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Sample records for neural pathways responsible

  1. Depression and treatment response: dynamic interplay of signaling pathways and altered neural processes.

    Science.gov (United States)

    Duric, Vanja; Duman, Ronald S

    2013-01-01

    Since the 1960s, when the first tricyclic and monoamine oxidase inhibitor antidepressant drugs were introduced, most of the ensuing agents were designed to target similar brain pathways that elevate serotonin and/or norepinephrine signaling. Fifty years later, the main goal of the current depression research is to develop faster-acting, more effective therapeutic agents with fewer side effects, as currently available antidepressants are plagued by delayed therapeutic onset and low response rates. Clinical and basic science research studies have made significant progress towards deciphering the pathophysiological events within the brain involved in development, maintenance, and treatment of major depressive disorder. Imaging and postmortem brain studies in depressed human subjects, in combination with animal behavioral models of depression, have identified a number of different cellular events, intracellular signaling pathways, proteins, and target genes that are modulated by stress and are potentially vital mediators of antidepressant action. In this review, we focus on several neural mechanisms, primarily within the hippocampus and prefrontal cortex, which have recently been implicated in depression and treatment response.

  2. Central neural pathways for thermoregulation

    Science.gov (United States)

    Morrison, Shaun F.; Nakamura, Kazuhiro

    2010-01-01

    Central neural circuits orchestrate a homeostatic repertoire to maintain body temperature during environmental temperature challenges and to alter body temperature during the inflammatory response. This review summarizes the functional organization of the neural pathways through which cutaneous thermal receptors alter thermoregulatory effectors: the cutaneous circulation for heat loss, the brown adipose tissue, skeletal muscle and heart for thermogenesis and species-dependent mechanisms (sweating, panting and saliva spreading) for evaporative heat loss. These effectors are regulated by parallel but distinct, effector-specific neural pathways that share a common peripheral thermal sensory input. The thermal afferent circuits include cutaneous thermal receptors, spinal dorsal horn neurons and lateral parabrachial nucleus neurons projecting to the preoptic area to influence warm-sensitive, inhibitory output neurons which control thermogenesis-promoting neurons in the dorsomedial hypothalamus that project to premotor neurons in the rostral ventromedial medulla, including the raphe pallidus, that descend to provide the excitation necessary to drive thermogenic thermal effectors. A distinct population of warm-sensitive preoptic neurons controls heat loss through an inhibitory input to raphe pallidus neurons controlling cutaneous vasoconstriction. PMID:21196160

  3. Nonassociative learning as gated neural integrator and differentiator in stimulus-response pathways

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    Young Daniel L

    2006-08-01

    Full Text Available Abstract Nonassociative learning is a basic neuroadaptive behavior exhibited across animal phyla and sensory modalities but its role in brain intelligence is unclear. Current literature on habituation and sensitization, the classic "dual process" of nonassociative learning, gives highly incongruous accounts between varying experimental paradigms. Here we propose a general theory of nonassociative learning featuring four base modes: habituation/primary sensitization in primary stimulus-response pathways, and desensitization/secondary sensitization in secondary stimulus-response pathways. Primary and secondary modes of nonassociative learning are distinguished by corresponding activity-dependent recall, or nonassociative gating, of neurotransmission memory. From the perspective of brain computation, nonassociative learning is a form of integral-differential calculus whereas nonassociative gating is a form of Boolean logic operator – both dynamically transforming the stimulus-response relationship. From the perspective of sensory integration, nonassociative gating provides temporal filtering whereas nonassociative learning affords low-pass, high-pass or band-pass/band-stop frequency filtering – effectively creating an intelligent sensory firewall that screens all stimuli for attention and resultant internal model adaptation and reaction. This unified framework ties together many salient characteristics of nonassociative learning and nonassociative gating and suggests a common kernel that correlates with a wide variety of sensorimotor integration behaviors such as central resetting and self-organization of sensory inputs, fail-safe sensorimotor compensation, integral-differential and gated modulation of sensorimotor feedbacks, alarm reaction, novelty detection and selective attention, as well as a variety of mental and neurological disorders such as sensorimotor instability, attention deficit hyperactivity, sensory defensiveness, autism

  4. Nonassociative learning as gated neural integrator and differentiator in stimulus-response pathways.

    Science.gov (United States)

    Poon, Chi-Sang; Young, Daniel L

    2006-08-08

    Nonassociative learning is a basic neuroadaptive behavior exhibited across animal phyla and sensory modalities but its role in brain intelligence is unclear. Current literature on habituation and sensitization, the classic "dual process" of nonassociative learning, gives highly incongruous accounts between varying experimental paradigms. Here we propose a general theory of nonassociative learning featuring four base modes: habituation/primary sensitization in primary stimulus-response pathways, and desensitization/secondary sensitization in secondary stimulus-response pathways. Primary and secondary modes of nonassociative learning are distinguished by corresponding activity-dependent recall, or nonassociative gating, of neurotransmission memory. From the perspective of brain computation, nonassociative learning is a form of integral-differential calculus whereas nonassociative gating is a form of Boolean logic operator--both dynamically transforming the stimulus-response relationship. From the perspective of sensory integration, nonassociative gating provides temporal filtering whereas nonassociative learning affords low-pass, high-pass or band-pass/band-stop frequency filtering--effectively creating an intelligent sensory firewall that screens all stimuli for attention and resultant internal model adaptation and reaction. This unified framework ties together many salient characteristics of nonassociative learning and nonassociative gating and suggests a common kernel that correlates with a wide variety of sensorimotor integration behaviors such as central resetting and self-organization of sensory inputs, fail-safe sensorimotor compensation, integral-differential and gated modulation of sensorimotor feedbacks, alarm reaction, novelty detection and selective attention, as well as a variety of mental and neurological disorders such as sensorimotor instability, attention deficit hyperactivity, sensory defensiveness, autism, nonassociative fear and anxiety

  5. Neural pathways for visual speech perception.

    Science.gov (United States)

    Bernstein, Lynne E; Liebenthal, Einat

    2014-01-01

    This paper examines the questions, what levels of speech can be perceived visually, and how is visual speech represented by the brain? Review of the literature leads to the conclusions that every level of psycholinguistic speech structure (i.e., phonetic features, phonemes, syllables, words, and prosody) can be perceived visually, although individuals differ in their abilities to do so; and that there are visual modality-specific representations of speech qua speech in higher-level vision brain areas. That is, the visual system represents the modal patterns of visual speech. The suggestion that the auditory speech pathway receives and represents visual speech is examined in light of neuroimaging evidence on the auditory speech pathways. We outline the generally agreed-upon organization of the visual ventral and dorsal pathways and examine several types of visual processing that might be related to speech through those pathways, specifically, face and body, orthography, and sign language processing. In this context, we examine the visual speech processing literature, which reveals widespread diverse patterns of activity in posterior temporal cortices in response to visual speech stimuli. We outline a model of the visual and auditory speech pathways and make several suggestions: (1) The visual perception of speech relies on visual pathway representations of speech qua speech. (2) A proposed site of these representations, the temporal visual speech area (TVSA) has been demonstrated in posterior temporal cortex, ventral and posterior to multisensory posterior superior temporal sulcus (pSTS). (3) Given that visual speech has dynamic and configural features, its representations in feedforward visual pathways are expected to integrate these features, possibly in TVSA.

  6. Neural pathways for visual speech perception

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    Lynne E Bernstein

    2014-12-01

    Full Text Available This paper examines the questions, what levels of speech can be perceived visually, and how is visual speech represented by the brain? Review of the literature leads to the conclusions that every level of psycholinguistic speech structure (i.e., phonetic features, phonemes, syllables, words, and prosody can be perceived visually, although individuals differ in their abilities to do so; and that there are visual modality-specific representations of speech qua speech in higher-level vision brain areas. That is, the visual system represents the modal patterns of visual speech. The suggestion that the auditory speech pathway receives and represents visual speech is examined in light of neuroimaging evidence on the auditory speech pathways. We outline the generally agreed-upon organization of the visual ventral and dorsal pathways and examine several types of visual processing that might be related to speech through those pathways, specifically, face and body, orthography, and sign language processing. In this context, we examine the visual speech processing literature, which reveals widespread diverse patterns activity in posterior temporal cortices in response to visual speech stimuli. We outline a model of the visual and auditory speech pathways and make several suggestions: (1 The visual perception of speech relies on visual pathway representations of speech qua speech. (2 A proposed site of these representations, the temporal visual speech area (TVSA has been demonstrated in posterior temporal cortex, ventral and posterior to multisensory posterior superior temporal sulcus (pSTS. (3 Given that visual speech has dynamic and configural features, its representations in feedforward visual pathways are expected to integrate these features, possibly in TVSA.

  7. Neural pathways for visual speech perception

    Science.gov (United States)

    Bernstein, Lynne E.; Liebenthal, Einat

    2014-01-01

    This paper examines the questions, what levels of speech can be perceived visually, and how is visual speech represented by the brain? Review of the literature leads to the conclusions that every level of psycholinguistic speech structure (i.e., phonetic features, phonemes, syllables, words, and prosody) can be perceived visually, although individuals differ in their abilities to do so; and that there are visual modality-specific representations of speech qua speech in higher-level vision brain areas. That is, the visual system represents the modal patterns of visual speech. The suggestion that the auditory speech pathway receives and represents visual speech is examined in light of neuroimaging evidence on the auditory speech pathways. We outline the generally agreed-upon organization of the visual ventral and dorsal pathways and examine several types of visual processing that might be related to speech through those pathways, specifically, face and body, orthography, and sign language processing. In this context, we examine the visual speech processing literature, which reveals widespread diverse patterns of activity in posterior temporal cortices in response to visual speech stimuli. We outline a model of the visual and auditory speech pathways and make several suggestions: (1) The visual perception of speech relies on visual pathway representations of speech qua speech. (2) A proposed site of these representations, the temporal visual speech area (TVSA) has been demonstrated in posterior temporal cortex, ventral and posterior to multisensory posterior superior temporal sulcus (pSTS). (3) Given that visual speech has dynamic and configural features, its representations in feedforward visual pathways are expected to integrate these features, possibly in TVSA. PMID:25520611

  8. Vergence Neural Pathways: A Systematic Narrative Literature Review.

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    Searle, Annabelle; Rowe, Fiona J

    2016-10-01

    Research in the neural pathway for vergence is less understood in comparison to the other four visual eye movements. The aim of this study was to review the literature on vergence neural pathways and associated disorders. A review of previous published literature though to March 2016 was conducted. Intracranial pathologies that affect entire neural functioning were found to cause convergence insufficiencies. In contrast, pathologies with a more localised intracranial lesion cause more specific vergence disorders. There is debate as to the potential presence of a "divergence centre." Detailed information on the divergence pathway is lacking and warrants further research.

  9. Dopamine system: Manager of neural pathways

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    Simon eHong

    2013-12-01

    Full Text Available There are a growing number of roles that midbrain dopamine (DA neurons assume, such as, reward, aversion, alerting and vigor. Here I propose a theory that may be able to explain why the suggested functions of DA came about. It has been suggested that largely parallel cortico-basal ganglia-thalamo-cortico loops exist to control different aspects of behavior. I propose that (1 the midbrain DA system is organized in a similar manner, with different groups of DA neurons corresponding to these parallel neural pathways (NPs. The DA system can be viewed as the manager of these parallel NPs in that it recruits and activates only the task-relevant NPs when they are needed. It is likely that the functions of those NPs that have been consistently activated by the corresponding DA groups are facilitated. I also propose that (2 there are two levels of DA roles: the How and What roles. The How role is encoded in tonic and phasic DA neuron firing patterns and gives a directive to its target NP: how vigorously its function needs to be carried out. The tonic DA firing is to maintain a certain level of DA in the target NPs to support their expected behavioral and mental functions; it is only when a sudden unexpected boost or suppression of activity is required by the relevant target NP that DA neurons in the corresponding NP act in a phasic manner. The What role is the implementational aspect of the role of DA in the target NP, such as binding to D1 receptors to boost working memory. This What aspect of DA explains why DA seems to assume different functions depending on the region of the brain in which it is involved. In terms of the role of the lateral habenula (LHb, the LHb is expected to suppress maladaptive behaviors and mental processes by controlling the DA system. The demand-based smart management by the DA system may have given animals an edge in evolution with adaptive behaviors and a better survival rate in resource-scarce situations.

  10. Dissecting neural pathways for forgetting in Drosophila olfactory aversive memory.

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    Shuai, Yichun; Hirokawa, Areekul; Ai, Yulian; Zhang, Min; Li, Wanhe; Zhong, Yi

    2015-12-01

    Recent studies have identified molecular pathways driving forgetting and supported the notion that forgetting is a biologically active process. The circuit mechanisms of forgetting, however, remain largely unknown. Here we report two sets of Drosophila neurons that account for the rapid forgetting of early olfactory aversive memory. We show that inactivating these neurons inhibits memory decay without altering learning, whereas activating them promotes forgetting. These neurons, including a cluster of dopaminergic neurons (PAM-β'1) and a pair of glutamatergic neurons (MBON-γ4>γ1γ2), terminate in distinct subdomains in the mushroom body and represent parallel neural pathways for regulating forgetting. Interestingly, although activity of these neurons is required for memory decay over time, they are not required for acute forgetting during reversal learning. Our results thus not only establish the presence of multiple neural pathways for forgetting in Drosophila but also suggest the existence of diverse circuit mechanisms of forgetting in different contexts.

  11. Neural reflex pathways in intestinal inflammation: hypotheses to viable therapy

    NARCIS (Netherlands)

    Willemze, Rose A.; Luyer, Misha D.; Buurman, Wim A.; de Jonge, Wouter J.

    2015-01-01

    Studies in neuroscience and immunology have clarified much of the anatomical and cellular basis for bidirectional interactions between the nervous and immune systems. As with other organs, intestinal immune responses and the development of immunity seems to be modulated by neural reflexes.

  12. Physiological evidence of neural pathways involved in reflexogenic penile erection in the rat.

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    Rampin, O; Giuliano, F; Dompeyre, P; Rousseau, J P

    1994-10-24

    To elucidate neural pathways responsible for the occurrence of reflexogenic erections, the response of the corpus cavernosum to electrical stimulation of the dorsal nerve of the penis (DNP) was measured in anesthetized, acutely spinalized rats. Stimulation elicited a dramatic increase in intracavernous pressure (ICP). ICP response was decreased by 70% after sectioning the pelvic nerve homolaterally to the stimulated DNP and abolished after bilateral section. ICP response was not impaired by curarization, but its latency was lengthened. Thus we physiologically evidenced a reflex loop independent from supraspinal centers between DNP and the pelvic nerve supporting penile reflexogenic erection.

