK 293 cells with slower growing glioma-derived precursors. These primary human cells patterned accurately on parylene and provided a similarly effective scaffold for neuronal adhesion. These findings advance the use of this microfabrication-compatible platform for neuronal patterning. Copyright © 2013 Wiley Periodicals, Inc.
-
Functional properties of human neuronal Kv11 channels
DEFF Research Database (Denmark)
Einarsen, Karoline; Calloe, Kirstine; Grunnet, Morten
2009-01-01
Kv11 potassium channels are important for regulation of the membrane potential. Kv11.2 and Kv11.3 are primarily found in the nervous system, where they most likely are involved in the regulation of neuronal excitability. Two isoforms of human Kv11.2 have been published so far. Here, we present...... current characteristics of the isoforms presented in this work may contribute to the regulation of neuronal excitability....
-
Knowing beans: Human mirror mechanisms revealed through motor adaptation
Directory of Open Access Journals (Sweden)
Arthur M Glenberg
2010-11-01
Full Text Available Human mirror mechanisms (MMs respond during both performed and observed action and appear to underlie action goal recognition. We introduce a behavioral procedure for discovering and clarifying functional MM properties: Blindfolded participants repeatedly move beans either toward or away from themselves to induce motor adaptation. Then, the bias for perceiving direction of ambiguous visual movement in depth is measured. Bias is affected by a number of beans moved, b movement direction, and c similarity of the visual stimulus to the hand used to move beans. This cross-modal adaptation pattern supports both the validity of human MMs and functionality of our testing instrument. We also discuss related work that extends the motor adaptation paradigm to investigate contributions of MMs to speech perception and language comprehension.
-
Contextual Modulation of Mirror and Countermirror Sensorimotor Associations
Cook, Richard; Dickinson, Anthony; Heyes, Cecilia
2012-01-01
Automatic imitation--the unintended copying of observed actions--is thought to be a behavioral product of the mirror neuron system (MNS). Evidence that the MNS develops through associative learning comes from previous research showing that automatic imitation is attenuated by countermirror training, in which the observation of one action is paired…
-
Gender differences in human single neuron responses to male emotional faces.
Newhoff, Morgan; Treiman, David M; Smith, Kris A; Steinmetz, Peter N
2015-01-01
Well-documented differences in the psychology and behavior of men and women have spurred extensive exploration of gender's role within the brain, particularly regarding emotional processing. While neuroanatomical studies clearly show differences between the sexes, the functional effects of these differences are less understood. Neuroimaging studies have shown inconsistent locations and magnitudes of gender differences in brain hemodynamic responses to emotion. To better understand the neurophysiology of these gender differences, we analyzed recordings of single neuron activity in the human brain as subjects of both genders viewed emotional expressions. This study included recordings of single-neuron activity of 14 (6 male) epileptic patients in four brain areas: amygdala (236 neurons), hippocampus (n = 270), anterior cingulate cortex (n = 256), and ventromedial prefrontal cortex (n = 174). Neural activity was recorded while participants viewed a series of avatar male faces portraying positive, negative or neutral expressions. Significant gender differences were found in the left amygdala, where 23% (n = 15∕66) of neurons in men were significantly affected by facial emotion, vs. 8% (n = 6∕76) of neurons in women. A Fisher's exact test comparing the two ratios found a highly significant difference between the two (p differences between genders at the single-neuron level in the human amygdala. These differences may reflect gender-based distinctions in evolved capacities for emotional processing and also demonstrate the importance of including subject gender as an independent factor in future studies of emotional processing by single neurons in the human amygdala.
-
Schwab, Andrew J; Ebert, Allison D
2014-01-01
Spinal muscular atrophy (SMA) is an autosomal recessive disorder leading to paralysis and early death due to reduced SMN protein. It is unclear why there is such a profound motor neuron loss, but recent evidence from fly and mouse studies indicate that cells comprising the whole sensory-motor circuit may contribute to motor neuron dysfunction and loss. Here, we used induced pluripotent stem cells derived from SMA patients to test whether sensory neurons directly contribute to motor neuron loss. We generated sensory neurons from SMA induced pluripotent stem cells and found no difference in neuron generation or survival, although there was a reduced calcium response to depolarizing stimuli. Using co-culture of SMA induced pluripotent stem cell derived sensory neurons with control induced pluripotent stem cell derived motor neurons, we found no significant reduction in motor neuron number or glutamate transporter boutons on motor neuron cell bodies or neurites. We conclude that SMA sensory neurons do not overtly contribute to motor neuron loss in this human stem cell system.
-
Directory of Open Access Journals (Sweden)
Lewis D. Evans
2018-03-01
Full Text Available Summary: In Alzheimer’s disease, neurofibrillary tangle pathology appears to spread along neuronal connections, proposed to be mediated by the release and uptake of abnormal, disease-specific forms of microtubule-binding protein tau MAPT. It is currently unclear whether transfer of tau between neurons is a toxic gain-of-function process in dementia or reflects a constitutive biological process. We report two entry mechanisms for monomeric tau to human neurons: a rapid dynamin-dependent phase typical of endocytosis and a second, slower actin-dependent phase of macropinocytosis. Aggregated tau entry is independent of actin polymerization and largely dynamin dependent, consistent with endocytosis and distinct from macropinocytosis, the major route for aggregated tau entry reported for non-neuronal cells. Anti-tau antibodies abrogate monomeric tau entry into neurons, but less efficiently in the case of aggregated tau, where internalized tau carries antibody with it into neurons. These data suggest that tau entry to human neurons is a physiological process and not a disease-specific phenomenon. : In contrast with predictions that transfer of the microtubule-associated protein tau between neurons is a toxic gain-of-function process in dementia, Evans et al. show that healthy human neurons efficiently take up both normal and aggregated tau, by distinct but overlapping uptake mechanisms. Keywords: Alzheimer’s disease, frontotemporal dementia, Tau, MAPT, iPSC, endocytosis, human neurons, intracellular transport
-
Development of Gonadotropin-Releasing Hormone-Secreting Neurons from Human Pluripotent Stem Cells
Directory of Open Access Journals (Sweden)
Carina Lund
2016-08-01
Full Text Available Gonadotropin-releasing hormone (GnRH neurons regulate human puberty and reproduction. Modeling their development and function in vitro would be of interest for both basic research and clinical translation. Here, we report a three-step protocol to differentiate human pluripotent stem cells (hPSCs into GnRH-secreting neurons. Firstly, hPSCs were differentiated to FOXG1, EMX2, and PAX6 expressing anterior neural progenitor cells (NPCs by dual SMAD inhibition. Secondly, NPCs were treated for 10 days with FGF8, which is a key ligand implicated in GnRH neuron ontogeny, and finally, the cells were matured with Notch inhibitor to bipolar TUJ1-positive neurons that robustly expressed GNRH1 and secreted GnRH decapeptide into the culture medium. The protocol was reproducible both in human embryonic stem cells and induced pluripotent stem cells, and thus provides a translational tool for investigating the mechanisms of human puberty and its disorders.
-
Directory of Open Access Journals (Sweden)
Vaughan G Macefield
2011-12-01
Full Text Available Postganglionic sympathetic axons in awake healthy human subjects, regardless of their identity as muscle vasoconstrictor, cutaneous vasoconstrictor or sudomotor neurones, discharge with a low firing probability (~30%, generate low firing rates (~0.5 Hz and typically fire only once per cardiac interval. The purpose of the present study was to use modelling of spike trains in an attempt to define the number of preganglionic neurones that drive an individual postganglionic neurone. Artificial spike trains were generated in 1-3 preganglionic neurones converging onto a single postganglionic neurone. Each preganglionic input fired with a mean interval distribution of either 1000, 1500, 2000, 2500 or 3000 ms and the standard deviation varied between 0.5, 1.0 and 2.0 x the mean interval; the discharge frequency of each preganglionic neurone exhibited positive skewness and kurtosis. Of the 45 patterns examined, the mean discharge properties of the postganglionic neurone could only be explained by it being driven by, on average, two preganglionic neurones firing with a mean interspike interval of 2500 ms and SD of 5000 ms. The mean firing rate resulting from this pattern was 0.22 Hz, comparable to that of spontaneously active muscle vasoconstrictor neurones in healthy subjects (0.40 Hz. Likewise, the distribution of the number of spikes per cardiac interval was similar between the modelled and actual data: 0 spikes (69.5 vs 66.6 %, 1 spike (25.6 vs 21.2 %, 2 spikes (4.3 vs 6.4 %, 3 spikes (0.5 vs 1.7 % and 4 spikes (0.1 vs 0.7 %. Although some features of the firing patterns could be explained by the postganglionic neurone being driven by a single preganglionic neurone, none of the emulated firing patterns generated by the firing of three preganglionic neurones matched the discharge of the real neurones. These modelling data indicate that, on average, human postganglionic sympathetic neurones are driven by two preganglionic inputs.
-
Predicting Intentions of a Familiar Significant Other Beyond the Mirror Neuron System
Directory of Open Access Journals (Sweden)
Stephanie Cacioppo
2017-08-01
Full Text Available Inferring intentions of others is one of the most intriguing issues in interpersonal interaction. Theories of embodied cognition and simulation suggest that this mechanism takes place through a direct and automatic matching process that occurs between an observed action and past actions. This process occurs via the reactivation of past self-related sensorimotor experiences within the inferior frontoparietal network (including the mirror neuron system, MNS. The working model is that the anticipatory representations of others' behaviors require internal predictive models of actions formed from pre-established, shared representations between the observer and the actor. This model suggests that observers should be better at predicting intentions performed by a familiar actor, rather than a stranger. However, little is known about the modulations of the intention brain network as a function of the familiarity between the observer and the actor. Here, we combined functional magnetic resonance imaging (fMRI with a behavioral intention inference task, in which participants were asked to predict intentions from three types of actors: A familiar actor (their significant other, themselves (another familiar actor, and a non-familiar actor (a stranger. Our results showed that the participants were better at inferring intentions performed by familiar actors than non-familiar actors and that this better performance was associated with greater activation within and beyond the inferior frontoparietal network i.e., in brain areas related to familiarity (e.g., precuneus. In addition, and in line with Hebbian principles of neural modulations, the more the participants reported being cognitively close to their partner, the less the brain areas associated with action self-other comparison (e.g., inferior parietal lobule, attention (e.g., superior parietal lobule, recollection (hippocampus, and pair bond (ventral tegmental area, VTA were recruited, suggesting that the
-
Calretinin as a marker for premotor neurons involved in upgaze in human brainstem
Directory of Open Access Journals (Sweden)
Christopher eAdamczyk
2015-12-01
Full Text Available Eye movements are generated by different premotor pathways. Damage to them can cause specific deficits of eye movements, such as saccades. For correlative clinico-anatomical post-mortem studies of cases with eye movement disorders it is essential to identify the functional cell groups of the oculomotor system in the human brain by marker proteins. Based on monkey studies, the premotor neurons of the saccadic system can be identified by the histochemical markers parvalbumin and perineuronal nets in humans. These areas involve the interstitial nucleus of Cajal (INC and the rostral interstitial nucleus of the medial longitudinal fascicle (RIMLF, which both contain premotor neurons for upgaze and downgaze. Recent monkey and human studies revealed a selective excitatory calretinin-positive input to the motoneurons mediating upgaze, but not to those for downgaze. Three premotor regions were identified as sources of calretinin input in monkey: y-group, INC and RIMLF. These findings suggest that the expression pattern of parvalbumin and calretinin may help to identify premotor neurons involved in up- or downgaze. In a post-mortem study of five human cases without neurological diseases we investigated the y-group, INC and RIMLF for the presence of parvalbumin and calretinin positive neurons including their co-expression. Adjacent thin paraffin sections were stained for the aggrecan component of perineuronal nets, parvalbumin or calretinin and glutamate decarboxylase. The comparative analysis of scanned thin sections of INC and RIMLF revealed medium-sized parvalbumin positive neurons with and without calretinin coexpression, which were intermingled. The parvalbumin/calretinin positive neurons in both nuclei are considered as excitatory premotor upgaze neurons. Accordingly, the parvalbumin-positive neurons lacking calretinin are considered as premotor downgaze neurons in RIMLF, but may in addition include inhibitory premotor upgaze neurons in the INC as
-
Gender Differences in Human Single Neuron Responses to Male Emotional Faces
Directory of Open Access Journals (Sweden)
Morgan eNewhoff
2015-09-01
Full Text Available Well-documented differences in the psychology and behavior of men and women have spurred extensive exploration of gender's role within the brain, particularly regarding emotional processing. While neuroanatomical studies clearly show differences between the sexes, the functional effects of these differences are less understood. Neuroimaging studies have shown inconsistent locations and magnitudes of gender differences in brain hemodynamic responses to emotion. To better understand the neurophysiology of these gender differences, we analyzed recordings of single neuron activity in the human brain as subjects of both genders viewed emotional expressions.This study included recordings of single-neuron activity of 14 (6 male epileptic patients in four brain areas: amygdala (236 neurons, hippocampus (n=270, anterior cingulate cortex (n=256, and ventromedial prefrontal cortex (n=174. Neural activity was recorded while participants viewed a series of avatar male faces portraying positive, negative or neutral expressions.Significant gender differences were found in the left amygdala, where 23% (n=15/66 of neurons in men were significantly affected by facial emotion, versus 8% (n=6/76 of neurons in women. A Fisher's exact test comparing the two ratios found a highly significant difference between the two (p<0.01. These results show specific differences between genders at the single-neuron level in the human amygdala. These differences may reflect gender-based distinctions in evolved capacities for emotional processing and also demonstrate the importance of including subject gender as an independent factor in future studies of emotional processing by single neurons in the human amygdala.
-
Hirata, Go; Aoki, Shigeru; Sakamaki, Kentaro; Takahashi, Tsuneo; Hirahara, Fumiki; Ishikawa, Hiroshi
2016-01-01
To investigate clinical features of mirror syndrome. We retrospectively reviewed 71 cases of fetal hydrops with or without mirror syndrome, and compared with respect to maternal age, the body mass index, the primipara rate, the gestational age at delivery, the timing of fetal hydrops onset, the severity of fetal edema, placental swelling, the laboratory data and the fetal mortality. The data are expressed as the medians. Mirror syndrome developed in 29% (10/35) of the cases with fetal hydrops. In mirror group, the onset time of fetal hydrops was significantly earlier (29 weeks versus 31 weeks, p = 0.011), and the severity of fetal hydrops (fetal edema/biparietal diameter) was significantly higher than non-mirror group (0.23 versus 0.16, p < 0.001). There was significantly higher serum human chorionic gonadotropin (hCG) (453,000 IU/L versus 80,000 IU/L, p < 0.001) and lower hemoglobin (8.9 g/dL versus 10.1 g/dL, p =0.002), hypoalbuminemia (2.3 mg/dL versus 2.7 mg/dL, p = 0.007), hyperuricemia (6.4 mg/dL versus 5.0 mg/dL, p = 0.043) in mirror group. Mirror syndrome is occurred frequently in early and severe fetal hydrops and cause hemodilution and elevation of serum hCG.
-
Kana, Rajesh K; Wadsworth, Heather M; Travers, Brittany G
2011-01-01
Although several studies suggest an imitation deficit as a key feature of autism, questions have been raised about the consistency of this finding and about the component skills involved in imitation. The primary aim of this review is to examine the uneven profile of imitation deficits found in autism in the context of the mirror neuron system (MNS) dysfunction hypothesis. We use the cortical underconnectivity framework (Just et al., 2004) to examine the coordination of brain areas that orchestrate the communication between the component skills underlying imitation. A comprehensive account of imitation deficit in autism should take into account the regions that are at the core of the MNS (e.g., IFG and IPL) and related regions that feed into the MNS (e.g., STS, Cerebellum) in their functioning and in their coordination. Our findings suggest that the MNS may be associated with mediating familiarity, attention, self-other matching, and social relevance, which may be vital in characterizing the imitation deficits in autism. Such an analysis may have greater clinical and therapeutic value. Published by Elsevier Ltd.
-
Neurite outgrowth in human iPSC-derived neurons
U.S. Environmental Protection Agency — Data on morphology of rat and human neurons in cell culture. This dataset is associated with the following publication: Druwe, I., T. Freudenrich , K. Wallace , T....
-
Topographical distribution and morphology of NADPH-diaphorase-stained neurons in the human claustrum
Hinova-Palova, Dimka V.; Edelstein, Lawrence; Landzhov, Boycho; Minkov, Minko; Malinova, Lina; Hristov, Stanislav; Denaro, Frank J.; Alexandrov, Alexandar; Kiriakova, Teodora; Brainova, Ilina; Paloff, Adrian; Ovtscharoff, Wladimir
2014-01-01
We studied the topographical distribution and morphological characteristics of NADPH-diaphorase-positive neurons and fibers in the human claustrum. These neurons were seen to be heterogeneously distributed throughout the claustrum. Taking into account the size and shape of stained perikarya as well as dendritic and axonal characteristics, Nicotinamide adenine dinucleotide phosphate-diaphorase (NADPHd)-positive neurons were categorized by diameter into three types: large, medium and small. Large neurons ranged from 25 to 35 μm in diameter and typically displayed elliptical or multipolar cell bodies. Medium neurons ranged from 20 to 25 μm in diameter and displayed multipolar, bipolar and irregular cell bodies. Small neurons ranged from 14 to 20 μm in diameter and most often displayed oval or elliptical cell bodies. Based on dendritic characteristics, these neurons were divided into spiny and aspiny subtypes. Our findings reveal two populations of NADPHd-positive neurons in the human claustrum—one comprised of large and medium cells consistent with a projection neuron phenotype, the other represented by small cells resembling the interneuron phenotype as defined by previous Golgi impregnation studies. PMID:24904317
-
Human iPSC-Derived Endothelial Cells and Microengineered Organ-Chip Enhance Neuronal Development
Directory of Open Access Journals (Sweden)
Samuel Sances
2018-04-01
Full Text Available Summary: Human stem cell-derived models of development and neurodegenerative diseases are challenged by cellular immaturity in vitro. Microengineered organ-on-chip (or Organ-Chip systems are designed to emulate microvolume cytoarchitecture and enable co-culture of distinct cell types. Brain microvascular endothelial cells (BMECs share common signaling pathways with neurons early in development, but their contribution to human neuronal maturation is largely unknown. To study this interaction and influence of microculture, we derived both spinal motor neurons and BMECs from human induced pluripotent stem cells and observed increased calcium transient function and Chip-specific gene expression in Organ-Chips compared with 96-well plates. Seeding BMECs in the Organ-Chip led to vascular-neural interaction and specific gene activation that further enhanced neuronal function and in vivo-like signatures. The results show that the vascular system has specific maturation effects on spinal cord neural tissue, and the use of Organ-Chips can move stem cell models closer to an in vivo condition. : Sances et al. combine Organ-Chip technology with human induced pluripotent stem cell-derived spinal motor neurons to study the maturation effects of Organ-Chip culture. By including microvascular cells also derived from the same patient line, the authors show enhancement of neuronal function, reproduction of vascular-neuron pathways, and specific gene activation that resembles in vivo spinal cord development. Keywords: organ-on-chip, spinal cord, iPSC, disease modeling, amyotrophic lateral sclerosis, microphysiological system, brain microvascular endothelial cells, spinal motor neurons, vasculature, microfluidic device
-
PINK1 is necessary for long term survival and mitochondrial function in human dopaminergic neurons.
Directory of Open Access Journals (Sweden)
Alison Wood-Kaczmar
2008-06-01
Full Text Available Parkinson's disease (PD is a common age-related neurodegenerative disease and it is critical to develop models which recapitulate the pathogenic process including the effect of the ageing process. Although the pathogenesis of sporadic PD is unknown, the identification of the mendelian genetic factor PINK1 has provided new mechanistic insights. In order to investigate the role of PINK1 in Parkinson's disease, we studied PINK1 loss of function in human and primary mouse neurons. Using RNAi, we created stable PINK1 knockdown in human dopaminergic neurons differentiated from foetal ventral mesencephalon stem cells, as well as in an immortalised human neuroblastoma cell line. We sought to validate our findings in primary neurons derived from a transgenic PINK1 knockout mouse. For the first time we demonstrate an age dependent neurodegenerative phenotype in human and mouse neurons. PINK1 deficiency leads to reduced long-term viability in human neurons, which die via the mitochondrial apoptosis pathway. Human neurons lacking PINK1 demonstrate features of marked oxidative stress with widespread mitochondrial dysfunction and abnormal mitochondrial morphology. We report that PINK1 plays a neuroprotective role in the mitochondria of mammalian neurons, especially against stress such as staurosporine. In addition we provide evidence that cellular compensatory mechanisms such as mitochondrial biogenesis and upregulation of lysosomal degradation pathways occur in PINK1 deficiency. The phenotypic effects of PINK1 loss-of-function described here in mammalian neurons provides mechanistic insight into the age-related degeneration of nigral dopaminergic neurons seen in PD.
-
Sieger, Tomáš; Serranová, Tereza; Růžička, Filip; Vostatek, Pavel; Wild, Jiří; Štastná, Daniela; Bonnet, Cecilia; Novák, Daniel; Růžička, Evžen; Urgošík, Dušan; Jech, Robert
2015-03-10
Both animal studies and studies using deep brain stimulation in humans have demonstrated the involvement of the subthalamic nucleus (STN) in motivational and emotional processes; however, participation of this nucleus in processing human emotion has not been investigated directly at the single-neuron level. We analyzed the relationship between the neuronal firing from intraoperative microrecordings from the STN during affective picture presentation in patients with Parkinson's disease (PD) and the affective ratings of emotional valence and arousal performed subsequently. We observed that 17% of neurons responded to emotional valence and arousal of visual stimuli according to individual ratings. The activity of some neurons was related to emotional valence, whereas different neurons responded to arousal. In addition, 14% of neurons responded to visual stimuli. Our results suggest the existence of neurons involved in processing or transmission of visual and emotional information in the human STN, and provide evidence of separate processing of the affective dimensions of valence and arousal at the level of single neurons as well.
-
Neurons in the white matter of the adult human neocortex
Directory of Open Access Journals (Sweden)
M Luisa Suarez-Sola
2009-06-01
Full Text Available The white matter (WM of the adult human neocortex contains the so-called “interstitial neurons”. They are most numerous in the superficial WM underlying the cortical gyri, and decrease in density toward the deep WM. They are morphologically heterogeneous. A subgroup of interstitial neurons display pyramidal-cell like morphologies, characterized by a polarized dendritic tree with a dominant apical dendrite, and covered with a variable number of dendritic spines. In addition, a large contingent of interstitial neurons can be classified as interneurons based on their neurochemical profile as well as on morphological criteria. WM- interneurons have multipolar or bipolar shapes and express GABA and a variety of other neuronal markers, such as calbindin and calretinin, the extracellular matrix protein reelin, or neuropeptide Y, somatostatin, and nitric oxide synthase. The heterogeneity of interstitial neurons may be relevant for the pathogenesis of Alzheimer disease and schizophrenia. Interstitial neurons are most prominent in human brain, and only rudimentary in the brain of non-primate mammals. These evolutionary differences have precluded adequate experimental work on this cell population, which is usually considered as a relict of the subplate, a transient compartment proper of development and without a known function in the adult brain. The primate-specific prominence of the subplate in late fetal stages points to an important role in the establishment of interstitial neurons. Neurons in the adult WM may be actively involved in coordinating inter-areal connectivity and regulation of blood flow. Further studies in primates will be needed to elucidate the developmental history, adult components and activities of this large neuronal system.
-
Directory of Open Access Journals (Sweden)
Meng-Lu Liu
2016-01-01
Full Text Available Subtype-specific neurons obtained from adult humans will be critical to modeling neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS. Here, we show that adult human skin fibroblasts can be directly and efficiently converted into highly pure motor neurons without passing through an induced pluripotent stem cell stage. These adult human induced motor neurons (hiMNs exhibit the cytological and electrophysiological features of spinal motor neurons and form functional neuromuscular junctions (NMJs with skeletal muscles. Importantly, hiMNs converted from ALS patient fibroblasts show disease-specific degeneration manifested through poor survival, soma shrinkage, hypoactivity, and an inability to form NMJs. A chemical screen revealed that the degenerative features of ALS hiMNs can be remarkably rescued by the small molecule kenpaullone. Taken together, our results define a direct and efficient strategy to obtain disease-relevant neuronal subtypes from adult human patients and reveal their promising value in disease modeling and drug identification.
-
Emmorey, Karen; Xu, Jiang; Gannon, Patrick; Goldin-Meadow, Susan; Braun, Allen
2010-01-01
Deaf signers have extensive experience using their hands to communicate. Using fMRI, we examined the neural systems engaged during the perception of manual communication in 14 deaf signers and 14 hearing non-signers. Participants passively viewed blocked video clips of pantomimes (e.g., peeling an imaginary banana) and action verbs in American Sign Language (ASL) that were rated as meaningless by non-signers (e.g., TO-DANCE). In contrast to visual fixation, pantomimes strongly activated fronto-parietal regions (the mirror neuron system, MNS) in hearing non-signers, but only bilateral middle temporal regions in deaf signers. When contrasted with ASL verbs, pantomimes selectively engaged inferior and superior parietal regions in hearing non-signers, but right superior temporal cortex in deaf signers. The perception of ASL verbs recruited similar regions as pantomimes for deaf signers, with some evidence of greater involvement of left inferior frontal gyrus for ASL verbs. Functional connectivity analyses with left hemisphere seed voxels (ventral premotor, inferior parietal lobule, fusiform gyrus) revealed robust connectivity with the MNS for the hearing non-signers. Deaf signers exhibited functional connectivity with the right hemisphere that was not observed for the hearing group for the fusiform gyrus seed voxel. We suggest that life-long experience with manual communication, and/or auditory deprivation, may alter regional connectivity and brain activation when viewing pantomimes. We conclude that the lack of activation within the MNS for deaf signers does not support an account of human communication that depends upon automatic sensorimotor resonance between perception and action.
-
Raghanti, Mary Ann; Conley, Tiffini; Sudduth, Jessica; Erwin, Joseph M.; Stimpson, Cheryl D.; Hof, Patrick R.; Sherwood, Chet C.
2012-01-01
We examined the distribution of neurons immunoreactive for neuropeptide Y (NPY) in the posterior part of the superior temporal cortex (Brodmann's area 22 or area Tpt) of humans and nonhuman haplorrhine primates. NPY has been implicated in learning and memory and the density of NPY-expressing cortical neurons and axons is reduced in depression, bipolar disorder, schizophrenia, and Alzheimer's disease. Due to the role that NPY plays in both cognition and neurodegenerative diseases, we tested the hypothesis that the density of cortical and interstitial neurons expressing NPY was increased in humans relative to other primate species. The study sample included great apes (chimpanzee and gorilla), Old World monkeys (pigtailed macaque, moor macaque, and baboon) and New World monkeys (squirrel monkey and capuchin). Stereologic methods were used to estimate the density of NPY-immunoreactive (-ir) neurons in layers I-VI of area Tpt and the subjacent white matter. Adjacent Nissl-stained sections were used to calculate local densities of all neurons. The ratio of NPY-ir neurons to total neurons within area Tpt and the total density of NPY-ir neurons within the white matter were compared among species. Overall, NPY-ir neurons represented only an average of 0.006% of the total neuron population. While there were significant differences among species, phylogenetic trends in NPY-ir neuron distributions were not observed and humans did not differ from other primates. However, variation among species warrants further investigation into the distribution of this neuromodulator system. PMID:23042407
-
Relationships between non-pathological dream-enactment and mirror behaviors.
Nielsen, Tore; Kuiken, Don
2013-09-01
Dream-enacting behaviors (DEBs) are behavioral expressions of forceful dream images often occurring during sleep-to-wakefulness transitions. We propose that DEBs reflect brain activity underlying social cognition, in particular, motor-affective resonance generated by the mirror neuron system. We developed a Mirror Behavior Questionnaire (MBQ) to assess some dimensions of mirror behaviors and investigated relationships between MBQ scores and DEBs in a large of university undergraduate cohort. MBQ scores were normally distributed and described by a four-factor structure (Empathy/Emotional Contagion, Behavioral Imitation, Sleepiness/Anger Contagion, Motor Skill Imitation). DEB scores correlated positively with MBQ total and factor scores even with social desirability, somnambulism and somniloquy controlled. Emotion-specific DEB items correlated with corresponding emotion-specific MBQ items, especially crying and smiling. Results provide preliminary evidence for cross-state relationships between propensities for dream-enacting and mirror behaviors--especially behaviors involving motor-affective resonance--and our suggestion that motor-affective resonance mediates dream-enactment imagery during sleep and emotional empathy during waking. Copyright © 2013 Elsevier Inc. All rights reserved.
-
Sallés, Laia; Gironès, Xavier; Lafuente, José Vicente
2015-01-06
The basic characteristics of Penfield homunculus (somatotopy and unique representation) have been questioned. The existence of a defined anatomo-functional organization within different segments of the same region is controversial. The presence of multiple motor representations in the primary motor area and in the parietal lobe interconnected by parieto-frontal circuits, which are widely overlapped, form a complex organization. Both features support the recovery of functions after brain injury. Regarding the movement organization, it is possible to yield a relevant impact through the understanding of actions and intentions of others, which is mediated by the activation of mirror-neuron systems. The implementation of cognitive functions (observation, image of the action and imitation) from the acute treatment phase allows the activation of motor representations without having to perform the action and it plays an important role in learning motor patterns. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.
-
Self-processing and the default mode network: Interactions with the mirror neuron system
Directory of Open Access Journals (Sweden)
Istvan eMolnar-Szakacs
2013-09-01
Full Text Available Recent evidence for the fractionation of the default mode network (DMN into functionally distinguishable subdivisions with unique patterns of connectivity calls for a reconceptualization of the relationship between this network and self-referential processing. Advances in resting-state functional connectivity analyses are beginning to reveal increasingly complex patterns of organization within the key nodes of the DMN - medial prefrontal cortex (MPFC and posterior cingulate cortex (PCC – as well as between these nodes and other brain systems. Here we review recent examinations of the relationships between the DMN and various aspects of self-relevant and social-cognitive processing in light of emerging evidence for heterogeneity within this network. Drawing from a rapidly evolving social cognitive neuroscience literature, we propose that embodied simulation and mentalizing are processes which allow us to gain insight into another's physical and mental state by providing privileged access to our own physical and mental states. Embodiment implies that the same neural systems are engaged for self- and other-understanding through a simulation mechanism, while mentalizing refers to the use of high-level conceptual information to make inferences about the mental states of self and others. These mechanisms work together to provide a coherent representation of the self and by extension, of others. Nodes of the DMN selectively interact with brain systems for embodiment and mentalizing, including the mirror neuron system, to produce appropriate mappings in the service of social cognitive demands.
-
Saygin, Ayse P; Dick, Frederic
2014-04-01
Like Cook et al., we suggest that mirror neurons are a fascinating product of cross-modal learning. As predicted by an associative account, responses in motor regions are observed for novel and/or abstract visual stimuli such as point-light and android movements. Domain-specific mirror responses also emerge as a function of audiomotor expertise that is slowly acquired over years of intensive training.
-
Mirror Lake: Past, present and future: Chapter 6
Likens, Gene E.; LaBaugh, James W.; Winter, Thomas C.; Likens, Gene E.
2009-01-01
This chapter discusses the hydrological and biogeochemical characteristics of Mirror Lake and the changes that resulted from air-land-water interactions and human activities. Since the formation of Mirror Lake, both the watershed and the lake have undergone many changes, such as vegetation development and basin filling. These changes are ongoing, and Mirror Lake is continuing along an aging pathway and ultimately, it will fill with sediment and no longer be a lake. The chapter also identifies major factors that affected the hydrology and biogeochemistry of Mirror Lake: acid rain, atmospheric deposition of lead and other heavy metals, increased human settlement around the lake, the construction of an interstate highway through the watershed of the Northeast Tributary, the construction of an access road through the West and Northeast watersheds to the lake, and climate change. The chapter also offers future recommendations for management and protection of Mirror Lake.
-
Human temporal cortical single neuron activity during working memory maintenance.
Zamora, Leona; Corina, David; Ojemann, George
2016-06-01
The Working Memory model of human memory, first introduced by Baddeley and Hitch (1974), has been one of the most influential psychological constructs in cognitive psychology and human neuroscience. However the neuronal correlates of core components of this model have yet to be fully elucidated. Here we present data from two studies where human temporal cortical single neuron activity was recorded during tasks differentially affecting the maintenance component of verbal working memory. In Study One we vary the presence or absence of distracting items for the entire period of memory storage. In Study Two we vary the duration of storage so that distractors filled all, or only one-third of the time the memory was stored. Extracellular single neuron recordings were obtained from 36 subjects undergoing awake temporal lobe resections for epilepsy, 25 in Study one, 11 in Study two. Recordings were obtained from a total of 166 lateral temporal cortex neurons during performance of one of these two tasks, 86 study one, 80 study two. Significant changes in activity with distractor manipulation were present in 74 of these neurons (45%), 38 Study one, 36 Study two. In 48 (65%) of those there was increased activity during the period when distracting items were absent, 26 Study One, 22 Study Two. The magnitude of this increase was greater for Study One, 47.6%, than Study Two, 8.1%, paralleling the reduction in memory errors in the absence of distracters, for Study One of 70.3%, Study Two 26.3% These findings establish that human lateral temporal cortex is part of the neural system for working memory, with activity during maintenance of that memory that parallels performance, suggesting it represents active rehearsal. In 31 of these neurons (65%) this activity was an extension of that during working memory encoding that differed significantly from the neural processes recorded during overt and silent language tasks without a recent memory component, 17 Study one, 14 Study two
-
Human Temporal Cortical Single Neuron Activity During Working Memory Maintenance
Zamora, Leona; Corina, David; Ojemann, George
2016-01-01
The Working Memory model of human memory, first introduced by Baddeley and Hitch (1974), has been one of the most influential psychological constructs in cognitive psychology and human neuroscience. However the neuronal correlates of core components of this model have yet to be fully elucidated. Here we present data from two studies where human temporal cortical single neuron activity was recorded during tasks differentially affecting the maintenance component of verbal working memory. In Study One we vary the presence or absence of distracting items for the entire period of memory storage. In Study Two we vary the duration of storage so that distractors filled all, or only one-third of the time the memory was stored. Extracellular single neuron recordings were obtained from 36 subjects undergoing awake temporal lobe resections for epilepsy, 25 in Study one, 11 in Study two. Recordings were obtained from a total of 166 lateral temporal cortex neurons during performance of one of these two tasks, 86 study one, 80 study two. Significant changes in activity with distractor manipulation were present in 74 of these neurons (45%), 38 Study one, 36 Study two. In 48 (65%) of those there was increased activity during the period when distracting items were absent, 26 Study One, 22 Study Two. The magnitude of this increase was greater for Study One, 47.6%, than Study Two, 8.1%, paralleling the reduction in memory errors in the absence of distracters, for Study One of 70.3%, Study Two 26.3% These findings establish that human lateral temporal cortex is part of the neural system for working memory, with activity during maintenance of that memory that parallels performance, suggesting it represents active rehearsal. In 31 of these neurons (65%) this activity was an extension of that during working memory encoding that differed significantly from the neural processes recorded during overt and silent language tasks without a recent memory component, 17 Study one, 14 Study two
-
Turati, Chiara; Natale, Elena; Bolognini, Nadia; Senna, Irene; Picozzi, Marta; Longhi, Elena; Cassia, Viola Macchi
2013-01-01
In primates and adult humans direct understanding of others' action is provided by mirror mechanisms matching action observation and action execution (e.g. Casile, Caggiano & Ferrari, 2011). Despite the growing body of evidence detailing the existence of these mechanisms in the adult human brain, their origins and early development are…
-
Napoli, Alessandro; Obeid, Iyad
2016-03-01
Electrical activity in embryonic brain tissue has typically been studied using Micro Electrode Array (MEA) technology to make dozens of simultaneous recordings from dissociated neuronal cultures, brain stem cell progenitors, or brain slices from fetal rodents. Although these rodent neuronal primary culture electrical properties are mostly investigated, it has not been yet established to what extent the electrical characteristics of rodent brain neuronal cultures can be generalized to those of humans. A direct comparison of spontaneous spiking activity between rodent and human primary neurons grown under the same in vitro conditions using MEA technology has never been carried out before and will be described in the present study. Human and rodent dissociated fetal brain neuronal cultures were established in-vitro by culturing on a glass grid of 60 planar microelectrodes neurons under identical conditions. Three different cultures of human neurons were produced from tissue sourced from a single aborted fetus (at 16-18 gestational weeks) and these were compared with seven different cultures of embryonic rat neurons (at 18 gestational days) originally isolated from a single rat. The results show that the human and rodent cultures behaved significantly differently. Whereas the rodent cultures demonstrated robust spontaneous activation and network activity after only 10 days, the human cultures required nearly 40 days to achieve a substantially weaker level of electrical function. These results suggest that rat neuron preparations may yield inferences that do not necessarily transfer to humans. © 2015 Wiley Periodicals, Inc.
-
Daitch, Amy L.; Foster, Brett L.; Schrouff, Jessica; Rangarajan, Vinitha; Kaşikçi, Itır; Gattas, Sandra; Parvizi, Josef
2016-01-01
Brain areas within the lateral parietal cortex (LPC) and ventral temporal cortex (VTC) have been shown to code for abstract quantity representations and for symbolic numerical representations, respectively. To explore the fast dynamics of activity within each region and the interaction between them, we used electrocorticography recordings from 16 neurosurgical subjects implanted with grids of electrodes over these two regions and tracked the activity within and between the regions as subjects performed three different numerical tasks. Although our results reconfirm the presence of math-selective hubs within the VTC and LPC, we report here a remarkable heterogeneity of neural responses within each region at both millimeter and millisecond scales. Moreover, we show that the heterogeneity of response profiles within each hub mirrors the distinct patterns of functional coupling between them. Our results support the existence of multiple bidirectional functional loops operating between discrete populations of neurons within the VTC and LPC during the visual processing of numerals and the performance of arithmetic functions. These findings reveal information about the dynamics of numerical processing in the brain and also provide insight into the fine-grained functional architecture and connectivity within the human brain. PMID:27821758
-
Mirror boxes and mirror mounts for photophysics beamline
International Nuclear Information System (INIS)
Raja Rao, P.M.; Raja Sekhar, B.N.; Das, N.C.; Khan, H.A.; Bhattacharya, S.S.; Roy, A.P.
1996-01-01
Photophysics beamline makes use of one metre Seya-Namioka monochromator and two toroidal mirrors in its fore optics. The first toroidal mirror (pre mirror) focuses light originating from the tangent point of the storage ring onto the entrance slit of the monochromator and second toroidal mirror (post mirror) collects light from the exit slit of the monochromator and focuses light onto the sample placed at a distance of about one metre away from the 2nd mirror. To steer light through monochromator and to focus it on the sample of 1mm x 1mm size require precision rotational and translational motion of the mirrors and this has been achieved with the help of precision mirror mounts. Since Indus-1 operates at pressures less than 10 -9 m.bar, the mirror mounts should be manipulated under similar ultra high vacuum conditions. Considering these requirements, two mirror boxes and two mirror mounts have been designed and fabricated. The coarse movements to the mirrors are imparted from outside the mirror chamber with the help of x-y tables and precision movements to the mirrors are achieved with the help of mirror mounts. The UHV compatibility and performance of the mirror mounts connected to mirror boxes under ultra high vacuum condition is evaluated. The details of the design, fabrication and performance evaluation are discussed in this report. 5 refs., 9 figs., 1 tab
-
Sadaoka, Tomohiko; Schwartz, Cindi L; Rajbhandari, Labchan; Venkatesan, Arun; Cohen, Jeffrey I
2018-01-01
Varicella-zoster virus (VZV) is highly cell associated when grown in culture and has a much higher (4,000- to 20,000-fold increased) particle-to-PFU ratio in vitro than herpes simplex virus (HSV). In contrast, VZV is highly infectious in vivo by airborne transmission. Neurons are major targets for VZV in vivo ; in neurons, the virus can establish latency and reactivate to produce infectious virus. Using neurons derived from human embryonic stem cells (hESC) and cell-free wild-type (WT) VZV, we demonstrated that neurons are nearly 100 times more permissive for WT VZV infection than very-early-passage human embryonic lung cells or MRC-5 diploid human fibroblasts, the cells used for vaccine production or virus isolation. The peak titers achieved after infection were ∼10-fold higher in human neurons than in MRC-5 cells, and the viral genome copy number-to-PFU ratio for VZV in human neurons was 500, compared with 50,000 for MRC-5 cells. Thus, VZV may not necessarily have a higher particle-to-PFU ratio than other herpesviruses; instead, the cells previously used to propagate virus in vitro may have been suboptimal. Furthermore, based on electron microscopy, neurons infected with VZV produced fewer defective or incomplete viral particles than MRC-5 cells. Our data suggest that neurons derived from hESC may have advantages compared to other cells for studies of VZV pathogenesis, for obtaining stocks of virus with high titers, and for isolating VZV from clinical specimens. IMPORTANCE Varicella-zoster virus (VZV) causes chickenpox and shingles. Cell-free VZV has been difficult to obtain, both for in vitro studies and for vaccine production. While numerous cells lines have been tested for their ability to produce high titers of VZV, the number of total virus particles relative to the number of viral particles that can form plaques in culture has been reported to be extremely high relative to that in other viruses. We show that VZV grows to much higher titers in human
-
Tramacere, Antonella; Pievani, Telmo; Ferrari, Pier F
2017-08-01
Considering the properties of mirror neurons (MNs) in terms of development and phylogeny, we offer a novel, unifying, and testable account of their evolution according to the available data and try to unify apparently discordant research, including the plasticity of MNs during development, their adaptive value and their phylogenetic relationships and continuity. We hypothesize that the MN system reflects a set of interrelated traits, each with an independent natural history due to unique selective pressures, and propose that there are at least three evolutionarily significant trends that gave raise to three subtypes: hand visuomotor, mouth visuomotor, and audio-vocal. Specifically, we put forward a mosaic evolution hypothesis, which posits that different types of MNs may have evolved at different rates within and among species. This evolutionary hypothesis represents an alternative to both adaptationist and associative models. Finally, the review offers a strong heuristic potential in predicting the circumstances under which specific variations and properties of MNs are expected. Such predictive value is critical to test new hypotheses about MN activity and its plastic changes, depending on the species, the neuroanatomical substrates, and the ecological niche. © 2016 Cambridge Philosophical Society.
-
Honaga, Eiko; Ishii, Ryouhei; Kurimoto, Ryu; Canuet, Leonides; Ikezawa, Koji; Takahashi, Hidetoshi; Nakahachi, Takayuki; Iwase, Masao; Mizuta, Ichiro; Yoshimine, Toshiki; Takeda, Masatoshi
2010-07-12
The mu rhythm is regarded as a physiological indicator of the human mirror neuron system (MNS). The dysfunctional MNS hypothesis in patients with autistic spectrum disorder (ASD) has often been tested using EEG and MEG, targeting mu rhythm suppression during action observation/execution, although with controversial results. We explored neural activity related to the MNS in patients with ASD, focusing on power increase in the beta frequency band after observation and execution of movements, known as post-movement beta rebound (PMBR). Multiple source beamformer (MSBF) and BrainVoyager QX were used for MEG source imaging and statistical group analysis, respectively. Seven patients with ASD and ten normal subjects participated in this study. During the MEG recordings, the subjects were asked to observe and later execute object-related hand actions performed by an experimenter. We found that both groups exhibited pronounced PMBR exceeding 20% when observing and executing actions with a similar topographic distribution of maximal activity. However, significantly reduced PMBR was found only during the observation condition in the patients relative to controls in cortical regions within the MNS, namely the sensorimotor area, premotor cortex and superior temporal gyrus. Reduced PMBR during the observation condition was also found in the medial prefrontal cortex. These results support the notion of a dysfunctional execution/observation matching system related to MNS impairment in patients with ASD, and the feasibility of using MEG to detect neural activity, in particular PMBR abnormalities, as an index of MNS dysfunction during performance of motor or cognitive tasks. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.
-
Negative Effects of High Glucose Exposure in Human Gonadotropin-Releasing Hormone Neurons
Morelli, Annamaria; Comeglio, Paolo; Sarchielli, Erica; Cellai, Ilaria; Vignozzi, Linda; Vannelli, Gabriella B.; Maggi, Mario
2013-01-01
Metabolic disorders are often associated with male hypogonadotropic hypogonadism, suggesting that hypothalamic defects involving GnRH neurons may impair the reproductive function. Among metabolic factors hyperglycemia has been implicated in the control of the reproductive axis at central level, both in humans and in animal models. To date, little is known about the direct effects of pathological high glucose concentrations on human GnRH neurons. In this study, we investigated the high glucose...
-
Single-neuron correlates of subjective vision in the human medial temporal lobe
Kreiman, Gabriel; Fried, Itzhak; Koch, Christof
2002-01-01
Visual information from the environment is transformed into perceptual sensations through several stages of neuronal processing. Flash suppression constitutes a striking example in which the same retinal input can give rise to two different conscious visual percepts. We directly recorded the responses of individual neurons during flash suppression in the human amygdala, entorhinal cortex, hippocampus, and parahippocampal gyrus, allowing us to explore the neuronal responses in untrained subjec...
-
Fried, Itzhak; Mukamel, Roy; Kreiman, Gabriel
2011-01-01
Understanding how self-initiated behavior is encoded by neuronal circuits in the human brain remains elusive. We recorded the activity of 1019 neurons while twelve subjects performed self-initiated finger movement. We report progressive neuronal recruitment over ∼1500 ms before subjects report making the decision to move. We observed progressive increase or decrease in neuronal firing rate, particularly in the supplementary motor area (SMA), as the reported time of decision was approached. A ...
-
2013-01-01
Background Environmental toxins are suspected to play a role in the pathogenesis of amyotrophic lateral sclerosis (ALS). In an attempt to determine which pathways these toxins can use to enter motor neurons we compared the distribution of mercury in the CNS of a human and of mice that had been exposed to inorganic mercury. Results In the human who had been exposed to metallic mercury, mercury was seen predominantly in the locus ceruleus and corticomotor neurons, as well as in scattered glial cells. In mice that had been exposed to mercury vapor or mercuric chloride, mercury was present in lower motor neurons in the spinal cord and brain stem. Conclusions In humans, inorganic mercury can be taken up predominantly by corticomotor neurons, possibly when the locus ceruleus is upregulated by stress. This toxin uptake into corticomotor neurons is in accord with the hypothesis that ALS originates in these upper motor neurons. In mice, inorganic mercury is taken up predominantly by lower motor neurons. The routes toxins use to enter motor neurons depends on the nature of the toxin, the duration of exposure, and possibly the amount of stress (for upper motor neuron uptake) and exercise (for lower motor neuron uptake) at the time of toxin exposure. PMID:24252585
-
2005-01-01
RICH 2, one of the two Ring Imaging Cherenkov detectors of the LHCb experiment, is being prepared to join the other detector elements ready for the first proton-proton collisions at LHC. The mirrors of the RICH2 detector are meticulously assembled in a clean room.In a large dark room, men in white move around an immense structure some 7 metres high, 10 metres wide and nearly 2.5 metres deep. Apparently effortlessly, they are installing the two large high-precision spherical mirrors. These mirrors will focus Cherenkov light, created by the charged particles that will traverse this detector, onto the photon detectors. Each spherical mirror wall is made up of facets like a fly's eye. Twenty-eight individual thin glass mirrors will all point to the same point in space to within a few micro-radians. The development of these mirrors has been technically demanding : Ideally they should be massless, sturdy, precise and have high reflectivity. In practice, though not massless, they are made from a mere 6 mm thin gl...
-
Chang, Liangtang; Zhang, Shikun; Poo, Mu-Ming; Gong, Neng
2017-03-21
Mirror self-recognition (MSR) is generally considered to be an intrinsic cognitive ability found only in humans and a few species of great apes. Rhesus monkeys do not spontaneously show MSR, but they have the ability to use a mirror as an instrument to find hidden objects. The mechanism underlying the transition from simple mirror use to MSR remains unclear. Here we show that rhesus monkeys could show MSR after learning precise visual-proprioceptive association for mirror images. We trained head-fixed monkeys on a chair in front of a mirror to touch with spatiotemporal precision a laser pointer light spot on an adjacent board that could only be seen in the mirror. After several weeks of training, when the same laser pointer light was projected to the monkey's face, a location not used in training, all three trained monkeys successfully touched the face area marked by the light spot in front of a mirror. All trained monkeys passed the standard face mark test for MSR both on the monkey chair and in their home cage. Importantly, distinct from untrained control monkeys, the trained monkeys showed typical mirror-induced self-directed behaviors in their home cage, such as using the mirror to explore normally unseen body parts. Thus, bodily self-consciousness may be a cognitive ability present in many more species than previously thought, and acquisition of precise visual-proprioceptive association for the images in the mirror is critical for revealing the MSR ability of the animal.
-
Modulations of mirroring activity by desire for social connection and relevance of movement.
Aragón, Oriana R; Sharer, Elizabeth A; Bargh, John A; Pineda, Jaime A
2014-11-01
Mirroring neurons fire both when an individual moves and observes another move in kind. This simulation of others' movements is thought to effortlessly and ubiquitously support empathetic connection and social understanding. However, at times this could be maladaptive. How could a boxer mirror a losing opponent's expressions of fatigue, feeling his weariness, precisely when strength is required? Clearly, the boxer must emotionally disconnect from his opponent and those expressions of fatigue must become irrelevant and not mirrored. But, movements that inform of his opponent's intentions to deliver an incoming blow are quite relevant and still should require mirroring. We tested these dimensions of emotional connectedness and relevance of movement in an electroencephalography experiment, where participants' desires to socially connect with a confederate were manipulated. Before manipulation, all participants mirrored the confederate's purely kinematic (a hand opening and closing) and goal-directed (a hand opening and closing around a token that the participant desired) hand movements. After manipulation, unfairly treated subjects ceased to mirror the purely kinematic movements but continued to mirror goal-relevant movements. Those treated fairly continued to mirror all movements. The results suggest that social mirroring can be adaptive in order to meet the demands of a varied social environment. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.
-
Directory of Open Access Journals (Sweden)
Evan Walker Carr
2014-07-01
Full Text Available The concept of mirroring has become rather ubiquitous. One of the most fundamental empirical and theoretical debates within research on mirroring concerns the role of mental representations: While some models argue that higher-order representational mechanisms underpin most cases of mirroring, other models argue that they only moderate a primarily non-representational process. As such, even though research on mirroring—along with its neural substrates, including the putative mirror neuron system—has grown tremendously, so too has confusion about what it actually means to mirror. Using recent research on spontaneous imitation, we argue that flexible mirroring effects can be fully embodied and dynamic—even in the absence of higher-order mental representations. We propose that mirroring can simply reflect an adaptive integration and utilization of cues obtained from the brain, body, and environment, which is especially evident within the social context. Such a view offers reconciliation among both representational and non-representational frameworks in cognitive neuroscience, which will facilitate revised interpretations of modern (and seemingly divergent findings on when and how these embodied mirroring responses are employed.
-
Simpson, Elizabeth A; Murray, Lynne; Paukner, Annika; Ferrari, Pier F
2014-01-01
There is strong evidence that neonates imitate previously unseen behaviours. These behaviours are predominantly used in social interactions, demonstrating neonates' ability and motivation to engage with others. Research on neonatal imitation can provide a wealth of information about the early mirror neuron system (MNS), namely its functional characteristics, its plasticity from birth and its relation to skills later in development. Although numerous studies document the existence of neonatal imitation in the laboratory, little is known about its natural occurrence during parent-infant interactions and its plasticity as a consequence of experience. We review these critical aspects of imitation, which we argue are necessary for understanding the early action-perception system. We address common criticisms and misunderstandings about neonatal imitation and discuss methodological differences among studies. Recent work reveals that individual differences in neonatal imitation positively correlate with later social, cognitive and motor development. We propose that such variation in neonatal imitation could reflect important individual differences of the MNS. Although postnatal experience is not necessary for imitation, we present evidence that neonatal imitation is influenced by experience in the first week of life.
-
Sagal, Jonathan; Zhan, Xiping; Xu, Jinchong; Tilghman, Jessica; Karuppagounder, Senthilkumar S; Chen, Li; Dawson, Valina L; Dawson, Ted M; Laterra, John; Ying, Mingyao
2014-08-01
Human pluripotent stem cells (PSCs) are a promising cell resource for various applications in regenerative medicine. Highly efficient approaches that differentiate human PSCs into functional lineage-specific neurons are critical for modeling neurological disorders and testing potential therapies. Proneural transcription factors are crucial drivers of neuron development and hold promise for driving highly efficient neuronal conversion in PSCs. Here, we study the functions of proneural transcription factor Atoh1 in the neuronal differentiation of PSCs. We show that Atoh1 is induced during the neuronal conversion of PSCs and that ectopic Atoh1 expression is sufficient to drive PSCs into neurons with high efficiency. Atoh1 induction, in combination with cell extrinsic factors, differentiates PSCs into functional dopaminergic (DA) neurons with >80% purity. Atoh1-induced DA neurons recapitulate key biochemical and electrophysiological features of midbrain DA neurons, the degeneration of which is responsible for clinical symptoms in Parkinson's disease (PD). Atoh1-induced DA neurons provide a reliable disease model for studying PD pathogenesis, such as neurotoxin-induced neurodegeneration in PD. Overall, our results determine the role of Atoh1 in regulating neuronal differentiation and neuron subtype specification of human PSCs. Our Atoh1-mediated differentiation approach will enable large-scale applications of PD patient-derived midbrain DA neurons in mechanistic studies and drug screening for both familial and sporadic PD. ©AlphaMed Press.
-
Neuron-Based Heredity and Human Evolution
Directory of Open Access Journals (Sweden)
Don Marshall Gash
2015-06-01
Full Text Available Abstract:Abstract: It is widely recognized that human evolution has been driven by two systems of heredity: one DNA-based and the other based on the transmission of behaviorally acquired information via nervous system functions. The genetic system is ancient, going back to the appearance of life on Earth. It is responsible for the evolutionary processes described by Darwin. By comparison, the nervous system is relatively newly minted and in its highest form, responsible for ideation and mind-to-mind transmission of information. Here the informational capabilities and functions of the two systems are compared. While employing quite different mechanisms for encoding, storing and transmission of information, both systems perform these generic hereditary functions. Three additional features of neuron-based heredity in humans are identified: the ability to transfer hereditary information to other members of their population, not just progeny; a selection process for the information being transferred; and a profoundly shorter time span for creation and dissemination of survival-enhancing information in a population. The mechanisms underlying neuron-based heredity involve hippocampal neurogenesis and memory and learning processes modifying and creating new neural assemblages changing brain structure and functions. A fundamental process in rewiring brain circuitry is through increased neural activity (use strengthening and increasing the number of synaptic connections. Decreased activity in circuitry (disuse leads to loss of synapses. Use and disuse modifying an organ to bring about new modes of living, habits and functions are processes are in line with Neolamarckian concepts of evolution (Packard, 1901. Evidence is presented of bipartite evolutionary processes – Darwinian and Neolamarckian – driving human descent from a common ancestor shared with the great apes.
-
Selective neuronal lapses precede human cognitive lapses following sleep deprivation.
Nir, Yuval; Andrillon, Thomas; Marmelshtein, Amit; Suthana, Nanthia; Cirelli, Chiara; Tononi, Giulio; Fried, Itzhak
2017-12-01
Sleep deprivation is a major source of morbidity with widespread health effects, including increased risk of hypertension, diabetes, obesity, heart attack, and stroke. Moreover, sleep deprivation brings about vehicle accidents and medical errors and is therefore an urgent topic of investigation. During sleep deprivation, homeostatic and circadian processes interact to build up sleep pressure, which results in slow behavioral performance (cognitive lapses) typically attributed to attentional thalamic and frontoparietal circuits, but the underlying mechanisms remain unclear. Recently, through study of electroencephalograms (EEGs) in humans and local field potentials (LFPs) in nonhuman primates and rodents it was found that, during sleep deprivation, regional 'sleep-like' slow and theta (slow/theta) waves co-occur with impaired behavioral performance during wakefulness. Here we used intracranial electrodes to record single-neuron activities and LFPs in human neurosurgical patients performing a face/nonface categorization psychomotor vigilance task (PVT) over multiple experimental sessions, including a session after full-night sleep deprivation. We find that, just before cognitive lapses, the selective spiking responses of individual neurons in the medial temporal lobe (MTL) are attenuated, delayed, and lengthened. These 'neuronal lapses' are evident on a trial-by-trial basis when comparing the slowest behavioral PVT reaction times to the fastest. Furthermore, during cognitive lapses, LFPs exhibit a relative local increase in slow/theta activity that is correlated with degraded single-neuron responses and with baseline theta activity. Our results show that cognitive lapses involve local state-dependent changes in neuronal activity already present in the MTL.
-
Directory of Open Access Journals (Sweden)
Agnete Kirkeby
2012-06-01
Full Text Available To model human neural-cell-fate specification and to provide cells for regenerative therapies, we have developed a method to generate human neural progenitors and neurons from human embryonic stem cells, which recapitulates human fetal brain development. Through the addition of a small molecule that activates canonical WNT signaling, we induced rapid and efficient dose-dependent specification of regionally defined neural progenitors ranging from telencephalic forebrain to posterior hindbrain fates. Ten days after initiation of differentiation, the progenitors could be transplanted to the adult rat striatum, where they formed neuron-rich and tumor-free grafts with maintained regional specification. Cells patterned toward a ventral midbrain (VM identity generated a high proportion of authentic dopaminergic neurons after transplantation. The dopamine neurons showed morphology, projection pattern, and protein expression identical to that of human fetal VM cells grafted in parallel. VM-patterned but not forebrain-patterned neurons released dopamine and reversed motor deficits in an animal model of Parkinson's disease.
-
Mirror-Image Equivalence and Interhemispheric Mirror-Image Reversal.
Corballis, Michael C
2018-01-01
Mirror-image confusions are common, especially in children and in some cases of neurological impairment. They can be a special impediment in activities such as reading and writing directional scripts, where mirror-image patterns (such as b and d ) must be distinguished. Treating mirror images as equivalent, though, can also be adaptive in the natural world, which carries no systematic left-right bias and where the same object or event can appear in opposite viewpoints. Mirror-image equivalence and confusion are natural consequences of a bilaterally symmetrical brain. In the course of learning, mirror-image equivalence may be established through a process of symmetrization, achieved through homotopic interhemispheric exchange in the formation of memory circuits. Such circuits would not distinguish between mirror images. Learning to discriminate mirror-image discriminations may depend either on existing brain asymmetries, or on extensive learning overriding the symmetrization process. The balance between mirror-image equivalence and mirror-image discrimination may nevertheless be precarious, with spontaneous confusions or reversals, such as mirror writing, sometimes appearing naturally or as a manifestation of conditions like dyslexia.
-
Mirror-Image Equivalence and Interhemispheric Mirror-Image Reversal
Directory of Open Access Journals (Sweden)
Michael C. Corballis
2018-04-01
Full Text Available Mirror-image confusions are common, especially in children and in some cases of neurological impairment. They can be a special impediment in activities such as reading and writing directional scripts, where mirror-image patterns (such as b and d must be distinguished. Treating mirror images as equivalent, though, can also be adaptive in the natural world, which carries no systematic left-right bias and where the same object or event can appear in opposite viewpoints. Mirror-image equivalence and confusion are natural consequences of a bilaterally symmetrical brain. In the course of learning, mirror-image equivalence may be established through a process of symmetrization, achieved through homotopic interhemispheric exchange in the formation of memory circuits. Such circuits would not distinguish between mirror images. Learning to discriminate mirror-image discriminations may depend either on existing brain asymmetries, or on extensive learning overriding the symmetrization process. The balance between mirror-image equivalence and mirror-image discrimination may nevertheless be precarious, with spontaneous confusions or reversals, such as mirror writing, sometimes appearing naturally or as a manifestation of conditions like dyslexia.
-
Directory of Open Access Journals (Sweden)
Vernon Furtado da Silva
2016-08-01
Full Text Available ABSTRACT This study focused upon the functional capacity of mirror neurons in autistic children. 30 individuals, 10 carriers of the autistic syndrome (GCA, 10 with intellectual impairments (GDI, and 10 non-autistics (GCN had registered eletroencephalogram from the brain area theoretically related to mirror neurons. Data collection procedure occurred prior to brain stimulation and after the stimulation session. During the second session, participants had to alternately process figures evoking neutral, happy, and/or sorrowful feelings. Results proved that, for all groups, the stimulation process in fact produced additional activation in the neural area under study. The level of activation was related to the format of emotional stimuli and the likelihood of boosting such stimuli. Since the increase of activation occurred in a model similar to the one observed for the control group, we may suggest that the difficulty people with autism have at expressing emotions is not due to nonexistence of mirror neurons.
-
Silva, Vernon Furtado da; Calomeni, Mauricio Rocha; Nunes, Rodolfo Alkmim Moreira; Pimentel, Carlos Elias; Martins, Gabriela Paes; Oliveira, Patrícia da Cruz Araruna; Silva, Patrícia Bagno; Silva, Alair Pedro Ribeiro de Souza E
2016-08-01
This study focused upon the functional capacity of mirror neurons in autistic children. 30 individuals, 10 carriers of the autistic syndrome (GCA), 10 with intellectual impairments (GDI), and 10 non-autistics (GCN) had registered eletroencephalogram from the brain area theoretically related to mirror neurons. Data collection procedure occurred prior to brain stimulation and after the stimulation session. During the second session, participants had to alternately process figures evoking neutral, happy, and/or sorrowful feelings. Results proved that, for all groups, the stimulation process in fact produced additional activation in the neural area under study. The level of activation was related to the format of emotional stimuli and the likelihood of boosting such stimuli. Since the increase of activation occurred in a model similar to the one observed for the control group, we may suggest that the difficulty people with autism have at expressing emotions is not due to nonexistence of mirror neurons.
-
Efficient and Cost-Effective Generation of Mature Neurons From Human Induced Pluripotent Stem Cells
Badja , Cherif; Maleeva , Galyna; El-Yazidi , Claire; Barruet , Emilie; Lasserre , Manon; Tropel , Philippe; Binetruy , Bernard; Bregestovski , Piotr; Magdinier , Frédérique
2014-01-01
The authors describe a feeder-free method of generating induced pluripotent stem cells by relying on the use of a chemically defined medium that overcomes the need for embryoid body formation and neuronal rosette isolation for neuronal precursors and terminally differentiated neuron production. This specific and efficient single-step strategy allows the production of mature neurons in 20–40 days with multiple applications, especially for modeling human pathologies.
-
Novel human neuronal tau model exhibiting neurofibrillary tangles and transcellular propagation.
Reilly, Patrick; Winston, Charisse N; Baron, Kelsey R; Trejo, Margarita; Rockenstein, Edward M; Akers, Johnny C; Kfoury, Najla; Diamond, Marc; Masliah, Eliezer; Rissman, Robert A; Yuan, Shauna H
2017-10-01
Tauopathies are a class of neurodegenerative diseases, including Alzheimer's disease, frontotemporal dementia and progressive supranuclear palsy, which are associated with the pathological aggregation of tau protein into neurofibrillary tangles (NFT). Studies have characterized tau as a "prion-like" protein given its ability to form distinct, stable amyloid conformations capable of transcellular and multigenerational propagation in clonal fashion. It has been proposed that progression of tauopathy could be due to the prion-like propagation of tau, suggesting the possibility that end-stage pathologies, like NFT formation, may require an instigating event such as tau seeding. To investigate this, we applied a novel human induced pluripotent stem cell (hiPSC) system we have developed to serve as a human neuronal model. We introduced the tau repeat domain (tau-RD) with P301L and V337M (tau-RD-LM) mutations into hiPSC-derived neurons and observed expression of tau-RD at levels similar to total tau in postmortem AD brains. Tau aggregation occurred without the addition of recombinant tau fibrils. The conditioned media from tau-RD cultures contained tau-RD seeds, which were capable of inducing aggregate formation in homotypic mode in non-transduced recipient neuronal cultures. The resultant NFTs were thioflavin-positive, silver stain-positive, and assumed fibrillary appearance on transmission electron microscopy (TEM) with immunogold, which revealed paired helical filament 1 (PHF1)-positive NFTs, representing possible recruitment of endogenous tau in the aggregates. Functionally, expression of tau-RD caused neurotoxicity that manifested as axon retraction, synaptic density reduction, and enlargement of lysosomes. The results of our hiPSC study were reinforced by the observation that Tau-RD-LM is excreted in exosomes, which mediated the transfer of human tau to wild-type mouse neurons in vivo. Our hiPSC human neuronal system provides a model for further studies of tau
-
Expression of Sirtuins in the Retinal Neurons of Mice, Rats, and Humans
Directory of Open Access Journals (Sweden)
Hongdou Luo
2017-11-01
Full Text Available Sirtuins are a class of histone deacetylases (HDACs that have been shown to regulate a range of pathophysiological processes such as cellular aging, inflammation, metabolism, and cell proliferation. There are seven mammalian Sirtuins (SIRT1-7 that play important roles in stress response, aging, and neurodegenerative diseases. However, the location and function of Sirtuins in neurons are not well defined. This study assessed the retinal expression of Sirtuins in mice, rats, and humans and measured the expression of Sirtuins in aged and injured retinas. Expression of all 7 Sirtuins was confirmed by Western blot and Real-Time PCR analysis in all three species. SIRT1 is highly expressed in mouse, rat, and human retinas, whereas SIRT2-7 expression was relatively lower in human retinas. Immunofluorescence was also used to examine the expression and localization of Sirtuins in rat retinal neurons. Importantly, we demonstrate a marked reduction of SIRT1 expression in aged retinal neurons as well as retinas injured by acute ischemia-reperfusion. On the other hand, none of the other Sirtuins exhibit any significant age-related changes in expression except for SIRT5, which was significantly higher in the retinas of adults compared to both young and aged rats. Our work presents the first composite analysis of Sirtuins in the retinal neurons of mice, rats, and humans, and suggests that increasing the expression and activity of SIRT1 may be beneficial for the treatment of glaucoma and other age-related eye dysfunction.
-
Negative Effects of High Glucose Exposure in Human Gonadotropin-Releasing Hormone Neurons
Directory of Open Access Journals (Sweden)
Annamaria Morelli
2013-01-01
Full Text Available Metabolic disorders are often associated with male hypogonadotropic hypogonadism, suggesting that hypothalamic defects involving GnRH neurons may impair the reproductive function. Among metabolic factors hyperglycemia has been implicated in the control of the reproductive axis at central level, both in humans and in animal models. To date, little is known about the direct effects of pathological high glucose concentrations on human GnRH neurons. In this study, we investigated the high glucose effects in the human GnRH-secreting FNC-B4 cells. Gene expression profiling by qRT-PCR, confirmed that FNC-B4 cells express GnRH and several genes relevant for GnRH neuron function (KISS1R, KISS1, sex steroid and leptin receptors, FGFR1, neuropilin 2, and semaphorins, along with glucose transporters (GLUT1, GLUT3, and GLUT4. High glucose exposure (22 mM; 40 mM significantly reduced gene and protein expression of GnRH, KISS1R, KISS1, and leptin receptor, as compared to normal glucose (5 mM. Consistent with previous studies, leptin treatment significantly induced GnRH mRNA expression at 5 mM glucose, but not in the presence of high glucose concentrations. In conclusion, our findings demonstrate a deleterious direct contribution of high glucose on human GnRH neurons, thus providing new insights into pathogenic mechanisms linking metabolic disorders to reproductive dysfunctions.
-
Arya, Kamal Narayan; Pandian, Shanta
2014-10-01
Broca's aphasia is the most challenging communication deficit in stroke. Left inferior frontal gyrus (IFG), a key region of the mirror-neuron system, gets lesioned in Broca's aphasia. Mirror therapy (MT), a form of action-observation, may trigger the mirror neurons. The aim of this study was to report a case of poststroke subject with Broca's aphasia, who exhibited an inadvertent and significant improvement in speech after MT for the paretic upper limb. The 20-month old stroke patient underwent MT through goal-directed tasks. He received a total absence of spontaneous speech, writing, and naming. After 45 sessions of task-based MT for the upper limb, he showed tremendous recovery in expressive communication. He had fluent and comprehensive communication; however, with a low pitch and minor pronunciation errors. He showed a substantial change (from 18/100 to 79/100) on the Communicative Effective Index, particularly, on items such as expressing emotions, one-to-one conversation, naming, and spontaneous conversation. Copyright © 2014 Elsevier Ltd. All rights reserved.