  13. Dynamic Encoding of Acoustic Features in Neural Responses to Continuous Speech.

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    Khalighinejad, Bahar; Cruzatto da Silva, Guilherme; Mesgarani, Nima

    2017-02-22

    Humans are unique in their ability to communicate using spoken language. However, it remains unclear how the speech signal is transformed and represented in the brain at different stages of the auditory pathway. In this study, we characterized electroencephalography responses to continuous speech by obtaining the time-locked responses to phoneme instances (phoneme-related potential). We showed that responses to different phoneme categories are organized by phonetic features. We found that each instance of a phoneme in continuous speech produces multiple distinguishable neural responses occurring as early as 50 ms and as late as 400 ms after the phoneme onset. Comparing the patterns of phoneme similarity in the neural responses and the acoustic signals confirms a repetitive appearance of acoustic distinctions of phonemes in the neural data. Analysis of the phonetic and speaker information in neural activations revealed that different time intervals jointly encode the acoustic similarity of both phonetic and speaker categories. These findings provide evidence for a dynamic neural transformation of low-level speech features as they propagate along the auditory pathway, and form an empirical framework to study the representational changes in learning, attention, and speech disorders.SIGNIFICANCE STATEMENT We characterized the properties of evoked neural responses to phoneme instances in continuous speech. We show that each instance of a phoneme in continuous speech produces several observable neural responses at different times occurring as early as 50 ms and as late as 400 ms after the phoneme onset. Each temporal event explicitly encodes the acoustic similarity of phonemes, and linguistic and nonlinguistic information are best represented at different time intervals. Finally, we show a joint encoding of phonetic and speaker information, where the neural representation of speakers is dependent on phoneme category. These findings provide compelling new evidence for

  14. Reduction in neural performance following recovery from anoxic stress is mimicked by AMPK pathway activation.

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    Tomas G A Money

    Full Text Available Nervous systems are energetically expensive to operate and maintain. Both synaptic and action potential signalling require a significant investment to maintain ion homeostasis. We have investigated the tuning of neural performance following a brief period of anoxia in a well-characterized visual pathway in the locust, the LGMD/DCMD looming motion-sensitive circuit. We hypothesised that the energetic cost of signalling can be dynamically modified by cellular mechanisms in response to metabolic stress. We examined whether recovery from anoxia resulted in a decrease in excitability of the electrophysiological properties in the DCMD neuron. We further examined the effect of these modifications on behavioural output. We show that recovery from anoxia affects metabolic rate, flight steering behaviour, and action potential properties. The effects of anoxia on action potentials can be mimicked by activation of the AMPK metabolic pathway. We suggest this is evidence of a coordinated cellular mechanism to reduce neural energetic demand following an anoxic stress. Together, this represents a dynamically-regulated means to link the energetic demands of neural signaling with the environmental constraints faced by the whole animal.

  15. Neural responses to advantageous and disadvantageous inequity

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    Klaus eFliessbach

    2012-06-01

    Full Text Available In this paper we study neural responses to inequitable distributions of rewards despite equal performance. We specifically focus on differences between advantageous (AI and disadvantageous inequity (DI. AI and DI were realized in a hyperscanning fMRI experiment with pairs of subjects simultaneously performing a task in adjacent scanners and observing both subjects' rewards. Results showed i hypoactivation of the ventral striatum under DI but not under AI; ii inequity induced activation of medial and dorsolateral prefrontal regions, that were stronger under DI than AI; iii correlations between subjective evaluations of DI and amygdala activity, and between AI evaluation and right ventrolateral prefrontal activity. Our study provides neurophysiological evidence for different cognitive processes that occur when exposed to DI and AI, respectively. Our data is compatible with the assumption that any form of inequity represents a norm violation, but that important differences between AI and DI emerge from an asymmetric involvement of status concerns.

  16. Neural synchrony during response production and inhibition.

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    Viktor Müller

    Full Text Available Inhibition of irrelevant information (conflict monitoring and/or of prepotent actions is an essential component of adaptive self-organized behavior. Neural dynamics underlying these functions has been studied in humans using event-related brain potentials (ERPs elicited in Go/NoGo tasks that require a speeded motor response to the Go stimuli and withholding a prepotent response when a NoGo stimulus is presented. However, averaged ERP waveforms provide only limited information about the neuronal mechanisms underlying stimulus processing, motor preparation, and response production or inhibition. In this study, we examine the cortical representation of conflict monitoring and response inhibition using time-frequency analysis of electroencephalographic (EEG recordings during continuous performance Go/NoGo task in 50 young adult females. We hypothesized that response inhibition would be associated with a transient boost in both temporal and spatial synchronization of prefrontal cortical activity, consistent with the role of the anterior cingulate and lateral prefrontal cortices in cognitive control. Overall, phase synchronization across trials measured by Phase Locking Index and phase synchronization between electrode sites measured by Phase Coherence were the highest in the Go and NoGo conditions, intermediate in the Warning condition, and the lowest under Neutral condition. The NoGo condition was characterized by significantly higher fronto-central synchronization in the 300-600 ms window, whereas in the Go condition, delta- and theta-band synchronization was higher in centro-parietal regions in the first 300 ms after the stimulus onset. The present findings suggest that response production and inhibition is supported by dynamic functional networks characterized by distinct patterns of temporal and spatial synchronization of brain oscillations.

  17. Impact of a Solution for the Study of Neural Pathways in Morphophysiology III

    OpenAIRE

    José Manuel Ruiz Medina; Alicia Ríos Carbonell; Gisela Trevín Fernández; Elnis Quiala Ballester; Vivian Santoya Varela

    2013-01-01

    Background: current conditions for teaching Morphophysiology subject and awareness of the historical difficulties that students face in understanding the morphological and functional characteristics of neural pathways require a solution. Objective: to create a set of means in order to provide a practical resource for the study of the morphological and functional characteristics of the neural pathways and to assess the impact of its implementation in Morphophysiology III teaching. Methods: we ...

  18. Overweight adolescents’ brain response to sweetened beverages mirrors addiction pathways

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    Claus, Eric D.; Hudson, Karen A.; Filbey, Francesca M.; Jimenez, Elizabeth Yakes; Lisdahl, Krista M.; Kong, Alberta S.

    2017-01-01

    Many adolescents struggle with overweight/obesity, which exponentially increases in the transition to adulthood. Overweight/obesity places youth at risk for serious health conditions, including type 2 diabetes. In adults, neural substrates implicated in addiction (e.g., orbitofrontal cortex (OFC), striatum, amygdala, and ventral tegmental area) have been found to be relevant to risk for overweight/obesity. In this study, we examined three hypotheses to disentangle the potential overlap between addiction and overweight/obesity processing by examining (1) brain response to high vs. low calorie beverages, (2) the strength of correspondence between biometrics, including body mass index (BMI) and insulin resistance, and brain response and (3) the relationship between a measure of food addiction and brain response using an established fMRI gustatory cue exposure task with a sample of overweight/obese youth (M age = 16.46; M BMI = 33.1). Greater BOLD response was observed across the OFC, inferior frontal gyrus (IFG), nucleus accumbens, right amygdala, and additional frontoparietal and temporal regions in neural processing of high vs. low calorie beverages. Further, BMI scores positively correlated with BOLD activation in the high calorie > low calorie contrast in the right postcentral gyrus and central operculum. Insulin resistance positively correlated with BOLD activation across the bilateral middle/superior temporal gyrus, left OFC, and superior parietal lobe. No relationships were observed between measures of food addiction and brain response. These findings support the activation of parallel addiction-related neural pathways in adolescents’ high calorie processing, while also suggesting the importance of refining conceptual and neurocognitive models to fit this developmental period. PMID:27392791

  19. Overweight adolescents' brain response to sweetened beverages mirrors addiction pathways.

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    Feldstein Ewing, Sarah W; Claus, Eric D; Hudson, Karen A; Filbey, Francesca M; Yakes Jimenez, Elizabeth; Lisdahl, Krista M; Kong, Alberta S

    2017-08-01

    Many adolescents struggle with overweight/obesity, which exponentially increases in the transition to adulthood. Overweight/obesity places youth at risk for serious health conditions, including type 2 diabetes. In adults, neural substrates implicated in addiction (e.g., orbitofrontal cortex (OFC), striatum, amygdala, and ventral tegmental area) have been found to be relevant to risk for overweight/obesity. In this study, we examined three hypotheses to disentangle the potential overlap between addiction and overweight/obesity processing by examining (1) brain response to high vs. low calorie beverages, (2) the strength of correspondence between biometrics, including body mass index (BMI) and insulin resistance, and brain response and (3) the relationship between a measure of food addiction and brain response using an established fMRI gustatory cue exposure task with a sample of overweight/obese youth (M age = 16.46; M BMI = 33.1). Greater BOLD response was observed across the OFC, inferior frontal gyrus (IFG), nucleus accumbens, right amygdala, and additional frontoparietal and temporal regions in neural processing of high vs. low calorie beverages. Further, BMI scores positively correlated with BOLD activation in the high calorie > low calorie contrast in the right postcentral gyrus and central operculum. Insulin resistance positively correlated with BOLD activation across the bilateral middle/superior temporal gyrus, left OFC, and superior parietal lobe. No relationships were observed between measures of food addiction and brain response. These findings support the activation of parallel addiction-related neural pathways in adolescents' high calorie processing, while also suggesting the importance of refining conceptual and neurocognitive models to fit this developmental period.

  20. Consecutive Acupuncture Stimulations Lead to Significantly Decreased Neural Responses

    NARCIS (Netherlands)

    Yeo, S.; Choe, I.H.; Noort, M.W.M.L. van den; Bosch, M.P.C.; Lim, S.

    2010-01-01

    Objective: Functional magnetic resonance imaging (fMRI), in combination with block design paradigms with consecutive acupuncture stimulations, has often been used to investigate the neural responses to acupuncture. In this study, we investigated whether previous acupuncture stimulations can affect

  1. Parallel neural pathways in higher visual centers of the Drosophila brain that mediate wavelength-specific behavior

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    Hideo eOtsuna

    2014-02-01

    Full Text Available Compared with connections between the retinae and primary visual centers, relatively less is known in both mammals and insects about the functional segregation of neural pathways connecting primary and higher centers of the visual processing cascade. Here, using the Drosophila visual system as a model, we demonstrate two levels of parallel computation in the pathways that connect primary visual centers of the optic lobe to computational circuits embedded within deeper centers in the central brain. We show that a seemingly simple achromatic behavior, namely phototaxis, is under the control of several independent pathways, each of which is responsible for navigation towards unique wavelengths. Silencing just one pathway is enough to disturb phototaxis towards one characteristic monochromatic source, whereas phototactic behavior towards white light is not affected. The response spectrum of each demonstrable pathway is different from that of individual photoreceptors, suggesting subtractive computations. A choice assay between two colors showed that these pathways are responsible for navigation towards, but not for the detection itself of, the monochromatic light. The present study provides novel insights about how visual information is separated and processed in parallel to achieve robust control of an innate behavior.

  2. Young adult smokers' neural response to graphic cigarette warning labels

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    Adam E. Green

    2016-06-01

    Conclusions: In this sample of young adult smokers, GWLs promoted neural activation in brain regions involved in cognitive and affective decision-making and memory formation and the effects of GWLs did not differ on branded or plain cigarette packaging. These findings complement other recent neuroimaging GWL studies conducted with older adult smokers and with adolescents by demonstrating similar patterns of neural activation in response to GWLs among young adult smokers.

  3. A dual-pathway neural architecture for specific temporal prediction.

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    Schwartze, Michael; Kotz, Sonja A

    2013-12-01

    Efficient behavior depends in part on the ability to predict the type and the timing of events in the environment. Specific temporal predictions require an internal representation of the temporal structure of events. Here we propose that temporal prediction recruits adaptive and non-adaptive oscillatory mechanisms involved in establishing such an internal representation. Partial structural and functional convergence of the underlying mechanisms allows speculation about an extended subcortico-cortical network. This network develops around a dual-pathway architecture, which establishes the basis for preparing the organism for perceptual integration, for the generation of specific temporal predictions, and for optimizing the brain's allocation of its limited resources. Key to these functions is rapid cerebellar transmission of an adaptively-filtered, event-based representation of temporal structure. Rapid cerebellar transmission engages a pathway comprising connections from early sensory processing stages to the cerebellum and from there to the thalamus, effectively bypassing more central stages of classical sensory pathways. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Embedding responses in spontaneous neural activity shaped through sequential learning.

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    Kurikawa, Tomoki; Kaneko, Kunihiko

    2013-01-01

    Recent experimental measurements have demonstrated that spontaneous neural activity in the absence of explicit external stimuli has remarkable spatiotemporal structure. This spontaneous activity has also been shown to play a key role in the response to external stimuli. To better understand this role, we proposed a viewpoint, "memories-as-bifurcations," that differs from the traditional "memories-as-attractors" viewpoint. Memory recall from the memories-as-bifurcations viewpoint occurs when the spontaneous neural activity is changed to an appropriate output activity upon application of an input, known as a bifurcation in dynamical systems theory, wherein the input modifies the flow structure of the neural dynamics. Learning, then, is a process that helps create neural dynamical systems such that a target output pattern is generated as an attractor upon a given input. Based on this novel viewpoint, we introduce in this paper an associative memory model with a sequential learning process. Using a simple hebbian-type learning, the model is able to memorize a large number of input/output mappings. The neural dynamics shaped through the learning exhibit different bifurcations to make the requested targets stable upon an increase in the input, and the neural activity in the absence of input shows chaotic dynamics with occasional approaches to the memorized target patterns. These results suggest that these dynamics facilitate the bifurcations to each target attractor upon application of the corresponding input, which thus increases the capacity for learning. This theoretical finding about the behavior of the spontaneous neural activity is consistent with recent experimental observations in which the neural activity without stimuli wanders among patterns evoked by previously applied signals. In addition, the neural networks shaped by learning properly reflect the correlations of input and target-output patterns in a similar manner to those designed in our previous study.

  5. Embedding responses in spontaneous neural activity shaped through sequential learning.

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    Tomoki Kurikawa

    Full Text Available Recent experimental measurements have demonstrated that spontaneous neural activity in the absence of explicit external stimuli has remarkable spatiotemporal structure. This spontaneous activity has also been shown to play a key role in the response to external stimuli. To better understand this role, we proposed a viewpoint, "memories-as-bifurcations," that differs from the traditional "memories-as-attractors" viewpoint. Memory recall from the memories-as-bifurcations viewpoint occurs when the spontaneous neural activity is changed to an appropriate output activity upon application of an input, known as a bifurcation in dynamical systems theory, wherein the input modifies the flow structure of the neural dynamics. Learning, then, is a process that helps create neural dynamical systems such that a target output pattern is generated as an attractor upon a given input. Based on this novel viewpoint, we introduce in this paper an associative memory model with a sequential learning process. Using a simple hebbian-type learning, the model is able to memorize a large number of input/output mappings. The neural dynamics shaped through the learning exhibit different bifurcations to make the requested targets stable upon an increase in the input, and the neural activity in the absence of input shows chaotic dynamics with occasional approaches to the memorized target patterns. These results suggest that these dynamics facilitate the bifurcations to each target attractor upon application of the corresponding input, which thus increases the capacity for learning. This theoretical finding about the behavior of the spontaneous neural activity is consistent with recent experimental observations in which the neural activity without stimuli wanders among patterns evoked by previously applied signals. In addition, the neural networks shaped by learning properly reflect the correlations of input and target-output patterns in a similar manner to those designed in

  6. Ets Factors Regulate Neural Stem Cell Depletion and Gliogenesis in Ras Pathway Glioma

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    Joshua J. Breunig

    2015-07-01

    Full Text Available As the list of putative driver mutations in glioma grows, we are just beginning to elucidate the effects of dysregulated developmental signaling pathways on the transformation of neural cells. We have employed a postnatal, mosaic, autochthonous glioma model that captures the first hours and days of gliomagenesis in more resolution than conventional genetically engineered mouse models of cancer. We provide evidence that disruption of the Nf1-Ras pathway in the ventricular zone at multiple signaling nodes uniformly results in rapid neural stem cell depletion, progenitor hyperproliferation, and gliogenic lineage restriction. Abolishing Ets subfamily activity, which is upregulated downstream of Ras, rescues these phenotypes and blocks glioma initiation. Thus, the Nf1-Ras-Ets axis might be one of the select molecular pathways that are perturbed for initiation and maintenance in glioma.