-
'It's All Done With Mirrors': V.S. Ramachandran and the Material Culture of Phantom Limb Research.
Guenther, Katja
2016-07-01
This article examines the material culture of neuroscientist Vilayanur S. Ramachandran's research into phantom limbs. In the 1990s Ramachandran used a 'mirror box' to 'resurrect' phantom limbs and thus to treat the pain that often accompanied them. The experimental success of his mirror therapy led Ramachandran to see mirrors as a useful model of brain function, a tendency that explains his attraction to work on 'mirror neurons'. I argue that Ramachandran's fascination with and repeated appeal to the mirror can be explained by the way it allowed him to confront a perennial problem in the mind and brain sciences, that of the relationship between a supposedly immaterial mind and a material brain. By producing what Ramachandran called a 'virtual reality', relating in varied and complex ways to the material world, the mirror reproduced a form of psycho-physical parallelism and dualistic ontology, while conforming to the materialist norms of neuroscience today.
-
"Mirror agnosia" in a patient with right occipitotemporal infarct
Directory of Open Access Journals (Sweden)
Menon Bijoy
2006-01-01
Full Text Available We report the clinical profile and investigation of K, a patient suffering from agnosia for the concept of "mirrors". Normal people rarely confuse a mirror image for the real image. Our patient ′K′ has intact attention, memory and language with a left visual neglect with left hemianopia. When shown an object on his left with a mirror kept sagitally on his right, K grabs for the reflection and even gropes behind the mirror for it. Yet, when shown the mirror alone, he is able to tell that it is a mirror. Thus the concept of a ′mirror′ is lost in the experimental paradigm. An explanation for mirror ′agnosia′ is provided and recent controversies in the analysis of visuospatial functions in humans is highlighted.
-
Direct conversion of human pluripotent stem cells into cranial motor neurons using a piggyBac vector
Directory of Open Access Journals (Sweden)
Riccardo De Santis
2018-05-01
Full Text Available Human pluripotent stem cells (PSCs are widely used for in vitro disease modeling. One of the challenges in the field is represented by the ability of converting human PSCs into specific disease-relevant cell types. The nervous system is composed of a wide variety of neuronal types with selective vulnerability in neurodegenerative diseases. This is particularly relevant for motor neuron diseases, in which different motor neurons populations show a different susceptibility to degeneration. Here we developed a fast and efficient method to convert human induced Pluripotent Stem Cells into cranial motor neurons of the branchiomotor and visceral motor subtype. These populations represent the motor neuron subgroup that is primarily affected by a severe form of amyotrophic lateral sclerosis with bulbar onset and worst prognosis. This goal was achieved by stable integration of an inducible vector, based on the piggyBac transposon, allowing controlled activation of Ngn2, Isl1 and Phox2a (NIP. The NIP module effectively produced electrophysiologically active cranial motor neurons. Our method can be easily extended to PSCs carrying disease-associated mutations, thus providing a useful tool to shed light on the cellular and molecular bases of selective motor neuron vulnerability in pathological conditions. Keywords: Spinal motor neuron, Cranial motor neuron, Induced pluripotent stem cells, Amyotrophic lateral sclerosis, Phox2a, piggyBac
-
The neural code for face orientation in the human fusiform face area.
Ramírez, Fernando M; Cichy, Radoslaw M; Allefeld, Carsten; Haynes, John-Dylan
2014-09-03
Humans recognize faces and objects with high speed and accuracy regardless of their orientation. Recent studies have proposed that orientation invariance in face recognition involves an intermediate representation where neural responses are similar for mirror-symmetric views. Here, we used fMRI, multivariate pattern analysis, and computational modeling to investigate the neural encoding of faces and vehicles at different rotational angles. Corroborating previous studies, we demonstrate a representation of face orientation in the fusiform face-selective area (FFA). We go beyond these studies by showing that this representation is category-selective and tolerant to retinal translation. Critically, by controlling for low-level confounds, we found the representation of orientation in FFA to be compatible with a linear angle code. Aspects of mirror-symmetric coding cannot be ruled out when FFA mean activity levels are considered as a dimension of coding. Finally, we used a parametric family of computational models, involving a biased sampling of view-tuned neuronal clusters, to compare different face angle encoding models. The best fitting model exhibited a predominance of neuronal clusters tuned to frontal views of faces. In sum, our findings suggest a category-selective and monotonic code of face orientation in the human FFA, in line with primate electrophysiology studies that observed mirror-symmetric tuning of neural responses at higher stages of the visual system, beyond the putative homolog of human FFA. Copyright © 2014 the authors 0270-6474/14/3412155-13$15.00/0.
-
Directory of Open Access Journals (Sweden)
Heather E Wheeler
Full Text Available There are no effective agents to prevent or treat chemotherapy-induced peripheral neuropathy (CIPN, the most common non-hematologic toxicity of chemotherapy. Therefore, we sought to evaluate the utility of human neuron-like cells derived from induced pluripotent stem cells (iPSCs as a means to study CIPN. We used high content imaging measurements of neurite outgrowth phenotypes to compare the changes that occur to iPSC-derived neuronal cells among drugs and among individuals in response to several classes of chemotherapeutics. Upon treatment of these neuronal cells with the neurotoxic drug paclitaxel, vincristine or cisplatin, we identified significant differences in five morphological phenotypes among drugs, including total outgrowth, mean/median/maximum process length, and mean outgrowth intensity (P < 0.05. The differences in damage among drugs reflect differences in their mechanisms of action and clinical CIPN manifestations. We show the potential of the model for gene perturbation studies by demonstrating decreased expression of TUBB2A results in significantly increased sensitivity of neurons to paclitaxel (0.23 ± 0.06 decrease in total neurite outgrowth, P = 0.011. The variance in several neurite outgrowth and apoptotic phenotypes upon treatment with one of the neurotoxic drugs is significantly greater between than within neurons derived from four different individuals (P < 0.05, demonstrating the potential of iPSC-derived neurons as a genetically diverse model for CIPN. The human neuron model will allow both for mechanistic studies of specific genes and genetic variants discovered in clinical studies and for screening of new drugs to prevent or treat CIPN.
-
Kamiński, Jan; Mamelak, Adam N; Birch, Kurtis; Mosher, Clayton P; Tagliati, Michele; Rutishauser, Ueli
2018-04-12
The encoding of information into long-term declarative memory is facilitated by dopamine. This process depends on hippocampal novelty signals, but it remains unknown how midbrain dopaminergic neurons are modulated by declarative-memory-based information. We recorded individual substantia nigra (SN) neurons and cortical field potentials in human patients performing a recognition memory task. We found that 25% of SN neurons were modulated by stimulus novelty. Extracellular waveform shape and anatomical location indicated that these memory-selective neurons were putatively dopaminergic. The responses of memory-selective neurons appeared 527 ms after stimulus onset, changed after a single trial, and were indicative of recognition accuracy. SN neurons phase locked to frontal cortical theta-frequency oscillations, and the extent of this coordination predicted successful memory formation. These data reveal that dopaminergic neurons in the human SN are modulated by memory signals and demonstrate a progression of information flow in the hippocampal-basal ganglia-frontal cortex loop for memory encoding. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.
-
[Unconscious sexual desire: fMRI and EEG evidences from self-expansion theory to mirror neurons].
Ortigue, Stephanie; Bianchi-Demicheli, Francesco
2010-03-24
Recent advances in cognitive-social neuroscience allow a better understanding of the mechanisms underlying dyadic relationships. From a neuronal viewpoint, desire in dyadic relationships involves a specific fronto-temporo-parietal network and also a subcortical network that mediates conscious and unconscious mechanisms of reward, satisfaction, attention, self representation and self-expansion. The integration of this neuroscientific knowledge on the unconscious neurobiological activation for sexual desire in the human brain will provide physicians with new therapeutical and neuroscientific tools to apprehend sexual disorders in couple.
-
A word in the hand: action, gesture and mental representation in humans and non-human primates
Cartmill, Erica A.; Beilock, Sian; Goldin-Meadow, Susan
2012-01-01
The movements we make with our hands both reflect our mental processes and help to shape them. Our actions and gestures can affect our mental representations of actions and objects. In this paper, we explore the relationship between action, gesture and thought in both humans and non-human primates and discuss its role in the evolution of language. Human gesture (specifically representational gesture) may provide a unique link between action and mental representation. It is kinaesthetically close to action and is, at the same time, symbolic. Non-human primates use gesture frequently to communicate, and do so flexibly. However, their gestures mainly resemble incomplete actions and lack the representational elements that characterize much of human gesture. Differences in the mirror neuron system provide a potential explanation for non-human primates' lack of representational gestures; the monkey mirror system does not respond to representational gestures, while the human system does. In humans, gesture grounds mental representation in action, but there is no evidence for this link in other primates. We argue that gesture played an important role in the transition to symbolic thought and language in human evolution, following a cognitive leap that allowed gesture to incorporate representational elements. PMID:22106432
-
Marino, Barbara F M; Ricciardelli, Paola
2017-07-01
The activation of the mirror-neuron circuit during the observation of motor acts is thought to be the basis of human capacity to read the intentions behind the behavior of others. Growing empirical evidence shows a different activation of the mirror-neuron resonance mechanism depending on how much the observer and the observed agent share their motor repertoires. Here, the possible modulatory effect of physical similarity between the observer and the agent was investigated in three studies. We used a visuo-motor priming task in which participants were asked to categorize manipulable and non-manipulable objects into natural or man-made kinds after having watched precision and power reach-to-grasp movements. Physical similarity was manipulated by presenting reach-to-grasp movements performed by the hands of actors of three different age ranges that are adults of the same age as the participants, children, and elderly. Faster responses were observed in trials where power grip movements were performed by the adults and precision grip movements were performed by the elderly (Main Study). This finding is not in keeping with the idea that physical similarity shapes the mirror-neuron resonance. Instead, it suggests an effect of the kinematic organization of the reach-to-grasp movements, which systematically changed with the actor age as revealed by a kinematic analysis. The differential effect played by adult and elderly actor primes was lost when static grasping hands (Control Study 1) and reach-to-grasp movements with uniform kinematic profiles (Control Study 2) were used. Therefore, we found preliminary evidence that mirror-neuron resonance is not shaped by physical similarity but by the kinematics of the observed action. This finding is novel as it suggests that human ability to read the intentions behind the behavior of others may benefit from a mere visual processing of spatiotemporal patterns.
-
Aplasics born without hands mirror the goal of hand actions with their feet
Gazzola, Valeria; van der Worp, Henk; Mulder, Theodorus; Wicker, Bruno; Rizzolatti, Giacomo; Keysers, Christian
2007-01-01
The premotor and parietal mirror neuron system (MNS) is thought to contribute to the understanding of observed actions by mapping them onto "corresponding" motor programs of the observer [1-24], but how would the MNS respond to the observation of hand actions if the observer never had hands? Would
-
Deactivation in the Sensorimotor Area during Observation of a Human Agent Performing Robotic Actions
Shimada, Sotaro
2010-01-01
It is well established that several motor areas, called the mirror-neuron system (MNS), are activated when an individual observes other's actions. However, whether the MNS responds similarly to robotic actions compared with human actions is still controversial. The present study investigated whether and how the motor area activity is influenced by…
-
Immunohistochemical Markers for Quantitative Studies of Neurons and Glia in Human Neocortex
DEFF Research Database (Denmark)
Lyck, Lise; Dalmau, Ishar; Chemnitz, John
2007-01-01
Reproducible visualisation of neurons and glia in human brain is essential for quantitative studies of the cellular changes in neurological disease. However, immunohistochemistry in human brain specimens is often compromised due to prolonged fixation. To select cell-lineage specific antibodies fo...
-
Functional Properties of Human Stem Cell-Derived Neurons in Health and Disease
Directory of Open Access Journals (Sweden)
Jason P. Weick
2016-01-01
Full Text Available Stem cell-derived neurons from various source materials present unique model systems to examine the fundamental properties of central nervous system (CNS development as well as the molecular underpinnings of disease phenotypes. In order to more accurately assess potential therapies for neurological disorders, multiple strategies have been employed in recent years to produce neuronal populations that accurately represent in vivo regional and transmitter phenotypes. These include new technologies such as direct conversion of somatic cell types into neurons and glia which may accelerate maturation and retain genetic hallmarks of aging. In addition, novel forms of genetic manipulations have brought human stem cells nearly on par with those of rodent with respect to gene targeting. For neurons of the CNS, the ultimate phenotypic characterization lies with their ability to recapitulate functional properties such as passive and active membrane characteristics, synaptic activity, and plasticity. These features critically depend on the coordinated expression and localization of hundreds of ion channels and receptors, as well as scaffolding and signaling molecules. In this review I will highlight the current state of knowledge regarding functional properties of human stem cell-derived neurons, with a primary focus on pluripotent stem cells. While significant advances have been made, critical hurdles must be overcome in order for this technology to support progression toward clinical applications.
-
Telgen, Sebastian; Parvin, Darius; Diedrichsen, Jörn
2014-10-08
Motor learning tasks are often classified into adaptation tasks, which involve the recalibration of an existing control policy (the mapping that determines both feedforward and feedback commands), and skill-learning tasks, requiring the acquisition of new control policies. We show here that this distinction also applies to two different visuomotor transformations during reaching in humans: Mirror-reversal (left-right reversal over a mid-sagittal axis) of visual feedback versus rotation of visual feedback around the movement origin. During mirror-reversal learning, correct movement initiation (feedforward commands) and online corrections (feedback responses) were only generated at longer latencies. The earliest responses were directed into a nonmirrored direction, even after two training sessions. In contrast, for visual rotation learning, no dependency of directional error on reaction time emerged, and fast feedback responses to visual displacements of the cursor were immediately adapted. These results suggest that the motor system acquires a new control policy for mirror reversal, which initially requires extra processing time, while it recalibrates an existing control policy for visual rotations, exploiting established fast computational processes. Importantly, memory for visual rotation decayed between sessions, whereas memory for mirror reversals showed offline gains, leading to better performance at the beginning of the second session than in the end of the first. With shifts in time-accuracy tradeoff and offline gains, mirror-reversal learning shares common features with other skill-learning tasks. We suggest that different neuronal mechanisms underlie the recalibration of an existing versus acquisition of a new control policy and that offline gains between sessions are a characteristic of latter. Copyright © 2014 the authors 0270-6474/14/3413768-12$15.00/0.
-
Heeley, Nicholas; Kirwan, Peter; Darwish, Tamana; Arnaud, Marion; Evans, Mark L; Merkle, Florian T; Reimann, Frank; Gribble, Fiona M; Blouet, Clemence
2018-04-01
Dietary proteins are sensed by hypothalamic neurons and strongly influence multiple aspects of metabolic health, including appetite, weight gain, and adiposity. However, little is known about the mechanisms by which hypothalamic neural circuits controlling behavior and metabolism sense protein availability. The aim of this study is to characterize how neurons from the mediobasal hypothalamus respond to a signal of protein availability: the amino acid l-leucine. We used primary cultures of post-weaning murine mediobasal hypothalamic neurons, hypothalamic neurons derived from human induced pluripotent stem cells, and calcium imaging to characterize rapid neuronal responses to physiological changes in extracellular l-Leucine concentration. A neurochemically diverse subset of both mouse and human hypothalamic neurons responded rapidly to l-leucine. Consistent with l-leucine's anorexigenic role, we found that 25% of mouse MBH POMC neurons were activated by l-leucine. 10% of MBH NPY neurons were inhibited by l-leucine, and leucine rapidly reduced AGRP secretion, providing a mechanism for the rapid leucine-induced inhibition of foraging behavior in rodents. Surprisingly, none of the candidate mechanisms previously implicated in hypothalamic leucine sensing (K ATP channels, mTORC1 signaling, amino-acid decarboxylation) were involved in the acute activity changes produced by l-leucine. Instead, our data indicate that leucine-induced neuronal activation involves a plasma membrane Ca 2+ channel, whereas leucine-induced neuronal inhibition is mediated by inhibition of a store-operated Ca 2+ current. A subset of neurons in the mediobasal hypothalamus rapidly respond to physiological changes in extracellular leucine concentration. Leucine can produce both increases and decreases in neuronal Ca 2+ concentrations in a neurochemically-diverse group of neurons, including some POMC and NPY/AGRP neurons. Our data reveal that leucine can signal through novel mechanisms to rapidly
-
Novel animal model defines genetic contributions for neuron-to-neuron transfer of α-synuclein.
Tyson, Trevor; Senchuk, Megan; Cooper, Jason F; George, Sonia; Van Raamsdonk, Jeremy M; Brundin, Patrik
2017-08-08
Cell-to-cell spreading of misfolded α-synuclein (α-syn) is suggested to contribute to the progression of neuropathology in Parkinson's disease (PD). Compelling evidence supports the hypothesis that misfolded α-syn transmits from neuron-to-neuron and seeds aggregation of the protein in the recipient cells. Furthermore, α-syn frequently appears to propagate in the brains of PD patients following a stereotypic pattern consistent with progressive spreading along anatomical pathways. We have generated a C. elegans model that mirrors this progression and allows us to monitor α-syn neuron-to-neuron transmission in a live animal over its lifespan. We found that modulation of autophagy or exo/endocytosis, affects α-syn transfer. Furthermore, we demonstrate that silencing C. elegans orthologs of PD-related genes also increases the accumulation of α-syn. This novel worm model is ideal for screening molecules and genes to identify those that modulate prion-like spreading of α-syn in order to target novel strategies for disease modification in PD and other synucleinopathies.
-
Institute of Scientific and Technical Information of China (English)
Zhi-Bo Wang; Xiaoqing Zhang; Xue-Jun Li
2013-01-01
Establishing human cell models of spinal muscular atrophy (SMA) to mimic motor neuron-specific phenotypes holds the key to understanding the pathogenesis of this devastating disease.Here,we developed a closely representative cell model of SMA by knocking down the disease-determining gene,survival motor neuron (SMN),in human embryonic stem cells (hESCs).Our study with this cell model demonstrated that knocking down of SMN does not interfere with neural induction or the initial specification of spinal motor neurons.Notably,the axonal outgrowth of spinal motor neurons was significantly impaired and these disease-mimicking neurons subsequently degenerated.Furthermore,these disease phenotypes were caused by SMN-full length (SMN-FL) but not SMN-A7 (lacking exon 7)knockdown,and were specific to spinal motor neurons.Restoring the expression of SMN-FL completely ameliorated all of the disease phenotypes,including specific axonal defects and motor neuron loss.Finally,knockdown of SMNFL led to excessive mitochondrial oxidative stress in human motor neuron progenitors.The involvement of oxidative stress in the degeneration of spinal motor neurons in the SMA cell model was further confirmed by the administration of N-acetylcysteine,a potent antioxidant,which prevented disease-related apoptosis and subsequent motor neuron death.Thus,we report here the successful establishment of an hESC-based SMA model,which exhibits disease gene isoform specificity,cell type specificity,and phenotype reversibility.Our model provides a unique paradigm for studying how motor neurons specifically degenerate and highlights the potential importance of antioxidants for the treatment of SMA.
-
International Nuclear Information System (INIS)
Carlson, G.A.; Moir, R.W.
1978-01-01
We have carried out conceptual design studies of fusion reactors based on the three current mirror confinement concepts: the standard mirror, the tandem mirror, and the field-reversed mirror. Recent studies of the standard mirror have emphasized its potential as a fusion-fission hybrid reactor, designed to produce fission fuel for fission reactors. We have designed a large commercial hybrid based on standard mirror confinement, and also a small pilot plant hybrid. Tandem mirror designs include a commercial 1000 MWe fusion power plant and a nearer term tandem mirror hybrid. Field-reversed mirror designs include a multicell commercial reactor producing 75 MWe and a single cell pilot plant
-
International Nuclear Information System (INIS)
Anon.
1978-01-01
Conceptual design studies were made of fusion reactors based on the three current mirror-confinement concepts: the standard mirror, the tandem mirror, and the field-reversed mirror. Recent studies of the standard mirror have emphasized its potential as a fusion-fission hybrid reactor, designed to produce fuel for fission reactors. We have designed a large commercial hybrid and a small pilot-plant hybrid based on standard mirror confinement. Tandem mirror designs include a commercial 1000-MWe fusion power plant and a nearer term tandem mirror hybrid. Field-reversed mirror designs include a multicell commercial reactor producing 75 MWe and a single-cell pilot plant
-
International Nuclear Information System (INIS)
Plum, Eric; Zheludev, Nikolay I.
2015-01-01
Mirrors are used in telescopes, microscopes, photo cameras, lasers, satellite dishes, and everywhere else, where redirection of electromagnetic radiation is required making them arguably the most important optical component. While conventional isotropic mirrors will reflect linear polarizations without change, the handedness of circularly polarized waves is reversed upon reflection. Here, we demonstrate a type of mirror reflecting one circular polarization without changing its handedness, while absorbing the other. The polarization-preserving mirror consists of a planar metasurface with a subwavelength pattern that cannot be superimposed with its mirror image without being lifted out of its plane, and a conventional mirror spaced by a fraction of the wavelength from the metasurface. Such mirrors enable circularly polarized lasers and Fabry-Pérot cavities with enhanced tunability, gyroscopic applications, polarization-sensitive detectors of electromagnetic waves, and can be used to enhance spectroscopies of chiral media
-
Mirror agnosia and the mirrored-self misidentification delusion: a hypnotic analogue.
Connors, Michael H; Cox, Rochelle E; Barnier, Amanda J; Langdon, Robyn; Coltheart, Max
2012-05-01
Mirrored-self misidentification is the delusional belief that one's reflection in the mirror is a stranger. Current theories suggest that one pathway to the delusion is mirror agnosia (a deficit in which patients are unable to use mirror knowledge when interacting with mirrors). This study examined whether a hypnotic suggestion for mirror agnosia can recreate features of the delusion. Ten high hypnotisable participants were given either a suggestion to not understand mirrors or to see the mirror as a window. Participants were asked to look into a mirror and describe what they saw. Participants were tested on their understanding of mirrors and received a series of challenges. Participants then received a detailed postexperimental inquiry. Three of five participants given the suggestion to not understand mirrors reported seeing a stranger and maintained this belief when challenged. These participants also showed signs of mirror agnosia. No participants given the suggestion to see a window reported seeing a stranger. Results indicate that a hypnotic suggestion for mirror agnosia can be used to recreate the mirrored-self misidentification delusion. Factors influencing the effectiveness of hypnotic analogues of psychopathology, such as participants' expectations and interpretations, are discussed.
-
Assessing neurodevelopmental effects of arsenolipids in pre-differentiated human neurons.
Witt, Barbara; Ebert, Franziska; Meyer, Sören; Francesconi, Kevin A; Schwerdtle, Tanja
2017-11-01
In the general population exposure to arsenic occurs mainly via diet. Highest arsenic concentrations are found in seafood, where arsenic is present predominantly in its organic forms including arsenolipids. Since recent studies have provided evidence that arsenolipids could reach the brain of an organism and exert toxicity in fully differentiated human neurons, this work aims to assess the neurodevelopmental toxicity of arsenolipids. Neurodevelopmental effects of three arsenic-containing hydrocarbons (AsHC), two arsenic-containing fatty acids (AsFA), arsenite and dimethylarsinic acid (DMA V ) were characterized in pre-differentiated human neurons. AsHCs and arsenite caused substantial cytotoxicity in a similar, low concentration range, whereas AsFAs and DMA V were less toxic. AsHCs were highly accessible for cells and exerted pronounced neurodevelopmental effects, with neurite outgrowth and the mitochondrial membrane potential being sensitive endpoints; arsenite did not substantially decrease those two endpoints. In fully differentiated neurons, arsenite and AsHCs caused neurite toxicity. These results indicate for a neurodevelopmental potential of AsHCs. Taken into account the possibility that AsHCs might easily reach the developing brain when exposed during early life, neurotoxicity and neurodevelopmental toxicity cannot be excluded. Further studies are needed in order to progress the urgently needed risk assessment. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
-
Fried, Itzhak; Mukamel, Roy; Kreiman, Gabriel
2011-01-01
Understanding how self-initiated behavior is encoded by neuronal circuits in the human brain remains elusive. We recorded the activity of 1019 neurons while twelve subjects performed self-initiated finger movement. We report progressive neuronal recruitment over ~1500 ms before subjects report making the decision to move. We observed progressive increase or decrease in neuronal firing rate, particularly in the supplementary motor area (SMA), as the reported time of decision was approached. A population of 256 SMA neurons is sufficient to predict in single trials the impending decision to move with accuracy greater than 80% already 700 ms prior to subjects’ awareness. Furthermore, we predict, with a precision of a few hundred ms, the actual time point of this voluntary decision to move. We implement a computational model whereby volition emerges once a change in internally generated firing rate of neuronal assemblies crosses a threshold. PMID:21315264
-
Mirror profile optimization for nano-focusing KB mirror
International Nuclear Information System (INIS)
Zhang Lin; Baker, Robert; Barrett, Ray; Cloetens, Peter; Dabin, Yves
2010-01-01
A KB focusing mirror width profile has been optimized to achieve nano-focusing for the nano-imaging end-station ID22NI at the ESRF. The complete mirror and flexure bender assembly has been modeled in 3D with finite element analysis using ANSYS. Bender stiffness, anticlastic effects and geometrical non-linear effects have been considered. Various points have been studied: anisotropy and crystal orientation, stress in the mirror and bender, actuator resolution and the mirror-bender adhesive bonding... Extremely high performance of the mirror is expected with residual slope error smaller than 0.6 μrad, peak-to-valley, compared to the bent slope of 3000 μrad.
-
Sato, Yuma; Watanabe, Shumpei; Fukuda, Yoshinari; Hashiguchi, Takao; Yanagi, Yusuke; Ohno, Shinji
2018-03-15
Measles virus (MV) usually causes acute infection but in rare cases persists in the brain, resulting in subacute sclerosing panencephalitis (SSPE). Since human neurons, an important target affected in the disease, do not express the known MV receptors (signaling lymphocyte activation molecule [SLAM] and nectin 4), how MV infects neurons and spreads between them is unknown. Recent studies have shown that many virus strains isolated from SSPE patients possess substitutions in the extracellular domain of the fusion (F) protein which confer enhanced fusion activity. Hyperfusogenic viruses with such mutations, unlike the wild-type MV, can induce cell-cell fusion even in SLAM- and nectin 4-negative cells and spread efficiently in human primary neurons and the brains of animal models. We show here that a hyperfusogenic mutant MV, IC323-F(T461I)-EGFP (IC323 with a fusion-enhancing T461I substitution in the F protein and expressing enhanced green fluorescent protein), but not the wild-type MV, spreads in differentiated NT2 cells, a widely used human neuron model. Confocal time-lapse imaging revealed the cell-to-cell spread of IC323-F(T461I)-EGFP between NT2 neurons without syncytium formation. The production of virus particles was strongly suppressed in NT2 neurons, also supporting cell-to-cell viral transmission. The spread of IC323-F(T461I)-EGFP was inhibited by a fusion inhibitor peptide as well as by some but not all of the anti-hemagglutinin antibodies which neutralize SLAM- or nectin-4-dependent MV infection, suggesting the presence of a distinct neuronal receptor. Our results indicate that MV spreads in a cell-to-cell manner between human neurons without causing syncytium formation and that the spread is dependent on the hyperfusogenic F protein, the hemagglutinin, and the putative neuronal receptor for MV. IMPORTANCE Measles virus (MV), in rare cases, persists in the human central nervous system (CNS) and causes subacute sclerosing panencephalitis (SSPE) several
-
Rubio, Alicia; Luoni, Mirko; Giannelli, Serena G; Radice, Isabella; Iannielli, Angelo; Cancellieri, Cinzia; Di Berardino, Claudia; Regalia, Giulia; Lazzari, Giovanna; Menegon, Andrea; Taverna, Stefano; Broccoli, Vania
2016-11-18
The CRISPR/Cas9 system is a rapid and customizable tool for gene editing in mammalian cells. In particular, this approach has widely opened new opportunities for genetic studies in neurological disease. Human neurons can be differentiated in vitro from hPSC (human Pluripotent Stem Cells), hNPCs (human Neural Precursor Cells) or even directly reprogrammed from fibroblasts. Here, we described a new platform which enables, rapid and efficient CRISPR/Cas9-mediated genome targeting simultaneously with three different paradigms for in vitro generation of neurons. This system was employed to inactivate two genes associated with neurological disorder (TSC2 and KCNQ2) and achieved up to 85% efficiency of gene targeting in the differentiated cells. In particular, we devised a protocol that, combining the expression of the CRISPR components with neurogenic factors, generated functional human neurons highly enriched for the desired genome modification in only 5 weeks. This new approach is easy, fast and that does not require the generation of stable isogenic clones, practice that is time consuming and for some genes not feasible.
-
Cannabidiol Activates Neuronal Precursor Genes in Human Gingival Mesenchymal Stromal Cells.
Soundara Rajan, Thangavelu; Giacoppo, Sabrina; Scionti, Domenico; Diomede, Francesca; Grassi, Gianpaolo; Pollastro, Federica; Piattelli, Adriano; Bramanti, Placido; Mazzon, Emanuela; Trubiani, Oriana
2017-06-01
In the last years, mesenchymal stromal cells (MSCs) from oral tissues have received considerable interest in regenerative medicine since they can be obtained with minimal invasive procedure and exhibit immunomodulatory properties. This study was aimed to investigate whether in vitro pre-treatment of MSCs obtained from human gingiva (hGMSCs) with Cannabidiol (CBD), a cannabinoid component produced by the plant Cannabis sativa, may promote human gingiva derived MSCs to differentiate toward neuronal precursor cells. Specifically, we have treated the hGMSCs with CBD (5 µM) for 24 h in order to evaluate the expression of genes involved in cannabidiol signaling, cell proliferation, self-renewal and multipotency, and neural progenitor cells differentiation. Next generation sequencing (NGS) demonstrated that CBD activates genes associated with G protein coupled receptor signaling in hGMSCs. Genes involved in DNA replication, cell cycle, proliferation, and apoptosis were regulated. Moreover, genes associated with the biological process of neuronal progenitor cells (NCPs) proliferation, neuron differentiation, neurogenesis, and nervous system development were significantly modulated. From our results, we hypothesize that human gingiva-derived MSCs conditioned with CBD could represent a valid method for improving the hGMSCs phenotype and thus might be a potential therapeutic tool in the treatment of neurodegenerative diseases. J. Cell. Biochem. 118: 1531-1546, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
-
Behmer, Lawrence P; Fournier, Lisa R
2016-11-01
Questions regarding the malleability of the mirror neuron system (MNS) continue to be debated. MNS activation has been reported when people observe another person performing biological goal-directed behaviors, such as grasping a cup. These findings support the importance of mapping goal-directed biological behavior onto one's motor repertoire as a means of understanding the actions of others. Still, other evidence supports the Associative Sequence Learning (ASL) model which predicts that the MNS responds to a variety of stimuli after sensorimotor learning, not simply biological behavior. MNS activity develops as a consequence of developing stimulus-response associations between a stimulus and its motor outcome. Findings from the ideomotor literature indicate that stimuli that are more ideomotor compatible with a response are accompanied by an increase in response activation compared to less compatible stimuli; however, non-compatible stimuli robustly activate a constituent response after sensorimotor learning. Here, we measured changes in the mu-rhythm, an EEG marker thought to index MNS activity, predicting that stimuli that differ along dimensions of ideomotor compatibility should show changes in mirror neuron activation as participants learn the respective stimulus-response associations. We observed robust mu-suppression for ideomotor-compatible hand actions and partially compatible dot animations prior to learning; however, compatible stimuli showed greater mu-suppression than partially or non-compatible stimuli after explicit learning. Additionally, non-compatible abstract stimuli exceeded baseline only after participants explicitly learned the motor responses associated with the stimuli. We conclude that the empirical differences between the biological and ASL accounts of the MNS can be explained by Ideomotor Theory. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
-
Bacigaluppi, Susanna; Donzelli, Elisabetta; De Cristofaro, Valentina; Bragazzi, Nicola Luigi; D'Amico, Giovanna; Scuteri, Arianna; Tredici, Giovanni
2016-09-19
Cerebral ischemia is characterized by both acute and delayed neuronal injuries. Neuro-protection is a major issue that should be properly addressed from a pharmacological point of view, and cell-based treatment approaches are of interest due to their potential pleiotropic effects. Endothelial progenitor cells have the advantage of being mobilized from the bone marrow into the circulation, but have been less studied than other stem cells, such as mesenchymal stem cells. Therefore, the comparison between human endothelial progenitor cells (hEPC) and human mesenchymal progenitor cells (hMSC) in terms of efficacy in rescuing neurons from cell death after transitory ischemia is the aim of the current study, in the effort to address further directions. In vitro model of oxygen-glucose deprivation (OGD) on a primary culture of rodent cortical neurons was set up with different durations of exposure: 1, 2 and 3hrs with assessment of neuron survival. The 2hrs OGD was chosen for the subsequent experiments. After 2hrs OGD neurons were either placed in indirect co-culture with hMSC or hEPC or cultured in hMSC or hEPC conditioned medium and cell viability was evaluated by MTT assay. At day 2 after 2hrs OGD exposure, mean neuronal survival was 47.9±24.2%. In contrast, after treatment with hEPC and hMSC indirect co-culture was 74.1±27.3%; and 69.4±18.8%, respectively. In contrast, treatment with conditioned medium did not provide any advantage in terms of survival to OGD neurons The study shows the efficacy of hEPC in indirect co-culture to rescue neurons from cell death after OGD, comparable to that of hMSC. hEPC deserve further studies given their potential interest for ischemia. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
-
Do-Young, Kim; Fenoglio, Kristina A.; Kerrigan, John F.; Rho, Jong M.