  7. Gustatory neural pathways revealed by genetic tracing from taste receptor cells.

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    Matsumoto, Ichiro

    2013-01-01

    Taste receptor cells encounter chemicals in foods and transmit this information to the gustatory neurons, which convey it further to the gustatory relay nuclei in the lower brainstem. Characterizing neurons involved in the transmission of gustatory information in the peripheral and central nervous systems helps us better understand how we perceive and discriminate tastes. However, it is difficult to anatomically identify them. Using cell-type-specific promoters/enhancers and a transneuronal tracer, we generated transgenic mice to visualize neurons in the gustatory neural pathways. We observed the tracer in the neurons of cranial sensory ganglia and the nucleus of the solitary tract in the medulla where gustatory neurons project. The tracer was also distributed in the reticular formation and several motor nuclei in the medulla that have not been recognized as gustatory ascending pathways. These transgenic mice revealed gustatory relay neurons in the known gustatory ascending pathway and an unexpected, thus presumably novel, neural circuit of gustatory system.

  8. Affective neural response to restricted interests in autism spectrum disorders.

    Science.gov (United States)

    Cascio, Carissa J; Foss-Feig, Jennifer H; Heacock, Jessica; Schauder, Kimberly B; Loring, Whitney A; Rogers, Baxter P; Pryweller, Jennifer R; Newsom, Cassandra R; Cockhren, Jurnell; Cao, Aize; Bolton, Scott

    2014-01-01

    Restricted interests are a class of repetitive behavior in autism spectrum disorders (ASD) whose intensity and narrow focus often contribute to significant interference with daily functioning. While numerous neuroimaging studies have investigated executive circuits as putative neural substrates of repetitive behavior, recent work implicates affective neural circuits in restricted interests. We sought to explore the role of affective neural circuits and determine how restricted interests are distinguished from hobbies or interests in typical development. We compared a group of children with ASD to a typically developing (TD) group of children with strong interests or hobbies, employing parent report, an operant behavioral task, and functional imaging with personalized stimuli based on individual interests. While performance on the operant task was similar between the two groups, parent report of intensity and interference of interests was significantly higher in the ASD group. Both the ASD and TD groups showed increased BOLD response in widespread affective neural regions to the pictures of their own interest. When viewing pictures of other children's interests, the TD group showed a similar pattern, whereas BOLD response in the ASD group was much more limited. Increased BOLD response in the insula and anterior cingulate cortex distinguished the ASD from the TD group, and parent report of the intensity and interference with daily life of the child's restricted interest predicted insula response. While affective neural network response and operant behavior are comparable in typical and restricted interests, the narrowness of focus that clinically distinguishes restricted interests in ASD is reflected in more interference in daily life and aberrantly enhanced insula and anterior cingulate response to individuals' own interests in the ASD group. These results further support the involvement of affective neural networks in repetitive behaviors in ASD. © 2013 The

  9. Neural Pathway of Renovative and Innovative Products Appreciation

    Science.gov (United States)

    Huang, Furong; Chiu, Chiyue; Luo, Jing

    2016-12-01

    According to the level of change an invention makes on existing things and how it overrides people’s mental schemas on established categories, new inventions can be classified into two groups: incremental inventions (i.e., renovations), which make minor improvements on existing designs, and radical inventions (i.e., innovations), which make major developments that enable people to do things they have never been able to do before. Although innovation and renovation are two fundamentally different types of creation that feature new changes ranging from those in product development to those in large scale social changes, and people tend to report higher subjective preferences for incremental inventions compared to radical inventions, the cognitive brain mechanisms underlying the mental representation of these two types of inventions remains unknown. Through the use of innovative and renovative designs as materials, we found that relative to non-creative designs, creative (renovative &innovative) designs enhanced memory or association-related activation in the right parahippocampus. In particular, innovations evoked more activation in the conceptual pathway for representing objects than did renovations, whereas renovations evoked more activation in the motor pathway than innovations. These results suggest that operating experiences may provide advantages for understanding and appreciating creative designs.

  10. Neural correlates of emotional responses to music: an EEG study.

    Science.gov (United States)

    Daly, Ian; Malik, Asad; Hwang, Faustina; Roesch, Etienne; Weaver, James; Kirke, Alexis; Williams, Duncan; Miranda, Eduardo; Nasuto, Slawomir J

    2014-06-24

    This paper presents an EEG study into the neural correlates of music-induced emotions. We presented participants with a large dataset containing musical pieces in different styles, and asked them to report on their induced emotional responses. We found neural correlates of music-induced emotion in a number of frequencies over the pre-frontal cortex. Additionally, we found a set of patterns of functional connectivity, defined by inter-channel coherence measures, to be significantly different between groups of music-induced emotional responses. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  11. Neural responses to expression and gaze in the posterior superior temporal sulcus interact with facial identity.

    Science.gov (United States)

    Baseler, Heidi A; Harris, Richard J; Young, Andrew W; Andrews, Timothy J

    2014-03-01

    Neural models of human face perception propose parallel pathways. One pathway (including posterior superior temporal sulcus, pSTS) is responsible for processing changeable aspects of faces such as gaze and expression, and the other pathway (including the fusiform face area, FFA) is responsible for relatively invariant aspects such as identity. However, to be socially meaningful, changes in expression and gaze must be tracked across an individual face. Our aim was to investigate how this is achieved. Using functional magnetic resonance imaging, we found a region in pSTS that responded more to sequences of faces varying in gaze and expression in which the identity was constant compared with sequences in which the identity varied. To determine whether this preferential response to same identity faces was due to the processing of identity in the pSTS or was a result of interactions between pSTS and other regions thought to code face identity, we measured the functional connectivity between face-selective regions. We found increased functional connectivity between the pSTS and FFA when participants viewed same identity faces compared with different identity faces. Together, these results suggest that distinct neural pathways involved in expression and identity interact to process the changeable features of the face in a socially meaningful way.

  12. 2010 Carl Ludwig Distinguished Lectureship of the APS Neural Control and Autonomic Regulation Section: Central neural pathways for thermoregulatory cold defense.

    Science.gov (United States)

    Morrison, Shaun F

    2011-05-01

    Central neural circuits orchestrate the homeostatic repertoire to maintain body temperature during environmental temperature challenges and to alter body temperature during the inflammatory response. This review summarizes the research leading to a model representing our current understanding of the neural pathways through which cutaneous thermal receptors alter thermoregulatory effectors: the cutaneous circulation for control of heat loss, and brown adipose tissue, skeletal muscle, and the heart for thermogenesis. The activation of these effectors is regulated by parallel but distinct, effector-specific core efferent pathways within the central nervous system (CNS) that share a common peripheral thermal sensory input. The thermal afferent circuit from cutaneous thermal receptors includes neurons in the spinal dorsal horn projecting to lateral parabrachial nucleus neurons that project to the medial aspect of the preoptic area. Within the preoptic area, warm-sensitive, inhibitory output neurons control heat production by reducing the discharge of thermogenesis-promoting neurons in the dorsomedial hypothalamus. The rostral ventromedial medulla, including the raphe pallidus, receives projections form the dorsomedial hypothalamus and contains spinally projecting premotor neurons that provide the excitatory drive to spinal circuits controlling the activity of thermogenic effectors. A distinct population of warm-sensitive preoptic neurons controls heat loss through an inhibitory input to raphe pallidus sympathetic premotor neurons controlling cutaneous vasoconstriction. The model proposed for central thermoregulatory control provides a platform for further understanding of the functional organization of central thermoregulation.

  13. Neural responses to exclusion predict susceptibility to social influence.

    Science.gov (United States)

    Falk, Emily B; Cascio, Christopher N; O'Donnell, Matthew Brook; Carp, Joshua; Tinney, Francis J; Bingham, C Raymond; Shope, Jean T; Ouimet, Marie Claude; Pradhan, Anuj K; Simons-Morton, Bruce G

    2014-05-01

    Social influence is prominent across the lifespan, but sensitivity to influence is especially high during adolescence and is often associated with increased risk taking. Such risk taking can have dire consequences. For example, in American adolescents, traffic-related crashes are leading causes of nonfatal injury and death. Neural measures may be especially useful in understanding the basic mechanisms of adolescents' vulnerability to peer influence. We examined neural responses to social exclusion as potential predictors of risk taking in the presence of peers in recently licensed adolescent drivers. Risk taking was assessed in a driving simulator session occurring approximately 1 week after the neuroimaging session. Increased activity in neural systems associated with the distress of social exclusion and mentalizing during an exclusion episode predicted increased risk taking in the presence of a peer (controlling for solo risk behavior) during a driving simulator session outside the neuroimaging laboratory 1 week later. These neural measures predicted risky driving behavior above and beyond self-reports of susceptibility to peer pressure and distress during exclusion. These results address the neural bases of social influence and risk taking; contribute to our understanding of social and emotional function in the adolescent brain; and link neural activity in specific, hypothesized, regions to risk-relevant outcomes beyond the neuroimaging laboratory. Results of this investigation are discussed in terms of the mechanisms underlying risk taking in adolescents and the public health implications for adolescent driving. Copyright © 2014 Society for Adolescent Health and Medicine. All rights reserved.

  14. Prediction and control of neural responses to pulsatile electrical stimulation

    Science.gov (United States)

    Campbell, Luke J.; Sly, David James; O'Leary, Stephen John

    2012-04-01

    This paper aims to predict and control the probability of firing of a neuron in response to pulsatile electrical stimulation of the type delivered by neural prostheses such as the cochlear implant, bionic eye or in deep brain stimulation. Using the cochlear implant as a model, we developed an efficient computational model that predicts the responses of auditory nerve fibers to electrical stimulation and evaluated the model's accuracy by comparing the model output with pooled responses from a group of guinea pig auditory nerve fibers. It was found that the model accurately predicted the changes in neural firing probability over time to constant and variable amplitude electrical pulse trains, including speech-derived signals, delivered at rates up to 889 pulses s-1. A simplified version of the model that did not incorporate adaptation was used to adaptively predict, within its limitations, the pulsatile electrical stimulus required to cause a desired response from neurons up to 250 pulses s-1. Future stimulation strategies for cochlear implants and other neural prostheses may be enhanced using similar models that account for the way that neural responses are altered by previous stimulation.

  15. Differentiating neural reward responsiveness in autism versus ADHD

    Directory of Open Access Journals (Sweden)

    Gregor Kohls

    2014-10-01

    Full Text Available Although attention deficit hyperactivity disorders (ADHD and autism spectrum disorders (ASD share certain neurocognitive characteristics, it has been hypothesized to differentiate the two disorders based on their brain's reward responsiveness to either social or monetary reward. Thus, the present fMRI study investigated neural activation in response to both reward types in age and IQ-matched boys with ADHD versus ASD relative to typically controls (TDC. A significant group by reward type interaction effect emerged in the ventral striatum with greater activation to monetary versus social reward only in TDC, whereas subjects with ADHD responded equally strong to both reward types, and subjects with ASD showed low striatal reactivity across both reward conditions. Moreover, disorder-specific neural abnormalities were revealed, including medial prefrontal hyperactivation in response to social reward in ADHD versus ventral striatal hypoactivation in response to monetary reward in ASD. Shared dysfunction was characterized by fronto-striato-parietal hypoactivation in both clinical groups when money was at stake. Interestingly, lower neural activation within parietal circuitry was associated with higher autistic traits across the entire study sample. In sum, the present findings concur with the assumption that both ASD and ADHD display distinct and shared neural dysfunction in response to reward.

  16. Neural Markers of Responsiveness to the Environment in Human Sleep

    DEFF Research Database (Denmark)

    Andrillon, Thomas; Poulsen, Andreas Trier; Hansen, Lars Kai

    2016-01-01

    Sleep is characterized by a loss of behavioral responsiveness. However, recent research has shown that the sleeping brain is not completely disconnected from its environment. How neural activity constrains the ability to process sensory information while asleep is yet unclear. Here, we instructed...... by Lempel-Ziv complexity (LZc), a measure shown to track arousal in sleep and anesthesia. Neural activity related to the semantic content of stimuli was conserved in light non-rapid eye movement (NREM) sleep. However, these processes were suppressed in deep NREM sleep and, importantly, also in REM sleep......, despite the recovery of wake-like neural activity in the latter. In NREM sleep, sensory activations were counterbalanced by evoked down states, which, when present, blocked further processing of external information. In addition, responsiveness markers correlated positively with baseline complexity, which...

  17. The alexithymic brain: the neural pathways linking alexithymia to physical disorders

    Directory of Open Access Journals (Sweden)

    Kano Michiko

    2013-01-01

    Full Text Available Abstract Alexithymia is a personality trait characterized by difficulties in identifying and describing feelings and is associated with psychiatric and psychosomatic disorders. The mechanisms underlying the link between emotional dysregulation and psychosomatic disorders are unclear. Recent progress in neuroimaging has provided important information regarding emotional experience in alexithymia. We have conducted three brain imaging studies on alexithymia, which we describe herein. This article considers the role of emotion in the development of physical symptoms and discusses a possible pathway that we have identified in our neuroimaging studies linking alexithymia with psychosomatic disorders. In terms of socio-affective processing, alexithymics demonstrate lower reactivity in brain regions associated with emotion. Many studies have reported reduced activation in limbic areas (e.g., cingulate cortex, anterior insula, amygdala and the prefrontal cortex when alexithymics attempt to feel other people’s feelings or retrieve their own emotional episodes, compared to nonalexithymics. With respect to primitive emotional reactions such as the response to pain, alexithymics show amplified activity in areas considered to be involved in physical sensation. In addition to greater hormonal arousal responses in alexithymics during visceral pain, increased activity has been reported in the insula, anterior cingulate cortex, and midbrain. Moreover, in complex social situations, alexithymics may not be able to use feelings to guide their behavior appropriately. The Iowa gambling task (IGT was developed to assess decision-making processes based on emotion-guided evaluation. When alexithymics perform the IGT, they fail to learn an advantageous decision-making strategy and show reduced activity in the medial prefrontal cortex, a key area for successful performance of the IGT, and increased activity in the caudate, a region associated with impulsive choice. The

  18. Abnormal neural responses to social exclusion in schizophrenia.

    Science.gov (United States)

    Gradin, Victoria B; Waiter, Gordon; Kumar, Poornima; Stickle, Catriona; Milders, Maarten; Matthews, Keith; Reid, Ian; Hall, Jeremy; Steele, J Douglas

    2012-01-01

    Social exclusion is an influential concept in politics, mental health and social psychology. Studies on healthy subjects have implicated the medial prefrontal cortex (mPFC), a region involved in emotional and social information processing, in neural responses to social exclusion. Impairments in social interactions are common in schizophrenia and are associated with reduced quality of life. Core symptoms such as delusions usually have a social content. However little is known about the neural underpinnings of social abnormalities. The aim of this study was to investigate the neural substrates of social exclusion in schizophrenia. Patients with schizophrenia and healthy controls underwent fMRI while participating in a popular social exclusion paradigm. This task involves passing a 'ball' between the participant and two cartoon representations of other subjects. The extent of social exclusion (ball not being passed to the participant) was parametrically varied throughout the task. Replicating previous findings, increasing social exclusion activated the mPFC in controls. In contrast, patients with schizophrenia failed to modulate mPFC responses with increasing exclusion. Furthermore, the blunted response to exclusion correlated with increased severity of positive symptoms. These data support the hypothesis that the neural response to social exclusion differs in schizophrenia, highlighting the mPFC as a potential substrate of impaired social interactions.