2009-01-01
SUMMARY The role of bicarbonate (HCO3-) in GABAA receptor-mediated depolarization of human hypothalamic hamartoma (HH) neurons was investigated using cellular electrophysiological and calcium imaging techniques. Activation of GABAA receptors with muscimol (30 μM) provoked neuronal excitation in over 70% of large (18-22 μM) HH neurons in HCO3- buffer. Subsequent perfusion of HCO3--free HEPES buffer produced partial suppression of muscimol-induced excitation. Additionally, 53% of large HH neurons under HCO3--free conditions exhibited reduced intracellular calcium accumulation by muscimol. These results suggest that HCO3- efflux through GABAA receptors on a subpopulation of large HH neurons may contribute to membrane depolarization and subsequent activation of L-type calcium channels. PMID:19022626
-
Gurwitz, David
2016-09-01
The development and clinical implementation of personalized medicine crucially depends on the availability of high-quality human biosamples; animal models, although capable of modeling complex human diseases, cannot reflect the large variation in the human genome, epigenome, transcriptome, proteome, and metabolome. Although the biosamples available from public biobanks that store human tissues and cells may represent the large human diversity for most diseases, these samples are not always sufficient for developing biomarkers for patient-tailored therapies for neuropsychiatric disorders. Postmortem human tissues are available from many biobanks; nevertheless, collections of neuronal human cells from large patient cohorts representing the human diversity remain scarce. Two tools are gaining popularity for personalized medicine research on neuropsychiatric disorders: human induced pluripotent stem cell-derived neurons and human lymphoblastoid cell lines. This review examines and contrasts the advantages and limitations of each tool for personalized medicine research.
-
Exclusive neuronal expression of SUCLA2 in the human brain
DEFF Research Database (Denmark)
Dobolyi, Arpád; Ostergaard, Elsebet; Bagó, Attila G
2015-01-01
associated with SUCLA2 mutations, the precise localization of SUCLA2 protein has never been investigated. Here, we show that immunoreactivity of A-SUCL-β in surgical human cortical tissue samples was present exclusively in neurons, identified by their morphology and visualized by double labeling...... was absent in glial cells, identified by antibodies directed against the glial markers GFAP and S100. Furthermore, in situ hybridization histochemistry demonstrated that SUCLA2 mRNA was present in Nissl-labeled neurons but not glial cells labeled with S100. Immunoreactivity of the GTP-forming β subunit (G......-SUCL-β) encoded by SUCLG2, or in situ hybridization histochemistry for SUCLG2 mRNA could not be demonstrated in either neurons or astrocytes. Western blotting of post mortem brain samples revealed minor G-SUCL-β immunoreactivity that was, however, not upregulated in samples obtained from diabetic versus non...
-
Mirror representations innate versus determined by experience: a viewpoint from learning theory.
Giese, Martin A
2014-04-01
From the viewpoint of pattern recognition and computational learning, mirror neurons form an interesting multimodal representation that links action perception and planning. While it seems unlikely that all details of such representations are specified by the genetic code, robust learning of such complex representations likely requires an appropriate interplay between plasticity, generalization, and anatomical constraints of the underlying neural architecture.
-
Directory of Open Access Journals (Sweden)
M. Catarina Silva
2016-09-01
Full Text Available Frontotemporal dementia (FTD and other tauopathies characterized by focal brain neurodegeneration and pathological accumulation of proteins are commonly associated with tau mutations. However, the mechanism of neuronal loss is not fully understood. To identify molecular events associated with tauopathy, we studied induced pluripotent stem cell (iPSC-derived neurons from individuals carrying the tau-A152T variant. We highlight the potential of in-depth phenotyping of human neuronal cell models for pre-clinical studies and identification of modulators of endogenous tau toxicity. Through a panel of biochemical and cellular assays, A152T neurons showed accumulation, redistribution, and decreased solubility of tau. Upregulation of tau was coupled to enhanced stress-inducible markers and cell vulnerability to proteotoxic, excitotoxic, and mitochondrial stressors, which was rescued upon CRISPR/Cas9-mediated targeting of tau or by pharmacological activation of autophagy. Our findings unmask tau-mediated perturbations of specific pathways associated with neuronal vulnerability, revealing potential early disease biomarkers and therapeutic targets for FTD and other tauopathies.
-
Activity of vasopressinergic neurones of the human supraoptic nucleus is age- and sex-dependent
Ishunina, T. A.; Salehi, A.; Hofman, M. A.; Swaab, D. F.
1999-01-01
In the human hypothalamus, arginine-vasopressin (AVP) is produced for a major part by the neurones of the supraoptic nucleus (SON). Since plasma AVP levels in men were reported to be higher than those of women and we did not find a sex difference in the neurone number, a higher vasopressinergic
-
The mirror mechanism in the parietal lobe.
Rizzolatti, Giacomo; Rozzi, Stefano
2018-01-01
The mirror mechanism is a basic mechanism that transforms sensory representations of others' actions into motor representations of the same actions in the brain of the observer. The mirror mechanism plays an important role in understanding actions of others. In the present chapter we discuss first the basic organization of the posterior parietal lobe in the monkey, stressing that it is best characterized as a motor scaffold, on the top of which sensory information is organized. We then describe the location of the mirror mechanism in the posterior parietal cortex of the monkey, and its functional role in areas PFG, and anterior, ventral, and lateral intraparietal areas. We will then present evidence that a similar functional organization is present in humans. We will conclude by discussing the role of the mirror mechanism in the recognition of action performed with tools. Copyright © 2018 Elsevier B.V. All rights reserved.
-
Neuronal Fibers and Neurotransmitter Receptor Expression in the Human Endolymphatic Sac
DEFF Research Database (Denmark)
Møller, Martin Nue; Kirkeby, Svend; Vikeså, Jonas
2017-01-01
in intracranial pressure homeostasis. The anatomical location towards the sigmoid sinus would suggest a possible endo- and/or paracrine signaling. However, neuronal connections may also apply, but it remains very scarcely explored in the human ES. STUDY DESIGN: DNA micro-arrays and immunohistochemistry were used...... of genes specific for neuronal signaling was determined and results for selected key molecules verified by immunohistochemistry. Transmission electron microscopy was used for ultrastructural analysis. RESULTS: For the transmission electron microscopy analysis, a direct innervation of the ES was observed...... with unmyelinated fibers imbedded in the ES epithelial lining. The microarrays confirmed, that several molecules involved in neuronal signaling were found expressed significantly in the ES DNA profile, such as the Cholecystokinin peptide and related receptors, Dopamine receptors 2 and 5, vesicular monoamine...
-
Directory of Open Access Journals (Sweden)
Tim D Aumann
Full Text Available Recent evidence indicates the number of dopaminergic neurons in the adult rodent hypothalamus and midbrain is regulated by environmental cues, including photoperiod, and that this occurs via up- or down-regulation of expression of genes and proteins that are important for dopamine (DA synthesis in extant neurons ('DA neurotransmitter switching'. If the same occurs in humans, it may have implications for neurological symptoms associated with DA imbalances. Here we tested whether there are differences in the number of tyrosine hydroxylase (TH, the rate-limiting enzyme in DA synthesis and DA transporter (DAT immunoreactive neurons in the midbrain of people who died in summer (long-day photoperiod, n = 5 versus winter (short-day photoperiod, n = 5. TH and DAT immunoreactivity in neurons and their processes was qualitatively higher in summer compared with winter. The density of TH immunopositive (TH+ neurons was significantly (~6-fold higher whereas the density of TH immunonegative (TH- neurons was significantly (~2.5-fold lower in summer compared with winter. The density of total neurons (TH+ and TH- combined was not different. The density of DAT+ neurons was ~2-fold higher whereas the density of DAT- neurons was ~2-fold lower in summer compared with winter, although these differences were not statistically significant. In contrast, midbrain nuclear volume, the density of supposed glia (small TH- cells, and the amount of TUNEL staining were the same in summer compared with winter. This study provides the first evidence of an association between environmental stimuli (photoperiod and the number of midbrain DA neurons in humans, and suggests DA neurotransmitter switching underlies this association.
-
Magnetic Resonance Microscopy of Human and Porcine Neurons and Cellular Processes
Flint, Jeremy J.; Hansen, Brian; Portnoy, Sharon; Lee, Choong-Heon; King, Michael A.; Fey, Michael; Vincent, Franck; Stanisz, Greg J; Vestergaard-Poulsen, Peter; Blackband, Stephen J
2012-01-01
With its unparalleled ability to safely generate high-contrast images of soft tissues, magnetic resonance imaging (MRI) has remained at the forefront of diagnostic clinical medicine. Unfortunately due to resolution limitations, clinical scans are most useful for detecting macroscopic structural changes associated with a small number of pathologies. Moreover, due to a longstanding inability to directly observe magnetic resonance (MR) signal behavior at the cellular level, such information is poorly characterized and generally must be inferred. With the advent of the MR microscope in 1986 came the ability to measure MR signal properties of theretofore unobservable tissue structures. Recently, further improvements in hardware technology have made possible the ability to visualize mammalian cellular structure. In the current study, we expand upon previous work by imaging the neuronal cell bodies and processes of human and porcine α-motor neurons. Complimentary imaging studies are conducted in pig tissue in order to demonstrate qualitative similarities to human samples. Also, apparent diffusion coefficient (ADC) maps were generated inside porcine α-motor neuron cell bodies and portions of their largest processes (mean = 1.7±0.5 μm2/ms based on 53 pixels) as well as in areas containing a mixture of extracellular space, microvasculature, and neuropil (0.59±0.37 μm2/ms based on 33 pixels). Three-dimensional reconstruction of MR images containing α-motor neurons shows the spatial arrangement of neuronal projections between adjacent cells. Such advancements in imaging portend the ability to construct accurate models of MR signal behavior based on direct observation and measurement of the components which comprise functional tissues. These tools would not only be useful for improving our interpretation of macroscopic MRI performed in the clinic, but they could potentially be used to develop new methods of differential diagnosis to aid in the early detection of a
-
Rana computatrix to human language: towards a computational neuroethology of language evolution.
Arbib, Michael A
2003-10-15
Walter's Machina speculatrix inspired the name Rana computatrix for a family of models of visuomotor coordination in the frog, which contributed to the development of computational neuroethology. We offer here an 'evolutionary' perspective on models in the same tradition for rat, monkey and human. For rat, we show how the frog-like taxon affordance model provides a basis for the spatial navigation mechanisms that involve the hippocampus and other brain regions. For monkey, we recall two models of neural mechanisms for visuomotor coordination. The first, for saccades, shows how interactions between the parietal and frontal cortex augment superior colliculus seen as the homologue of frog tectum. The second, for grasping, continues the theme of parieto-frontal interactions, linking parietal affordances to motor schemas in premotor cortex. It further emphasizes the mirror system for grasping, in which neurons are active both when the monkey executes a specific grasp and when it observes a similar grasp executed by others. The model of human-brain mechanisms is based on the mirror-system hypothesis of the evolution of the language-ready brain, which sees the human Broca's area as an evolved extension of the mirror system for grasping.
-
Tong, Zhi-Bin; Hogberg, Helena; Kuo, David; Sakamuru, Srilatha; Xia, Menghang; Smirnova, Lena; Hartung, Thomas; Gerhold, David
2017-02-01
More than 75 000 man-made chemicals contaminate the environment; many of these have not been tested for toxicities. These chemicals demand quantitative high-throughput screening assays to assess them for causative roles in neurotoxicities, including Parkinson's disease and other neurodegenerative disorders. To facilitate high throughput screening for cytotoxicity to neurons, three human neuronal cellular models were compared: SH-SY5Y neuroblastoma cells, LUHMES conditionally-immortalized dopaminergic neurons, and Neural Stem Cells (NSC) derived from human fetal brain. These three cell lines were evaluated for rapidity and degree of differentiation, and sensitivity to 32 known or candidate neurotoxicants. First, expression of neural differentiation genes was assayed during a 7-day differentiation period. Of the three cell lines, LUHMES showed the highest gene expression of neuronal markers after differentiation. Both in the undifferentiated state and after 7 days of neuronal differentiation, LUHMES cells exhibited greater cytotoxic sensitivity to most of 32 suspected or known neurotoxicants than SH-SY5Y or NSCs. LUHMES cells were also unique in being more susceptible to several compounds in the differentiating state than in the undifferentiated state; including known neurotoxicants colchicine, methyl-mercury (II), and vincristine. Gene expression results suggest that differentiating LUHMES cells may be susceptible to apoptosis because they express low levels of anti-apoptotic genes BCL2 and BIRC5/survivin, whereas SH-SY5Y cells may be resistant to apoptosis because they express high levels of BCL2, BIRC5/survivin, and BIRC3 genes. Thus, LUHMES cells exhibited favorable characteristics for neuro-cytotoxicity screening: rapid differentiation into neurons that exhibit high level expression neuronal marker genes, and marked sensitivity of LUHMES cells to known neurotoxicants. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.
-
High-resolution adaptive optics scanning laser ophthalmoscope with multiple deformable mirrors
Chen, Diana C.; Olivier, Scot S.; Jones; Steven M.
2010-02-23
An adaptive optics scanning laser ophthalmoscopes is introduced to produce non-invasive views of the human retina. The use of dual deformable mirrors improved the dynamic range for correction of the wavefront aberrations compared with the use of the MEMS mirror alone, and improved the quality of the wavefront correction compared with the use of the bimorph mirror alone. The large-stroke bimorph deformable mirror improved the capability for axial sectioning with the confocal imaging system by providing an easier way to move the focus axially through different layers of the retina.
-
Directory of Open Access Journals (Sweden)
Anna Chatzidaki
Full Text Available Neurons derived from human induced pluripotent stem cells (iPSCs represent a potentially valuable tool for the characterisation of neuronal receptors and ion channels. Previous studies on iPSC-derived neuronal cells have reported the functional characterisation of a variety of receptors and ion channels, including glutamate receptors, γ-aminobutyric acid (GABA receptors and several voltage-gated ion channels. In the present study we have examined the expression and functional properties of nicotinic acetylcholine receptors (nAChRs in human iPSC-derived neurons. Gene expression analysis indicated the presence of transcripts encoding several nAChR subunits, with highest levels detected for α3-α7, β1, β2 and β4 subunits (encoded by CHRNA3-CHRNA7, CHRNB1, CHRNB2 and CHRNB4 genes. In addition, similarly high transcript levels were detected for the truncated dupα7 subunit transcript, encoded by the partially duplicated gene CHRFAM7A, which has been associated with psychiatric disorders such as schizophrenia. The functional properties of these nAChRs have been examined by calcium fluorescence and by patch-clamp recordings. The data obtained suggest that the majority of functional nAChRs expressed in these cells have pharmacological properties typical of α7 receptors. Large responses were induced by a selective α7 agonist (compound B, in the presence of the α7-selective positive allosteric modulator (PAM PNU-120596, which were blocked by the α7-selective antagonist methyllycaconitine (MLA. In addition, a small proportion of the neurons express nAChRs with properties typical of heteromeric (non-α7 containing nAChR subtypes. These cells therefore represent a great tool to advance our understanding of the properties of native human nAChRs, α7 in particular.
-
Neuronal human BACE1 knockin induces systemic diabetes in mice.
Plucińska, Kaja; Dekeryte, Ruta; Koss, David; Shearer, Kirsty; Mody, Nimesh; Whitfield, Phillip D; Doherty, Mary K; Mingarelli, Marco; Welch, Andy; Riedel, Gernot; Delibegovic, Mirela; Platt, Bettina
2016-07-01
β-Secretase 1 (BACE1) is a key enzyme in Alzheimer's disease pathogenesis that catalyses the amyloidogenic cleavage of amyloid precursor protein (APP). Recently, global Bace1 deletion was shown to protect against diet-induced obesity and diabetes, suggesting that BACE1 is a potential regulator of glucose homeostasis. Here, we investigated whether increased neuronal BACE1 is sufficient to alter systemic glucose metabolism, using a neuron-specific human BACE1 knockin mouse model (PLB4). Glucose homeostasis and adiposity were determined by glucose tolerance tests and EchoMRI, lipid species were measured by quantitative lipidomics, and biochemical and molecular alterations were assessed by western blotting, quantitative PCR and ELISAs. Glucose uptake in the brain and upper body was measured via (18)FDG-PET imaging. Physiological and molecular analyses demonstrated that centrally expressed human BACE1 induced systemic glucose intolerance in mice from 4 months of age onward, alongside a fatty liver phenotype and impaired hepatic glycogen storage. This diabetic phenotype was associated with hypothalamic pathology, i.e. deregulation of the melanocortin system, and advanced endoplasmic reticulum (ER) stress indicated by elevated central C/EBP homologous protein (CHOP) signalling and hyperphosphorylation of its regulator eukaryotic translation initiation factor 2α (eIF2α). In vivo (18)FDG-PET imaging further confirmed brain glucose hypometabolism in these mice; this corresponded with altered neuronal insulin-related signalling, enhanced protein tyrosine phosphatase 1B (PTP1B) and retinol-binding protein 4 (RBP4) levels, along with upregulation of the ribosomal protein and lipid translation machinery. Increased forebrain and plasma lipid accumulation (i.e. ceramides, triacylglycerols, phospholipids) was identified via lipidomics analysis. Our data reveal that neuronal BACE1 is a key regulator of metabolic homeostasis and provide a potential mechanism for the high
-
Topological mirror superconductivity.
Zhang, Fan; Kane, C L; Mele, E J
2013-08-02
We demonstrate the existence of topological superconductors (SCs) protected by mirror and time-reversal symmetries. D-dimensional (D=1, 2, 3) crystalline SCs are characterized by 2(D-1) independent integer topological invariants, which take the form of mirror Berry phases. These invariants determine the distribution of Majorana modes on a mirror symmetric boundary. The parity of total mirror Berry phase is the Z(2) index of a class DIII SC, implying that a DIII topological SC with a mirror line must also be a topological mirror SC but not vice versa and that a DIII SC with a mirror plane is always time-reversal trivial but can be mirror topological. We introduce representative models and suggest experimental signatures in feasible systems. Advances in quantum computing, the case for nodal SCs, the case for class D, and topological SCs protected by rotational symmetries are pointed out.
-
Directory of Open Access Journals (Sweden)
Yves De Maeseneer
2016-07-01
Full Text Available In this article we present a theological-anthropological exploration, interpreting the figure of the angel as a mirror of our human condition. The point of departure is an analysis of Hans Urs von Balthasar’s approach to two major sources of our imagination of the angel: Bonaventure (1221−1274 and Maria Rainer Rilke (1875−1926. A comparison of his accounts of the Franciscan theologian and the Modern poet, respectively, reveals remarkable parallels in discourse, clustered around the tensions between vulnerability and openness, immanence and transcendence, and love and loss. Both Rilke and Bonaventure reject the classical angel figure as a human ideal, as it cannot integrate the paradoxes of human existence. Their alternative visions of what it means to be human, have many terms in common: heart, vulnerability, mortality, openness, abyss, suspension, transparency, receptivity, descent (kenosis, humility, poverty, etc. However, their meaning is different because Rilke does not recognize an absolute transcendence as the source of love and the vis-a-vis of the human. This immanentism leaves him no other option than the vain attempt to exorcize the angel figure altogether, while Bonaventure’s vision preserves the angel as an anthropological mirror, albeit an angel radically transfigured by God’s wounded love.
-
Do 'literate' pigeons (Columba livia) show mirror-word generalization?
Scarf, Damian; Corballis, Michael C; Güntürkün, Onur; Colombo, Michael
2017-09-01
Many children pass through a mirror stage in reading, where they write individual letters or digits in mirror and find it difficult to correctly utilize letters that are mirror images of one another (e.g., b and d). This phenomenon is thought to reflect the fact that the brain does not naturally discriminate left from right. Indeed, it has been argued that reading acquisition involves the inhibition of this default process. In the current study, we tested the ability of literate pigeons, which had learned to discriminate between 30 and 62 words from 7832 nonwords, to discriminate between words and their mirror counterparts. Subjects were sensitive to the left-right orientation of the individual letters, but not the order of letters within a word. This finding may reflect the fact that, in the absence of human-unique top-down processes, the inhibition of mirror generalization may be limited.
-
Singh, Sanjay; Sayers, Scott; Walter, James S; Thomas, Donald; Dieter, Robert S; Nee, Lisa M; Wurster, Robert D
2013-08-19
Autonomic imbalances including parasympathetic withdrawal and sympathetic overactivity are cardinal features of heart failure regardless of etiology; however, mechanisms underlying these imbalances remain unknown. Animal model studies of heart and visceral organ hypertrophy predict that nerve growth factor levels should be elevated in heart failure; whether this is so in human heart failure, though, remains unclear. We tested the hypotheses that neurons in cardiac ganglia are hypertrophied in human, canine, and rat heart failure and that nerve growth factor, which we hypothesize is elevated in the failing heart, contributes to this neuronal hypertrophy. Somal morphology of neurons from human (579.54±14.34 versus 327.45±9.17 μm(2); Phearts (767.80±18.37 versus 650.23±9.84 μm(2); Pneurons from spontaneously hypertensive rat hearts (327.98±3.15 versus 271.29±2.79 μm(2); Pneurons in cardiac ganglia compared with controls. Western blot analysis shows that nerve growth factor levels in the explanted, failing human heart are 250% greater than levels in healthy donor hearts. Neurons from cardiac ganglia cultured with nerve growth factor are significantly larger and have greater dendritic arborization than neurons in control cultures. Hypertrophied neurons are significantly less excitable than smaller ones; thus, hypertrophy of vagal postganglionic neurons in cardiac ganglia would help to explain the parasympathetic withdrawal that accompanies heart failure. Furthermore, our observations suggest that nerve growth factor, which is elevated in the failing human heart, causes hypertrophy of neurons in cardiac ganglia.
-
Neuronal NOS localises to human airway cilia.
Jackson, Claire L; Lucas, Jane S; Walker, Woolf T; Owen, Holly; Premadeva, Irnthu; Lackie, Peter M
2015-01-30
Airway NO synthase (NOS) isoenzymes are responsible for rapid and localised nitric oxide (NO) production and are expressed in airway epithelium. We sought to determine the localisation of neuronal NOS (nNOS) in airway epithelium due to the paucity of evidence. Sections of healthy human bronchial tissue in glycol methacrylate resin and human nasal polyps in paraffin wax were immunohistochemically labelled and reproducibly demonstrated nNOS immunoreactivity, particularly at the proximal portion of cilia; this immunoreactivity was blocked by a specific nNOS peptide fragment. Healthy human epithelial cells differentiated at an air-liquid interface (ALI) confirmed the presence of all three NOS isoenzymes by immunofluorescence labelling. Only nNOS immunoreactivity was specific to the ciliary axonemeand co-localised with the cilia marker β-tubulin in the proximal part of the ciliary axoneme. We report a novel localisation of nNOS at the proximal portion of cilia in airway epithelium and conclude that its independent and local regulation of NO levels is crucial for normal cilia function. Copyright © 2014 Elsevier Inc. All rights reserved.
-
Enticott, Peter G; Kennedy, Hayley A; Rinehart, Nicole J; Bradshaw, John L; Tonge, Bruce J; Daskalakis, Zafiris J; Fitzgerald, Paul B
2013-01-01
The mirror neuron hypothesis of autism is highly controversial, in part because there are conflicting reports as to whether putative indices of mirror system activity are actually deficient in autism spectrum disorder (ASD). Recent evidence suggests that a typical putative mirror system response may be seen in people with an ASD when there is a degree of social relevance to the visual stimuli used to elicit that response. Individuals with ASD (n = 32) and matched neurotypical controls (n = 32) completed a transcranial magnetic stimulation (TMS) experiment in which the left primary motor cortex (M1) was stimulated during the observation of static hands, individual (i.e., one person) hand actions, and interactive (i.e., two person) hand actions. Motor-evoked potentials (MEP) were recorded from the contralateral first dorsal interosseous, and used to generate an index of interpersonal motor resonance (IMR; a putative measure of mirror system activity) during action observation. There was no difference between ASD and NT groups in the level of IMR during the observation of these actions. These findings provide evidence against a global mirror system deficit in ASD, and this evidence appears to extend beyond stimuli that have social relevance. Attentional and visual processing influences may be important for understanding the apparent role of IMR in the pathophysiology of ASD.
-
Directed differentiation of basal forebrain cholinergic neurons from human pluripotent stem cells.
Hu, Yao; Qu, Zhuang-Yin; Cao, Shi-Ying; Li, Qi; Ma, Lixiang; Krencik, Robert; Xu, Min; Liu, Yan
2016-06-15
Basal forebrain cholinergic neurons (BFCNs) play critical roles in learning, memory and cognition. Dysfunction or degeneration of BFCNs may connect to neuropathology, such as Alzheimer's disease, Down's syndrome and dementia. Generation of functional BFCNs may contribute to the studies of cell-based therapy and pathogenesis that is related to learning and memory deficits. Here we describe a detail method for robust generation of BFCNs from human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs). In this method, BFCN progenitors are patterned from hESC or hiPSC-derived primitive neuroepithelial cells, with the treatment of sonic hedgehog (SHH) or combination with its agonist Purmorphamine, and by co-culturing with human astrocytes. At day 20, ∼90% hPSC-derived progenitors expressed NKX2.1, which is a transcriptional marker for MGE. Moreover, around 40% of NKX2.1+ cells co-expressed OLIG2 and ∼15% of NKX2.1+ cells co-expressed ISLET1, which are ventral markers. At day 35, ∼40% neurons robustly express ChAT, most of which are co-labeled with NKX2.1, ISLET1 and FOXG1, indicating the basal forebrain-like identity. At day 45, these neurons express mature neuronal markers MAP2, Synapsin, and VAChT. In this method, undefined conditions including genetic modification or cell-sorting are avoided. As a choice, feeder free conditions are used to avoid ingredients of animal origin. Moreover, Purmorphamine can be substituted for SHH to induce ventral progenitors effectively and economically. We provide an efficient method to generate BFCNs from multiple hPSC lines, which offers the potential application for disease modeling and pharmacological studies. Copyright © 2016 Elsevier B.V. All rights reserved.
-
Gjurchinovski, Aleksandar; Skeparovski, Aleksandar
2008-01-01
Reflection of light from a plane mirror in uniform rectilinear motion is a century-old problem, intimately related to the foundations of special relativity. The problem was first investigated by Einstein in his famous 1905 paper by using the Lorentz transformations to switch from the mirror's rest frame to the frame where the mirror moves at a…
-
Functional Maturation of Human Stem Cell-Derived Neurons in Long-Term Cultures.
Directory of Open Access Journals (Sweden)
Rebecca S Lam
Full Text Available Differentiated neurons can be rapidly acquired, within days, by inducing stem cells to express neurogenic transcription factors. We developed a protocol to maintain long-term cultures of human neurons, called iNGNs, which are obtained by inducing Neurogenin-1 and Neurogenin-2 expression in induced pluripotent stem cells. We followed the functional development of iNGNs over months and they showed many hallmark properties for neuronal maturation, including robust electrical and synaptic activity. Using iNGNs expressing a variant of channelrhodopsin-2, called CatCh, we could control iNGN activity with blue light stimulation. In combination with optogenetic tools, iNGNs offer opportunities for studies that require precise spatial and temporal resolution. iNGNs developed spontaneous network activity, and these networks had excitatory glutamatergic synapses, which we characterized with single-cell synaptic recordings. AMPA glutamatergic receptor activity was especially dominant in postsynaptic recordings, whereas NMDA glutamatergic receptor activity was absent from postsynaptic recordings but present in extrasynaptic recordings. Our results on long-term cultures of iNGNs could help in future studies elucidating mechanisms of human synaptogenesis and neurotransmission, along with the ability to scale-up the size of the cultures.
-
Culture, the Crack'd Mirror, and the Neuroethics of Disease.
Gillett, Grant
2016-10-01
Human beings are sensorimotor coupled to the actual world and also attuned to the symbolic world of culture and the techniques of adaptation that culture provides. The self-image and self-shaping mediated by that mirror directly affects the neurocognitive structures that integrate human neural activity and reshape its processing capacities through top-down or autopoietic effects. Thus a crack'd mirror, which disrupts the processes of enactive self-configuration, can be disabling for an individual. That is exactly what happens in postcolonial or immigration contexts in which individuals' cultural adaptations are marginalized and disconnected in diverse and often painful and disorienting ways. The crack'd mirror is therefore a powerful trope for neuroethics and helps us understand the social and moral pathologies of many indigenous and immigrant communities.
-
Directory of Open Access Journals (Sweden)
Dustin R. Wakeman
2017-07-01
Full Text Available A major challenge for clinical application of pluripotent stem cell therapy for Parkinson's disease (PD is large-scale manufacturing and cryopreservation of neurons that can be efficiently prepared with minimal manipulation. To address this obstacle, midbrain dopamine neurons were derived from human induced pluripotent stem cells (iPSC-mDA and cryopreserved in large production lots for biochemical and transplantation studies. Cryopreserved, post-mitotic iPSC-mDA neurons retained high viability with gene, protein, and electrophysiological signatures consistent with midbrain floor-plate lineage. To test therapeutic efficacy, cryopreserved iPSC-mDA neurons were transplanted without subculturing into the 6-OHDA-lesioned rat and MPTP-lesioned non-human-primate models of PD. Grafted neurons retained midbrain lineage with extensive fiber innervation in both rodents and monkeys. Behavioral assessment in 6-OHDA-lesioned rats demonstrated significant reversal in functional deficits up to 6 months post transplantation with reinnervation of the host striatum and no aberrant growth, supporting the translational development of pluripotent cell-based therapies in PD.
-
Young, Gareth T; Gutteridge, Alex; Fox, Heather DE; Wilbrey, Anna L; Cao, Lishuang; Cho, Lily T; Brown, Adam R; Benn, Caroline L; Kammonen, Laura R; Friedman, Julia H; Bictash, Magda; Whiting, Paul; Bilsland, James G; Stevens, Edward B
2014-08-01
The generation of human sensory neurons by directed differentiation of pluripotent stem cells opens new opportunities for investigating the biology of pain. The inability to generate this cell type has meant that up until now their study has been reliant on the use of rodent models. Here, we use a combination of population and single-cell techniques to perform a detailed molecular, electrophysiological, and pharmacological phenotyping of sensory neurons derived from human embryonic stem cells. We describe the evolution of cell populations over 6 weeks of directed differentiation; a process that results in the generation of a largely homogeneous population of neurons that are both molecularly and functionally comparable to human sensory neurons derived from mature dorsal root ganglia. This work opens the prospect of using pluripotent stem-cell-derived sensory neurons to study human neuronal physiology and as in vitro models for drug discovery in pain and sensory disorders.
-
Gjurchinovski, Aleksandar; Skeparovski, Aleksandar
2008-10-01
Reflection of light from a plane mirror in uniform rectilinear motion is a century-old problem, intimately related to the foundations of special relativity.1-4 The problem was first investigated by Einstein in his famous 1905 paper by using the Lorentz transformations to switch from the mirror's rest frame to the frame where the mirror moves at a constant velocity.5 Einstein showed an intriguing fact that the usual law of reflection would not hold in the case of a uniformly moving mirror, that is, the angles of incidence and reflection of the light would not equal each other. Later on, it has been shown that the law of reflection at a moving mirror can be obtained in various alternative ways,6-10 but none of them seems suitable for bringing this interesting subject into the high school classroom.
-
Design of a Virtual Player for Joint Improvisation with Humans in the Mirror Game.
Zhai, Chao; Alderisio, Francesco; Słowiński, Piotr; Tsaneva-Atanasova, Krasimira; di Bernardo, Mario
2016-01-01
Joint improvisation is often observed among humans performing joint action tasks. Exploring the underlying cognitive and neural mechanisms behind the emergence of joint improvisation is an open research challenge. This paper investigates jointly improvised movements between two participants in the mirror game, a paradigmatic joint task example. First, experiments involving movement coordination of different dyads of human players are performed in order to build a human benchmark. No designation of leader and follower is given beforehand. We find that joint improvisation is characterized by the lack of a leader and high levels of movement synchronization. Then, a theoretical model is proposed to capture some features of their interaction, and a set of experiments is carried out to test and validate the model ability to reproduce the experimental observations. Furthermore, the model is used to drive a computer avatar able to successfully improvise joint motion with a human participant in real time. Finally, a convergence analysis of the proposed model is carried out to confirm its ability to reproduce joint movements between the participants.
-
Angiotensinergic and noradrenergic neurons in the rat and human heart.
Patil, Jaspal; Stucki, Silvan; Nussberger, Juerg; Schaffner, Thomas; Gygax, Susanne; Bohlender, Juergen; Imboden, Hans
2011-02-25
Although the physiological and pharmacological evidences suggest a role for angiotensin II (Ang II) with the mammalian heart, the source and precise location of Ang II are unknown. To visualize and quantitate Ang II in atria, ventricular walls and interventricular septum of the rat and human heart and to explore the feasibility of local Ang II production and function, we investigated by different methods the expression of proteins involved in the generation and function of Ang II. We found mRNA of angiotensinogen (Ang-N), of angiotensin converting enzyme, of the angiotensin type receptors AT(1A) and AT₂ (AT(1B) not detected) as well as of cathepsin D in any part of the hearts. No renin mRNA was traceable. Ang-N mRNA was visualized by in situ hybridization in atrial ganglial neurons. Ang II and dopamine-β-hydroxylase (DβH) were either colocalized inside the same neuronal cell or the neurons were specialized for Ang II or DβH. Within these neurons, the vesicular acetylcholine transporter (VAChT) was neither colocalized with Ang II nor DβH, but VAChT-staining was found with synapses en passant encircle these neuronal cells. The fibers containing Ang II exhibited with blood vessels and with cardiomyocytes supposedly angiotensinergic synapses en passant. In rat heart, right atrial median Ang II concentration appeared higher than septal and ventricular Ang II. The distinct colocalization of neuronal Ang II with DβH in the heart may indicate that Ang II participates together with norepinephrine in the regulation of cardiac functions: produced as a cardiac neurotransmitter Ang II may have inotropic, chronotropic or dromotropic effects in atria and ventricles and contributes to blood pressure regulation. Copyright © 2010 Elsevier B.V. All rights reserved.