  19. Neural circuitry underlying affective response to peer feedback in adolescence.

    Science.gov (United States)

    Guyer, Amanda E; Choate, Victoria R; Pine, Daniel S; Nelson, Eric E

    2012-01-01

    Peer feedback affects adolescents' behaviors, cognitions and emotions. We examined neural circuitry underlying adolescents' emotional response to peer feedback using a functional neuroimaging paradigm whereby, 36 adolescents (aged 9-17 years) believed they would interact with unknown peers postscan. Neural activity was expected to vary based on adolescents' perceptions of peers and feedback type. Ventrolateral prefrontal cortex (vlPFC) activity was found when adolescents indicated how they felt following feedback (acceptance or rejection) from peers of low vs high interest. Greater activation in both cortical (e.g. superior temporal gyrus, insula, anterior cingulate) and subcortical (e.g. striatum, thalamus) regions emerged in response to acceptance vs rejection feedback. Response to acceptance also varied by age and gender in similar regions (e.g. superior temporal gyrus, fusiform, insula), with greater age-related increases in activation to acceptance vs rejection for females than males. Affective response to rejection vs acceptance did not yield significantly greater neural activity in any region. vlPFC response suggests cognitive flexibility in reappraising initial perceptions of peers following feedback. Striatal response suggests that acceptance is a potent social reward for adolescents, an interpretation supported by more positive self-reported affective response to acceptance than rejection from high- but not low-interest peers.

  20. PLZF regulates fibroblast growth factor responsiveness and maintenance of neural progenitors.

    Directory of Open Access Journals (Sweden)

    Zachary B Gaber

    2013-10-01

    Full Text Available Distinct classes of neurons and glial cells in the developing spinal cord arise at specific times and in specific quantities from spatially discrete neural progenitor domains. Thus, adjacent domains can exhibit marked differences in their proliferative potential and timing of differentiation. However, remarkably little is known about the mechanisms that account for this regional control. Here, we show that the transcription factor Promyelocytic Leukemia Zinc Finger (PLZF plays a critical role shaping patterns of neuronal differentiation by gating the expression of Fibroblast Growth Factor (FGF Receptor 3 and responsiveness of progenitors to FGFs. PLZF elevation increases FGFR3 expression and STAT3 pathway activity, suppresses neurogenesis, and biases progenitors towards glial cell production. In contrast, PLZF loss reduces FGFR3 levels, leading to premature neuronal differentiation. Together, these findings reveal a novel transcriptional strategy for spatially tuning the responsiveness of distinct neural progenitor groups to broadly distributed mitogenic signals in the embryonic environment.

  1. Personality traits modulate neural responses to emotions expressed in music.

    Science.gov (United States)

    Park, Mona; Hennig-Fast, Kristina; Bao, Yan; Carl, Petra; Pöppel, Ernst; Welker, Lorenz; Reiser, Maximilian; Meindl, Thomas; Gutyrchik, Evgeny

    2013-07-26

    Music communicates and evokes emotions. The number of studies on the neural correlates of musical emotion processing is increasing but few have investigated the factors that modulate these neural activations. Previous research has shown that personality traits account for individual variability of neural responses. In this study, we used functional magnetic resonance imaging (fMRI) to investigate how the dimensions Extraversion and Neuroticism are related to differences in brain reactivity to musical stimuli expressing the emotions happiness, sadness and fear. 12 participants (7 female, M=20.33 years) completed the NEO-Five Factor Inventory (NEO-FFI) and were scanned while performing a passive listening task. Neurofunctional analyses revealed significant positive correlations between Neuroticism scores and activations in bilateral basal ganglia, insula and orbitofrontal cortex in response to music expressing happiness. Extraversion scores were marginally negatively correlated with activations in the right amygdala in response to music expressing fear. Our findings show that subjects' personality may have a predictive power in the neural correlates of musical emotion processing and should be considered in the context of experimental group homogeneity. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. Sub-meninges Implantation Reduces Immune Response to Neural Implants

    Science.gov (United States)

    Markwardt, Neil T.; Stokol, Jodi; Rennaker, Robert L.

    2013-01-01

    Glial scar formation around neural interfaces inhibits their ability to acquire usable signals from the surrounding neurons. To improve neural recording performance, the inflammatory response and glial scarring must be minimized. Previous work has indicated that meningeally derived cells participate in the immune response, and it is possible that the meninges may grow down around the shank of a neural implant, contributing to the formation of the glial scar. This study examines whether the glial scar can be reduced by placing a neural probe completely below the meninges. Rats were implanted with sets of loose microwire implants placed either completely below the meninges or implanted conventionally with the upper end penetrating the meninges, but not attached to the skull. Histological analysis was performed 4 weeks following surgical implantation to evaluate the glial scar. Our results found that sub-meninges implants showed an average reduction in reactive astrocyte activity of 63% compared to trans-meninges implants. Microglial activity was also reduced for sub-meninges implants. These results suggest that techniques that isolate implants from the meninges offer the potential to reduce the encapsulation response which should improve chronic recording quality and stability. PMID:23370311

  3. Regional cerebral glucose metabolic changes in oculopalatal myoclonus: implication for neural pathways, underlying the disorder

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Sang Soo; Moon, So Young; Kim, Ji Soo; Kim, Sang Eun [College of Medicine, Seoul National University, Seoul (Korea, Republic of)

    2004-07-01

    Palatal myoclonus (PM) is characterized by rhythmic involuntary jerky movements of the soft palate of the throat. When associated with eye movements, it is called oculopalatal myoclonus (OPM). Ordinary PM is characterized by hypertrophic olivary degeneration, a trans-synaptic degeneration following loss of neuronal input to the inferior olivary nucleus due to an interruption of the Guillain-Mollaret triangle usually by a hemorrhage. However, the neural pathways underlying the disorder are uncertain. In an attempt to understand the pathologic neural pathways, we examined the metabolic correlates of this tremulous condition. Brain FDG PET scans were acquired in 8 patients with OPM (age, 49.9{+-}4.6 y: all males: 7 with pontine hemorrhage, 1 with diffuse brainstem infarction) and age-matched 50 healthy males (age, 50.7{+-} 9.0) and the regional glucose metabolism compared using SPM99. For group analysis, the hemispheres containing lesions were assigned to the right side of the brain. Patients with OPM had significant hypometabolism in the ipsilateral (to the lesion) brainstem and superior temporal and parahippocampal gyri (P < 0.05 corrected, k = 100). By contrast, there was significant hypermetabolism in the contralateral middle and inferior temporal gyri, thalamus, middle frontal gyrus and precuneus (P < 0.05 corrected, k=l00). Our data demonstrate the distinct metabolic changes between several ipsilateral and contralateral brain regions (hypometabolism vs. hypermetabolism) in patients with OPM. This may provide clues for understanding the neural pathways underlying the disorder.

  4. Involvement of catecholaminergic medullary pathways in cardiovascular responses to acute changes in circulating volume

    Directory of Open Access Journals (Sweden)

    S.L. Cravo

    2011-09-01

    Full Text Available Water deprivation and hypernatremia are major challenges for water and sodium homeostasis. Cellular integrity requires maintenance of water and sodium concentration within narrow limits. This regulation is obtained through engagement of multiple mechanisms and neural pathways that regulate the volume and composition of the extracellular fluid. The purpose of this short review is to summarize the literature on central neural mechanisms underlying cardiovascular, hormonal and autonomic responses to circulating volume changes, and some of the findings obtained in the last 12 years by our laboratory. We review data on neural pathways that start with afferents in the carotid body that project to medullary relays in the nucleus tractus solitarii and caudal ventrolateral medulla, which in turn project to the median preoptic nucleus in the forebrain. We also review data suggesting that noradrenergic A1 cells in the caudal ventrolateral medulla represent an essential link in neural pathways controlling extracellular fluid volume and renal sodium excretion. Finally, recent data from our laboratory suggest that these structures may also be involved in the beneficial effects of intravenous infusion of hypertonic saline on recovery from hemorrhagic shock.

  5. Response variance in functional maps: neural darwinism revisited.

    Directory of Open Access Journals (Sweden)

    Hirokazu Takahashi

    Full Text Available The mechanisms by which functional maps and map plasticity contribute to cortical computation remain controversial. Recent studies have revisited the theory of neural Darwinism to interpret the learning-induced map plasticity and neuronal heterogeneity observed in the cortex. Here, we hypothesize that the Darwinian principle provides a substrate to explain the relationship between neuron heterogeneity and cortical functional maps. We demonstrate in the rat auditory cortex that the degree of response variance is closely correlated with the size of its representational area. Further, we show that the response variance within a given population is altered through training. These results suggest that larger representational areas may help to accommodate heterogeneous populations of neurons. Thus, functional maps and map plasticity are likely to play essential roles in Darwinian computation, serving as effective, but not absolutely necessary, structures to generate diverse response properties within a neural population.

  6. Response variance in functional maps: neural darwinism revisited.

    Science.gov (United States)

    Takahashi, Hirokazu; Yokota, Ryo; Kanzaki, Ryohei

    2013-01-01

    The mechanisms by which functional maps and map plasticity contribute to cortical computation remain controversial. Recent studies have revisited the theory of neural Darwinism to interpret the learning-induced map plasticity and neuronal heterogeneity observed in the cortex. Here, we hypothesize that the Darwinian principle provides a substrate to explain the relationship between neuron heterogeneity and cortical functional maps. We demonstrate in the rat auditory cortex that the degree of response variance is closely correlated with the size of its representational area. Further, we show that the response variance within a given population is altered through training. These results suggest that larger representational areas may help to accommodate heterogeneous populations of neurons. Thus, functional maps and map plasticity are likely to play essential roles in Darwinian computation, serving as effective, but not absolutely necessary, structures to generate diverse response properties within a neural population.

  7. Neural mechanisms linking social status and inflammatory responses to social stress

    Science.gov (United States)

    Dedovic, Katarina; Slavich, George M.; Jarcho, Michael R.; Breen, Elizabeth C.; Bower, Julienne E.; Irwin, Michael R.; Eisenberger, Naomi I.

    2016-01-01

    Social stratification has important implications for health and well-being, with individuals lower in standing in a hierarchy experiencing worse outcomes than those higher up the social ladder. Separate lines of past research suggest that alterations in inflammatory processes and neural responses to threat may link lower social status with poorer outcomes. This study was designed to bridge these literatures to investigate the neurocognitive mechanisms linking subjective social status and inflammation. Thirty-one participants reported their subjective social status, and underwent a functional magnetic resonance imaging scan while they were socially evaluated. Participants also provided blood samples before and after the stressor, which were analysed for changes in inflammation. Results showed that lower subjective social status was associated with greater increases in inflammation. Neuroimaging data revealed lower subjective social status was associated with greater neural activity in the dorsomedial prefrontal cortex (DMPFC) in response to negative feedback. Finally, results indicated that activation in the DMPFC in response to negative feedback mediated the relation between social status and increases in inflammatory activity. This study provides the first evidence of a neurocognitive pathway linking subjective social status and inflammation, thus furthering our understanding of how social hierarchies shape neural and physiological responses to social interactions. PMID:26979965

  8. Neural mechanisms linking social status and inflammatory responses to social stress.

    Science.gov (United States)

    Muscatell, Keely A; Dedovic, Katarina; Slavich, George M; Jarcho, Michael R; Breen, Elizabeth C; Bower, Julienne E; Irwin, Michael R; Eisenberger, Naomi I

    2016-06-01

    Social stratification has important implications for health and well-being, with individuals lower in standing in a hierarchy experiencing worse outcomes than those higher up the social ladder. Separate lines of past research suggest that alterations in inflammatory processes and neural responses to threat may link lower social status with poorer outcomes. This study was designed to bridge these literatures to investigate the neurocognitive mechanisms linking subjective social status and inflammation. Thirty-one participants reported their subjective social status, and underwent a functional magnetic resonance imaging scan while they were socially evaluated. Participants also provided blood samples before and after the stressor, which were analysed for changes in inflammation. Results showed that lower subjective social status was associated with greater increases in inflammation. Neuroimaging data revealed lower subjective social status was associated with greater neural activity in the dorsomedial prefrontal cortex (DMPFC) in response to negative feedback. Finally, results indicated that activation in the DMPFC in response to negative feedback mediated the relation between social status and increases in inflammatory activity. This study provides the first evidence of a neurocognitive pathway linking subjective social status and inflammation, thus furthering our understanding of how social hierarchies shape neural and physiological responses to social interactions. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  9. AAV-mediated Anterograde Transsynaptic Tagging: Mapping Input-Defined Functional Neural Pathways for Defense Behavior

    Science.gov (United States)

    Zingg, Brian; Chou, Xiao-lin; Zhang, Zheng-gang; Mesik, Lukas; Liang, Feixue; Tao, Huizhong Whit; Zhang, Li I.

    2017-01-01

    To decipher neural circuits underlying brain functions, viral tracers are widely applied to map input and output connectivity of specific neuronal populations. Despite the successful application of retrograde transsynaptic viruses for identifying presynaptic neurons of transduced neurons, analogous anterograde transsynaptic tools for tagging postsynaptically targeted neurons remain under development. Here, we report that adeno-associated virus (AAV1 and AAV9) exhibit anterograde transsynaptic spread properties. AAV1-Cre from transduced presynaptic neurons effectively and specifically drove Cre-dependent transgene expression in selected postsynaptic neuronal targets, and thus allowed the tracing and functional manipulation of axonal projections from the latter input-defined neuronal population. Application of this tool in superior colliculus (SC) revealed that SC neuron subpopulations receiving corticocollicular projections from auditory and visual cortex specifically drove flight and freezing, two different types of defense behavior, respectively. Such anterograde transsynaptic tagging is thus useful for forward screening of distinct functional neural pathways embedded in complex brain circuits. PMID:27989459

  10. Synaptic plasticity-related neural oscillations on hippocampus-prefrontal cortex pathway in depression.

    Science.gov (United States)

    Zheng, C; Zhang, T

    2015-04-30

    It is believed that phase synchronization facilitates neural communication and neural plasticity throughout the hippocampal-cortical network, and further supports cognition and memory. The pathway from the ventral hippocampus to the medial prefrontal cortex (mPFC) is thought to play a significant role in emotional memory processing. Therefore, the information transmission on the pathway was hypothesized to be disrupted in the depressive state, which could be related to its impaired synaptic plasticity. In this study, local field potentials (LFPs) from both ventral CA1 (vCA1) and mPFC were recorded in both normal and chronic unpredictable stress (CUS) model rats under urethane anesthesia. LFPs of all rats were recorded before and after the long-term potentiation (LTP) induced on the vCA1-mPFC pathway in order to figure out the correlation of oscillatory synchronization of LFPs and synaptic plasticity. Our results showed the vCA1-to-mPFC unidirectional phase coupling of the theta rhythm, rather than the power of either region, was significantly enhanced by LTP induction, with less enhancement in the CUS model rats compared to that in the normal rats. In addition, theta phase coupling was positively correlated with synaptic plasticity on vCA1-mPFC pathway. Moreover, the theta-slow gamma phase-amplitude coupling in vCA1 was long-term enhanced after high frequency stimulation. These results suggest that the impaired synaptic plasticity in vCA1-mPFC pathway could be reflected by the attenuated theta phase coupling and theta-gamma cross frequency coupling of LFPs in the depression state. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  11. Pentobarbital anesthesia alters neural responses in the precedence effect.

    Science.gov (United States)

    Song, Penglong; Wang, Ningyu; Wang, Hui; Xie, Yan; Jia, Jun; Li, Huijun

    2011-07-01

    The precedence effect (PE) is thought to be beneficial for proper localization and perception of sounds. The majority of recent physiological studies focus on the neural discharges correlated with PE in the inferior colliculus (IC). Pentobarbital anesthesia is widely used in physiological studies. However, little is known of the effect of pentobarbital on the discharge of neurons in PE. Neuronal responses in the IC from 23 male SD rats were recorded by standard extracellular recording techniques following presentation of 4 ms white noise bursts, presented from either or both of two loud speakers, at different interstimulus delays (ISDs). The neural responses were recorded for off-line analysis before or after intraperitoneal administration of pentobarbital at a loading or maintenance dose. Data were assessed by one-way repeated measures analysis of variance and pairwise comparisons. When the ipsilateral stimuli were leading, pentobarbital at a loading dose significantly increased normalized response to lagging stimuli during recovery from anesthesia. However, it was not the case when the contralateral stimuli were leading. At a maintenance dose, the normalized response to lagging stimuli were significantly reduced, independent of whether contralateral or ipsilateral stimuli were leading. These data show that pentobarbital have no effect on the normalized response of leading stimuli but can prolong the recovery time of lagging stimuli to paired sources produced PE illusions, which was gradually attenuated during recovery from anesthesia. Thus, extracellular recording immediately after administration of pentobarbital should be avoided in physiological studies of neural correlates of PE. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  12. Common neural substrates for inhibition of spoken and manual responses.

    Science.gov (United States)

    Xue, Gui; Aron, Adam R; Poldrack, Russell A

    2008-08-01

    The inhibition of speech acts is a critical aspect of human executive control over thought and action, but its neural underpinnings are poorly understood. Using functional magnetic resonance imaging and the stop-signal paradigm, we examined the neural correlates of speech control in comparison to manual motor control. Initiation of a verbal response activated left inferior frontal cortex (IFC: Broca's area). Successful inhibition of speech (naming of letters or pseudowords) engaged a region of right IFC (including pars opercularis and anterior insular cortex) as well as presupplementary motor area (pre-SMA); these regions were also activated by successful inhibition of a hand response (i.e., a button press). Moreover, the speed with which subjects inhibited their responses, stop-signal reaction time, was significantly correlated between speech and manual inhibition tasks. These findings suggest a functional dissociation of left and right IFC in initiating versus inhibiting vocal responses, and that manual responses and speech acts share a common inhibitory mechanism localized in the right IFC and pre-SMA.

  13. Neural network connectivity and response latency modelled by stochastic processes

    DEFF Research Database (Denmark)

    Tamborrino, Massimiliano

    is connected to thousands of other neurons. The rst question is: how to model neural networks through stochastic processes? A multivariate Ornstein-Uhlenbeck process, obtained as a diffusion approximation of a jump process, is the proposed answer. Obviously, dependencies between neurons imply dependencies...... between their spike times. Therefore, the second question is: how to detect neural network connectivity from simultaneously recorded spike trains? Answering this question corresponds to investigate the joint distribution of sequences of rst passage times. A non-parametric method based on copulas...... generation of pikes. When a stimulus is applied to the network, the spontaneous rings may prevail and hamper detection of the effects of the stimulus. Therefore, the spontaneous rings cannot be ignored and the response latency has to be detected on top of a background signal. Everything becomes more dicult...

  14. Compassion training alters altruism and neural responses to suffering.

    Science.gov (United States)

    Weng, Helen Y; Fox, Andrew S; Shackman, Alexander J; Stodola, Diane E; Caldwell, Jessica Z K; Olson, Matthew C; Rogers, Gregory M; Davidson, Richard J

    2013-07-01

    Compassion is a key motivator of altruistic behavior, but little is known about individuals' capacity to cultivate compassion through training. We examined whether compassion may be systematically trained by testing whether (a) short-term compassion training increases altruistic behavior and (b) individual differences in altruism are associated with training-induced changes in neural responses to suffering. In healthy adults, we found that compassion training increased altruistic redistribution of funds to a victim encountered outside of the training context. Furthermore, increased altruistic behavior after compassion training was associated with altered activation in brain regions implicated in social cognition and emotion regulation, including the inferior parietal cortex and dorsolateral prefrontal cortex (DLPFC), and in DLPFC connectivity with the nucleus accumbens. These results suggest that compassion can be cultivated with training and that greater altruistic behavior may emerge from increased engagement of neural systems implicated in understanding the suffering of other people, executive and emotional control, and reward processing.

  15. All-trans retinoic acid promotes neural lineage entry by pluripotent embryonic stem cells via multiple pathways

    Directory of Open Access Journals (Sweden)

    Fang Bo

    2009-07-01

    Full Text Available Abstract Background All-trans retinoic acid (RA is one of the most important morphogens with pleiotropic actions. Its embryonic distribution correlates with neural differentiation in the developing central nervous system. To explore the precise effects of RA on neural differentiation of mouse embryonic stem cells (ESCs, we detected expression of RA nuclear receptors and RA-metabolizing enzymes in mouse ESCs and investigated the roles of RA in adherent monolayer culture. Results Upon addition of RA, cell differentiation was directed rapidly and exclusively into the neural lineage. Conversely, pharmacological interference with RA signaling suppressed this neural differentiation. Inhibition of fibroblast growth factor (FGF signaling did not suppress significantly neural differentiation in RA-treated cultures. Pharmacological interference with extracellular signal-regulated kinase (ERK pathway or activation of Wnt pathway effectively blocked the RA-promoted neural specification. ERK phosphorylation was enhanced in RA-treated cultures at the early stage of differentiation. Conclusion RA can promote neural lineage entry by ESCs in adherent monolayer culture systems. This effect depends on RA signaling and its crosstalk with the ERK and Wnt pathways.

  16. Wnt/beta-catenin pathway: modulating anticancer immune response

    Directory of Open Access Journals (Sweden)

    Sachin Gopalkrishna Pai

    2017-05-01

    Full Text Available Abstract Wnt/β-catenin signaling, a highly conserved pathway through evolution, regulates key cellular functions including proliferation, differentiation, migration, genetic stability, apoptosis, and stem cell renewal. The Wnt pathway mediates biological processes by a canonical or noncanonical pathway, depending on the involvement of β-catenin in signal transduction. β-catenin is a core component of the cadherin protein complex, whose stabilization is essential for the activation of Wnt/β-catenin signaling. As multiple aberrations in this pathway occur in numerous cancers, WNT-directed therapy represents an area of significant developmental therapeutics focus. The recently described role of Wnt/β-catenin pathway in regulating immune cell infiltration of the tumor microenvironment renewed the interest, given its potential impact on responses to immunotherapy treatments. This article summarizes the role of Wnt/β-catenin pathway in cancer and ongoing therapeutic strategies involving this pathway.

  17. Expressive suppression and neural responsiveness to nonverbal affective cues

    Science.gov (United States)

    Petrican, Raluca; Rosenbaum, R. Shayna; Grady, Cheryl

    2016-01-01

    responsiveness to nonverbal affective cues, while also suggesting one explanation for the suppressors’ poorer cognitive performance in social situations. Moreover, our results point to a potential neural mechanism supporting the development and perpetuation of expressive suppression as an emotion regulation strategy. PMID:26365712

  18. Intelligence moderates neural responses to monetary reward and punishment.

    Science.gov (United States)

    Hawes, Daniel R; DeYoung, Colin G; Gray, Jeremy R; Rustichini, Aldo

    2014-05-01

    The relations between intelligence (IQ) and neural responses to monetary gains and losses were investigated in a simple decision task. In 94 healthy adults, typical responses of striatal blood oxygen level-dependent (BOLD) signal after monetary reward and punishment were weaker for subjects with higher IQ. IQ-moderated differential responses to gains and losses were also found for regions in the medial prefrontal cortex, posterior cingulate cortex, and left inferior frontal cortex. These regions have previously been identified with the subjective utility of monetary outcomes. Analysis of subjects' behavior revealed a correlation between IQ and the extent to which choices were related to experienced decision outcomes in preceding trials. Specifically, higher IQ predicted behavior to be more strongly correlated with an extended period of previously experienced decision outcomes, whereas lower IQ predicted behavior to be correlated exclusively to the most recent decision outcomes. We link these behavioral and imaging findings to a theoretical model capable of describing a role for intelligence during the evaluation of rewards generated by unknown probabilistic processes. Our results demonstrate neural differences in how people of different intelligence respond to experienced monetary rewards and punishments. Our theoretical discussion offers a functional description for how these individual differences may be linked to choice behavior. Together, our results and model support the hypothesis that observed correlations between intelligence and preferences may be rooted in the way decision outcomes are experienced ex post, rather than deriving exclusively from how choices are evaluated ex ante.

  19. [Selective ablation of certain neural pathways by gene transfer using viral vectors: analysis of primate basal ganglia functions by using immunotoxin-mediated tract targeting].

    Science.gov (United States)

    Takada, Masahiko

    2013-06-01

    Using a neuron-specific retrograde gene-transfer vector based on the lentivirus, we established immunotoxin (IT)-mediated tract targeting in the primate brain; this technique allows ablation of a neuronal population constituting a certain pathway. Here, we introduce a recent study on selective removal of the cortico-subthalamic "hyperdirect" pathway. Together with the direct and indirect pathways, the hyperdirect pathway plays a crucial role in motor information processing in the basal ganglia. This pathway links the motor-related areas of the frontal lobe directly to the subthalamic nucleus (STN) without relay at the striatum. After electrical stimulation of the motor-related areas, such as the supplementary motor area (SMA), triphasic responses consisting of an early excitation, an inhibition, and a late excitation are usually detected in the internal segment of the globus pallidus (GPi). Several lines of evidence suggest that the early excitation may be derived from the hyperdirect pathway. We injected the lentiviral vector expressing human interleukin-2 receptor α-subunit into the monkey STN. IT was then injected into the SMA. We recorded GPi neuron responses to SMA stimulation. We found that the early excitation was reduced neither with the inhibition nor with the late excitation. The spontaneous firing rate and pattern of GPi neurons remained unchanged. This indicated that IT-mediated tract targeting successfully and selectively eliminated the hyperdirect pathway from the basal ganglia circuitry without affecting the spontaneous activity of STN neurons. This electrophysiological finding was confirmed using anatomical data obtained from retrograde and anterograde neural tracings. The present results show that the cortically driven early excitation in GPi neurons is mediated by the hyperdirect pathway. The IT-mediated tract targeting technique will provide us with novel strategies for elucidating various neural network functions.

  20. A Decline in Response Variability Improves Neural Signal Detection during Auditory Task Performance.

    Science.gov (United States)

    von Trapp, Gardiner; Buran, Bradley N; Sen, Kamal; Semple, Malcolm N; Sanes, Dan H

    2016-10-26

    The detection of a sensory stimulus arises from a significant change in neural activity, but a sensory neuron's response is rarely identical to successive presentations of the same stimulus. Large trial-to-trial variability would limit the central nervous system's ability to reliably detect a stimulus, presumably affecting perceptual performance. However, if response variability were to decrease while firing rate remained constant, then neural sensitivity could improve. Here, we asked whether engagement in an auditory detection task can modulate response variability, thereby increasing neural sensitivity. We recorded telemetrically from the core auditory cortex of gerbils, both while they engaged in an amplitude-modulation detection task and while they sat quietly listening to the identical stimuli. Using a signal detection theory framework, we found that neural sensitivity was improved during task performance, and this improvement was closely associated with a decrease in response variability. Moreover, units with the greatest change in response variability had absolute neural thresholds most closely aligned with simultaneously measured perceptual thresholds. Our findings suggest that the limitations imposed by response variability diminish during task performance, thereby improving the sensitivity of neural encoding and potentially leading to better perceptual sensitivity. The detection of a sensory stimulus arises from a significant change in neural activity. However, trial-to-trial variability of the neural response may limit perceptual performance. If the neural response to a stimulus is quite variable, then the response on a given trial could be confused with the pattern of neural activity generated when the stimulus is absent. Therefore, a neural mechanism that served to reduce response variability would allow for better stimulus detection. By recording from the cortex of freely moving animals engaged in an auditory detection task, we found that variability

  1. Fetal DNA hypermethylation in tight junction pathway is associated with neural tube defects: A genome-wide DNA methylation analysis.

    Science.gov (United States)

    Wang, Linlin; Lin, Shanshan; Zhang, Ji; Tian, Tian; Jin, Lei; Ren, Aiguo

    2017-02-01

    Neural tube defects (NTDs) are a spectrum of severe congenital malformations of fusion failure of the neural tube during early embryogenesis. Evidence on aberrant DNA methylation in NTD development remains scarce, especially when exposure to environmental pollutant is taken into consideration. DNA methylation profiling was quantified using the Infinium HumanMethylation450 array in neural tissues from 10 NTD cases and 8 non-malformed controls (stage 1). Subsequent validation was performed using a Sequenom MassARRAY system in neural tissues from 20 NTD cases and 20 non-malformed controls (stage 2). Correlation analysis of differentially methylated CpG sites in fetal neural tissues and polycyclic aromatic hydrocarbons concentrations in fetal neural tissues and maternal serum was conducted. Differentially methylated CpG sites of neural tissues were further validated in fetal mice with NTDs induced by benzo(a)pyrene given to pregnant mice. Differentially hypermethylated CpG sites in neural tissues from 17 genes and 6 pathways were identified in stage 1. Subsequently, differentially hypermethylated CpG sites in neural tissues from 6 genes (BDKRB2, CTNNA1, CYFIP2, MMP7, MYH2, and TIAM2) were confirmed in stage 2. Correlation analysis showed that methylated CpG sites in CTNNA1 and MYH2 from NTD cases were positively correlated to polycyclic aromatic hydrocarbon level in fetal neural tissues and maternal serum. The correlation was confirmed in NTD-affected fetal mice that were exposed to benzo(a)pyrene in utero. In conclusion, hypermethylation of the CTNNA1 and MYH2 genes in tight junction pathway is associated with the risk for NTDs, and the DNA methylation aberration may be caused by exposure to benzo(a)pyrene.

  2. Roman Catholic beliefs produce characteristic neural responses to moral dilemmas

    Science.gov (United States)

    Flexas, Albert; de Miguel, Pedro; Cela-Conde, Camilo J.; Munar, Enric

    2014-01-01

    This study provides exploratory evidence about how behavioral and neural responses to standard moral dilemmas are influenced by religious belief. Eleven Catholics and 13 Atheists (all female) judged 48 moral dilemmas. Differential neural activity between the two groups was found in precuneus and in prefrontal, frontal and temporal regions. Furthermore, a double dissociation showed that Catholics recruited different areas for deontological (precuneus; temporoparietal junction) and utilitarian moral judgments [dorsolateral prefrontal cortex (DLPFC); temporal poles], whereas Atheists did not (superior parietal gyrus for both types of judgment). Finally, we tested how both groups responded to personal and impersonal moral dilemmas: Catholics showed enhanced activity in DLPFC and posterior cingulate cortex during utilitarian moral judgments to impersonal moral dilemmas and enhanced responses in anterior cingulate cortex and superior temporal sulcus during deontological moral judgments to personal moral dilemmas. Our results indicate that moral judgment can be influenced by an acquired set of norms and conventions transmitted through religious indoctrination and practice. Catholic individuals may hold enhanced awareness of the incommensurability between two unequivocal doctrines of the Catholic belief set, triggered explicitly in a moral dilemma: help and care in all circumstances—but thou shalt not kill. PMID:23160812

  3. Reward-related neural responses are dependent on the beneficiary.

    Science.gov (United States)

    Braams, Barbara R; Güroğlu, Berna; de Water, Erik; Meuwese, Rosa; Koolschijn, P Cédric; Peper, Jiska S; Crone, Eveline A

    2014-07-01

    Prior studies have suggested that positive social interactions are experienced as rewarding. Yet, it is not well understood how social relationships influence neural responses to other persons' gains. In this study, we investigated neural responses during a gambling task in which healthy participants (N = 31; 18 females) could win or lose money for themselves, their best friend or a disliked other (antagonist). At the moment of receiving outcome, person-related activity was observed in the dorsal medial prefrontal cortex (dmPFC), precuneus and temporal parietal junction (TPJ), showing higher activity for friends and antagonists than for self, and this activity was independent of outcome. The only region showing an interaction between the person-participants played for and outcome was the ventral striatum. Specifically, the striatum was more active following gains than losses for self and friends, whereas for the antagonist this pattern was reversed. Together, these results show that, in a context with social and reward information, social aspects are processed in brain regions associated with social cognition (mPFC, TPJ), and reward aspects are processed in primary reward areas (striatum). Furthermore, there is an interaction of social and reward information in the striatum, such that reward-related activity was dependent on social relationship. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  4. Nutrient pathways and neural tube defects: a semi-Bayesian hierarchical analysis.