-
Qi, Yuchen; Zhang, Xin-Jun; Renier, Nicolas; Wu, Zhuhao; Atkin, Talia; Sun, Ziyi; Ozair, M. Zeeshan; Tchieu, Jason; Zimmer, Bastian; Fattahi, Faranak; Ganat, Yosif; Azevedo, Ricardo; Zeltner, Nadja; Brivanlou, Ali H.; Karayiorgou, Maria; Gogos, Joseph; Tomishima, Mark; Tessier-Lavigne, Marc; Shi, Song-Hai; Studer, Lorenz
2017-01-01
Considerable progress has been made in converting human pluripotent stem cells (hPSCs) into functional neurons. However, the protracted timing of human neuron specification and functional maturation remains a key challenge that hampers the routine application of hPSC-derived lineages in disease modeling and regenerative medicine. Using a combinatorial small-molecule screen, we previously identified conditions for the rapid differentiation of hPSCs into peripheral sensory neurons. Here we generalize the approach to central nervous system (CNS) fates by developing a small-molecule approach for accelerated induction of early-born cortical neurons. Combinatorial application of 6 pathway inhibitors induces post-mitotic cortical neurons with functional electrophysiological properties by day 16 of differentiation, in the absence of glial cell co-culture. The resulting neurons, transplanted at 8 days of differentiation into the postnatal mouse cortex, are functional and establish long-distance projections, as shown using iDISCO whole brain imaging. Accelerated differentiation into cortical neuron fates should facilitate hPSC-based strategies for disease modeling and cell therapy in CNS disorders. PMID:28112759
-
Directory of Open Access Journals (Sweden)
Alfred Xuyang Sun
2016-08-01
Full Text Available Gamma-aminobutyric acid (GABA-releasing interneurons play an important modulatory role in the cortex and have been implicated in multiple neurological disorders. Patient-derived interneurons could provide a foundation for studying the pathogenesis of these diseases as well as for identifying potential therapeutic targets. Here, we identified a set of genetic factors that could robustly induce human pluripotent stem cells (hPSCs into GABAergic neurons (iGNs with high efficiency. We demonstrated that the human iGNs express neurochemical markers and exhibit mature electrophysiological properties within 6–8 weeks. Furthermore, in vitro, iGNs could form functional synapses with other iGNs or with human-induced glutamatergic neurons (iENs. Upon transplantation into immunodeficient mice, human iGNs underwent synaptic maturation and integration into host neural circuits. Taken together, our rapid and highly efficient single-step protocol to generate iGNs may be useful to both mechanistic and translational studies of human interneurons.
-
Amorphous Metals and Composites as Mirrors and Mirror Assemblies
Hofmann, Douglas C. (Inventor); Davis, Gregory L. (Inventor); Agnes, Gregory S. (Inventor); Shapiro, Andrew A. (Inventor)
2016-01-01
A mirror or mirror assembly fabricated by molding, pressing, assembling, or depositing one or more bulk metal glass (BMG), bulk metal glass composite (BMGMC), or amorphous metal (AM) parts and where the optical surface and backing of the mirror can be fabricated without machining or polishing by utilizing the unique molding capabilities of this class of materials.
-
International Nuclear Information System (INIS)
Carlson, G.A.; Moir, R.W.
1976-01-01
Recent mirror reactor conceptual design studies are described. Considered in detail is the design of ''standard'' Yin-Yang fusion power reactors with classical and enhanced confinement. It is shown that to be economically competitive with estimates for other future energy sources, mirror reactors require a considerable increase in Q, or major design simplifications, or preferably both. These improvements may require a departure from the ''standard'' configuration. Two attractive possibilities, both of which would use much of the same physics and technology as the ''standard'' mirror, are the field reversed mirror and the end-stoppered mirror
-
Neuroprotective effects of rosmarinic acid on ciguatoxin in primary human neurons.
Braidy, N; Matin, A; Rossi, F; Chinain, M; Laurent, D; Guillemin, G J
2014-02-01
Ciguatoxin (CTX), is a toxic compound produced by microalgae (dinoflagellate) Gambierdiscus spp., and is bio-accumulated and bio-transformed through the marine food chain causing neurological deficits. To determine the mechanism of CTX-mediated cytotoxicity in human neurons, we measured extracellular lactate dehydrogenase (LDH) activity, intracellular levels of nicotinamide adenine dinucleotide (NAD(+)) and H2AX phosphorylation at serine 139 as a measure for DNA damage in primary cultures of human neurons treated with Pacific (P)-CTX-1B and P-CTX-3C. We found these marine toxins can induce a time and dose-dependent increase in extracellular LDH activity, with a concomitant decline in intracellular NAD(+) levels and increased DNA damage at the concentration range of 5-200 nM. We also showed that pre- and post-treatment with rosmarinic acid (RA), the active constituent of the Heliotropium foertherianum (Boraginaceae) can attenuate CTX-mediated neurotoxicity. These results further highlight the potential of RA in the treatment of CTX-induced neurological deficits.
-
Directory of Open Access Journals (Sweden)
Deborah Prè
Full Text Available Many protocols have been designed to differentiate human embryonic stem cells (ESCs and human induced pluripotent stem cells (iPSCs into neurons. Despite the relevance of electrophysiological properties for proper neuronal function, little is known about the evolution over time of important neuronal electrophysiological parameters in iPSC-derived neurons. Yet, understanding the development of basic electrophysiological characteristics of iPSC-derived neurons is critical for evaluating their usefulness in basic and translational research. Therefore, we analyzed the basic electrophysiological parameters of forebrain neurons differentiated from human iPSCs, from day 31 to day 55 after the initiation of neuronal differentiation. We assayed the developmental progression of various properties, including resting membrane potential, action potential, sodium and potassium channel currents, somatic calcium transients and synaptic activity. During the maturation of iPSC-derived neurons, the resting membrane potential became more negative, the expression of voltage-gated sodium channels increased, the membrane became capable of generating action potentials following adequate depolarization and, at day 48-55, 50% of the cells were capable of firing action potentials in response to a prolonged depolarizing current step, of which 30% produced multiple action potentials. The percentage of cells exhibiting miniature excitatory post-synaptic currents increased over time with a significant increase in their frequency and amplitude. These changes were associated with an increase of Ca2+ transient frequency. Co-culturing iPSC-derived neurons with mouse glial cells enhanced the development of electrophysiological parameters as compared to pure iPSC-derived neuronal cultures. This study demonstrates the importance of properly evaluating the electrophysiological status of the newly generated neurons when using stem cell technology, as electrophysiological properties of
-
Mueller, Jerel K.; Grigsby, Erinn M.; Prevosto, Vincent; Petraglia, Frank W.; Rao, Hrishikesh; Deng, Zhi-De; Peterchev, Angel V.; Sommer, Marc A.; Egner, Tobias; Platt, Michael L.; Grill, Warren M.
2014-01-01
Transcranial magnetic stimulation (TMS) is a widely used, noninvasive method for stimulating nervous tissue, yet its mechanisms of effect are poorly understood. Here we report novel methods for studying the influence of TMS on single neurons in the brain of alert non-human primates. We designed a TMS coil that focuses its effect near the tip of a recording electrode and recording electronics that enable direct acquisition of neuronal signals at the site of peak stimulus strength minimally per...
-
Duñabeitia, Jon Andoni; Dimitropoulou, María; Estévez, Adelina; Carreiras, Manuel
2013-01-01
The visual word recognition system recruits neuronal systems originally developed for object perception which are characterized by orientation insensitivity to mirror reversals. It has been proposed that during reading acquisition beginning readers have to “unlearn” this natural tolerance to mirror reversals in order to efficiently discriminate letters and words. Therefore, it is supposed that this unlearning process takes place in a gradual way and that reading expertise modulates mirror-letter discrimination. However, to date no supporting evidence for this has been obtained. We present data from an eye-movement study that investigated the degree of sensitivity to mirror-letters in a group of beginning readers and a group of expert readers. Participants had to decide which of the two strings presented on a screen corresponded to an auditorily presented word. Visual displays always included the correct target word and one distractor word. Results showed that those distractors that were the same as the target word except for the mirror lateralization of two internal letters attracted participants’ attention more than distractors created by replacement of two internal letters. Interestingly, the time course of the effects was found to be different for the two groups, with beginning readers showing a greater tolerance (decreased sensitivity) to mirror-letters than expert readers. Implications of these findings are discussed within the framework of preceding evidence showing how reading expertise modulates letter identification. PMID:24273596
-
Jinzenji, Masao
2018-01-01
This book furnishes a brief introduction to classical mirror symmetry, a term that denotes the process of computing Gromov–Witten invariants of a Calabi–Yau threefold by using the Picard–Fuchs differential equation of period integrals of its mirror Calabi–Yau threefold. The book concentrates on the best-known example, the quintic hypersurface in 4-dimensional projective space, and its mirror manifold. First, there is a brief review of the process of discovery of mirror symmetry and the striking result proposed in the celebrated paper by Candelas and his collaborators. Next, some elementary results of complex manifolds and Chern classes needed for study of mirror symmetry are explained. Then the topological sigma models, the A-model and the B-model, are introduced. The classical mirror symmetry hypothesis is explained as the equivalence between the correlation function of the A-model of a quintic hyper-surface and that of the B-model of its mirror manifold. On the B-model side, the process of construct...
-
Directory of Open Access Journals (Sweden)
Heikki Kiiski
2013-05-01
The possibilities of human pluripotent stem cell-derived neural cells from the basic research tool to a treatment option in regenerative medicine have been well recognized. These cells also offer an interesting tool for in vitro models of neuronal networks to be used for drug screening and neurotoxicological studies and for patient/disease specific in vitro models. Here, as aiming to develop a reductionistic in vitro human neuronal network model, we tested whether human embryonic stem cell (hESC-derived neural cells could be cultured in human cerebrospinal fluid (CSF in order to better mimic the in vivo conditions. Our results showed that CSF altered the differentiation of hESC-derived neural cells towards glial cells at the expense of neuronal differentiation. The proliferation rate was reduced in CSF cultures. However, even though the use of CSF as the culture medium altered the glial vs. neuronal differentiation rate, the pre-existing spontaneous activity of the neuronal networks persisted throughout the study. These results suggest that it is possible to develop fully human cell and culture-based environments that can further be modified for various in vitro modeling purposes.
-
Progranulin levels in status epilepticus as a marker of neuronal recovery and neuroprotection.
Huchtemann, T; Körtvélyessy, P; Feistner, H; Heinze, H J; Bittner, D
2015-08-01
Recently, a mouse model showed that progranulin, a mediator in neuroinflammation and a neuronal growth factor, was elevated in the hippocampus after status epilepticus (SE). This elevated level might mirror compensating neuronal mechanisms after SE. Studies concerning neuronal recovery and neuroprotective mechanisms after SE in humans are scarce, so we tested for progranulinin the cerebrospinal fluid (CSF) after various types of SE. We performed a retrospective analysis of progranulin levels in CSF in patients (n = 24) who underwent lumbar puncture as part of diagnostic workup after having SE and in patients after having one single tonic-clonic seizure who comprised the control group (n = 8). In our group with SE, progranulin levels in CSF were not significantly elevated compared to our control group. Furthermore, there was no correlation between progranulin levels and the time interval between lumbar puncture and SE. Additionally, in cases of higher CSF progranulin levels, we found no impact on the clinical outcome after SE. Although our cohort is heterogeneous and not fully sufficient, we conclude that progranulin in CSF is not elevated after SE in our cohort. Therefore, our results do not suggest a change in cerebral progranulin metabolism as a possible neuroregenerative or neuroprotective mechanism in humans after SE in acute and subacute phases. A larger cohort study is needed to further strengthen this result. This article is part of a Special Issue entitled "Status Epilepticus". Copyright © 2015 Elsevier Inc. All rights reserved.
-
Young, Gareth T; Gutteridge, Alex; Fox, Heather DE; Wilbrey, Anna L; Cao, Lishuang; Cho, Lily T; Brown, Adam R; Benn, Caroline L; Kammonen, Laura R; Friedman, Julia H; Bictash, Magda; Whiting, Paul; Bilsland, James G; Stevens, Edward B
2014-01-01
The generation of human sensory neurons by directed differentiation of pluripotent stem cells opens new opportunities for investigating the biology of pain. The inability to generate this cell type has meant that up until now their study has been reliant on the use of rodent models. Here, we use a combination of population and single-cell techniques to perform a detailed molecular, electrophysiological, and pharmacological phenotyping of sensory neurons derived from human embryonic stem cells. We describe the evolution of cell populations over 6 weeks of directed differentiation; a process that results in the generation of a largely homogeneous population of neurons that are both molecularly and functionally comparable to human sensory neurons derived from mature dorsal root ganglia. This work opens the prospect of using pluripotent stem-cell–derived sensory neurons to study human neuronal physiology and as in vitro models for drug discovery in pain and sensory disorders. PMID:24832007
-
Bianchi, M; Moser, C; Lazzarini, C; Vecchiato, E; Crespi, F
2002-03-01
Low levels of central serotonin (5-HT) have been related to the state of depression, and 5-HT is the major target of the newer antidepressant drugs such as selective serotonin reuptake inhibitors (SSRIs). Neurons and platelets display structural and functional similarities, so that the latter have been proposed as a peripheral model of central functions. In particular, in blood more than 99% of 5-HT is contained in platelets, so that one could consider changes in 5-HT levels in platelets as a mirror of changes in central 5-HT. Here, this hypothesis has been studied via the analysis of the influence of: (1) the forced swimming test (FST, which has been proved to be of utility to predict the clinical efficacy of antidepressants in rodents) and (2) treatment with the SSRI fluoxetine upon 5-HT levels monitored in brain regions and in peripheral platelets by means of electrochemical in vivo and ex vivo measurements. The results obtained confirm that the FST increases immobility; furthermore they show a parallel and significant decrease in cerebral (brain homogenate) and peripheral (in platelet-rich plasma, PRP) voltammetric 5-HT levels following the FST in naive rats. In addition, subchronic treatment with fluoxetine was followed by a significant increase in 5-HT levels in PRP, while the same SSRI treatment performed within the FST resulted in a decrease in the 5-HT levels in PRP. However, this decrease was inferior to that observed without SSRI treatment. These data suggest that there is an inverse relationship between immobility and the levels of 5-HT in PRP and that these peripheral 5-HT levels are sensitive to: (1) the FST, (2) the treatment with fluoxetine and (3) the combination of both treatments, i.e. SSRI + FST. It has been reported that SSRI treatment at first inhibits the 5-HT transporter in brain, resulting in increased extracellular 5-HT, while following sustained SSRI treatments decreased intracellular levels of central 5-HT were observed. Accordingly, the
-
Tandem mirror and field-reversed mirror experiments
Energy Technology Data Exchange (ETDEWEB)
Coensgen, F.H.; Simonen, T.C.; Turner, W.C.
1979-08-21
This paper is largely devoted to tandem mirror and field-reversed mirror experiments at the Lawrence Livermore Laboratory (LLL), and briefly summarizes results of experiments in which field-reversal has been achieved. In the tandem experiment, high-energy, high-density plasmas (nearly identical to 2XIIB plasmas) are located at each end of a solenoid where plasma ions are electrostatically confined by the high positive poentials arising in the end plug plasma. End plug ions are magnetically confined, and electrons are electrostatically confined by the overall positive potential of the system. The field-reversed mirror reactor consists of several small field-reversed mirror plasmas linked together for economic reasons. In the LLL Beta II experiment, generation of a field-reversed plasma ring will be investigated using a high-energy plasma gun with a transverse radial magnetic field. This plasma will be further heated and sustained by injection of intense, high-energy neutral beams.
-
Voisin, Claire
1999-01-01
This is the English translation of Professor Voisin's book reflecting the discovery of the mirror symmetry phenomenon. The first chapter is devoted to the geometry of Calabi-Yau manifolds, and the second describes, as motivation, the ideas from quantum field theory that led to the discovery of mirror symmetry. The other chapters deal with more specialized aspects of the subject: the work of Candelas, de la Ossa, Greene, and Parkes, based on the fact that under the mirror symmetry hypothesis, the variation of Hodge structure of a Calabi-Yau threefold determines the Gromov-Witten invariants of its mirror; Batyrev's construction, which exhibits the mirror symmetry phenomenon between hypersurfaces of toric Fano varieties, after a combinatorial classification of the latter; the mathematical construction of the Gromov-Witten potential, and the proof of its crucial property (that it satisfies the WDVV equation), which makes it possible to construct a flat connection underlying a variation of Hodge structure in the ...
-
Technology of mirror machines: LLL facilities for magnetic mirror fusion experiments
International Nuclear Information System (INIS)
Batzer, T.H.
1977-01-01
Significant progress in plasma confinement and temperature has been achieved in the 2XIIB facility at Livermore. These encouraging results, and their theoretical corroboration, have provided a firm basis for the design of a new generation of magnetic mirror experiments, adding support to the mirror concept of a fusion reactor. Two new mirror experiments have been proposed to succeed the currently operating 2XIIB facility. The first of these called TMX (Tandem Mirror Experiment) has been approved and is currently under construction. TMX is designed to utilize the intrinsic positive plasma potential of two strong, and relatively small, minimum B mirror cells to enhance the confinement of a much larger, magnetically weaker, centrally-located mirror cell. The second facility, MFTF (Mirror Fusion Test Facility), is currently in preliminary design with line item approval anticipated for FY 78. MFTF is designed primarily to exploit the experimental and theoretical results derived from 2XIIB. Beyond that, MFTF will develop the technology for the transition from the present small mirror experiments to large steady-state devices such as the mirror FERF/FTR. The sheer magnitude of the plasma volume, magnetic field, neutral beam power, and vacuum pumping capacity, particularly in the case of MFTF, has placed new and exciting demands on engineering technology. An engineering overview of MFTF, TMX, and associated MFE activities at Livermore will be presented
-
[Motion control of moving mirror based on fixed-mirror adjustment in FTIR spectrometer].
Li, Zhong-bing; Xu, Xian-ze; Le, Yi; Xu, Feng-qiu; Li, Jun-wei
2012-08-01
The performance of the uniform motion of the moving mirror, which is the only constant motion part in FTIR spectrometer, and the performance of the alignment of the fixed mirror play a key role in FTIR spectrometer, and affect the interference effect and the quality of the spectrogram and may restrict the precision and resolution of the instrument directly. The present article focuses on the research on the uniform motion of the moving mirror and the alignment of the fixed mirror. In order to improve the FTIR spectrometer, the maglev support system was designed for the moving mirror and the phase detection technology was adopted to adjust the tilt angle between the moving mirror and the fixed mirror. This paper also introduces an improved fuzzy PID control algorithm to get the accurate speed of the moving mirror and realize the control strategy from both hardware design and algorithm. The results show that the development of the moving mirror motion control system gets sufficient accuracy and real-time, which can ensure the uniform motion of the moving mirror and the alignment of the fixed mirror.
-
Directory of Open Access Journals (Sweden)
Danko Georgiev
Full Text Available The cognitive deficits of schizophrenia appear to be associated with altered cortical GABA neurotransmission in the subsets of inhibitory neurons that express either parvalbumin (PV or somatostatin (SST. Identification of molecular mechanisms that operate selectively in these neurons is essential for developing targeted therapeutic strategies that do not influence other cell types. Consequently, we sought to identify, in the human cortex, gene products that are expressed selectively by PV and/or SST neurons, and that might contribute to their distinctive functional properties. Based on previously reported expression patterns in the cortex of mice and humans, we selected four genes: KCNS3, LHX6, KCNAB1, and PPP1R2, encoding K(+ channel Kv9.3 modulatory α-subunit, LIM homeobox protein 6, K(+ channel Kvβ1 subunit, and protein phosphatase 1 regulatory subunit 2, respectively, and examined their colocalization with PV or SST mRNAs in the human prefrontal cortex using dual-label in situ hybridization with (35S- and digoxigenin-labeled antisense riboprobes. KCNS3 mRNA was detected in almost all PV neurons, but not in SST neurons, and PV mRNA was detected in >90% of KCNS3 mRNA-expressing neurons. LHX6 mRNA was detected in almost all PV and >90% of SST neurons, while among all LHX6 mRNA-expressing neurons 50% expressed PV mRNA and >44% expressed SST mRNA. KCNAB1 and PPP1R2 mRNAs were detected in much larger populations of cortical neurons than PV or SST neurons. These findings indicate that KCNS3 is a selective marker of PV neurons, whereas LHX6 is expressed by both PV and SST neurons. KCNS3 and LHX6 might be useful for characterizing cell-type specific molecular alterations of cortical GABA neurotransmission and for the development of novel treatments targeting PV and/or SST neurons in schizophrenia.
-
Kayama, Tasuku; Suzuki, Ikuro; Odawara, Aoi; Sasaki, Takuya; Ikegaya, Yuji
2018-01-01
In culture conditions, human induced-pluripotent stem cells (hiPSC)-derived neurons form synaptic connections with other cells and establish neuronal networks, which are expected to be an in vitro model system for drug discovery screening and toxicity testing. While early studies demonstrated effects of co-culture of hiPSC-derived neurons with astroglial cells on survival and maturation of hiPSC-derived neurons, the population spiking patterns of such hiPSC-derived neurons have not been fully characterized. In this study, we analyzed temporal spiking patterns of hiPSC-derived neurons recorded by a multi-electrode array system. We discovered that specific sets of hiPSC-derived neurons co-cultured with astrocytes showed more frequent and highly coherent non-random synchronized spike trains and more dynamic changes in overall spike patterns over time. These temporally coordinated spiking patterns are physiological signs of organized circuits of hiPSC-derived neurons and suggest benefits of co-culture of hiPSC-derived neurons with astrocytes. Copyright © 2017 Elsevier Inc. All rights reserved.
-
2016-09-01
cells derived from human induced pluripotent stem cells (hiPSCs), originating from GW...AWARD NUMBER: W81XWH-15-1-0433 TITLE: Microtubule Abnormalities Underlying Gulf War Illness in Neurons from Human- Induced Pluripotent Cells ...A simple blood sample is taken from the soldier, and then transduced, using reliable established methods , to make the cells pluripotent .
-
Inferior olive mirrors joint dynamics to implement an inverse controller.
Alvarez-Icaza, Rodrigo; Boahen, Kwabena
2012-10-01
To produce smooth and coordinated motion, our nervous systems need to generate precisely timed muscle activation patterns that, due to axonal conduction delay, must be generated in a predictive and feedforward manner. Kawato proposed that the cerebellum accomplishes this by acting as an inverse controller that modulates descending motor commands to predictively drive the spinal cord such that the musculoskeletal dynamics are canceled out. This and other cerebellar theories do not, however, account for the rich biophysical properties expressed by the olivocerebellar complex's various cell types, making these theories difficult to verify experimentally. Here we propose that a multizonal microcomplex's (MZMC) inferior olivary neurons use their subthreshold oscillations to mirror a musculoskeletal joint's underdamped dynamics, thereby achieving inverse control. We used control theory to map a joint's inverse model onto an MZMC's biophysics, and we used biophysical modeling to confirm that inferior olivary neurons can express the dynamics required to mirror biomechanical joints. We then combined both techniques to predict how experimentally injecting current into the inferior olive would affect overall motor output performance. We found that this experimental manipulation unmasked a joint's natural dynamics, as observed by motor output ringing at the joint's natural frequency, with amplitude proportional to the amount of current. These results support the proposal that the cerebellum-in particular an MZMC-is an inverse controller; the results also provide a biophysical implementation for this controller and allow one to make an experimentally testable prediction.
-
DEFF Research Database (Denmark)
Sundberg, Maria; Bogetofte, Helle; Lawson, Tristan
2013-01-01
of safety and efficacy of stem cell-derived DA neurons. The aim of this study was to improve the safety of human- and non-human primate iPSC (PiPSC)-derived DA neurons. According to our results, NCAM(+) /CD29(low) sorting enriched VM DA neurons from pluripotent stem cell-derived neural cell populations......The main motor symptoms of Parkinson's disease are due to the loss of dopaminergic (DA) neurons in the ventral midbrain (VM). For the future treatment of Parkinson's disease with cell transplantation it is important to develop efficient differentiation methods for production of human iPSCs and h......ESCs-derived midbrain-type DA neurons. Here we describe an efficient differentiation and sorting strategy for DA neurons from both human ES/iPS cells and non-human primate iPSCs. The use of non-human primate iPSCs for neuronal differentiation and autologous transplantation is important for preclinical evaluation...
-
Xiao, Li; Ide, Ryoji; Saiki, Chikako; Kumazawa, Yasuo; Okamura, Hisashi
2017-08-11
The adult mammalian central nerve system has fundamental difficulties regarding effective neuroregeneration. The aim of this study is to investigate whether human dental pulp cells (DPCs) can promote neuroregeneration by (i) being differentiated toward neuronal cells and/or (ii) stimulating local neurogenesis in the adult hippocampus. Using immunostaining, we demonstrated that adult human dental pulp contains multipotent DPCs, including STRO-1, CD146 and P75-positive stem cells. DPC-formed spheroids were able to differentiate into neuronal, vascular, osteogenic and cartilaginous lineages under osteogenic induction. However, under neuronal inductive conditions, cells in the DPC-formed spheroids differentiated toward neuronal rather than other lineages. Electrophysiological study showed that these cells consistently exhibit the capacity to produce action potentials, suggesting that they have a functional feature in neuronal cells. We further co-cultivated DPCs with adult mouse hippocampal slices on matrigel in vitro. Immunostaining and presto blue assay showed that DPCs were able to stimulate the growth of neuronal cells (especially neurons) in both the CA1 zone and the edges of the hippocampal slices. Brain-derived neurotrophic factor (BDNF), was expressed in co-cultivated DPCs. In conclusion, our data demonstrated that DPCs are well-suited to differentiate into the neuronal lineage. They are able to stimulate neurogenesis in the adult mouse hippocampus through neurotrophic support in vitro.
-
Neurobiological approaches to a better understanding of human nature and human values
Directory of Open Access Journals (Sweden)
Gerald Hüther
2006-04-01
Full Text Available The most important finding made in the field of neurobiological research during the last decade is the discovery of the enormous experience-dependent plasticity of the human brain. The elaboration and stabilization of synaptic connectivity, and therefore, the complexity of neuronal networks in the higher brain centres depend to a far greater extent than previously believed on how – or rather, for which purpose – an individual uses his brain, the goals pursued, the experiences made in the course of his life, the models used for orientation, the values providing stability and eliciting a sense of commitment. The transmission and internalization of culture-specific abilities and of culture-specific values is achieved primarily during childhood by nonverbal communication (mirror neuron system, imitation learning as well as by implicit and explicit experiences (reward system, avoidance and reinforcement learning. Therefore the structural and functional organization of the human brain is crucially determined by social and cultural factors. Especially the frontal cortex with its highly complex neuronal networks involved in executive functions, evaluation an decision making must be conceptualized as a social, culturally shaped construct. The most important prerequisites for the transgenerational transmission of human values and their deep implementation into the higher frontocortical networks of the brains of subsequent generations are secure affectional relationships and a broad spectrum of different challenges. Only under such conditions, children are able to stabilize sufficiently complex networks and internal representations for metacognitive competences in their brains. This delicate process of experience-dependent organization of neuronal connectivity is seriously and often also persistently hampered or prematurely terminated by uncontrollable stress experiences. This danger ought be minimized by education programs aiming at the implementation
-
Pyramidal neurons in the septal and temporal CA1 field of the human and hedgehog tenrec hippocampus.
Liagkouras, Ioannis; Michaloudi, Helen; Batzios, Christos; Psaroulis, Dimitrios; Georgiadis, Marios; Künzle, Heinz; Papadopoulos, Georgios C
2008-07-07
The present study examines comparatively the cellular density of disector-counted/Nissl-stained CA1 pyramidal neurons and the morphometric characteristics (dendritic number/length, spine number/density and Sholl-counted dendritic branch points/20 microm) of the basal and apical dendritic systems of Golgi-impregnated CA1 neurons, in the septal and temporal hippocampus of the human and hedgehog tenrec brain. The obtained results indicate that in both hippocampal parts the cellular density of the CA1 pyramidal neurons is lower in human than in tenrec. However, while the human pyramidal cell density is higher in the septal hippocampal part than in the temporal one, in the tenrec the density of these cells is higher in the temporal part. The dendritic tree of the CA1 pyramidal cells, more developed in the septal than in temporal hippocampus in both species studied, is in general more complex in the human hippocampus. The basal and the apical dendritic systems exhibit species related morphometric differences, while dendrites of different orders exhibit differences in their number and length, and in their spine density. Finally, in both species, as well as hippocampal parts and dendritic systems, changes of dendritic morphometric features along ascending dendritic orders fluctuate in a similar way, as do the number of dendritic branch points in relation to the distance from the neuron soma.
-
Directory of Open Access Journals (Sweden)
Jessica Alves de Medeiros Araújo
2018-06-01
Full Text Available Reprogramming of somatic cells into induced pluripotent stem cells (iPS or directly into cells from a different lineage, including neurons, has revolutionized research in regenerative medicine in recent years. Mesenchymal stem cells are good candidates for lineage reprogramming and autologous transplantation, since they can be easily isolated from accessible sources in adult humans, such as bone marrow and dental tissues. Here, we demonstrate that expression of the transcription factors (TFs SRY (sex determining region Y-box 2 (Sox2, Mammalian achaete-scute homolog 1 (Ascl1, or Neurogenin 2 (Neurog2 is sufficient for reprogramming human umbilical cord mesenchymal stem cells (hUCMSC into induced neurons (iNs. Furthermore, the combination of Sox2/Ascl1 or Sox2/Neurog2 is sufficient to reprogram up to 50% of transfected hUCMSCs into iNs showing electrical properties of mature neurons and establishing synaptic contacts with co-culture primary neurons. Finally, we show evidence supporting the notion that different combinations of TFs (Sox2/Ascl1 and Sox2/Neurog2 may induce multiple and overlapping neuronal phenotypes in lineage-reprogrammed iNs, suggesting that neuronal fate is determined by a combination of signals involving the TFs used for reprogramming but also the internal state of the converted cell. Altogether, the data presented here contribute to the advancement of techniques aiming at obtaining specific neuronal phenotypes from lineage-converted human somatic cells to treat neurological disorders.
-
Directory of Open Access Journals (Sweden)
Frank Rattay
Full Text Available Our knowledge about the neural code in the auditory nerve is based to a large extent on experiments on cats. Several anatomical differences between auditory neurons in human and cat are expected to lead to functional differences in speed and safety of spike conduction.Confocal microscopy was used to systematically evaluate peripheral and central process diameters, commonness of myelination and morphology of spiral ganglion neurons (SGNs along the cochlea of three human and three cats. Based on these morphometric data, model analysis reveales that spike conduction in SGNs is characterized by four phases: a postsynaptic delay, constant velocity in the peripheral process, a presomatic delay and constant velocity in the central process. The majority of SGNs are type I, connecting the inner hair cells with the brainstem. In contrast to those of humans, type I neurons of the cat are entirely myelinated. Biophysical model evaluation showed delayed and weak spikes in the human soma region as a consequence of a lack of myelin. The simulated spike conduction times are in accordance with normal interwave latencies from auditory brainstem response recordings from man and cat. Simulated 400 pA postsynaptic currents from inner hair cell ribbon synapses were 15 times above threshold. They enforced quick and synchronous spiking. Both of these properties were not present in type II cells as they receive fewer and much weaker (∼26 pA synaptic stimuli.Wasting synaptic energy boosts spike initiation, which guarantees the rapid transmission of temporal fine structure of auditory signals. However, a lack of myelin in the soma regions of human type I neurons causes a large delay in spike conduction in comparison with cat neurons. The absent myelin, in combination with a longer peripheral process, causes quantitative differences of temporal parameters in the electrically stimulated human cochlea compared to the cat cochlea.
-
Rattay, Frank; Potrusil, Thomas; Wenger, Cornelia; Wise, Andrew K.; Glueckert, Rudolf; Schrott-Fischer, Anneliese
2013-01-01
Background Our knowledge about the neural code in the auditory nerve is based to a large extent on experiments on cats. Several anatomical differences between auditory neurons in human and cat are expected to lead to functional differences in speed and safety of spike conduction. Methodology/Principal Findings Confocal microscopy was used to systematically evaluate peripheral and central process diameters, commonness of myelination and morphology of spiral ganglion neurons (SGNs) along the cochlea of three human and three cats. Based on these morphometric data, model analysis reveales that spike conduction in SGNs is characterized by four phases: a postsynaptic delay, constant velocity in the peripheral process, a presomatic delay and constant velocity in the central process. The majority of SGNs are type I, connecting the inner hair cells with the brainstem. In contrast to those of humans, type I neurons of the cat are entirely myelinated. Biophysical model evaluation showed delayed and weak spikes in the human soma region as a consequence of a lack of myelin. The simulated spike conduction times are in accordance with normal interwave latencies from auditory brainstem response recordings from man and cat. Simulated 400 pA postsynaptic currents from inner hair cell ribbon synapses were 15 times above threshold. They enforced quick and synchronous spiking. Both of these properties were not present in type II cells as they receive fewer and much weaker (∼26 pA) synaptic stimuli. Conclusions/Significance Wasting synaptic energy boosts spike initiation, which guarantees the rapid transmission of temporal fine structure of auditory signals. However, a lack of myelin in the soma regions of human type I neurons causes a large delay in spike conduction in comparison with cat neurons. The absent myelin, in combination with a longer peripheral process, causes quantitative differences of temporal parameters in the electrically stimulated human cochlea compared to the cat
-
Arbib, Michael A.
2010-01-01
We develop the view that the involvement of mirror neurons in embodied experience grounds brain structures that underlie language, but that many other brain regions are involved. We stress the cooperation between the dorsal and ventral streams in praxis and language. Both have perceptual and motor schemas but the perceptual schemas in the dorsal…
-
Mohanty, Madhu C; Deshpande, Jagadish M
2013-01-01
Polioviruses are the causative agent of paralytic poliomyelitis. Attenuated polioviruses (Sabin oral poliovirus vaccine strains) do not replicate efficiently in neurons as compared to the wild type polioviruses and therefore do not cause disease. This study was aimed to investigate the differential host immune response to wild type 1 poliovirus (wild PV) and Sabin attenuated type 1 poliovirus (Sabin PV) in cultured human neuronal cells. By using flow cytometry and real time PCR methods we examined host innate immune responses and compared the role of toll like receptors (TLRs) and cytoplasmic RNA helicases in cultured human neuronal cells (SK-N-SH) infected with Sabin PV and wild PV. Human neuronal cells expressed very low levels of TLRs constitutively. Sabin PV infection induced significantly higher expression of TLR3, TLR7 and melanoma differentiation-associated protein-5 (MDA-5) m-RNA in neuronal cells at the beginning of infection (up to 4 h) as compared to wild PV. Further, Sabin PV also induced the expression of interferon α/β at early time point of infection. The induced expression of IFN α/β gene by Sabin PV in neuronal cells could be suppressed by inhibiting TLR7. Neuronal cell innate immune response to Sabin and wild polioviruses differ significantly for TLR3, TLR7, MDA5 and type 1 interferons. Effects of TLR7 activation and interferon production and Sabin virus replication in neuronal cells need to be actively investigated in future studies.
-
Value encoding in single neurons in the human amygdala during decision making.
Jenison, Rick L; Rangel, Antonio; Oya, Hiroyuki; Kawasaki, Hiroto; Howard, Matthew A
2011-01-05
A growing consensus suggests that the brain makes simple choices by assigning values to the stimuli under consideration and then comparing these values to make a decision. However, the network involved in computing the values has not yet been fully characterized. Here, we investigated whether the human amygdala plays a role in the computation of stimulus values at the time of decision making. We recorded single neuron activity from the amygdala of awake patients while they made simple purchase decisions over food items. We found 16 amygdala neurons, located primarily in the basolateral nucleus that responded linearly to the values assigned to individual items.
-
International Nuclear Information System (INIS)
Fowler, T.K.
1978-01-01
The mirror approach is now the principal alternate to the tokamak in the U.S. magnetic fusion energy program. The program is now focused on two new concepts that can obtain high values of Q, defined as the ratio of fusion power output to the neutral beam power injected to sustain the reaction. These are the tandem mirror and field reversed mirror concepts. Theoretically both concepts should be able to attain Q = 5 or more, as compared with Q approximately 1 in previous mirror designs. Success with either or both of these approaches would point the way toward fusion power plants with many attractive features. The linear geometry of mirror systems offers a distinct alternative to the toroidal tokamak. As a direct consequence of this difference in geometry, it is generally possible to build mirror systems in smaller units of modular construction that can probably be made to operate in steady-state. During the next 5 years the main mirror facilities in the U.S. will be the 2XIIB (renamed Beta II); a tandem mirror experiment caled TMX; and the Mirror Fusion Test Facility (MFTF) scheduled to be completed in 1981 at a cost of $94 million. As a background for discussing this program and mirror reactor concepts in later lectures, the current status of mirror physics will be reviewed by comparing theory and experimental data in four critical areas. These are adiabatic confinement of individual ions, electron heat losses out of the ends of the machine, the achievement of beta values of order unity; and stabilization of ''loss cone'' modes
-
CpG methylation differences between neurons and glia are highly conserved from mouse to human.
Kessler, Noah J; Van Baak, Timothy E; Baker, Maria S; Laritsky, Eleonora; Coarfa, Cristian; Waterland, Robert A
2016-01-15
Understanding epigenetic differences that distinguish neurons and glia is of fundamental importance to the nascent field of neuroepigenetics. A recent study used genome-wide bisulfite sequencing to survey differences in DNA methylation between these two cell types, in both humans and mice. That study minimized the importance of cell type-specific differences in CpG methylation, claiming these are restricted to localized genomic regions, and instead emphasized that widespread and highly conserved differences in non-CpG methylation distinguish neurons and glia. We reanalyzed the data from that study and came to markedly different conclusions. In particular, we found widespread cell type-specific differences in CpG methylation, with a genome-wide tendency for neuronal CpG-hypermethylation punctuated by regions of glia-specific hypermethylation. Alarmingly, our analysis indicated that the majority of genes identified by the primary study as exhibiting cell type-specific CpG methylation differences were misclassified. To verify the accuracy of our analysis, we isolated neuronal and glial DNA from mouse cortex and performed quantitative bisulfite pyrosequencing at nine loci. The pyrosequencing results corroborated our analysis, without exception. Most interestingly, we found that gene-associated neuron vs. glia CpG methylation differences are highly conserved across human and mouse, and are very likely to be functional. In addition to underscoring the importance of independent verification to confirm the conclusions of genome-wide epigenetic analyses, our data indicate that CpG methylation plays a major role in neuroepigenetics, and that the mouse is likely an excellent model in which to study the role of DNA methylation in human neurodevelopment and disease. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
-
Wang, Chi Chiu; Kadota, Mitsutaka; Nishigaki, Ryuichi; Kazuki, Yasuhiro; Shirayoshi, Yasuaki; Rogers, Michael Scott; Gojobori, Takashi; Ikeo, Kazuho; Oshimura, Mitsuo
2004-02-06
Defects in neurogenesis and neuronal differentiation in the fetal brain of Down syndrome (DS) patients lead to the apparent neuropathological abnormalities and contribute to the phenotypic characters of mental retardation, and premature development of Alzheimer's disease, those being the most common phenotype in DS. In order to understand the molecular mechanism underlying the cause of phenotypic abnormalities in the DS brain, we have utilized an in vitro model of TT2F mouse embryonic stem cells containing a single human chromosome 21 (hChr21) to study neuron development and neuronal differentiation by microarray containing 15K developmentally expressed cDNAs. Defective neuronal differentiation in the presence of extra hChr21 manifested primarily the post-transcriptional and translational modification, such as Mrpl10, SNAPC3, Srprb, SF3a60 in the early neuronal stem cell stage, and Mrps18a, Eef1g, and Ubce8 in the late differentiated stage. Hierarchical clustering patterned specific expression of hChr21 gene dosage effects on neuron outgrowth, migration, and differentiation, such as Syngr2, Dncic2, Eif3sf, and Peg3.
-
Directory of Open Access Journals (Sweden)
Ioana Neagoe
2018-04-01
Full Text Available Abnormal signaling pathways mediated by N-methyl-d-aspartate receptors (NMDARs have been implicated in the pathogenesis of various CNS disorders and have been long considered as promising points of therapeutic intervention. However, few efforts have been previously described concerning evaluation of therapeutic modulators of NMDARs and their downstream pathways in human neurons with endogenous expression of NMDARs. In the present study, we assessed expression, functionality, and subunit composition of endogenous NMDARs in human induced pluripotent stem cell (hiPSC-derived cortical neurons (iCell Neurons and iCell GlutaNeurons. We initially confirmed the expected pharmacological response of iCell Neurons and iCell GlutaNeurons to NMDA by patch-clamp recordings. Subsequent pharmacological interrogation using GluN2 subunit-selective antagonists revealed the predominance of GluN2B in both iCell Neurons and iCell GlutaNeurons. This observation was also supported by qRT-PCR and Western blot analyses of GluN2 subunit expression as well as pharmacological experiments using positive allosteric modulators with distinct GluN2 subunit selectivity. We conclude that iCell Neurons and iCell GlutaNeurons express functional GluN2B-containing NMDARs and could serve as a valuable system for development and validation of GluN2B-modulating pharmaceutical agents. Keywords: Human induced pluripotent stem cell-derived neurons, iCell Neurons, iCell GlutaNeurons, NMDA receptors, GluN2B, Positive allosteric modulators
-
DEFF Research Database (Denmark)
Aldana, Blanca I; Zhang, Yu; Lihme, Maria Fog
2017-01-01
pathways in neurons derived from human induced pluripotent stem cells (hiPSC). With this aim, cultures of hiPSC-derived neurons were incubated with [U-(13)C]glucose, [U-(13)C]glutamate or [U-(13)C]glutamine. Isotopic labeling in metabolites was determined using gas chromatography coupled to mass...
-
Vőfély, Gergő; Berecz, Tünde; Szabó, Eszter; Szebényi, Kornélia; Hathy, Edit; Orbán, Tamás I; Sarkadi, Balázs; Homolya, László; Marchetto, Maria C; Réthelyi, János M; Apáti, Ágota
2018-04-01
Pluripotent stem cell derived human neuronal progenitor cells (hPSC-NPCs) and their mature neuronal cell culture derivatives may efficiently be used for central nervous system (CNS) drug screening, including the investigation of ligand-induced calcium signalization. We have established hippocampal NPC cultures derived from human induced PSCs, which were previously generated by non-integrating Sendai virus reprogramming. Using established protocols these NPCs were differentiated into hippocampal dentate gyrus neurons. In order to study calcium signaling without the need of dye loading, we have stably expressed an advanced calcium indicator protein (GCaMP6fast) in the NPCs using the Sleeping Beauty transposon system. We observed no significant effects of the long-term GCaMP6 expression on NPC morphology, gene expression pattern or neural differentiation capacity. In order to compare the functional properties of GCaMP6-expressing neural cells and the corresponding parental cells loaded with calcium indicator dye Fluo-4, a detailed characterization of calcium signals was performed. We found that the calcium signals induced by ATP, glutamate, LPA, or proteases - were similar in these two systems. Moreover, the presence of the calcium indicator protein allowed for a sensitive, repeatable detection of changes in calcium signaling during the process of neurogenesis and neuronal maturation. Copyright © 2018 Elsevier Inc. All rights reserved.
-
Directory of Open Access Journals (Sweden)
Peter eEnticott
2013-05-01
Full Text Available The mirror neuron hypothesis of autism is highly controversial, in part because there are conflicting reports as to whether putative indices of mirror system activity are actually deficient in autism spectrum disorder (ASD. Recent evidence suggests that a typical putative mirror system response may be seen in people with an ASD when there is a degree of social relevance to the visual stimuli used to elicit that response. Individuals with ASD (n = 32 and matched neurotypical controls (n = 32 completed a transcranial magnetic stimulation (TMS experiment in which the left primary motor cortex was stimulated during the observation of static hands, individual (i.e., one person hand actions, and interactive (i.e., two person hand actions. Motor-evoked potentials (MEP were recorded from the contralateral first dorsal interosseous, and used to generate an index of interpersonal motor resonance (IMR; a putative measure of mirror system activity during action observation. There was no difference between ASD and NT groups in the level of IMR during the observation of these actions. These findings provide evidence against a global mirror system deficit in ASD, and this evidence appears to extend beyond stimuli that have social relevance. Attentional and visual processing influences may be important for understanding the apparent role of IMR in the pathophysiology of ASD.
-
Yousefi, Behnam; Sanooghi, Davood; Faghihi, Faezeh; Joghataei, Mohammad Taghi; Latifi, Nourahmad
2017-04-01
Many people suffer from spinal cord injuries annually. These deficits usually threaten the quality of life of patients. As a postpartum medically waste product, human Umbilical Cord Blood (UCB) is a rich source of stem cells with self- renewal properties and neural differentiation capacity which made it useful in regenerative medicine. Since there is no report on potential of human umbilical cord blood-derived mesenchymal stem cells into motor neurons, we set out to evaluate the differentiation properties of these cells into motor neuron-like cells through administration of Retinoic Acid(RA), Sonic Hedgehog(Shh) and BDNF using a three- step in vitro procedure. The results were evaluated using Real-time PCR, Flowcytometry and Immunocytochemistry for two weeks. Our data showed that the cells changed into bipolar morphology and could express markers related to motor neuron; including Hb-9, Pax-6, Islet-1, NF-H, ChAT at the level of mRNA and protein. We could also quantitatively evaluate the expression of Islet-1, ChAT and NF-H at 7 and 14days post- induction using flowcytometry. It is concluded that human UCB-MSCs is potent to express motor neuron- related markers in the presence of RA, Shh and BDNF through a three- step protocol; thus it could be a suitable cell candidate for regeneration of motor neurons in spinal cord injuries. Copyright © 2017. Published by Elsevier B.V.
-
Directory of Open Access Journals (Sweden)
Yuzo Takayama
Full Text Available Morphology and function of the nervous system is maintained via well-coordinated processes both in central and peripheral nervous tissues, which govern the homeostasis of organs/tissues. Impairments of the nervous system induce neuronal disorders such as peripheral neuropathy or cardiac arrhythmia. Although further investigation is warranted to reveal the molecular mechanisms of progression in such diseases, appropriate model systems mimicking the patient-specific communication between neurons and organs are not established yet. In this study, we reconstructed the neuronal network in vitro either between neurons of the human induced pluripotent stem (iPS cell derived peripheral nervous system (PNS and central nervous system (CNS, or between PNS neurons and cardiac cells in a morphologically and functionally compartmentalized manner. Networks were constructed in photolithographically microfabricated devices with two culture compartments connected by 20 microtunnels. We confirmed that PNS and CNS neurons connected via synapses and formed a network. Additionally, calcium-imaging experiments showed that the bundles originating from the PNS neurons were functionally active and responded reproducibly to external stimuli. Next, we confirmed that CNS neurons showed an increase in calcium activity during electrical stimulation of networked bundles from PNS neurons in order to demonstrate the formation of functional cell-cell interactions. We also confirmed the formation of synapses between PNS neurons and mature cardiac cells. These results indicate that compartmentalized culture devices are promising tools for reconstructing network-wide connections between PNS neurons and various organs, and might help to understand patient-specific molecular and functional mechanisms under normal and pathological conditions.
-
Miller, Rikki L A; Francoeur, Miranda J; Gibson, Brett M; Mair, Robert G
2017-01-01
The mediodorsal nucleus (MD) interacts with medial prefrontal cortex (mPFC) to support learning and adaptive decision-making. MD receives driver (layer 5) and modulatory (layer 6) projections from PFC and is the main source of driver thalamic projections to middle cortical layers of PFC. Little is known about the activity of MD neurons and their influence on PFC during decision-making. We recorded MD neurons in rats performing a dynamic delayed nonmatching to position (dDNMTP) task and compared results to a previous study of mPFC with the same task (Onos et al., 2016). Criterion event-related responses were observed for 22% (254/1179) of neurons recorded in MD, 237 (93%) of which exhibited activity consistent with mPFC response types. More MD than mPFC neurons exhibited responses related to movement (45% vs. 29%) and reinforcement (51% vs. 27%). MD had few responses related to lever presses, and none related to preparation or memory delay, which constituted 43% of event-related activity in mPFC. Comparison of averaged normalized population activity and population response times confirmed the broad similarity of common response types in MD and mPFC and revealed differences in the onset and offset of some response types. Our results show that MD represents information about actions and outcomes essential for decision-making during dDNMTP, consistent with evidence from lesion studies that MD supports reward-based learning and action-selection. These findings support the hypothesis that MD reinforces task-relevant neural activity in PFC that gives rise to adaptive behavior.
-
Hadaway, James; Blackwell, Lisa; Matthews, Gary; Eng, Ron; Stahl, Phil; Hraba, John; Thornton, Gary
2002-01-01
The results of cryo tests performed at the XRCF on the above mirrors will be presented. Each mirror was tested from room-temperature to around 30 K. The first three were tested together on a 3-mirror stand in the large chamber using the PhaseCam interferometer, while the Kodak mirror was tested in the small chamber using the EPI interferometer.
-
Unsworth, C P; Graham, E S; Delivopoulos, E; Dragunow, M; Murray, A F
2010-12-15
In this communication, we describe a new method which has enabled the first patterning of human neurons (derived from the human teratocarcinoma cell line (hNT)) on parylene-C/silicon dioxide substrates. We reveal the details of the nanofabrication processes, cell differentiation and culturing protocols necessary to successfully pattern hNT neurons which are each key aspects of this new method. The benefits in patterning human neurons on silicon chip using an accessible cell line and robust patterning technology are of widespread value. Thus, using a combined technology such as this will facilitate the detailed study of the pathological human brain at both the single cell and network level. Copyright © 2010 Elsevier B.V. All rights reserved.
-
Khalouei, Sam; Chow, Ari M; Brown, Ian R
2014-05-01
The localization of yellow fluorescent protein (YFP)-tagged HSP70 proteins was employed to identify stress-sensitive sites in human neurons following temperature elevation. Stable lines of human SH-SY5Y neuronal cells were established that expressed YFP-tagged protein products of the human inducible HSP70 genes HSPA6 (HSP70B') and HSPA1A (HSP70-1). Following a brief period of thermal stress, YFP-tagged HSPA6 and HSPA1A rapidly appeared at centrioles in the cytoplasm of human neuronal cells, with HSPA6 demonstrating a more prolonged signal compared to HSPA1A. Each centriole is composed of a distal end and a proximal end, the latter linking the centriole doublet. The YFP-tagged HSP70 proteins targeted the proximal end of centrioles (identified by γ-tubulin marker) rather than the distal end (centrin marker). Centrioles play key roles in cellular polarity and migration during neuronal differentiation. The proximal end of the centriole, which is involved in centriole stabilization, may be stress-sensitive in post-mitotic, differentiating human neurons.
-
Directory of Open Access Journals (Sweden)
Ping-Hsing Tsai
2015-06-01
Conclusion: We have developed a safer method to generate integration-free and nonviral human iPSCs from adult somatic cells. This induction method will be useful for the derivation of human integration-free iPSCs and will also be applicable to the generation of iPSCs-derived neuronal cells for drug screening or therapeutics in the near future.
-
Optimal staining methods for delineation of cortical areas and neuron counts in human brains.
Uylings, H B; Zilles, K; Rajkowska, G
1999-04-01
For cytoarchitectonic delineation of cortical areas in human brain, the Gallyas staining for somata with its sharp contrast between cell bodies and neuropil is preferable to the classical Nissl staining, the more so when an image analysis system is used. This Gallyas staining, however, does not appear to be appropriate for counting neuron numbers in pertinent brain areas, due to the lack of distinct cytological features between small neurons and glial cells. For cell counting Nissl is preferable. In an optimal design for cell counting at least both the Gallyas and the Nissl staining must be applied, the former staining for cytoarchitectural delineaton of cortical areas and the latter for counting the number of neurons in the pertinent cortical areas. Copyright 1999 Academic Press.
-
Zhang, Nan; Wen, Qingping; Ren, Lu; Liang, Wenbo; Xia, Yang; Zhang, Xiaodan; Zhao, Dan; Sun, Dong; Hu, Yv; Hao, Haiguang; Yan, Yaping; Zhang, Guangxian; Yang, Jingxian; Kang, Tingguo
2013-01-01
Arctigenin (Arc) has been shown to act on scopolamine-induced memory deficit mice and to provide a neuroprotective effect on cultured cortical neurons from glutamate-induced neurodegeneration through mechanisms not completely defined. Here, we investigated the neuroprotective effect of Arc on H89-induced cell damage and its potential mechanisms in mouse cortical neurons and human SH-SY5Y neuroblastoma cells. We found that Arc prevented cell viability loss induced by H89 in human SH-SY5Y cells. Moreover, Arc reduced intracellular beta amyloid (Aβ) production induced by H89 in neurons and human SH-SY5Y cells, and Arc also inhibited the presenilin 1(PS1) protein level in neurons. In addition, neural apoptosis in both types of cells, inhibition of neurite outgrowth in human SH-SY5Y cells and reduction of synaptic marker synaptophysin (SYN) expression in neurons were also observed after H89 exposure. All these effects induced by H89 were markedly reversed by Arc treatment. Arc also significantly attenuated downregulation of the phosphorylation of CREB (p-CREB) induced by H89, which may contribute to the neuroprotective effects of Arc. These results demonstrated that Arc exerted the ability to protect neurons and SH-SY5Y cells against H89-induced cell injury via upregulation of p-CREB. PMID:24025424
-
Directory of Open Access Journals (Sweden)
Tingguo Kang
2013-09-01
Full Text Available Arctigenin (Arc has been shown to act on scopolamine-induced memory deficit mice and to provide a neuroprotective effect on cultured cortical neurons from glutamate-induced neurodegeneration through mechanisms not completely defined. Here, we investigated the neuroprotective effect of Arc on H89-induced cell damage and its potential mechanisms in mouse cortical neurons and human SH-SY5Y neuroblastoma cells. We found that Arc prevented cell viability loss induced by H89 in human SH-SY5Y cells. Moreover, Arc reduced intracellular beta amyloid (Aβ production induced by H89 in neurons and human SH-SY5Y cells, and Arc also inhibited the presenilin 1(PS1 protein level in neurons. In addition, neural apoptosis in both types of cells, inhibition of neurite outgrowth in human SH-SY5Y cells and reduction of synaptic marker synaptophysin (SYN expression in neurons were also observed after H89 exposure. All these effects induced by H89 were markedly reversed by Arc treatment. Arc also significantly attenuated downregulation of the phosphorylation of CREB (p-CREB induced by H89, which may contribute to the neuroprotective effects of Arc. These results demonstrated that Arc exerted the ability to protect neurons and SH-SY5Y cells against H89-induced cell injury via upregulation of p-CREB.
-
Directory of Open Access Journals (Sweden)
Madhu C Mohanty
2013-01-01
Full Text Available Background & objectives: Polioviruses are the causative agent of paralytic poliomyelitis. Attenuated polioviruses (Sabin oral poliovirus vaccine strains do not replicate efficiently in neurons as compared to the wild type polioviruses and therefore do not cause disease. This study was aimed to investigate the differential host immune response to wild type 1 poliovirus (wild PV and Sabin attenuated type 1 poliovirus (Sabin PV in cultured human neuronal cells. Methods: By using flow cytometry and real time PCR methods we examined host innate immune responses and compared the role of toll like receptors (TLRs and cytoplasmic RNA helicases in cultured human neuronal cells (SK-N-SH infected with Sabin PV and wild PV. Results: Human neuronal cells expressed very low levels of TLRs constitutively. Sabin PV infection induced significantly higher expression of TLR3, TLR7 and melanoma differentiation-associated protein-5 (MDA-5 m-RNA in neuronal cells at the beginning of infection (up to 4 h as compared to wild PV. Further, Sabin PV also induced the expression of interferon α/β at early time point of infection. The induced expression of IFN α/β gene by Sabin PV in neuronal cells could be suppressed by inhibiting TLR7. Interpretation & conclusions: Neuronal cell innate immune response to Sabin and wild polioviruses differ significantly for TLR3, TLR7, MDA5 and type 1 interferons. Effects of TLR7 activation and interferon production and Sabin virus replication in neuronal cells need to be actively investigated in future studies.
-
International Nuclear Information System (INIS)
Simonen, T.; Cohen, R.; Correll, D.; Fowler, K.; Post, D.; Berk, H.; Horton, W.; Hooper, E.B.; Fisch, N.; Hassam, A.; Baldwin, D.; Pearlstein, D.; Logan, G.; Turner, B.; Moir, R.; Molvik, A.; Ryutov, D.; Ivanov, A.A; Kesner, J.; Cohen, B.; McLean, H.; Tamano, T.; Tang, X.Z.; Imai, T.
2008-01-01
Experimental results, theory and innovative ideas now point with increased confidence to the possibility of a Gas Dynamic Trap (GDT) neutron source which would be on the path to an attractively simple Axisymmetric Tandem Mirror (ATM) power plant. Although magnetic mirror research was terminated in the US 20 years ago, experiments continued in Japan (Gamma 10) and Russia (GDT), with a very small US effort. This research has now yielded data, increased understanding, and generated ideas resulting in the new concepts described here. Early mirror research was carried out with circular axisymmetric magnets. These plasmas were MHD unstable due to the unfavorable magnetic curvature near the mid-plane. Then the minimum-B concept emerged in which the field line curvature was everywhere favorable and the plasma was situated in a MHD stable magnetic well (70% average beta in 2XII-B). The Ioffe-bar or baseball-coil became the standard for over 40 years. In the 1980's, driven by success with minimum-B stabilization and the control of ion cyclotron instabilities in PR6 and 2XII-B, mirrors were viewed as a potentially attractive concept with near-term advantages as a lower Q neutron source for applications such as a hybrid fission fuel factory or toxic waste burner. However there are down sides to the minimum-B geometry: coil construction is complex; restraining magnetic forces limit field strength and mirror ratios. Furthermore, the magnetic field lines have geodesic curvature which introduces resonant and neoclassical radial transport as observed in early tandem mirror experiments. So what now leads us to think that simple axisymmetric mirror plasmas can be stable? The Russian GDT experiment achieves on-axis 60% beta by peaking of the kinetic plasma pressure near the mirror throat (where the curvature is favorable) to counter-balance the average unfavorable mid-plane curvature. Then a modest augmentation of plasma pressure in the expander results in stability. The GDT
-
Energy Technology Data Exchange (ETDEWEB)
Simonen, T; Cohen, R; Correll, D; Fowler, K; Post, D; Berk, H; Horton, W; Hooper, E B; Fisch, N; Hassam, A; Baldwin, D; Pearlstein, D; Logan, G; Turner, B; Moir, R; Molvik, A; Ryutov, D; Ivanov, A A; Kesner, J; Cohen, B; McLean, H; Tamano, T; Tang, X Z; Imai, T
2008-10-24
Experimental results, theory and innovative ideas now point with increased confidence to the possibility of a Gas Dynamic Trap (GDT) neutron source which would be on the path to an attractively simple Axisymmetric Tandem Mirror (ATM) power plant. Although magnetic mirror research was terminated in the US 20 years ago, experiments continued in Japan (Gamma 10) and Russia (GDT), with a very small US effort. This research has now yielded data, increased understanding, and generated ideas resulting in the new concepts described here. Early mirror research was carried out with circular axisymmetric magnets. These plasmas were MHD unstable due to the unfavorable magnetic curvature near the mid-plane. Then the minimum-B concept emerged in which the field line curvature was everywhere favorable and the plasma was situated in a MHD stable magnetic well (70% average beta in 2XII-B). The Ioffe-bar or baseball-coil became the standard for over 40 years. In the 1980's, driven by success with minimum-B stabilization and the control of ion cyclotron instabilities in PR6 and 2XII-B, mirrors were viewed as a potentially attractive concept with near-term advantages as a lower Q neutron source for applications such as a hybrid fission fuel factory or toxic waste burner. However there are down sides to the minimum-B geometry: coil construction is complex; restraining magnetic forces limit field strength and mirror ratios. Furthermore, the magnetic field lines have geodesic curvature which introduces resonant and neoclassical radial transport as observed in early tandem mirror experiments. So what now leads us to think that simple axisymmetric mirror plasmas can be stable? The Russian GDT experiment achieves on-axis 60% beta by peaking of the kinetic plasma pressure near the mirror throat (where the curvature is favorable) to counter-balance the average unfavorable mid-plane curvature. Then a modest augmentation of plasma pressure in the expander results in stability. The GDT
-
Heavy metals in locus ceruleus and motor neurons in motor neuron disease.
Pamphlett, Roger; Kum Jew, Stephen
2013-12-12
The causes of sporadic amyotrophic lateral sclerosis (SALS) and other types of motor neuron disease (MND) remain largely unknown. Heavy metals have long been implicated in MND, and it has recently been shown that inorganic mercury selectively enters human locus ceruleus (LC) and motor neurons. We therefore used silver nitrate autometallography (AMG) to look for AMG-stainable heavy metals (inorganic mercury and bismuth) in LC and motor neurons of 24 patients with MND (18 with SALS and 6 with familial MND) and in the LC of 24 controls. Heavy metals in neurons were found in significantly more MND patients than in controls when comparing: (1) the presence of any versus no heavy metal-containing LC neurons (MND 88%, controls 42%), (2) the median percentage of heavy metal-containing LC neurons (MND 9.5%, control 0.0%), and (3) numbers of individuals with heavy metal-containing LC neurons in the upper half of the percentage range (MND 75%, controls 25%). In MND patients, 67% of remaining spinal motor neurons contained heavy metals; smaller percentages were found in hypoglossal, nucleus ambiguus and oculomotor neurons, but none in cortical motor neurons. The majority of MND patients had heavy metals in both LC and spinal motor neurons. No glia or other neurons, including neuromelanin-containing neurons of the substantia nigra, contained stainable heavy metals. Uptake of heavy metals by LC and lower motor neurons appears to be fairly common in humans, though heavy metal staining in the LC, most likely due to inorganic mercury, was seen significantly more often in MND patients than in controls. The LC innervates many cell types that are affected in MND, and it is possible that MND is triggered by toxicant-induced interactions between LC and motor neurons.
-
Heavy metals in locus ceruleus and motor neurons in motor neuron disease
2013-01-01
Background The causes of sporadic amyotrophic lateral sclerosis (SALS) and other types of motor neuron disease (MND) remain largely unknown. Heavy metals have long been implicated in MND, and it has recently been shown that inorganic mercury selectively enters human locus ceruleus (LC) and motor neurons. We therefore used silver nitrate autometallography (AMG) to look for AMG-stainable heavy metals (inorganic mercury and bismuth) in LC and motor neurons of 24 patients with MND (18 with SALS and 6 with familial MND) and in the LC of 24 controls. Results Heavy metals in neurons were found in significantly more MND patients than in controls when comparing: (1) the presence of any versus no heavy metal-containing LC neurons (MND 88%, controls 42%), (2) the median percentage of heavy metal-containing LC neurons (MND 9.5%, control 0.0%), and (3) numbers of individuals with heavy metal-containing LC neurons in the upper half of the percentage range (MND 75%, controls 25%). In MND patients, 67% of remaining spinal motor neurons contained heavy metals; smaller percentages were found in hypoglossal, nucleus ambiguus and oculomotor neurons, but none in cortical motor neurons. The majority of MND patients had heavy metals in both LC and spinal motor neurons. No glia or other neurons, including neuromelanin-containing neurons of the substantia nigra, contained stainable heavy metals. Conclusions Uptake of heavy metals by LC and lower motor neurons appears to be fairly common in humans, though heavy metal staining in the LC, most likely due to inorganic mercury, was seen significantly more often in MND patients than in controls. The LC innervates many cell types that are affected in MND, and it is possible that MND is triggered by toxicant-induced interactions between LC and motor neurons. PMID:24330485
-
From grasp to language: embodied concepts and the challenge of abstraction.
Arbib, Michael A
2008-01-01
The discovery of mirror neurons in the macaque monkey and the discovery of a homologous "mirror system for grasping" in Broca's area in the human brain has revived the gestural origins theory of the evolution of the human capability for language, enriching it with the suggestion that mirror neurons provide the neurological core for this evolution. However, this notion of "mirror neuron support for the transition from grasp to language" has been worked out in very different ways in the Mirror System Hypothesis model [Arbib, M.A., 2005a. From monkey-like action recognition to human language: an evolutionary framework for neurolinguistics (with commentaries and author's response). Behavioral and Brain Sciences 28, 105-167; Rizzolatti, G., Arbib, M.A., 1998. Language within our grasp. Trends in Neuroscience 21(5), 188-194] and the Embodied Concept model [Gallese, V., Lakoff, G., 2005. The brain's concepts: the role of the sensory-motor system in reason and language. Cognitive Neuropsychology 22, 455-479]. The present paper provides a critique of the latter to enrich analysis of the former, developing the role of schema theory [Arbib, M.A., 1981. Perceptual structures and distributed motor control. In: Brooks, V.B. (Ed.), Handbook of Physiology--The Nervous System II. Motor Control. American Physiological Society, pp. 1449-1480].
-
Hunt, C P J; Pouton, C W; Haynes, J M
2017-06-01
In the developing ventral telencephalon, cells of the lateral ganglionic eminence (LGE) give rise to all medium spiny neurons (MSNs). This development occurs in response to a highly orchestrated series of morphogenetic stimuli that pattern the resultant neurons as they develop. Striatal MSNs are characterised by expression of dopamine receptors, dopamine-and cyclic AMP-regulated phosphoprotein (DARPP32) and the neurotransmitter GABA. In this study, we demonstrate that fine tuning Wnt and hedgehog (SHH) signaling early in human embryonic stem cell differentiation can induce a subpallial progenitor molecular profile. Stimulation of TGFβ signaling pathway by activin-A further supports patterning of progenitors to striatal precursors which adopt an LGE-specific gene signature. Moreover, we report that these MSNs also express markers associated with mature neuron function (cannabinoid, adenosine and dopamine receptors). To facilitate live-cell identification we generated a human embryonic stem cell line using CRISPR-mediated gene editing at the DARPP32 locus (DARPP32 WT/eGFP-AMP-LacZ ). The addition of dopamine to MSNs either increased, decreased or had no effect on intracellular calcium, indicating the presence of multiple dopamine receptor subtypes. In summary, we demonstrate greater control over early fate decisions using activin-A, Wnt and SHH to direct differentiation into MSNs. We also generate a DARPP32 reporter line that enables deeper pharmacological profiling and interrogation of complex receptor interactions in human MSNs. Copyright © 2017 Elsevier Ltd. All rights reserved.