    Science.gov (United States)

    Carmichael, Suzan L; Witte, John S; Shaw, Gary M

    2009-01-01

    We used conventional and hierarchical logistic regression to examine the association of neural tube defects (NTDs) with intake of 26 nutrients that contribute to the mechanistic pathways of methylation, glycemic control, and oxidative stress, all of which have been implicated in NTD etiology. The hierarchical approach produces more plausible, more stable estimates than the conventional approach, while adjusting for potential confounding by other nutrients. Analyses included 386 cases and 408 nonmalformed controls with complete data on nutrients and potential confounders (race/ethnicity, education, obesity, and intake of vitamin supplements) from a population-based case-control study of deliveries in California from 1989 to 1991. Nutrients were specified as continuous, and their units were standardized to have a mean of zero and standard deviation (SD) of 1 for comparability of units across pathways. ORs reflect a 1-SD increase in the corresponding nutrient. Among women who took vitamin supplements, semi-Bayesian hierarchical modeling results suggested no associations between nutrient intake and NTDs. Among women who did not take supplements, both conventional and hierarchical models (HM) suggested an inverse association between lutein intake and NTD risk (HM odds ratio [OR] = 0.6; 95% confidence interval = 0.5-0.9) and a positive association with sucrose (HM OR 1.4; 1.1-1.8) and glycemic index (HM OR 1.3; 1.0-1.6). Our findings for lutein, glycemic index, and sucrose suggest that further study of NTDs and the glycemic control and oxidative stress pathways is warranted.

  5. Adolescents' behavioral and neural responses to e-cigarette advertising.

    Science.gov (United States)

    Chen, Yvonnes; Fowler, Carina H; Papa, Vlad B; Lepping, Rebecca J; Brucks, Morgan G; Fox, Andrew T; Martin, Laura E

    2018-03-01

    Although adolescents are a group heavily targeted by the e-cigarette industry, research in cue-reactivity has not previously examined adolescents' behavioral and neural responses to e-cigarette advertising. This study addressed this gap through two experiments. In Experiment One, adult traditional cigarette smokers (n = 41) and non-smokers (n = 41) answered questions about e-cigarette and neutral advertising images. The 40 e-cigarette advertising images that most increased desire to use the product were matched to 40 neutral advertising images with similar content. In Experiment Two, the 80 advertising images selected in Experiment One were presented to adolescents (n = 30) during an functional magnetic resonance imaging brain scan. There was a range of traditional cigarette smoking across the sample with some adolescents engaging in daily smoking and others who had never smoked. Adolescents self-reported that viewing the e-cigarette advertising images increased their desire to smoke. Additionally, all participants regardless of smoking statuses showed significantly greater brain activation to e-cigarette advertisements in areas associated with cognitive control (left middle frontal gyrus), reward (right medial frontal gyrus), visual processing/attention (left lingual gyrus/fusiform gyrus, right inferior parietal lobule, left posterior cingulate, left angular gyrus) and memory (right parahippocampus, left insula). Further, an exploratory analysis showed that compared with age-matched non-smokers (n = 7), adolescent smokers (n = 7) displayed significantly greater neural activation to e-cigarette advertising images in the left inferior temporal gyrus/fusiform gyrus, compared with their responses to neutral advertising images. Overall, participants' brain responses to e-cigarette advertisements suggest a need to further investigate the long-run impact of e-cigarette advertising on adolescents. © 2017 Society for the Study of Addiction.

  6. AAV-Mediated Anterograde Transsynaptic Tagging: Mapping Corticocollicular Input-Defined Neural Pathways for Defense Behaviors.

    Science.gov (United States)

    Zingg, Brian; Chou, Xiao-Lin; Zhang, Zheng-Gang; Mesik, Lukas; Liang, Feixue; Tao, Huizhong Whit; Zhang, Li I

    2017-01-04

    To decipher neural circuits underlying brain functions, viral tracers are widely applied to map input and output connectivity of neuronal populations. Despite the successful application of retrograde transsynaptic viruses for identifying presynaptic neurons of transduced neurons, analogous anterograde transsynaptic tools for tagging postsynaptically targeted neurons remain under development. Here, we discovered that adeno-associated viruses (AAV1 and AAV9) exhibit anterograde transsynaptic spread properties. AAV1-Cre from transduced presynaptic neurons effectively and specifically drives Cre-dependent transgene expression in selected postsynaptic neuronal targets, thus allowing axonal tracing and functional manipulations of the latter input-defined neuronal population. Its application in superior colliculus (SC) reveals that SC neuron subpopulations receiving corticocollicular projections from auditory and visual cortex specifically drive flight and freezing, two different types of defense behavior, respectively. Together with an intersectional approach, AAV-mediated anterograde transsynaptic tagging can categorize neurons by their inputs and molecular identity, and allow forward screening of distinct functional neural pathways embedded in complex brain circuits. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. A DSP for sensing the bladder volume through afferent neural pathways.

    Science.gov (United States)

    Mendez, Arnaldo; Belghith, Abrar; Sawan, Mohamad

    2014-08-01

    In this paper, we present a digital signal processor (DSP) capable of monitoring the urinary bladder volume through afferent neural pathways. The DSP carries out real-time detection and can discriminate extracellular action potentials, also known as on-the-fly spike sorting. Next, the DSP performs a decoding method to estimate either three qualitative levels of fullness or the bladder volume value, depending on the selected output mode. The proposed DSP was tested using both realistic synthetic signals with a known ground-truth, and real signals from bladder afferent nerves recorded during acute experiments with animal models. The spike sorting processing circuit yielded an average accuracy of 92% using signals with highly correlated spike waveforms and low signal-to-noise ratios. The volume estimation circuits, tested with real signals, reproduced accuracies achieved by offline simulations in Matlab, i.e., 94% and 97% for quantitative and qualitative estimations, respectively. To assess feasibility, the DSP was deployed in the Actel FPGA Igloo AGL1000V2, which showed a power consumption of 0.5 mW and a latency of 2.1 ms at a 333 kHz core frequency. These performance results demonstrate that an implantable bladder sensor that perform the detection, discrimination and decoding of afferent neural activity is feasible.

  8. Proposers’ Economic Status Affects Behavioral and Neural Responses to Unfairness

    Directory of Open Access Journals (Sweden)

    Yijie Zheng

    2017-05-01

    Full Text Available Economic status played an important role in the modulation of economic decision making. The present fMRI study aimed at investigating how economic status modulated behavioral and neural responses to unfairness in a modified Ultimatum Game (UG. During scanning, participants played as responders in the UG, and they were informed of the economic status of proposers before receiving offers. At the behavioral level, higher rejection rates and lower fairness ratings were revealed when proposers were in high economic status than in low economic status. Besides, the most time-consuming decisions tended to occur at lower unfairness level when the proposers were in high (relative to low economic status. At the neural level, stronger activation of left thalamus was revealed when fair offers were proposed by proposers in high rather than in low economic status. Greater activation of right medial prefrontal cortex was revealed during acceptance to unfair offers in high economic status condition rather than in low economic status condition. Taken together, these findings shed light on the significance of proposers’ economic status in responders’ social decision making in UG.

  9. Intraoperative Neural Response Telemetry and Neural Recovery Function: a Comparative Study between Adults and Children

    Directory of Open Access Journals (Sweden)

    Carvalho, Bettina

    2014-04-01

    Full Text Available Introduction Neural response telemetry (NRT is a method of capturing the action potential of the distal portion of the auditory nerve in cochlear implant (CI users, using the CI itself to elicit and record the answers. In addition, it can also measure the recovery function of the auditory nerve (REC, that is, the refractory properties of the nerve. It is not clear in the literature whether the responses from adults are the same as those from children. Objective To compare the results of NRT and REC between adults and children undergoing CI surgery. Methods Cross-sectional, descriptive, and retrospective study of the results of NRT and REC for patients undergoing IC at our service. The NRT is assessed by the level of amplitude (microvolts and REC as a function of three parameters: A (saturation level, in microvolts, t0 (absolute refractory period, in seconds, and tau (curve of the model function, measured in three electrodes (apical, medial, and basal. Results Fifty-two patients were evaluated with intraoperative NRT (26 adults and 26 children, and 24 with REC (12 adults and 12 children. No statistically significant difference was found between intraoperative responses of adults and children for NRT or for REC's three parameters, except for parameter A of the basal electrode. Conclusion The results of intraoperative NRT and REC were not different between adults and children, except for parameter A of the basal electrode.

  10. Intraoperative Neural Response Telemetry and Neural Recovery Function: a Comparative Study between Adults and Children

    Science.gov (United States)

    Carvalho, Bettina; Hamerschmidt, Rogerio; Wiemes, Gislaine

    2014-01-01

    Introduction Neural response telemetry (NRT) is a method of capturing the action potential of the distal portion of the auditory nerve in cochlear implant (CI) users, using the CI itself to elicit and record the answers. In addition, it can also measure the recovery function of the auditory nerve (REC), that is, the refractory properties of the nerve. It is not clear in the literature whether the responses from adults are the same as those from children. Objective To compare the results of NRT and REC between adults and children undergoing CI surgery. Methods Cross-sectional, descriptive, and retrospective study of the results of NRT and REC for patients undergoing IC at our service. The NRT is assessed by the level of amplitude (microvolts) and REC as a function of three parameters: A (saturation level, in microvolts), t0 (absolute refractory period, in seconds), and tau (curve of the model function), measured in three electrodes (apical, medial, and basal). Results Fifty-two patients were evaluated with intraoperative NRT (26 adults and 26 children), and 24 with REC (12 adults and 12 children). No statistically significant difference was found between intraoperative responses of adults and children for NRT or for REC's three parameters, except for parameter A of the basal electrode. Conclusion The results of intraoperative NRT and REC were not different between adults and children, except for parameter A of the basal electrode. PMID:25992145

  11. Hierarchical Feature Extraction With Local Neural Response for Image Recognition.

    Science.gov (United States)

    Li, Hong; Wei, Yantao; Li, Luoqing; Chen, C L P

    2013-04-01

    In this paper, a hierarchical feature extraction method is proposed for image recognition. The key idea of the proposed method is to extract an effective feature, called local neural response (LNR), of the input image with nontrivial discrimination and invariance properties by alternating between local coding and maximum pooling operation. The local coding, which is carried out on the locally linear manifold, can extract the salient feature of image patches and leads to a sparse measure matrix on which maximum pooling is carried out. The maximum pooling operation builds the translation invariance into the model. We also show that other invariant properties, such as rotation and scaling, can be induced by the proposed model. In addition, a template selection algorithm is presented to reduce computational complexity and to improve the discrimination ability of the LNR. Experimental results show that our method is robust to local distortion and clutter compared with state-of-the-art algorithms.

  12. Intraurethral stimulation evokes bladder responses via 2 distinct reflex pathways.

    Science.gov (United States)

    Woock, John P; Yoo, Paul B; Grill, Warren M

    2009-07-01

    Recent animal studies have shown that selective activation of pudendal nerve branches can evoke bladder responses through 2 distinct reflex pathways. We examined intraurethral electrical stimulation as a minimally invasive means of selectively activating these pathways in the cat. Bladder responses evoked by intraurethral electrical stimulation were measured in alpha-chloralose anesthetized male cats at different stimulation frequencies, stimulation intensities and intraurethral locations. Intraurethral electrical stimulation evoked inhibitory and excitatory bladder reflexes depending on stimulation frequency and location. Stimulation in the penile urethra 0 to 3 cm from the urethral meatus at 33 Hz evoked bladder contraction and at 10 Hz it evoked bladder relaxation. These responses were abolished after bilateral transection of the dorsal penile nerves. Stimulation in the membranous urethra 5 to 7 cm from the urethral meatus at 2, 10 and 33 Hz evoked bladder contractions. These responses were abolished after bilateral transection of the cranial sensory nerves. Following acute spinal cord transection bladder contractions were still evoked by 33 Hz stimulation in the penile urethra but not by stimulation at any frequency in the membranous urethra. Intraurethral electrical stimulation selectively evoked bladder responses by activating 2 distinct pudendal afferent pathways. Responses depended on stimulation frequency and location. Intraurethral electrical stimulation is a valid means of determining the pathways involved in bladder responses evoked by pudendal nerve stimulation.

  13. Threat modulates neural responses to looming visual stimuli.

    Science.gov (United States)

    Vagnoni, Eleonora; Lourenco, Stella F; Longo, Matthew R

    2015-09-01

    Objects on a collision course with an observer produce a specific pattern of optical expansion on the retina known as looming, which in theory exactly specifies the time-to-collision (TTC) of approaching objects. It was recently demonstrated that the affective content of looming stimuli influences perceived TTC, with threatening objects judged as approaching sooner than non-threatening objects. Here, the neural mechanisms by which perceived threat modulates spatiotemporal perception were investigated. Participants judged the TTC of threatening (snakes, spiders) or non-threatening (butterflies, rabbits) stimuli, which expanded in size at a rate indicating one of five TTCs. Visual-evoked potentials (VEPs) and oscillatory neural responses measured with electroencephalography were analysed. The arrival time of threatening stimuli was underestimated compared with non-threatening stimuli, though an interaction suggested that this underestimation was not constant across TTCs. Further, both speed of approach and threat modulated both VEPs and oscillatory responses. Speed of approach modulated the N1 parietal and oscillations in the beta band. Threat modulated several VEP components (P1, N1 frontal, N1 occipital, early posterior negativity and late positive potential) and oscillations in the alpha and high gamma band. The results for the high gamma band suggest an interaction between these two factors. Previous evidence suggests that looming stimuli activate sensorimotor areas, even in the absence of an intended action. The current results show that threat disrupts the synchronization over the sensorimotor areas that are likely activated by the presentation of a looming stimulus. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  14. Empathy and Stress Related Neural Responses in Maternal Decision Making

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    S. Shaun Ho

    2014-06-01

    Full Text Available Mothers need to make caregiving decisions to meet the needs of children, which may or may not result in positive child feedback. Variations in caregivers’ emotional reactivity to unpleasant child-feedback may be partially explained by their dispositional empathy levels. Furthermore, empathic response to the child’s unpleasant feedback likely helps mothers to regulate their own stress. We investigated the relationship between maternal dispositional empathy, stress reactivity, and neural correlates of child feedback to caregiving decisions. In Part 1 of the study, 33 female participants were recruited to undergo a lab-based mild stressor, the Social Evaluation Test (SET, and then in Part 2 of the study, a subset of the participants, fourteen mothers, performed a Parenting Decision Making Task (PDMT in an fMRI setting. Four dimensions of dispositional empathy based on the Interpersonal Reactivity Index were measured in all participants – Personal Distress, Empathic Concern, Perspective Taking, and Fantasy. Overall, we found that the Personal Distress and Perspective Taking were associated with greater and lesser cortisol reactivity, respectively. The four types of empathy were distinctly associated with the negative (versus positive child feedback activation in the brain. Personal Distress was associated with amygdala and hypothalamus activation, Empathic Concern with the left ventral striatum, ventrolateral prefrontal cortex (VLPFC, and supplemental motor area (SMA activation, and Fantasy with the septal area, right SMA and VLPFC activation. Interestingly, hypothalamus-septal coupling during the negative feedback condition was associated with less PDMT-related cortisol reactivity. The roles of distinct forms of dispositional empathy in neural and stress responses are discussed.

  15. Musical training shapes neural responses to melodic and prosodic expectation.

    Science.gov (United States)

    Zioga, Ioanna; Di Bernardi Luft, Caroline; Bhattacharya, Joydeep

    2016-11-01

    Current research on music processing and syntax or semantics in language suggests that music and language share partially overlapping neural resources. Pitch also constitutes a common denominator, forming melody in music and prosody in language. Further, pitch perception is modulated by musical training. The present study investigated how music and language interact on pitch dimension and whether musical training plays a role in this interaction. For this purpose, we used melodies ending on an expected or unexpected note (melodic expectancy being estimated by a computational model) paired with prosodic utterances which were either expected (statements with falling pitch) or relatively unexpected (questions with rising pitch). Participants' (22 musicians, 20 nonmusicians) ERPs and behavioural responses in a statement/question discrimination task were recorded. Participants were faster for simultaneous expectancy violations in the melodic and linguistic stimuli. Further, musicians performed better than nonmusicians, which may be related to their increased pitch tracking ability. At the neural level, prosodic violations elicited a front-central positive ERP around 150ms after the onset of the last word/note, while musicians presented reduced P600 in response to strong incongruities (questions on low-probability notes). Critically, musicians' P800 amplitudes were proportional to their level of musical training, suggesting that expertise might shape the pitch processing of language. The beneficial aspect of expertise could be attributed to its strengthening effect of general executive functions. These findings offer novel contributions to our understanding of shared higher-order mechanisms between music and language processing on pitch dimension, and further demonstrate a potential modulation by musical expertise. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  16. FoxO3 coordinates metabolic pathways to maintain redox balance in neural stem cells.

    Science.gov (United States)

    Yeo, Hyeonju; Lyssiotis, Costas A; Zhang, Yuqing; Ying, Haoqiang; Asara, John M; Cantley, Lewis C; Paik, Ji-Hye

    2013-10-02

    Forkhead Box O (FoxO) transcription factors act in adult stem cells to preserve their regenerative potential. Previously, we reported that FoxO maintains the long-term proliferative capacity of neural stem/progenitor cells (NPCs), and that this occurs, in part, through the maintenance of redox homeostasis. Herein, we demonstrate that among the FoxO3-regulated genes in NPCs are a host of enzymes in central carbon metabolism that act to combat reactive oxygen species (ROS) by directing the flow of glucose and glutamine carbon into defined metabolic pathways. Characterization of the metabolic circuit observed upon loss of FoxO3 revealed a drop in glutaminolysis and filling of the tricarboxylic acid (TCA) cycle. Additionally, we found that glucose uptake, glucose metabolism and oxidative pentose phosphate pathway activity were similarly repressed in the absence of FoxO3. Finally, we demonstrate that impaired glucose and glutamine metabolism compromises the proliferative potential of NPCs and that this is exacerbated following FoxO3 loss. Collectively, our findings show that a FoxO3-dependent metabolic programme supports redox balance and the neurogenic potential of NPCs.

  17. Neural correlates of social perception on response bias.

    Science.gov (United States)

    Shin, Yeon Soon; Kim, Hye-Young; Han, Sanghoon

    2014-07-01

    Accurate person perception is crucial in social decision-making. One of the central elements in successful social perception is the ability to understand another's response bias; this is because the same behavior can represent different inner states depending on whether other people are yea-sayers or naysayers. In the present study, we have tried to investigate how the internal biases of others are perceived. Using a multi-trial learning paradigm, perceivers made predictions about a target's responses to various suggested activities and then received feedback for each prediction trial-by-trial. Our hypotheses were that (1) the internal decision criterion of the targets would be realized through repeated experiences, and (2) due to positive-negative asymmetry, yea-sayers would be recognized more gradually than naysayers through the probabilistic integration of repeated experiences. To find neural evidence that tracks probabilistic integration when forming person knowledge on response biases, we employed a model-based fMRI with a State-Space Model. We discovered that person knowledge about yea-sayers modulated several brain regions, including caudate nucleus, DLPFC, hippocampus, etc. Moreover, when person knowledge was updated with incorrect performance feedback, brain regions including the caudate nucleus, DLPFC, dmPFC, and TPJ were also involved. There were overlapping regions for both processes, caudate nucleus and DLPFC, suggesting that these regions take crucial roles in forming person knowledge with repeated feedback, while reflecting acquired information up to the current prediction. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Lymphovascular and neural regulation of metastasis: Shared tumour signalling pathways and novel therapeutic approaches

    Science.gov (United States)

    Le, C.P.; Karnezis, T.; Achen, M. G.; Stacker, S.A.; Sloan, E.K.

    2014-01-01

    The progression of cancer is supported by a wide variety of non-neoplastic cell types which make up the tumour stroma, including immune cells, endothelial cells, cancer-associated fibroblasts and nerve fibres. These host cells contribute molecular signals that enhance primary tumour growth and provide physical avenues for metastatic dissemination. This article provides an overview of the role of blood vessels, lymphatic vessels and nerve fibres in the tumour microenvironment, and highlights the interconnected molecular signalling pathways that control their development and activation in cancer. Further the review highlights the known pharmacological agents which target these pathways and discusses the potential therapeutic uses of drugs that target angiogenesis, lymphangiogenesis and stress response pathways in the different stages of cancer care. PMID:24267548

  19. NR2B-containing NMDA receptors promote neural progenitor cell proliferation through CaMKIV/CREB pathway

    Energy Technology Data Exchange (ETDEWEB)

    Li, Mei, E-mail: limeihit@163.com [Department of Anatomy and Neurobiology, Xuzhou Medical College, Xuzhou (China); Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, Nanjing (China); Zhang, Dong-Qing; Wang, Xiang-Zhen [Department of Anatomy and Neurobiology, Xuzhou Medical College, Xuzhou (China); Xu, Tie-Jun, E-mail: xztjxu@163.com [Department of Anatomy and Neurobiology, Xuzhou Medical College, Xuzhou (China); Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, Nanjing (China)

    2011-08-12

    Highlights: {yields} The NR2B component of the NMDARs is important for the NSPC proliferation. {yields} pCaMKIV and pCREB exist in NSPCs. {yields} The CaMKIV/CREB pathway mediates NSPC proliferation. -- Abstract: Accumulating evidence indicates the involvement of N-methyl-D-aspartate receptors (NMDARs) in regulating neural stem/progenitor cell (NSPC) proliferation. Functional properties of NMDARs can be markedly influenced by incorporating the regulatory subunit NR2B. Here, we aim to analyze the effect of NR2B-containing NMDARs on the proliferation of hippocampal NSPCs and to explore the mechanism responsible for this effect. NSPCs were shown to express NMDAR subunits NR1 and NR2B. The NR2B selective antagonist, Ro 25-6981, prevented the NMDA-induced increase in cell proliferation. Moreover, we demonstrated that the phosphorylation levels of calcium/calmodulin-dependent protein kinase IV (CaMKIV) and cAMP response element binding protein (CREB) were increased by NMDA treatment, whereas Ro 25-6981 decreased them. The role that NR2B-containing NMDARs plays in NSPC proliferation was abolished when CREB phosphorylation was attenuated by CaMKIV silencing. These results suggest that NR2B-containing NMDARs have a positive role in regulating NSPC proliferation, which may be mediated through CaMKIV phosphorylation and subsequent induction of CREB activation.

  20. Subtypes of trait impulsivity differentially correlate with neural responses to food choices

    NARCIS (Netherlands)

    van der Laan, Laura N.; Barendse, Marjolein E. A.; Viergever, Max A.; Smeets, Paul A. M.

    2016-01-01

    Impulsivity is a personality trait that is linked to unhealthy eating and overweight. A few studies assessed how impulsivity relates to neural responses to anticipating and tasting food, but it is unknown how impulsivity relates to neural responses during food choice. Although impulsivity is a

  1. Broadband noise masks suppress neural responses to narrowband stimuli

    Directory of Open Access Journals (Sweden)

    Daniel Hart Baker

    2014-07-01

    Full Text Available White pixel noise is widely used to estimate the level of internal noise in a system by injecting external variance into the detecting mechanism. Recent work (Baker & Meese, 2012, J Vis, 12(10:20 has provided psychophysical evidence that such noise masks might also cause suppression that could invalidate estimates of internal noise. Here we measure neural population responses directly, using steady-state visual evoked potentials, elicited by target stimuli embedded in different mask types. Sinusoidal target gratings of 1c/deg flickered at 5Hz, and were shown in isolation, or with superimposed orthogonal grating masks or 2D white noise masks, flickering at 7Hz. Compared with responses to a blank screen, the Fourier amplitude at the target frequency increased monotonically as a function of target contrast when no mask was present. Both orthogonal and white noise masks caused rightward shifts of the contrast response function, providing evidence of contrast gain control suppression. We also calculated within-observer amplitude variance across trials. This increased in proportion to the target response, implying signal-dependent (i.e. multiplicative noise at the system level, the implications of which we discuss for behavioural tasks. This measure of variance was reduced by both mask types, consistent with the changes in mean target response. An alternative variety of noise, which we term zero-dimensional noise, involves trial-by-trial jittering of the target contrast. This type of noise produced no gain control suppression, and increased the amplitude variance across trials.

  2. Metformin Acts on Two Different Molecular Pathways to Enhance Adult Neural Precursor Proliferation/Self-Renewal and Differentiation

    Directory of Open Access Journals (Sweden)

    Michael Fatt

    2015-12-01

    Full Text Available The recruitment of endogenous adult neural stem cells for brain repair is a promising regenerative therapeutic strategy. This strategy involves stimulation of multiple stages of adult neural stem cell development, including proliferation, self-renewal, and differentiation. Currently, there is a lack of a single therapeutic approach that can act on these multiple stages of adult neural stem cell development to enhance neural regeneration. Here we show that metformin, an FDA-approved diabetes drug, promotes proliferation, self-renewal, and differentiation of adult neural precursors (NPCs. Specifically, we show that metformin enhances adult NPC proliferation and self-renewal dependent upon the p53 family member and transcription factor TAp73, while it promotes neuronal differentiation of these cells by activating the AMPK-aPKC-CBP pathway. Thus, metformin represents an optimal candidate neuro-regenerative agent that is capable of not only expanding the adult NPC population but also subsequently driving them toward neuronal differentiation by activating two distinct molecular pathways.

  3. Amphetamine alters neural response to sucrose in healthy women.

    Science.gov (United States)

    Melrose, A James; Bailer, Ursula; Wierenga, Christina E; Bischoff-Grethe, Amanda; Paulus, Martin P; Kaye, Walter H

    2016-06-30

    Amphetamine, likely via action on the brain's dopaminergic systems, induces anorectic eating behavior and blunts dopaminergic midbrain activation to rewards. Past work has hypothesized that this blunted reward responsivity is a result of increasing tonic over phasic DA activity. We sought to extend past findings to sweet taste during fMRI following single-blind administration of dextroamphetamine and placebo in 11 healthy women. We hypothesized that neural response in both limbic and cognitive sweet taste circuits would mirror past work with monetary rewards by effectively blunting sweet taste reward, and 'equalizing' it's rewarding taste with receipt of water. Behavioral results showed that amphetamine reduced self-reported hunger (supporting the existence of amphetamine anorexia) and increased self-report euphoria. In addition, region of Interest analysis revealed significant treatment by taste interactions in the middle insula and dorsal anterior cingulate confirming the 'equalizing' hypothesis in the cingulate, but unlike monetary reinforcers, the insula actually evinced enhanced separation between tastes on the amphetamine day. These results suggest a divergence from prior research using monetary reinforcers when extended to primary reinforcers, and may hint that altering dopaminergic signaling in the insula and anterior cingulate may be a target for pharmacological manipulation of appetite, and the treatment of obesity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. Endoplasmic reticulum stress pathway required for immune homeostasis is neurally controlled by arrestin-1.

    Science.gov (United States)

    Singh, Varsha; Aballay, Alejandro

    2012-09-28

    In response to pathogen infection, the host innate immune system activates microbial killing pathways and cellular stress pathways that need to be balanced because insufficient or excessive immune responses have deleterious consequences. Recent studies demonstrate that two G protein-coupled receptors (GPCRs) in the nervous system of Caenorhabditis elegans control immune homeostasis. To investigate further how GPCR signaling controls immune homeostasis at the organismal level, we studied arrestin-1 (ARR-1), which is the only GPCR adaptor protein in C. elegans. The results indicate that ARR-1 is required for GPCR signaling in ASH, ASI, AQR, PQR, and URX neurons, which control the unfolded protein response and a p38 mitogen-activated protein kinase signaling pathway required for innate immunity. ARR-1 activity also controlled immunity through ADF chemosensory and AFD thermosensory neurons that regulate longevity. Furthermore, we found that although ARR-1 played a key role in the control of immunity by AFD thermosensory neurons, it did not control longevity through these cells. However, ARR-1 partially controlled longevity through ADF neurons.

  5. Female mice deficient in alpha-fetoprotein show female-typical neural responses to conspecific-derived pheromones.

    Directory of Open Access Journals (Sweden)

    Olivier Brock

    Full Text Available The neural mechanisms controlling sexual behavior are sexually differentiated by the perinatal actions of sex steroid hormones. We recently observed using female mice deficient in alpha-fetoprotein (AFP-KO and which lack the protective actions of AFP against maternal estradiol, that exposure to prenatal estradiol completely defeminized the potential to show lordosis behavior in adulthood. Furthermore, AFP-KO females failed to show any male-directed mate preferences following treatment with estradiol and progesterone, indicating a reduced sexual motivation to seek out the male. In the present study, we asked whether neural responses to male- and female-derived odors are also affected in AFP-KO female mice. Therefore, we compared patterns of Fos, the protein product of the immediate early gene, c-fos, commonly used as a marker of neuronal activation, between wild-type (WT and AFP-KO female mice following exposure to male or estrous female urine. We also tested WT males to confirm the previously observed sex differences in neural responses to male urinary odors. Interestingly, AFP-KO females showed normal, female-like Fos responses, i.e. exposure to urinary odors from male but not estrous female mice induced equivalent levels of Fos protein in the accessory olfactory pathways (e.g. the medial part of the preoptic nucleus, the bed nucleus of the stria terminalis, the amygdala, and the lateral part of the ventromedial hypothalamic nucleus as well as in the main olfactory pathways (e.g. the piriform cortex and the anterior cortical amygdaloid nucleus, as WT females. By contrast, WT males did not show any significant induction of Fos protein in these brain areas upon exposure to either male or estrous female urinary odors. These results thus suggest that prenatal estradiol is not involved in the sexual differentiation of neural Fos responses to male-derived odors.

  6. Oxidative stress response pathways: Fission yeast as archetype

    DEFF Research Database (Denmark)

    Papadakis, Manos A.; Workman, Christopher

    2015-01-01

    Schizosaccharomyces pombe is a popular model eukaryotic organism to study diverse aspects of mammalian biology, including responses to cellular stress triggered by redox imbalances within its compartments. The review considers the current knowledge on the signaling pathways that govern the transc...