-
Wu, Xian; Yang, Xiangkun; Majumder, Anirban; Swetenburg, Raymond; Goodfellow, Forrest T; Bartlett, Michael G; Stice, Steven L
2017-06-01
Human neural progenitor cells are capable of independent, directed differentiation into astrocytes, oligodendrocytes and neurons and thus offer a potential cell source for developmental neurotoxicity (DNT) systems. Human neural progenitor-derived astrocyte-neuron cocultured at defined ratios mimic cellular heterogeneity and interaction in the central nervous system. Cytochrome P450 enzymes are expressed at a relatively high level in astrocytes and may play a critical role in the biotransformation of endogenous or exogenous compounds, including chlorpyrifos, an organophosphate insecticide that affects the central nervous system. P450 enzymes metabolize chlorpyrifos to chlorpyrifos-oxon, which is then metabolized primarily to 3, 5, 6-trichloropyridinol in addition to diethylphosphate and diethylthiophosphate. These end metabolites are less neurotoxic than chlorpyrifos and chlorpyrifos-oxon. Our objective was to identify the interactive role of astrocytes and neurons in chlorpyrifos-induced human DNT. In neuron-only cultures, chlorpyrifos inhibited neurite length, neurite number and branch points per neuron in a dose-dependent manner during a 48 h exposure, starting at 10 μM. However, in astrocyte-neuron cocultures, astrocytes protected neurons from the effects of chlorpyrifos at higher concentrations, up to and including 30 μM chlorpyrifos and endogenous astrocyte P450 enzymes effectively metabolized chlorpyrifos. The P450 inhibitor SKF525A partly negated the protective effect of astrocytes, allowing reduction in branch points with chlorpyrifos (10 μM). Thus, the scalable and defined astrocyte-neuron cocultures model that we established here has potentially identified a role for P450 enzymes in astrocytic neuroprotection against chlorpyrifos and provides a novel model for addressing DNT in a more accurate multicellular environment. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For
-
Energy Technology Data Exchange (ETDEWEB)
Wang, Xin; Xu, Mei; Frank, Jacqueline A. [Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536 (United States); Ke, Zun-ji [Department of Biochemistry, Shanghai University of Traditional Chinese Medicine, Shanghai, China 201203 (China); Luo, Jia, E-mail: jialuo888@uky.edu [Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536 (United States); Department of Biochemistry, Shanghai University of Traditional Chinese Medicine, Shanghai, China 201203 (China)
2017-04-01
Thiamine (vitamin B1) deficiency (TD) plays a major role in the etiology of Wernicke's encephalopathy (WE) which is a severe neurological disorder. TD induces selective neuronal cell death, neuroinflammation, endoplasmic reticulum (ER) stress and oxidative stress in the brain which are commonly observed in many aging-related neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and progressive supranuclear palsy (PSP). However, the underlying cellular and molecular mechanisms remain unclear. The progress in this line of research is hindered due to the lack of appropriate in vitro models. The neurons derived for the human induced pluripotent stem cells (hiPSCs) provide a relevant and powerful tool for the research in pharmaceutical and environmental neurotoxicity. In this study, we for the first time used human induced pluripotent stem cells (hiPSCs)-derived neurons (iCell neurons) to investigate the mechanisms of TD-induced neurodegeneration. We showed that TD caused a concentration- and duration-dependent death of iCell neurons. TD induced ER stress which was evident by the increase in ER stress markers, such as GRP78, XBP-1, CHOP, ATF-6, phosphorylated eIF2α, and cleaved caspase-12. TD also triggered oxidative stress which was shown by the increase in the expression 2,4-dinitrophenyl (DNP) and 4-hydroxynonenal (HNE). ER stress inhibitors (STF-083010 and salubrinal) and antioxidant N-acetyl cysteine (NAC) were effective in alleviating TD-induced death of iCell neurons, supporting the involvement of ER stress and oxidative stress. It establishes that the iCell neurons are a novel tool to investigate cellular and molecular mechanisms for TD-induced neurodegeneration. - Highlights: • Thiamine deficiency (TD) causes death of human neurons in culture. • TD induces both endoplasmic reticulum (ER) stress and oxidative stress. • Alleviating ER stress and oxidative stress reduces TD
-
International Nuclear Information System (INIS)
Wang, Xin; Xu, Mei; Frank, Jacqueline A.; Ke, Zun-ji; Luo, Jia
2017-01-01
Thiamine (vitamin B1) deficiency (TD) plays a major role in the etiology of Wernicke's encephalopathy (WE) which is a severe neurological disorder. TD induces selective neuronal cell death, neuroinflammation, endoplasmic reticulum (ER) stress and oxidative stress in the brain which are commonly observed in many aging-related neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and progressive supranuclear palsy (PSP). However, the underlying cellular and molecular mechanisms remain unclear. The progress in this line of research is hindered due to the lack of appropriate in vitro models. The neurons derived for the human induced pluripotent stem cells (hiPSCs) provide a relevant and powerful tool for the research in pharmaceutical and environmental neurotoxicity. In this study, we for the first time used human induced pluripotent stem cells (hiPSCs)-derived neurons (iCell neurons) to investigate the mechanisms of TD-induced neurodegeneration. We showed that TD caused a concentration- and duration-dependent death of iCell neurons. TD induced ER stress which was evident by the increase in ER stress markers, such as GRP78, XBP-1, CHOP, ATF-6, phosphorylated eIF2α, and cleaved caspase-12. TD also triggered oxidative stress which was shown by the increase in the expression 2,4-dinitrophenyl (DNP) and 4-hydroxynonenal (HNE). ER stress inhibitors (STF-083010 and salubrinal) and antioxidant N-acetyl cysteine (NAC) were effective in alleviating TD-induced death of iCell neurons, supporting the involvement of ER stress and oxidative stress. It establishes that the iCell neurons are a novel tool to investigate cellular and molecular mechanisms for TD-induced neurodegeneration. - Highlights: • Thiamine deficiency (TD) causes death of human neurons in culture. • TD induces both endoplasmic reticulum (ER) stress and oxidative stress. • Alleviating ER stress and oxidative stress reduces TD
-
fMRI Evidence of ‘Mirror’ Responses to Geometric Shapes
Press, Clare; Catmur, Caroline; Cook, Richard; Widmann, Hannah; Heyes, Cecilia; Bird, Geoffrey
2012-01-01
Mirror neurons may be a genetic adaptation for social interaction [1]. Alternatively, the associative hypothesis [2], [3] proposes that the development of mirror neurons is driven by sensorimotor learning, and that, given suitable experience, mirror neurons will respond to any stimulus. This hypothesis was tested using fMRI adaptation to index populations of cells with mirror properties. After sensorimotor training, where geometric shapes were paired with hand actions, BOLD response was measured while human participants experienced runs of events in which shape observation alternated with action execution or observation. Adaptation from shapes to action execution, and critically, observation, occurred in ventral premotor cortex (PMv) and inferior parietal lobule (IPL). Adaptation from shapes to execution indicates that neuronal populations responding to the shapes had motor properties, while adaptation to observation demonstrates that these populations had mirror properties. These results indicate that sensorimotor training induced populations of cells with mirror properties in PMv and IPL to respond to the observation of arbitrary shapes. They suggest that the mirror system has not been shaped by evolution to respond in a mirror fashion to biological actions; instead, its development is mediated by stimulus-general processes of learning within a system adapted for visuomotor control. PMID:23251653
-
Lipski, Witold J; Wozny, Thomas A; Alhourani, Ahmad; Kondylis, Efstathios D; Turner, Robert S; Crammond, Donald J; Richardson, Robert Mark
2017-09-01
Coupled oscillatory activity recorded between sensorimotor regions of the basal ganglia-thalamocortical loop is thought to reflect information transfer relevant to movement. A neuronal firing-rate model of basal ganglia-thalamocortical circuitry, however, has dominated thinking about basal ganglia function for the past three decades, without knowledge of the relationship between basal ganglia single neuron firing and cortical population activity during movement itself. We recorded activity from 34 subthalamic nucleus (STN) neurons, simultaneously with cortical local field potentials and motor output, in 11 subjects with Parkinson's disease (PD) undergoing awake deep brain stimulator lead placement. STN firing demonstrated phase synchronization to both low- and high-beta-frequency cortical oscillations, and to the amplitude envelope of gamma oscillations, in motor cortex. We found that during movement, the magnitude of this synchronization was dynamically modulated in a phase-frequency-specific manner. Importantly, we found that phase synchronization was not correlated with changes in neuronal firing rate. Furthermore, we found that these relationships were not exclusive to motor cortex, because STN firing also demonstrated phase synchronization to both premotor and sensory cortex. The data indicate that models of basal ganglia function ultimately will need to account for the activity of populations of STN neurons that are bound in distinct functional networks with both motor and sensory cortices and code for movement parameters independent of changes in firing rate. NEW & NOTEWORTHY Current models of basal ganglia-thalamocortical networks do not adequately explain simple motor functions, let alone dysfunction in movement disorders. Our findings provide data that inform models of human basal ganglia function by demonstrating how movement is encoded by networks of subthalamic nucleus (STN) neurons via dynamic phase synchronization with cortex. The data also
-
APP Metabolism Regulates Tau Proteostasis in Human Cerebral Cortex Neurons
Directory of Open Access Journals (Sweden)
Steven Moore
2015-05-01
Full Text Available Accumulation of Aβ peptide fragments of the APP protein and neurofibrillary tangles of the microtubule-associated protein tau are the cellular hallmarks of Alzheimer’s disease (AD. To investigate the relationship between APP metabolism and tau protein levels and phosphorylation, we studied human-stem-cell-derived forebrain neurons with genetic forms of AD, all of which increase the release of pathogenic Aβ peptides. We identified marked increases in intracellular tau in genetic forms of AD that either mutated APP or increased its dosage, suggesting that APP metabolism is coupled to changes in tau proteostasis. Manipulating APP metabolism by β-secretase and γ-secretase inhibition, as well as γ-secretase modulation, results in specific increases and decreases in tau protein levels. These data demonstrate that APP metabolism regulates tau proteostasis and suggest that the relationship between APP processing and tau is not mediated solely through extracellular Aβ signaling to neurons.
-
APP metabolism regulates tau proteostasis in human cerebral cortex neurons.
Moore, Steven; Evans, Lewis D B; Andersson, Therese; Portelius, Erik; Smith, James; Dias, Tatyana B; Saurat, Nathalie; McGlade, Amelia; Kirwan, Peter; Blennow, Kaj; Hardy, John; Zetterberg, Henrik; Livesey, Frederick J
2015-05-05
Accumulation of Aβ peptide fragments of the APP protein and neurofibrillary tangles of the microtubule-associated protein tau are the cellular hallmarks of Alzheimer's disease (AD). To investigate the relationship between APP metabolism and tau protein levels and phosphorylation, we studied human-stem-cell-derived forebrain neurons with genetic forms of AD, all of which increase the release of pathogenic Aβ peptides. We identified marked increases in intracellular tau in genetic forms of AD that either mutated APP or increased its dosage, suggesting that APP metabolism is coupled to changes in tau proteostasis. Manipulating APP metabolism by β-secretase and γ-secretase inhibition, as well as γ-secretase modulation, results in specific increases and decreases in tau protein levels. These data demonstrate that APP metabolism regulates tau proteostasis and suggest that the relationship between APP processing and tau is not mediated solely through extracellular Aβ signaling to neurons. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
-
Nightmare frequency is related to a propensity for mirror behaviors.
Nielsen, Tore; Powell, Russell A; Kuiken, Don
2013-12-01
behaviors during wakefulness, while among males nightmares are associated with threat-related mirror behaviors during wakefulness. They thus support the possibility that the association between mirror behaviors and dream-enacting behaviors is due to a common mirror neuron mechanism that underlies mirror behaviors and nightmares and that involves motor, rather than emotional, resonance. These results have implications for understanding the comorbidity of nightmares and other pathological symptoms such as imitative suicidal behaviors, the influence of observational learning on dissociative symptomatology, and the predominance of threat and aggression in the dream enacting behaviors of REM sleep behavior disorder. Copyright © 2013 Elsevier Inc. All rights reserved.
-
Directory of Open Access Journals (Sweden)
Yuta eMiyazaki
2016-01-01
Full Text Available AbstractThe radial and tangential neural migration pathways are two major neuronal migration streams in humans that are critical during corticogenesis. Corticogenesis is a complex process of neuronal proliferation that is followed by neuronal migration and the formation of axonal connections. Existing histological assessments of these two neuronal migration pathways have limitations inherent to microscopic studies and are confined to small anatomic regions of interest. Thus, little evidence is available about their three-dimensional fiber pathways and development throughout the entire brain. In this study, we imaged and analyzed radial and tangential migration pathways in the whole human brain using high-angular resolution diffusion MR imaging (HARDI tractography. We imaged ten fixed, postmortem fetal (17 gestational weeks (GW, 18 GW, 19 GW, three 20 GW, three 21 GW and 22 GW and eight in vivo newborn (two 30 GW, 34 GW, 35 GW and four 40 GW brains with no neurological/pathological conditions. We statistically compared the volume of the left and right radial and tangential migration pathways, and the volume of the radial migration pathways of the anterior and posterior regions of the brain. In specimens 22 GW or younger, the volume of radial migration pathways of the left hemisphere was significantly larger than that of the right hemisphere. The volume of posterior radial migration pathways was also larger when compared to the anterior pathways in specimens 22 GW or younger. In contrast, no significant differences were observed in the radial migration pathways of brains older than 22 GW. Moreover, our study did not identify any significant differences in volumetric laterality in the tangential migration pathways. These results suggest that these two neuronal migration pathways develop and regress differently, and radial neuronal migration varies regionally based on hemispheric and anterior-posterior laterality, potentially explaining regional
-
Seth, Rohit; Corniola, Rikki S.; Gower-Winter, Shannon D.; Morgan, Thomas J., Jr.; Bishop, Brian; Levenson, Cathy W.
2015-01-01
Previous studies have shown that zinc deficiency leads to apoptosis of neuronal precursor cells in vivo and in vitro. In addition to the role of p53 as a nuclear transcription factor in zinc deficient cultured human neuronal precursors (NT-2), we have now identified the translocation of phosphorylated p53 to the mitochondria and p53-dependent…
-
Human-Specific Histone Methylation Signatures at Transcription Start Sites in Prefrontal Neurons
Cheung, Iris; Bharadwaj, Rahul; Chou, Hsin-Jung; Houston, Isaac B.; Peter, Cyril J.; Mitchell, Amanda C.; Yao, Wei-Dong; Myers, Richard H.; Chen, Jiang-fan; Preuss, Todd M.; Rogaev, Evgeny I.; Jensen, Jeffrey D.; Weng, Zhiping; Akbarian, Schahram
2012-01-01
Cognitive abilities and disorders unique to humans are thought to result from adaptively driven changes in brain transcriptomes, but little is known about the role of cis-regulatory changes affecting transcription start sites (TSS). Here, we mapped in human, chimpanzee, and macaque prefrontal cortex the genome-wide distribution of histone H3 trimethylated at lysine 4 (H3K4me3), an epigenetic mark sharply regulated at TSS, and identified 471 sequences with human-specific enrichment or depletion. Among these were 33 loci selectively methylated in neuronal but not non-neuronal chromatin from children and adults, including TSS at DPP10 (2q14.1), CNTN4 and CHL1 (3p26.3), and other neuropsychiatric susceptibility genes. Regulatory sequences at DPP10 and additional loci carried a strong footprint of hominid adaptation, including elevated nucleotide substitution rates and regulatory motifs absent in other primates (including archaic hominins), with evidence for selective pressures during more recent evolution and adaptive fixations in modern populations. Chromosome conformation capture at two neurodevelopmental disease loci, 2q14.1 and 16p11.2, revealed higher order chromatin structures resulting in physical contact of multiple human-specific H3K4me3 peaks spaced 0.5–1 Mb apart, in conjunction with a novel cis-bound antisense RNA linked to Polycomb repressor proteins and downregulated DPP10 expression. Therefore, coordinated epigenetic regulation via newly derived TSS chromatin could play an important role in the emergence of human-specific gene expression networks in brain that contribute to cognitive functions and neurological disease susceptibility in modern day humans. PMID:23185133
-
Intuitive optics: what great apes infer from mirrors and shadows.
Völter, Christoph J; Call, Josep
2018-05-02
There is ongoing debate about the extent to which nonhuman animals, like humans, can go beyond first-order perceptual information to abstract structural information from their environment. To provide more empirical evidence regarding this question, we examined what type of information great apes (chimpanzees, bonobos, and orangutans) gain from optical effects such as shadows and mirror images. In an initial experiment, we investigated whether apes would use mirror images and shadows to locate hidden food. We found that all examined ape species used these cues to find the food. Follow-up experiments showed that apes neither confused these optical effects with the food rewards nor did they merely associate cues with food. First, naïve chimpanzees used the shadow of the hidden food to locate it but they did not learn within the same number of trials to use a perceptually similar rubber patch as indicator of the hidden food reward. Second, apes made use of the mirror images to estimate the distance of the hidden food from their own body. Depending on the distance, apes either pointed into the direction of the food or tried to access the hidden food directly. Third, apes showed some sensitivity to the geometrical relation between mirror orientation and mirrored objects when searching hidden food. Fourth, apes tended to interpret mirror images and pictures of these mirror images differently depending on their prior knowledge. Together, these findings suggest that apes are sensitive to the optical relation between mirror images and shadows and their physical referents.
-
Ishii, Misawa Niki; Yamamoto, Koji; Shoji, Masanobu; Asami, Asano; Kawamata, Yuji
2017-08-15
Accurate risk assessment for drug-induced seizure is expected to be performed before entering clinical studies because of its severity and fatal damage to drug development. Induced pluripotent stem cell (iPSC) technology has allowed the use of human neurons and glial cells in toxicology studies. Recently, several studies showed the advantage of co-culture system of human iPSC (hiPSC)-derived neurons with rodent/human primary astrocytes regarding neuronal functions. However, the application of hiPSC-derived neurons for seizure risk assessment has not yet been fully addressed, and not at all when co-cultured with hiPSC-derived astrocytes. Here, we characterized hiPSC-derived neurons co-cultured with hiPSC-derived astrocytes to discuss how hiPSC-derived neurons are useful to assess seizure risk of drugs. First, we detected the frequency of spikes and synchronized bursts hiPSC-derived neurons when co-cultured with hiPSC-derived astrocytes for 8 weeks. This synchronized burst was suppressed by the treatment with 6-cyano-7-nitroquinoxaline-2,3-dione, α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor antagonist, and D-(-)-2-amino-5-phosphonopentanoic acid, an N-Methyl-d-aspartate (NMDA) receptor antagonist. These data suggested that co-cultured hiPSC-derived neurons formed synaptic connections mediated by AMPA and NMDA receptors. We also demonstrated that co-cultured hiPSC-derived neurons showed epileptiform activity upon treatment with gabazine or kaliotoxin. Finally, we performed single-cell transcriptome analysis in hiPSC-derived neurons and found that hiPSC-derived astrocytes activated the pathways involved in the activities of AMPA and NMDA receptor functions, neuronal polarity, and axon guidance in hiPSC-derived neurons. These data suggested that hiPSC-derived astrocytes promoted the development of action potential, synaptic functions, and neuronal networks in hiPSC-derived neurons, and then these functional alterations result in the epileptiform
-
Transduced human copper chaperone for Cu,Zn-SOD (PEP-1-CCS) protects against neuronal cell death.
Choi, Soo Hyun; Kim, Dae Won; Kim, So Young; An, Jae Jin; Lee, Sun Hwa; Choi, Hee Soon; Sohn, Eun Jung; Hwang, Seok-Il; Won, Moo Ho; Kang, Tae-Cheon; Kwon, Hyung Joo; Kang, Jung Hoon; Cho, Sung-Woo; Park, Jinseu; Eum, Won Sik; Choi, Soo Young
2005-12-31
Reactive oxygen species (ROS) contribute to the development of various human diseases. Cu,Zn-superoxide dismutase (SOD) is one of the major means by which cells counteract the deleterious effects of ROS. SOD activity is dependent upon bound copper ions supplied by its partner metallochaperone protein, copper chaperone for SOD (CCS). In the present study, we investigated the protective effects of PEP-1-CCS against neuronal cell death and ischemic insults. When PEP-1-CCS was added to the culture medium of neuronal cells, it rapidly entered the cells and protected them against paraquat-induced cell death. Moreover, transduced PEP-1-CCS markedly increased endogenous SOD activity in the cells. Immunohistochemical analysis revealed that it prevented neuronal cell death in the hippocampus in response to transient forebrain ischemia. These results suggest that CCS is essential to activate SOD, and that transduction of PEP-1-CCS provides a potential strategy for therapeutic delivery in various human diseases including stroke related to SOD or ROS.
-
Gatti, Roberto; Rocca, Maria A; Fumagalli, Silvia; Cattrysse, Erik; Kerckhofs, Eric; Falini, Andrea; Filippi, Massimo
2017-04-01
Action observation and execution activate regions that are part of the motor and mirror neuron systems (MNS). Using functional magnetic resonance (fMRI), we defined the presence and extent of MNS activation during three different motor tasks with the dominant, right-upper limb in healthy individuals. The influence of the modality of task administration (execution, observation, observation and execution) was also investigated. fMRI scans during the execution (E) of a motor task, the observation (O) of a video showing the same task performed by another person and the simultaneous observation and execution (OE) of the task were obtained from three groups of healthy subjects (15 subjects per group) randomized to perform: a simple motor (SM) task, a complex motor (CM) task and a finalistic motor (FM) task. Manual dexterity was assessed using the 9-hole peg test and maximum finger tapping frequency. MNS activation was higher during FM than SM or CM tasks, independently from the modality of administration (E, O, or OE). Inferior frontal gyrus recruitment was more significant during SM than CM tasks in the E and O conditions. Compared to SM and FM, CM task resulted in increased recruitment of brain regions involved in complex motor task performance. Compared to O and E, OE resulted in the recruitment of additional, specific, brain areas in the cerebellum, temporal and parietal lobes. The modality of administration and the type of task modulated MNS recruitment during motor acts. This might have practical implications for the set-up of individualized motor rehabilitation strategies.
-
Exploring Visuomotor Priming Following Biological and Non-Biological Stimuli
Gowen, E.; Bradshaw, C.; Galpin, A.; Lawrence, A.; Poliakoff, E.
2010-01-01
Observation of human actions influences the observer's own motor system, termed visuomotor priming, and is believed to be caused by automatic activation of mirror neurons. Evidence suggests that priming effects are larger for biological (human) as opposed to non-biological (object) stimuli and enhanced when viewing stimuli in mirror compared to…
-
International Nuclear Information System (INIS)
Rattanachayoto, P.; Tritanon, O.; Laothamatas, J.; Sungkarat, W.
2012-01-01
Alzheimer's disease (AD) is the most common cause of dementia. There are lots of old people suffering from the disease. Mild cognitive impairment (MCI) is a transitional state between normal aging and dementia. An individual with MCI has an increased risk of developing AD. The mirror neuron system (MNS), activated during the observation and execution of actions, has been linked with cognitive processes.The objective of this study is to examine the MNS abnormalities in elders with MCI and AD. Ninety-two subjects (5 MCI,7 mild AD, and 80 cognitively normal) were studied by using functional magnetic resonance imaging (fMRI). In the fMRI experiment, subjects were asked to observe a video showing hand movement (tearing a piece of paper) and a control condition (observing a fixation point).The image data were analyzed using SPM2 (Statistical Parametric Mapping).There were significant activations of bilateral inferior frontal lobule and inferior parietal lobule due to the observation of hand movement.The brain activations of the normal group were statistical significant greater than those in the MCI and mild AD groups.There was no significant difference between the MCI and mild AD groups. Elders with MCI and mild AD had fewer MNS activations than the normal controls, suggesting that the dysfunction of MNS may underlie cognitive impairments in MCI and AD patients.These findings imply that fMRI is sufficiently sensitive to detect MNS changes occurring in MCI and AD.
-
A neuron-astrocyte transistor-like model for neuromorphic dressed neurons.
Valenza, G; Pioggia, G; Armato, A; Ferro, M; Scilingo, E P; De Rossi, D
2011-09-01
Experimental evidences on the role of the synaptic glia as an active partner together with the bold synapse in neuronal signaling and dynamics of neural tissue strongly suggest to investigate on a more realistic neuron-glia model for better understanding human brain processing. Among the glial cells, the astrocytes play a crucial role in the tripartite synapsis, i.e. the dressed neuron. A well-known two-way astrocyte-neuron interaction can be found in the literature, completely revising the purely supportive role for the glia. The aim of this study is to provide a computationally efficient model for neuron-glia interaction. The neuron-glia interactions were simulated by implementing the Li-Rinzel model for an astrocyte and the Izhikevich model for a neuron. Assuming the dressed neuron dynamics similar to the nonlinear input-output characteristics of a bipolar junction transistor, we derived our computationally efficient model. This model may represent the fundamental computational unit for the development of real-time artificial neuron-glia networks opening new perspectives in pattern recognition systems and in brain neurophysiology. Copyright © 2011 Elsevier Ltd. All rights reserved.
-
Gittins, Rebecca; Harrison, Paul J
2004-03-15
There are an increasing number of quantitative morphometric studies of the human cerebral cortex, especially as part of comparative investigations of major psychiatric disorders. In this context, the present study had two aims. First, to provide quantitative data regarding key neuronal morphometric parameters in the anterior cingulate cortex. Second, to compare the results of conventional Nissl staining with those observed after immunostaining with NeuN, an antibody becoming widely used as a selective neuronal marker. We stained adjacent sections of area 24b from 16 adult brains with cresyl violet or NeuN. We measured the density of pyramidal and non-pyramidal neurons, and the size and shape of pyramidal neurons, in laminae II, III, Va, Vb and VI, using two-dimensional counting methods. Strong correlations between the two modes of staining were seen for all variables. However, NeuN gave slightly higher estimates of neuronal density and size, and a more circular perikaryal shape. Brain pH was correlated with neuronal size, measured with both methods, and with neuronal shape. Age and post-mortem interval showed no correlations with any parameter. These data confirm the value of NeuN as a tool for quantitative neuronal morphometric studies in routinely processed human brain tissue. Absolute values are highly correlated between NeuN and cresyl violet stains, but cannot be interchanged. NeuN may be particularly useful when it is important to distinguish small neurons from glia, such as in cytoarchitectural studies of the cerebral cortex in depression and schizophrenia.
-
International Nuclear Information System (INIS)
Carlson, G.A.; Schultz, K.R.; Smith, A.C. Jr.
1978-01-01
Basic requirements for the pilot plants are that they produce a net product and that they have a potential for commercial upgrade. We have investigated a small standard mirror fusion-fission hybrid, a two-component tandem mirror hybrid, and two versions of a field-reversed mirror fusion reactor--one a steady state, single cell reactor with a neutral beam-sustained plasma, the other a moving ring field-reversed mirror where the plasma passes through a reaction chamber with no energy addition
-
Anand, U; Sinisi, M; Fox, M; MacQuillan, A; Quick, T; Korchev, Y; Bountra, C; McCarthy, T; Anand, P
2016-01-01
Mycolactone is a polyketide toxin secreted by the mycobacterium Mycobacterium ulcerans, responsible for the extensive hypoalgesic skin lesions characteristic of patients with Buruli ulcer. A recent pre-clinical study proposed that mycolactone may produce analgesia via activation of the angiotensin II type 2 receptor (AT2R). In contrast, AT2R antagonist EMA401 has shown analgesic efficacy in animal models and clinical trials for neuropathic pain. We therefore investigated the morphological and functional effects of mycolactone in cultured human and rat dorsal root ganglia (DRG) neurons and the role of AT2R using EMA401. Primary sensory neurons were prepared from avulsed cervical human DRG and rat DRG; 24 h after plating, neurons were incubated for 24 to 96 h with synthetic mycolactone A/B, followed by immunostaining with antibodies to PGP9.5, Gap43, β tubulin, or Mitotracker dye staining. Acute functional effects were examined by measuring capsaicin responses with calcium imaging in DRG neuronal cultures treated with mycolactone. Morphological effects: Mycolactone-treated cultures showed dramatically reduced numbers of surviving neurons and non-neuronal cells, reduced Gap43 and β tubulin expression, degenerating neurites and reduced cell body diameter, compared with controls. Dose-related reduction of neurite length was observed in mycolactone-treated cultures. Mitochondria were distributed throughout the length of neurites and soma of control neurons, but clustered in the neurites and soma of mycolactone-treated neurons. Functional effects: Mycolactone-treated human and rat DRG neurons showed dose-related inhibition of capsaicin responses, which were reversed by calcineurin inhibitor cyclosporine and phosphodiesterase inhibitor 3-isobutyl-1-Methylxanthine, indicating involvement of cAMP/ATP reduction. The morphological and functional effects of mycolactone were not altered by Angiotensin II or AT2R antagonist EMA401. Mycolactone induces toxic effects in DRG
-
Directory of Open Access Journals (Sweden)
Melissa L M Khoo
Full Text Available Bone marrow-derived human mesenchymal stem cells (hMSCs have shown promise in in vitro neuronal differentiation and in cellular therapy for neurodegenerative disorders, including Parkinson' disease. However, the effects of intracerebral transplantation are not well defined, and studies do not agreed on the optimal neuronal differentiation method. Here, we investigated three growth factor-based neuronal differentiation procedures (using FGF-2/EGF/PDGF/SHH/FGF-8/GDNF, and found all to be capable of eliciting an immature neural phenotype, in terms of cell morphology and gene/protein expression. The neuronal-priming (FGF-2/EGF method induced neurosphere-like formation and the highest NES and NR4A2 expression by hMSCs. Transplantation of undifferentiated and neuronal-primed hMSCs into the striatum and substantia nigra of 6-OHDA-lesioned hemiparkinsonian rats revealed transient graft survival of 7 days, despite the reported immunosuppressive properties of MSCs and cyclosporine-immunosuppression of rats. Neither differentiation of hMSCs nor induction of host neurogenesis was observed at injection sites, and hMSCs continued producing mesodermal fibronectin. Strategies for improving engraftment and differentiation post-transplantation, such as prior in vitro neuronal-priming, nigral and striatal grafting, and co-transplantation of olfactory ensheathing cells that promote neural regeneration, were unable to provide advantages. Innate inflammatory responses (Iba-1-positive microglia/macrophage and GFAP-positive astrocyte activation and accumulation were detected around grafts within 7 days. Our findings indicate that growth factor-based methods allow hMSC differentiation toward immature neuronal-like cells, and contrary to previous reports, only transient survival and engraftment of hMSCs occurs following transplantation in immunosuppressed hemiparkinsonian rats. In addition, suppression of host innate inflammatory responses may be a key factor for
-
Bronze rainbow hologram mirrors
Dawson, P.
2006-02-01
This project draws on holographic embossing techniques, ancient artistic conventions of bronze mirror design and modelling and casting processes to accomplish portraiture of reflection. Laser scanning, 3D computer graphics and holographic imaging are employed to enable a permanent 3D static holographic image to appear integrated with the real-time moving reflection of a viewer's face in a polished bronze disc. The disc and the figure which holds it (caryatid) are cast in bronze from a lost wax model, a technique which has been used for millennia to make personal mirrors. The Caryatid form of bronze mirror which went through many permutations in ancient Egyptian, Greece and Rome shows a plethora of expressive figure poses ranging from sleek nudes to highly embellished multifigure arrangements. The prototype of this series was made for Australian choreographer Graeme Murphy, Artistic Director of the Sydney Dance Company. Each subsequent mirror will be unique in figure and holographic imagery as arranged between artist and subject. Conceptually this project references both the modern experience of viewing mirrors retrieved from ancient tombs, which due to deterioration of the surface no longer reflect, and the functioning of Chinese Magic mirrors, which have the ability to project a predetermined image. Inspired by the metaphorical potential of these mirrors, which do not reflect the immediate reality of the viewer, this bronze hologram mirror series enables each viewer to reflect upon himself or herself observing simultaneously the holographic image and their own partially obliterated reflection.
-
Modulation of the mirror system by social relevance.
Kilner, James M; Marchant, Jennifer L; Frith, Chris D
2006-09-01
When we observe the actions of others, certain areas of the brain are activated in a similar manner as to when we perform the same actions ourselves. This 'mirror system' includes areas in the ventral premotor cortex and the inferior parietal lobule. Experimental studies suggest that action observation automatically elicits activity in the observer, which precisely mirrors the activity observed. In this case we would expect this activity to be independent of observer's viewpoint. Here we use whole-head magnetoencephalography (MEG) to record cortical activity of human subjects whilst they watched a series of videos of an actor making a movement recorded from different viewpoints. We show that one cortical response to action observation (oscillatory activity in the 7-12 Hz frequency range) is modulated by the relationship between the observer and the actor. We suggest that this modulation reflects a mechanism that filters information into the 'mirror system', allowing only socially relevant information to pass.
-
Human periapical cyst-mesenchymal stem cells differentiate into neuronal cells.
Marrelli, M; Paduano, F; Tatullo, M
2015-06-01
It was recently reported that human periapical cysts (hPCys), a commonly occurring odontogenic cystic lesion of inflammatory origin, contain mesenchymal stem cells (MSCs) with the capacity for self-renewal and multilineage differentiation. In this study, periapical inflammatory cysts were compared with dental pulp to determine whether this tissue may be an alternative accessible tissue source of MSCs that retain the potential for neurogenic differentiation. Flow cytometry and immunofluorescence analysis indicated that hPCy-MSCs and dental pulp stem cells spontaneously expressed the neuron-specific protein β-III tubulin and the neural stem-/astrocyte-specific protein glial fibrillary acidic protein (GFAP) in their basal state before differentiation occurs. Furthermore, undifferentiated hPCy-MSCs showed a higher expression of transcripts for neuronal markers (β-III tubulin, NF-M, MAP2) and neural-related transcription factors (MSX-1, Foxa2, En-1) as compared with dental pulp stem cells. After exposure to neurogenic differentiation conditions (neural media containing epidermal growth factor [EGF], basic fibroblast growth factor [bFGF], and retinoic acid), the hPCy-MSCs showed enhanced expression of β-III tubulin and GFAP proteins, as well as increased expression of neurofilaments medium, neurofilaments heavy, and neuron-specific enolase at the transcript level. In addition, neurally differentiated hPCy-MSCs showed upregulated expression of the neural transcription factors Pitx3, Foxa2, Nurr1, and the dopamine-related genes tyrosine hydroxylase and dopamine transporter. The present study demonstrated for the first time that hPCy-MSCs have a predisposition toward the neural phenotype that is increased when exposed to neural differentiation cues, based on upregulation of a comprehensive set of proteins and genes that define neuronal cells. In conclusion, these results provide evidence that hPCy-MSCs might be another optimal source of neural/glial cells for cell
-
Wilkinson, Molly; Kane, Tara; Wang, Rongpin; Takahashi, Emi
2017-12-01
The thalamus plays an important role in signal relays in the brain, with thalamocortical (TC) neuronal pathways linked to various sensory/cognitive functions. In this study, we aimed to see fetal and postnatal development of the thalamus including neuronal migration to the thalamus and the emergence/maturation of the TC pathways. Pathways from/to the thalami of human postmortem fetuses and in vivo subjects ranging from newborns to adults with no neurological histories were studied using high angular resolution diffusion MR imaging (HARDI) tractography. Pathways likely linked to neuronal migration from the ventricular zone and ganglionic eminence (GE) to the thalami were both successfully detected. Between the ventricular zone and thalami, more tractography pathways were found in anterior compared with posterior regions, which was well in agreement with postnatal observations that the anterior TC segment had more tract count and volume than the posterior segment. Three different pathways likely linked to neuronal migration from the GE to the thalami were detected. No hemispheric asymmetry of the TC pathways was quantitatively observed during development. These results suggest that HARDI tractography is useful to identify multiple differential neuronal migration pathways in human brains, and regional differences in brain development in fetal ages persisted in postnatal development. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
-
Mirror Fusion Test Facility: an intermediate device to a mirror fusion reactor
International Nuclear Information System (INIS)
Karpenko, V.N.
1983-01-01
The Mirror Fusion Test Facility (MFTF-B) now under construction at Lawrence Livermore National Laboratory represents more than an order-of-magnitude step from earlier magnetic-mirror experiments toward a future mirror fusion reactor. In fact, when the device begins operating in 1986, the Lawson criteria of ntau = 10 14 cm -3 .s will almost be achieved for D-T equivalent operation, thus signifying scientific breakeven. Major steps have been taken to develop MFTF-B technologies for tandem mirrors. Steady-state, high-field, superconducting magnets at reactor-revelant scales are used in the machine. The 30-s beam pulses, ECRH, and ICRH will also introduce steady-state technologies in those systems
-
International Nuclear Information System (INIS)
Moir, R.W.
1981-01-01
A mirror plasma apparatus which utilizes shielding by arc discharge to form a blanket plasma and lithium walls to reduce neutron damage to the wall of the apparatus. An embodiment involves a rotating liquid lithium blanket for a tandem mirror plasma apparatus wherein the first wall of the central mirror cell is made of liquid lithium which is spun with angular velocity great enough to keep the liquid lithium against the first material wall, a blanket plasma preventing the lithium vapor from contaminating the plasma
-
Zagoura, Dimitra; Canovas-Jorda, David; Pistollato, Francesca; Bremer-Hoffmann, Susanne; Bal-Price, Anna
2017-06-01
Human induced pluripotent stem cells (hiPSCs) are considered as a powerful tool for drug and chemical screening and development of new in vitro testing strategies in the field of toxicology, including neurotoxicity evaluation. These cells are able to expand and efficiently differentiate into different types of neuronal and glial cells as well as peripheral neurons. These human cells-based neuronal models serve as test systems for mechanistic studies on different pathways involved in neurotoxicity. One of the well-known mechanisms that are activated by chemically-induced oxidative stress is the Nrf2 signaling pathway. Therefore, in the current study, we evaluated whether Nrf2 signaling machinery is expressed in human induced pluripotent stem cells (hiPSCs)-derived mixed neuronal/glial culture and if so whether it becomes activated by rotenone-induced oxidative stress mediated by complex I inhibition of mitochondrial respiration. Rotenone was found to induce the activation of Nrf2 signaling particularly at the highest tested concentration (100 nM), as shown by Nrf2 nuclear translocation and the up-regulation of the Nrf2-downstream antioxidant enzymes, NQO1 and SRXN1. Interestingly, exposure to rotenone also increased the number of astroglial cells in which Nrf2 activation may play an important role in neuroprotection. Moreover, rotenone caused cell death of dopaminergic neurons since a decreased percentage of tyrosine hydroxylase (TH + ) cells was observed. The obtained results suggest that hiPSC-derived mixed neuronal/glial culture could be a valuable in vitro human model for the establishment of neuronal specific assays in order to link Nrf2 pathway activation (biomarker of oxidative stress) with additional neuronal specific readouts that could be applied to in vitro neurotoxicity evaluation. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.
-
Directory of Open Access Journals (Sweden)
Yuhai Zhao
2017-12-01
Full Text Available Several independent laboratories have recently reported the detection of bacterial nucleic acid sequences or bacterial-derived neurotoxins, such as highly inflammatory lipopolysaccharide (LPS, within Alzheimer’s disease (AD affected brain tissues. Whether these bacterial neurotoxins originate from the gastrointestinal (GI tract microbiome, a possible brain microbiome or some dormant pathological microbiome is currently not well understood. Previous studies indicate that the co-localization of pro-inflammatory LPS with AD-affected brain cell nuclei suggests that there may be a contribution of this neurotoxin to genotoxic events that support inflammatory neurodegeneration and failure in homeostatic gene expression. In this report we provide evidence that in sporadic AD, LPS progressively accumulates in neuronal parenchyma and appears to preferentially associate with the periphery of neuronal nuclei. Run-on transcription studies utilizing [α-32P]-uridine triphosphate incorporation into newly synthesized total RNA further indicates that human neuronal-glial (HNG cells in primary co-culture incubated with LPS exhibit significantly reduced output of DNA transcription products. These studies suggest that in AD LPS may impair the efficient readout of neuronal genetic information normally required for the homeostatic operation of brain cell function and may contribute to a progressive disruption in the read-out of genetic information.
-
D’Avanzo, Carla; Sliwinski, Christopher; Wagner, Steven L.; Tanzi, Rudolph E.; Kim, Doo Yeon; Kovacs, Dora M.
2015-01-01
Soluble γ-secretase modulators (SGSMs) selectively decrease toxic amyloid β (Aβ) peptides (Aβ42). However, their effect on the physiologic functions of γ-secretase has not been tested in human model systems. γ-Secretase regulates fate determination of neural progenitor cells. Thus, we studied the impact of SGSMs on the neuronal differentiation of ReNcell VM (ReN) human neural progenitor cells (hNPCs). Quantitative PCR analysis showed that treatment of neurosphere-like ReN cell aggregate cultures with γ-secretase inhibitors (GSIs), but not SGSMs, induced a 2- to 4-fold increase in the expression of the neuronal markers Tuj1 and doublecortin. GSI treatment also induced neuronal marker protein expression, as shown by Western blot analysis. In the same conditions, SGSM treatment selectively reduced endogenous Aβ42 levels by ∼80%. Mechanistically, we found that Notch target gene expressions were selectively inhibited by a GSI, not by SGSM treatment. We can assert, for the first time, that SGSMs do not affect the neuronal differentiation of hNPCs while selectively decreasing endogenous Aβ42 levels in the same conditions. Our results suggest that our hNPC differentiation system can serve as a useful model to test the impact of GSIs and SGSMs on both endogenous Aβ levels and γ-secretase physiologic functions including endogenous Notch signaling.—D’Avanzo, C., Sliwinski, C., Wagner, S. L., Tanzi, R. E., Kim, D. Y., Kovacs, D. M. γ-Secretase modulators reduce endogenous amyloid β42 levels in human neural progenitor cells without altering neuronal differentiation. PMID:25903103
-
International Nuclear Information System (INIS)
Aspinwall, P.S.; Luetken, C.A.
1991-01-01
We analyze the mirror manifold hypothesis in one and three dimensions using the simplest available representations of the N = 2 superconformal algebra. The symmetries of these tensor models can be divided out to give an explicit representation of the mirror, and we give a simple group theoretical algorithm for determining which symmetries should be used. We show that the mirror of a superconformal field theory does not always have a geometrical interpretation, but when it does, deformations of complex structure of one manifold are reflected in deformations of the Kaehler form of the mirror manifold, and we show how the large radius limit of a manifold corresponds to a large complex structure limit in the mirror manifold. The mirror of the Tian-Yau three generation model is constructed both as a conformal field theory and as an algebraic variety with Euler number six. The Hodge numbers of this manifolds are fixed, but the intersection numbes are highly ambiguous, presumably reflected a rich structure of multicritical points in the moduli space of the field theory. (orig.)
-
Directory of Open Access Journals (Sweden)
Hayder eAmin
2016-03-01
Full Text Available The recent availability of human induced pluripotent stem cells (hiPSCs holds great promise as a novel source of human-derived neurons for cell and tissue therapies as well as for in vitro drug screenings that might replace the use of animal models. However, there is still a considerable lack of knowledge on the functional properties of hiPSC-derived neuronal networks, thus limiting their application. Here, upon optimization of cell culture protocols, we demonstrate that both spontaneous and evoked electrical spiking activities of these networks can be characterized on-chip by taking advantage of the resolution provided by CMOS multielectrode arrays (CMOS-MEAs. These devices feature a large and closely-spaced array of 4096 simultaneously recording electrodes and multi-site on-chip electrical stimulation. Our results show that networks of human-derived neurons can respond to electrical stimulation with a physiological repertoire of spike waveforms after three months of cell culture, a period of time during which the network undergoes the expression of developing patterns of spontaneous spiking activity. To achieve this, we have investigated the impact on the network formation and on the emerging network-wide functional properties induced by different biochemical substrates, i.e. poly-dl-ornithine (PDLO, poly-l-ornithine (PLO, and polyethylenimine (PEI, that were used as adhesion promoters for the cell culture. Interestingly, we found that neuronal networks grown on PDLO coated substrates show significantly higher spontaneous firing activity, reliable responses to low-frequency electrical stimuli, and an appropriate level of PSD-95 that may denote a physiological neuronal maturation profile and synapse stabilization. However, our results also suggest that even three-month culture might not be sufficient for human-derived neuronal network maturation. Taken together, our results highlight the tight relationship existing between substrate coatings
-
Hodgin, Katie L; Graham, Dan J
2016-01-01
Previous research has indicated that self-awareness-inducing mirrors can successfully incite behaviors that align with one's personal values, such as helping others. Other research has found a large discrepancy between the high percentage of young adults who report valuing the healthfulness of physical activity (PA) and the low percentage who actually meet PA participation standards. However, few studies have examined how mirror exposure and both perceived and actual body size influence highly valued PA participation among college students. The present study assessed stair versus elevator use on a western college campus and hypothesized that mirror exposure would increase the more personally healthy transportation method of stair use. In accordance with previous research, it was also hypothesized that males and those with a lower body mass index (BMI) would be more likely to take the stairs, and that body size distorting mirrors would impact the stair-elevator decision. One hundred sixty-seven students (51% male) enrolled in an introductory psychology course were recruited to take a survey about their "transportation choices" at an indoor campus parking garage. Participants were individually exposed to either no mirror, a standard full-length mirror, or a full-length mirror manipulated to make the reflected body size appear either slightly thinner or slightly wider than normal before being asked to go to the fourth floor of the garage for a survey. Participants' choice of floor-climbing method (stairs or elevator) was recorded, and they were administered an Internet-based survey assessing demographic information, BMI, self-awareness, perceived body size, and other variables likely to be associated with stair use. Results from logistic regression analyses revealed that participants who were not exposed to a mirror [odds ratios (OR) = 0.37, 95% CI: 0.14-0.96], males (OR = 0.33, 95% CI: 0.13-0.85), those with lower BMI (OR = 0.84, 95% CI: 0.71-0.99), those
-
Directory of Open Access Journals (Sweden)
Katie L Hodgin
2016-04-01
Full Text Available AbstractPrevious research has indicated that self-awareness-inducing mirrors can successfully incite behaviors that align with one’s personal values, such as helping others. Other research has found a large discrepancy between the high percentage of young adults who report valuing the healthfulness of physical activity (PA and the low percentage who actually meet PA participation standards. Few studies, however, have examined how mirror exposure and both perceived and actual body size influence highly-valued PA participation among college students. The present study assessed stair versus elevator use on a western college campus and hypothesized that mirror exposure would increase the more personally-healthy transportation method of stair use. In accordance with previous research, it was also hypothesized that males and those with a lower body mass index (BMI would be more likely to take the stairs, and that body-size distorting mirrors would impact the stair-elevator decision. One hundred and sixty-seven students (51% male enrolled in an introductory psychology course were recruited to take a survey about their transportation choices at an indoor campus parking garage. Participants were individually exposed to either no mirror, a standard full-length mirror, or a full-length mirror manipulated to make the reflected body size appear either slightly thinner or slightly wider than normal before being asked to go to the fourth floor of the garage for a survey. Participants’ choice of floor climbing method (stairs or elevator was recorded and they were administered an internet-based survey assessing demographic information, BMI, self-awareness, perceived body size, and other variables likely to be associated with stair use. Results from logistic regression analyses revealed that participants who were not exposed to a mirror (OR = 0.37, 95% CI: 0.14 – 0.96, males (OR = 0.33, 95% CI: 0.13 – 0.85, those with lower BMI (OR = 0.84, 95% CI: 0.71
-
Directory of Open Access Journals (Sweden)
Linn Wicklund
Full Text Available Cognitive impairment in Alzheimer's disease (AD patients is associated with a decline in the levels of growth factors, impairment of axonal transport and marked degeneration of basal forebrain cholinergic neurons (BFCNs. Neurogenesis persists in the adult human brain, and the stimulation of regenerative processes in the CNS is an attractive prospect for neuroreplacement therapy in neurodegenerative diseases such as AD. Currently, it is still not clear how the pathophysiological environment in the AD brain affects stem cell biology. Previous studies investigating the effects of the β-amyloid (Aβ peptide on neurogenesis have been inconclusive, since both neurogenic and neurotoxic effects on progenitor cell populations have been reported. In this study, we treated pluripotent human embryonic stem (hES cells with nerve growth factor (NGF as well as with fibrillar and oligomeric Aβ1-40 and Aβ1-42 (nM-µM concentrations and thereafter studied the differentiation in vitro during 28-35 days. The process applied real time quantitative PCR, immunocytochemistry as well as functional studies of intracellular calcium signaling. Treatment with NGF promoted the differentiation into functionally mature BFCNs. In comparison to untreated cells, oligomeric Aβ1-40 increased the number of functional neurons, whereas oligomeric Aβ1-42 suppressed the number of functional neurons. Interestingly, oligomeric Aβ exposure did not influence the number of hES cell-derived neurons compared with untreated cells, while in contrast fibrillar Aβ1-40 and Aβ1-42 induced gliogenesis. These findings indicate that Aβ1-42 oligomers may impair the function of stem cell-derived neurons. We propose that it may be possible for future AD therapies to promote the maturation of functional stem cell-derived neurons by altering the brain microenvironment with trophic support and by targeting different aggregation forms of Aβ.
-
A comparative study of the effect of oxidative stress on the cytoskeleton in human cortical neurons
International Nuclear Information System (INIS)
Allani, Pramod K.; Sum, Tak; Bhansali, Suraj G.; Mukherjee, Suman K.; Sonee, Manisha
2004-01-01
Cytoskeleton disruption is a process by which oxidative stress disrupts cellular function. This study compares and contrasts the effect of oxidative stress on the three major cytoskeleton filaments, microfilaments (MFs), microtubule (MT), and vimentin in human cortical neuronal cell line (HCN2). HCN2 cells were treated with 100 μM tertiary butylhydroperoxide (t-BuOOH), a free radical generating neurotoxin for 1, 3, or 6 h. Cell viability studies demonstrated significant cell death although the morphology studies showed that there was a substantial loss in neurites of neurons treated with t-BuOOH for 6 h. Because the cytoskeleton plays a role in neurite outgrowth, the effect of oxidative stress on the cytoskeletal was studied. In neurons subjected to oxidative stress for 30 min or 1 h, there were no major changes in microfilament distribution though there was altered distribution of microtubule and vimentin filaments as compared to controls. However, loss and disruption of all the three cytoskeletal filaments was observed at later times (3 and 6 h), which was confirmed by Western Blot analysis. Further studies were done to measure the gene expression levels of actin, tubulin, and vimentin. Results indicated that the overall loss of the cytoskeletal proteins in neurons treated with free radical generating toxin might not be a direct result of the downregulation of the cytoskeletal genes. This study shows that free radical generation in human neurons leads to the disruption of the cytoskeleton, though there may be a difference in the susceptibility to oxidative stress among the individual components of the cytoskeletal filaments
-
Lu, Dahua; He, Lixin; Xiang, Wei; Ai, Wei-Min; Cao, Ye; Wang, Xiao-Sheng; Pan, Aihua; Luo, Xue-Gang; Li, Zhiyuan; Yan, Xiao-Xin
2013-01-01
The CA3 area serves a key relay on the tri-synaptic loop of the hippocampal formation which supports multiple forms of mnemonic processing, especially spatial learning and memory. To date, morphometric data about human CA3 pyramidal neurons are relatively rare, with little information available for their pre- and postnatal development. Herein, we report a set of developmental trajectory data, including somal growth, dendritic elongation and branching, and spine formation, of human CA3 pyramidal neurons from midgestation stage to middle childhood. Golgi-impregnated CA3 pyramidal neurons in fetuses at 19, 20, 26, 35, and 38 weeks of gestation (GW) and a child at 8 years of age (Y) were analyzed by Neurolucida morphometry. Somal size of the impregnated CA3 cells increased age-dependently among the cases. The length of the apical and basal dendrites of these neurons increased between 26 GW to 38 GW, and appeared to remain stable afterward until 8 Y. Dendritic branching points increased from 26 GW to 38 GW, with that on the apical dendrites slightly reduced at 8 Y. Spine density on the apical and basal dendrites increased progressively from 26 GW to 8 Y. These data suggest that somal growth and dendritic arborization of human CA3 pyramidal neurons occur largely during the second to third trimester. Spine development and likely synaptogenesis on CA3 pyramidal cells progress during the third prenatal trimester and may continue throughout childhood. Copyright © 2012 Wiley Periodicals, Inc.
-
Gasdynamic Mirror Fusion Propulsion Experiment
Emrich, Bill; Rodgers, Stephen L. (Technical Monitor)
2000-01-01
A gasdynamic mirror (GDM) fusion propulsion experiment is currently being constructed at the NASA Marshall Space Flight Center (MSFC) to test the feasibility of this particular type of fusion device. Because of the open magnetic field line configuration of mirror fusion devices, they are particularly well suited for propulsion system applications since they allow for the easy ejection of thrust producing plasma. Currently, the MSFC GDM is constructed in three segments. The vacuum chamber mirror segment, the plasma injector mirror segment, and the main plasma chamber segment. Enough magnets are currently available to construct up to three main plasma chamber segments. The mirror segments are also segmented such that they can be expanded to accommodate new end plugging strategies with out requiring the disassembly of the entire mirror segment. The plasma for the experiment is generated in a microwave cavity located between the main magnets and the mirror magnets. Ion heating is accomplished through ambipolar diffusion. The objective of the experiment is to investigate the stability characteristics of the gasdynamic mirror and to map a region of parameter space within which the plasma can be confined in a stable steady state configuration. The mirror ratio, plasma density, and plasma "b" will be varied over a range of values and measurements subsequently taken to determine the degree of plasma stability.
-
Review of mirror fusion reactor designs
International Nuclear Information System (INIS)
Bender, D.J.
1977-01-01
Three magnetic confinement concepts, based on the mirror principle, are described. These mirror concepts are summarized as follows: (1) fusion-fission hybrid reactor, (2) tandem mirror reactor, and (3) reversed field mirror reactor
-
International Nuclear Information System (INIS)
Robay, Dimitri; Patel, Heema; Simpson, Michael A.; Brown, Nigel A.; Crosby, Andrew H.
2006-01-01
Mutation of spartin (SPG20) underlies a complicated form of hereditary spastic paraplegia, a disorder principally defined by the degeneration of upper motor neurons. Using a polyclonal antibody against spartin to gain insight into the function of the endogenous molecule, we show that the endogenous molecule is present in two main isoforms of 85 kDa and 100 kDa, and 75 kDa and 85 kDa in human and murine, respectively, with restricted subcellular localization. Immunohistochemical studies on human and mouse embryo sections and in vitro cell studies indicate that spartin is likely to possess both nuclear and cytoplasmic functions. The nuclear expression of spartin closely mirrors that of the snRNP (small nuclear ribonucleoprotein) marker α-Sm, a component of the spliceosome. Spartin is also enriched at the centrosome within mitotic structures. Notably we show that spartin protein undergoes dynamic positional changes in differentiating human SH-SY5Y cells. In undifferentiated non-neuronal cells, spartin displays a nuclear and diffuse cytosolic profile, whereas spartin transiently accumulates in the trans-Golgi network and subsequently decorates discrete puncta along neurites in terminally differentiated neuroblastic cells. Investigation of these spartin-positive vesicles reveals that a large proportion colocalizes with the synaptic vesicle marker synaptotagmin. Spartin is also enriched in synaptic-like structures and in synaptic vesicle-enriched fraction
-
Smooth leader or sharp follower? Playing the mirror game with a robot.
Kashi, Shir; Levy-Tzedek, Shelly
2018-01-01
The increasing number of opportunities for human-robot interactions in various settings, from industry through home use to rehabilitation, creates a need to understand how to best personalize human-robot interactions to fit both the user and the task at hand. In the current experiment, we explored a human-robot collaborative task of joint movement, in the context of an interactive game. We set out to test people's preferences when interacting with a robotic arm, playing a leader-follower imitation game (the mirror game). Twenty two young participants played the mirror game with the robotic arm, where one player (person or robot) followed the movements of the other. Each partner (person and robot) was leading part of the time, and following part of the time. When the robotic arm was leading the joint movement, it performed movements that were either sharp or smooth, which participants were later asked to rate. The greatest preference was given to smooth movements. Half of the participants preferred to lead, and half preferred to follow. Importantly, we found that the movements of the robotic arm primed the subsequent movements performed by the participants. The priming effect by the robot on the movements of the human should be considered when designing interactions with robots. Our results demonstrate individual differences in preferences regarding the role of the human and the joint motion path of the robot and the human when performing the mirror game collaborative task, and highlight the importance of personalized human-robot interactions.
-
McGeown, Laura; Davis, Ron
2018-02-15
The social modeling of eating effect refers to the consistently demonstrated phenomenon that individuals tend to match their quantity of food intake to their eating companion. The current study sought to explore whether activity within the mirror neuron system (MNS) mediates the social modeling of eating effect as a function of EEG frontal asymmetry and body mass index (BMI). Under the guise of rating empathy, 93 female undergraduates viewed a female video confederate "incidentally" consume either a low or high intake of chips while electroencephalogram (EEG) activity was recorded. Subsequent ad libitum chip consumption was quantified. A first- and second-stage dual moderation model revealed that frontal asymmetry and BMI moderated an indirect effect of model consumption on participants' food consumption as mediated by MNS activity at electrode site C3, a 3 b 3 =-0.718, SE=0.365, 95% CI [-1.632, -0.161]. Left frontal asymmetry was associated with greater mu activity and a positive association between model and participant chip consumption, while right frontal asymmetry was associated with less mu activity and a negative association between model and participant consumption. Across all levels of frontal asymmetry, the effect was only significant among those with a BMI at the 50th percentile or lower. Thus, among leaner individuals, the MNS was demonstrated to mediate social modeling of eating, as moderated by frontal asymmetry. These findings are integrated within the normative account of social modeling of eating. It is proposed that the normative framework may benefit from consideration of both conscious and unconscious operation of intake norms. Copyright © 2017 Elsevier B.V. All rights reserved.
-
Neuron-derived IgG protects neurons from complement-dependent cytotoxicity.
Zhang, Jie; Niu, Na; Li, Bingjie; McNutt, Michael A
2013-12-01
Passive immunity of the nervous system has traditionally been thought to be predominantly due to the blood-brain barrier. This concept must now be revisited based on the existence of neuron-derived IgG. The conventional concept is that IgG is produced solely by mature B lymphocytes, but it has now been found to be synthesized by murine and human neurons. However, the function of this endogenous IgG is poorly understood. In this study, we confirm IgG production by rat cortical neurons at the protein and mRNA levels, with 69.0 ± 5.8% of cortical neurons IgG-positive. Injury to primary-culture neurons was induced by complement leading to increases in IgG production. Blockage of neuron-derived IgG resulted in more neuronal death and early apoptosis in the presence of complement. In addition, FcγRI was found in microglia and astrocytes. Expression of FcγR I in microglia was increased by exposure to neuron-derived IgG. Release of NO from microglia triggered by complement was attenuated by neuron-derived IgG, and this attenuation could be reversed by IgG neutralization. These data demonstrate that neuron-derived IgG is protective of neurons against injury induced by complement and microglial activation. IgG appears to play an important role in maintaining the stability of the nervous system.
-
Bahney, Jami; von Bartheld, Christopher S
2018-04-01
The cellular composition of brains shows largely conserved, gradual evolutionary trends between species. In the primate spinal cord, however, the glia-neuron ratio was reported to be greatly increased over that in the rodent spinal cord. Here, we re-examined the cellular composition of the spinal cord of one human and one nonhuman primate species by employing two different counting methods, the isotropic fractionator and stereology. We also determined whether segmental differences in cellular composition, possibly reflecting increased fine motor control of the upper extremities, may explain a sharply increased glia-neuron ratio in primates. In the cynomolgus monkey spinal cord, the isotropic fractionator and stereology yielded 206-275 million cells, of which 13.3-25.1% were neurons (28-69 million). Stereological estimates yielded 21.1% endothelial cells and 65.5% glial cells (glia-neuron ratio of 4.9-5.6). In human spinal cords, the isotropic fractionator and stereology generated estimates of 1.5-1.7 billion cells and 197-222 million neurons (13.4% neurons, 12.2% endothelial cells, 74.8% glial cells), and a glia-neuron ratio of 5.6-7.1, with estimates of neuron numbers in the human spinal cord based on morphological criteria. The non-neuronal to neuron ratios in human and cynomolgus monkey spinal cords were 6.5 and 3.2, respectively, suggesting that previous reports overestimated this ratio. We did not find significant segmental differences in the cellular composition between cervical, thoracic and lumbar levels. When compared with brain regions, the spinal cord showed gradual increases of the glia-neuron ratio with increasing brain mass, similar to the cerebral cortex and the brainstem. Anat Rec, 301:697-710, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
-
The obsidian mirror The obsidian mirror
Directory of Open Access Journals (Sweden)
Maria do Socorro Reis Amorin
2008-04-01
Full Text Available The author James Norman is an American who has always lived in Mexico during the summer. He seems to love Mexican - Indian traditions and he is well acquainted with the pre-historic culture as it is shown in his book: "The Obsidian Mirror". "The Obsidian Mirror" is a mysterious story about an archeologist: Quigley that lives in a small village in Mexico-San Marcos. He is searching for antiques that belong to some tribes of pre-historic Indians in order to find out their mysteries. Quigley becomes so engaged in his work that his mind has reached a stage that is impossible to separate between Quigley the archeologist, and Quigley as an ancient Indian. The culture, the myth, the sensation of Omen - characteristics of the Indians are within himself. As a result, Quigley acts sometimes as a real Indian. The author James Norman is an American who has always lived in Mexico during the summer. He seems to love Mexican - Indian traditions and he is well acquainted with the pre-historic culture as it is shown in his book: "The Obsidian Mirror". "The Obsidian Mirror" is a mysterious story about an archeologist: Quigley that lives in a small village in Mexico-San Marcos. He is searching for antiques that belong to some tribes of pre-historic Indians in order to find out their mysteries. Quigley becomes so engaged in his work that his mind has reached a stage that is impossible to separate between Quigley the archeologist, and Quigley as an ancient Indian. The culture, the myth, the sensation of Omen - characteristics of the Indians are within himself. As a result, Quigley acts sometimes as a real Indian.
-
Krasilenko, Vladimir G.; Nikolsky, Alexander I.; Lazarev, Alexander A.; Lazareva, Maria V.
2008-03-01
In the paper the actuality of neurophysiologically motivated neuron arrays with flexibly programmable functions and operations with possibility to select required accuracy and type of nonlinear transformation and learning are shown. We consider neurons design and simulation results of multichannel spatio-time algebraic accumulation - integration of optical signals. Advantages for nonlinear transformation and summation - integration are shown. The offered circuits are simple and can have intellectual properties such as learning and adaptation. The integrator-neuron is based on CMOS current mirrors and comparators. The performance: consumable power - 100...500 μW, signal period- 0.1...1ms, input optical signals power - 0.2...20 μW time delays - less 1μs, the number of optical signals - 2...10, integration time - 10...100 of signal periods, accuracy or integration error - about 1%. Various modifications of the neuron-integrators with improved performance and for different applications are considered in the paper.
-
Valdiglesias, Vanessa; Costa, Carla; Sharma, Vyom; Kiliç, Gözde; Pásaro, Eduardo; Teixeira, João Paulo; Dhawan, Alok; Laffon, Blanca
2013-07-01
Titanium dioxide (TiO2) are among most frequently used nanoparticles (NPs). They are present in a variety of consumer products, including food industry in which they are employed as an additive. The potential toxic effects of these NPs on mammal cells have been extensively studied. However, studies regarding neurotoxicity and specific effects on neuronal systems are very scarce and, to our knowledge, no studies on human neuronal cells have been reported so far. Therefore, the main objective of this work was to investigate the effects of two types of TiO₂ NPs, with different crystalline structure, on human SHSY5Y neuronal cells. After NPs characterization, a battery of assays was performed to evaluate the viability, cytotoxicity, genotoxicity and oxidative damage in TiO₂ NP-exposed SHSY5Y cells. Results obtained showed that the behaviour of both types of NPs resulted quite comparable. They did not reduce the viability of neuronal cells but were effectively internalized by the cells and induced dose-dependent cell cycle alterations, apoptosis by intrinsic pathway, and genotoxicity not related with double strand break production. Furthermore, all these effects were not associated with oxidative damage production and, consequently, further investigations on the specific mechanisms underlying the effects observed in this study are required. Copyright © 2013 Elsevier Ltd. All rights reserved.
-
Chien, Hsiang-Yun; Gau, Susan Shur-Fen; Hsu, Yung-Chin; Chen, Yu-Jen; Lo, Yu-Chun; Shih, Yao-Chia; Tseng, Wen-Yih Isaac
2015-12-01
Previous studies using neural activity recording and neuroimaging techniques have reported functional deficits in the mirror neuron system (MNS) for individuals with autism spectrum disorder (ASD). However, a few studies focusing on gray and white matter structures of the MNS have yielded inconsistent results. The current study recruited adolescents and young adults with ASD (aged 15-26 years) and age-matched typically developing (TD) controls (aged 14-25 years). The cortical thickness (CT) and microstructural integrity of the tracts connecting the regions forming the classical MNS were investigated. High-resolution T1-weighted imaging and diffusion spectrum imaging were performed to quantify the CT and tract integrity, respectively. The structural covariance of the CT of the MNS regions revealed a weaker coordination of the MNS network in ASD. A strong correlation was found between the integrity of the right frontoparietal tracts and the social communication subscores measured by the Chinese version of the Social Communication Questionnaire. The results showed that there were no significant mean differences in the CTs and tract integrity between the ASD and TD groups, but revealed a moderate or even reverse age effect on the frontal MNS structures in ASD. In conclusion, aberrant structural coordination may be an underlying factor affecting the function of the MNS in ASD patients. The association between the right frontoparietal tracts and social communication performance implies a neural correlate of communication processing in the autistic brain. This study provides evidence of abnormal MNS structures and their influence on social communication in individuals with ASD. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
-
Wang, Xin; Xu, Mei; Frank, Jacqueline A; Ke, Zun-Ji; Luo, Jia
2017-04-01
Thiamine (vitamin B1) deficiency (TD) plays a major role in the etiology of Wernicke's encephalopathy (WE) which is a severe neurological disorder. TD induces selective neuronal cell death, neuroinflammation, endoplasmic reticulum (ER) stress and oxidative stress in the brain which are commonly observed in many aging-related neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and progressive supranuclear palsy (PSP). However, the underlying cellular and molecular mechanisms remain unclear. The progress in this line of research is hindered due to the lack of appropriate in vitro models. The neurons derived for the human induced pluripotent stem cells (hiPSCs) provide a relevant and powerful tool for the research in pharmaceutical and environmental neurotoxicity. In this study, we for the first time used human induced pluripotent stem cells (hiPSCs)-derived neurons (iCell neurons) to investigate the mechanisms of TD-induced neurodegeneration. We showed that TD caused a concentration- and duration-dependent death of iCell neurons. TD induced ER stress which was evident by the increase in ER stress markers, such as GRP78, XBP-1, CHOP, ATF-6, phosphorylated eIF2α, and cleaved caspase-12. TD also triggered oxidative stress which was shown by the increase in the expression 2,4-dinitrophenyl (DNP) and 4-hydroxynonenal (HNE). ER stress inhibitors (STF-083010 and salubrinal) and antioxidant N-acetyl cysteine (NAC) were effective in alleviating TD-induced death of iCell neurons, supporting the involvement of ER stress and oxidative stress. It establishes that the iCell neurons are a novel tool to investigate cellular and molecular mechanisms for TD-induced neurodegeneration. Copyright © 2017 Elsevier Inc. All rights reserved.
-
Directory of Open Access Journals (Sweden)
Yael Mandelblat-Cerf
Full Text Available Previous studies support the notion that sensorimotor learning involves multiple processes. We investigated the neuronal basis of these processes by recording single-unit activity in motor cortex of non-human primates (Macaca fascicularis, during adaptation to force-field perturbations. Perturbed trials (reaching to one direction were practiced along with unperturbed trials (to other directions. The number of perturbed trials relative to the unperturbed ones was either low or high, in two separate practice schedules. Unsurprisingly, practice under high-rate resulted in faster learning with more pronounced generalization, as compared to the low-rate practice. However, generalization and retention of behavioral and neuronal effects following practice in high-rate were less stable; namely, the faster learning was forgotten faster. We examined two subgroups of cells and showed that, during learning, the changes in firing-rate in one subgroup depended on the number of practiced trials, but not on time. In contrast, changes in the second subgroup depended on time and practice; the changes in firing-rate, following the same number of perturbed trials, were larger under high-rate than low-rate learning. After learning, the neuronal changes gradually decayed. In the first subgroup, the decay pace did not depend on the practice rate, whereas in the second subgroup, the decay pace was greater following high-rate practice. This group shows neuronal representation that mirrors the behavioral performance, evolving faster but also decaying faster at learning under high-rate, as compared to low-rate. The results suggest that the stability of a new learned skill and its neuronal representation are affected by the acquisition schedule.
-
Detectability of Neuronal Currents in Human Brain with Magnetic Resonance Spectroscopy.
Energy Technology Data Exchange (ETDEWEB)
Jones, Howland D. T. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Thomas, Edward V. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Harper, Jason C. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Mayer, Andrew R. [Mind Research Network, Albuquerque, NM (United States); Univ. of New Mexico, Albuquerque, NM (United States); Caprihan, Arvind [Mind Research Network, Albuquerque, NM (United States); Gasparovic, Charles [Mind Research Network, Albuquerque, NM (United States); Univ. of New Mexico, Albuquerque, NM (United States); Blagoev, Krastan B. [Mind Research Network, Albuquerque, NM (United States); Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Haaland, David M. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)
2012-09-01
Magnetic resonance spectroscopy has been used in a high-risk, high-payoff search for neuronal current (NC) signals in the free induction decay (FID) data from the visual cortex of human subjects during visual stimulation. If successful, this approach could make possible the detection of neuronal currents in the brain at high spatial and temporal resolution. Our initial experiments indicated the presence of a statistically significant change in the FID containing the NC relative to FIDs with the NC absent, and this signal was consistent with the presence of NC. Unfortunately, two follow-on experiments were not able to confirm or replicate the positive findings of the first experiment. However, even if the result from the first experiment were evidence of NC in the FID, it is clear that its effect is so small, that a true NC imaging experiment would not be possible with the current instrumentation and experimental protocol used here.