  7. Cochlear response telemetry: intracochlear electrocochleography via cochlear implant neural response telemetry pilot study results.

    Science.gov (United States)

    Campbell, Luke; Kaicer, Arielle; Briggs, Robert; O'Leary, Stephen

    2015-03-01

    To record cochlear responses to acoustic stimulation (electrocochleography) directly from a cochlear implant (CI) in awake recipients with residual hearing, using an adaptation of Neural Response Telemetry (NRT) that achieves a 10-ms recording window. Modern cochlear implants contain circuitry for recording neural responses to electrical stimulation, which is known in Cochlear Ltd systems as NRT. We adapted NRT to achieve an extended recording window long enough to record an acoustic electrocochleogram. This paper reports recordings made with this system in recipients with residual hearing. Subjects were adults with CI422 CIs who retained audiometric thresholds between 75 and 90 dB HL at 500 Hz in their implanted ear. The CI was interfaced to a laptop via a Freedom speech processor connected by USB. Calibrated acoustic stimuli (clicks and tone bursts between 500 and 1,500 Hz) were presented via insert tube phones to the implanted ear. Responses were acquired through the adapted NRT system. Recordings were made from apical, mid-array, and basal electrodes. Electrocochleography responses were compared with audiometric thresholds. Electrocochleography could be recorded from all five subjects. The compound action potential, cochlear microphonic, and summating potentials were identified. Good quality recordings were most reliably attained from apical electrodes using 40 to 100 repetitions. Audiometric thresholds were similar to compound action potential thresholds. Intracochlear responses to acoustic stimulation can be recorded directly from the CI in awake recipients with residual hearing. This may prove useful for monitoring postoperative hearing and for device fitting.

  8. Chondroitin sulfate proteoglycans regulate the growth, differentiation and migration of multipotent neural precursor cells through the integrin signaling pathway

    Directory of Open Access Journals (Sweden)

    Lü He-Zuo

    2009-10-01

    Full Text Available Abstract Background Neural precursor cells (NPCs are defined by their ability to proliferate, self-renew, and retain the potential to differentiate into neurons and glia. Deciphering the factors that regulate their behaviors will greatly aid in their use as potential therapeutic agents or targets. Chondroitin sulfate proteoglycans (CSPGs are prominent components of the extracellular matrix (ECM in the central nervous system (CNS and are assumed to play important roles in controlling neuronal differentiation and development. Results In the present study, we demonstrated that CSPGs were constitutively expressed on the NPCs isolated from the E16 rat embryonic brain. When chondroitinase ABC was used to abolish the function of endogenous CSPGs on NPCs, it induced a series of biological responses including the proliferation, differentiation and migration of NPCs, indicating that CSPGs may play a critical role in NPC development and differentiation. Finally, we provided evidence suggesting that integrin signaling pathway may be involved in the effects of CSPGs on NPCs. Conclusion The present study investigating the influence and mechanisms of CSPGs on the differentiation and migration of NPCs should help us to understand the basic biology of NPCs during CNS development and provide new insights into developing new strategies for the treatment of the neurological disorders in the CNS.

  9. Early life social stress induced changes in depression and anxiety associated neural pathways which are correlated with impaired maternal care.

    Science.gov (United States)

    Murgatroyd, Christopher A; Peña, Catherine J; Podda, Giovanni; Nestler, Eric J; Nephew, Benjamin C

    2015-08-01

    Exposures to various types of early life stress can be robust predictors of the development of psychiatric disorders, including depression and anxiety. The objective of the current study was to investigate the roles of the translationally relevant targets of central vasopressin, oxytocin, ghrelin, orexin, glucocorticoid, and the brain-derived neurotrophic factor (BDNF) pathway in an early chronic social stress (ECSS) based rodent model of postpartum depression and anxiety. The present study reports novel changes in gene expression and extracellular signal related kinase (ERK) protein levels in the brains of ECSS exposed rat dams that display previously reported depressed maternal care and increased maternal anxiety. Decreases in oxytocin, orexin, and ERK proteins, increases in ghrelin receptor, glucocorticoid and mineralocorticoid receptor mRNA levels, and bidirectional changes in vasopressin underscore related work on the adverse long-term effects of early life stress on neural activity and plasticity, maternal behavior, responses to stress, and depression and anxiety-related behavior. The differences in gene and protein expression and robust correlations between expression and maternal care and anxiety support increased focus on these targets in animal and clinical studies of the adverse effects of early life stress, especially those focusing on depression and anxiety in mothers and the transgenerational effects of these disorders on offspring. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Two neural streams, one voice: pathways for theme and variation in the songbird brain.

    Science.gov (United States)

    Bertram, R; Daou, A; Hyson, R L; Johnson, F; Wu, W

    2014-09-26

    Birdsong offers a unique model system to understand how a developing brain - once given a set of purely acoustic targets - teaches itself the vocal-tract gestures necessary to imitate those sounds. Like human infants, to juvenile male zebra finches (Taeniopygia guttata) falls the burden of initiating the vocal-motor learning of adult sounds. In both species, adult caregivers provide only a set of sounds to be imitated, with little or no information about the vocal-tract gestures used to produce the sounds. Here, we focus on the central control of birdsong and review the recent discovery that zebra finch song is under dual premotor control. Distinct forebrain pathways for structured (theme) and unstructured (variation) singing not only raise new questions about mechanisms of sensory-motor integration, but also provide a fascinating new research opportunity. A cortical locus for a motor memory of the learned song is now firmly established, meaning that anatomical, physiological, and computational approaches are poised to reveal the neural mechanisms used by the brain to compose the songs of birds. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  11. Nrf2/ARE Pathway Involved in Oxidative Stress Induced by Paraquat in Human Neural Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Tingting Dou

    2016-01-01

    Full Text Available Compelling evidences have shown that diverse environmental insults arising during early life can either directly lead to a reduction in the number of dopaminergic neurons or cause an increased susceptibility to neurons degeneration with subsequent environmental insults or with aging alone. Oxidative stress is considered the main effect of neurotoxins exposure. In this study, we investigated the oxidative stress effect of Paraquat (PQ on immortalized human embryonic neural progenitor cells by treating them with various concentrations of PQ. We show that PQ can decrease the activity of SOD and CAT but increase MDA and LDH level. Furthermore, the activities of Cyc and caspase-9 were found increased significantly at 10 μM of PQ treatment. The cytoplasmic Nrf2 protein expressions were upregulated at 10 μM but fell back at 100 μM. The nuclear Nrf2 protein expressions were upregulated as well as the downstream mRNA expressions of HO-1 and NQO1 in a dose-dependent manner. In addition, the proteins expression of PKC and CKII was also increased significantly even at 1 μM. The results suggested that Nrf2/ARE pathway is involved in mild to moderate PQ-induced oxidative stress which is evident from dampened Nrf2 activity and low expression of antioxidant genes in PQ induced oxidative damage.

  12. A segregated neural pathway for prefrontal top-down control of tactile discrimination.

    Science.gov (United States)

    Gogulski, Juha; Boldt, Robert; Savolainen, Petri; Guzmán-López, Jessica; Carlson, Synnöve; Pertovaara, Antti

    2015-01-01

    It has proven difficult to separate functional areas in the prefrontal cortex (PFC), an area implicated in attention, memory, and distraction handling. Here, we assessed in healthy human subjects whether PFC subareas have different roles in top-down regulation of sensory functions by determining how the neural links between the PFC and the primary somatosensory cortex (S1) modulate tactile perceptions. Anatomical connections between the S1 representation area of the cutaneous test site and the PFC were determined using probabilistic tractography. Single-pulse navigated transcranial magnetic stimulation of the middle frontal gyrus-S1 link, but not that of the superior frontal gyrus-S1 link, impaired the ability to discriminate between single and twin tactile pulses. The impairment occurred within a restricted time window and skin area. The spatially and temporally organized top-down control of tactile discrimination through a segregated PFC-S1 pathway suggests functional specialization of PFC subareas in fine-tuned regulation of information processing. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. Insights into the neural basis of response inhibition from cognitive and clinical neuroscience.

    Science.gov (United States)

    Chambers, Christopher D; Garavan, Hugh; Bellgrove, Mark A

    2009-05-01

    Neural mechanisms of cognitive control enable us to initiate, coordinate and update behaviour. Central to successful control is the ability to suppress actions that are no longer relevant or required. In this article, we review the contribution of cognitive neuroscience, molecular genetics and clinical investigations to understanding how response inhibition is mediated in the human brain. In Section 1, we consider insights into the neural basis of inhibitory control from the effects of neural interference, neural dysfunction, and drug addiction. In Section 2, we explore the functional specificity of inhibitory mechanisms among a range of related processes, including response selection, working memory, and attention. In Section 3, we focus on the contribution of response inhibition to understanding flexible behaviour, including the effects of learning and individual differences. Finally, in Section 4, we propose a series of technical and conceptual objectives for future studies addressing the neural basis of inhibition.

  14. The sleep and circadian modulation of neural reward pathways: a protocol for a pair of systematic reviews.

    Science.gov (United States)

    Byrne, Jamie E M; Murray, Greg

    2017-12-02

    Animal research suggests that neural reward activation may be systematically modulated by sleep and circadian function. Whether humans also exhibit sleep and circadian modulation of neural reward pathways is unclear. This area is in need of further research, as it has implications for the involvement of sleep and circadian function in reward-related disorders. The aim of this paper is to describe the protocol for a pair of systematic literature reviews to synthesise existing literature related to (1) sleep and (2) circadian modulation of neural reward pathways in healthy human populations. A systematic review of relevant online databases (Scopus, PubMed, Web of Science, ProQuest, PsycINFO and EBSCOhost) will be conducted. Reference lists, relevant reviews and supplementary data will be searched for additional articles. Articles will be included if (a) they contain a sleep- or circadian-related predictor variable with a neural reward outcome variable, (b) use a functional magnetic resonance imaging protocol and (c) use human samples. Articles will be excluded if study participants had disorders known to affect the reward system. The articles will be screened by two independent authors. Two authors will complete the data extraction form, with two authors independently completing the quality assessment tool for the selected articles, with a consensus reached with a third author if needed. Narrative synthesis methods will be used to analyse the data. The findings from this pair of systematic literature reviews will assist in the identification of the pathways involved in the sleep and circadian function modulation of neural reward in healthy individuals, with implications for disorders characterised by dysregulation in sleep, circadian rhythms and reward function. PROSPERO CRD42017064994.

  15. Behavioral and neural responses to infant and adult tears : The impact of maternal love withdrawal

    NARCIS (Netherlands)

    Riem, M.M.E.; van IJzendoorn, M.H.; De Carli, P.; Vingerhoets, A.J.J.M.; Bakermans-Kranenburg, M. J.

    2017-01-01

    The current study examined behavioral and neural responses to infant and adult tears, taking into account childhood experiences with parental love-withdrawal. With functional MRI (fMRI), we measured neural reactivity to pictures of infants and adults with and without tears on their faces in

  16. Proliferating resident microglia express the stem cell antigen CD34 in response to acute neural injury

    DEFF Research Database (Denmark)

    Ladeby, Rune; Wirenfeldt, Martin; Dalmau, Ishar

    2005-01-01

    Reactive microgliosis is a highly characteristic response to neural injury and disease, which may influence neurodegenerative processes and neural plasticity. We have investigated the origin and characteristics of reactive microglia in the acute phase of their activation in the dentate gyrus...

  17. Recapitulation of the forward nuclear auxin response pathway in yeast.

    Science.gov (United States)

    Pierre-Jerome, Edith; Jang, Seunghee S; Havens, Kyle A; Nemhauser, Jennifer L; Klavins, Eric

    2014-07-01

    Auxin influences nearly every aspect of plant biology through a simple signaling pathway; however, it remains unclear how much of the diversity in auxin effects is explained by variation in the core signaling components and which properties of these components may contribute to diversification in response dynamics. Here, we recapitulated the entire Arabidopsis thaliana forward nuclear auxin signal transduction pathway in Saccharomyces cerevisiae to test whether signaling module composition enables tuning of the dynamic response. Sensitivity analysis guided by a small mathematical model revealed the centrality of auxin/indole-3-acetic acid (Aux/IAA) transcriptional corepressors in controlling response dynamics and highlighted the strong influence of natural variation in Aux/IAA degradation rates on circuit performance. When the basic auxin response circuit was expanded to include multiple Aux/IAAs, we found that dominance relationships between coexpressed Aux/IAAs were sufficient to generate distinct response modules similar to those seen during plant development. Our work provides a new method for dissecting auxin signaling and demonstrates the key role of Aux/IAAs in tuning auxin response dynamics.

  18. Oxidative stress response pathways: Fission yeast as archetype.

    Science.gov (United States)

    Papadakis, Manos A; Workman, Christopher T

    2015-01-01

    Schizosaccharomyces pombe is a popular model eukaryotic organism to study diverse aspects of mammalian biology, including responses to cellular stress triggered by redox imbalances within its compartments. The review considers the current knowledge on the signaling pathways that govern the transcriptional response of fission yeast cells to elevated levels of hydrogen peroxide. Particular attention is paid to the mechanisms that yeast cells employ to promote cell survival in conditions of intermediate and acute oxidative stress. The role of the Sty1/Spc1/Phh1 mitogen-activated protein kinase in regulating gene expression at multiple levels is discussed in detail.

  19. With a little help from my friends: androgens tap BDNF signaling pathways to alter neural circuits.

    Science.gov (United States)

    Ottem, E N; Bailey, D J; Jordan, C L; Breedlove, S M

    2013-06-03

    Gonadal androgens are critical for the development and maintenance of sexually dimorphic regions of the male nervous system, which is critical for male-specific behavior and physiological functioning. In rodents, the motoneurons of the spinal nucleus of the bulbocavernosus (SNB) provide a useful example of a neural system dependent on androgen. Unless rescued by perinatal androgens, the SNB motoneurons will undergo apoptotic cell death. In adulthood, SNB motoneurons remain dependent on androgen, as castration leads to somal atrophy and dendritic retraction. In a second vertebrate model, the zebra finch, androgens are critical for the development of several brain nuclei involved in song production in males. Androgen deprivation during a critical period during postnatal development disrupts song acquisition and dimorphic size-associated nuclei. Mechanisms by which androgens exert masculinizing effects in each model system remain elusive. Recent studies suggest that brain-derived neurotrophic factor (BDNF) may play a role in androgen-dependent masculinization and maintenance of both SNB motoneurons and song nuclei of birds. This review aims to summarize studies demonstrating that BDNF signaling via its tyrosine receptor kinase (TrkB) receptor may work cooperatively with androgens to maintain somal and dendritic morphology of SNB motoneurons. We further describe studies that suggest the cellular origin of BDNF is of particular importance in androgen-dependent regulation of SNB motoneurons. We review evidence that androgens and BDNF may synergistically influence song development and plasticity in bird species. Finally, we provide hypothetical models of mechanisms that may underlie androgen- and BDNF-dependent signaling pathways. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

  20. Estrogen Stimulates Proliferation and Differentiation of Neural Stem/Progenitor Cells through Different Signal Transduction Pathways

    Directory of Open Access Journals (Sweden)

    Makiko Okada

    2010-10-01

    Full Text Available Our previous study indicated that both 17β-estradiol (E2, known to be an endogenous estrogen, and bisphenol A (BPA, known to be a xenoestrogen, could positively influence the proliferation or differentiation of neural stem/progenitor cells (NS/PCs. The aim of the present study was to identify the signal transduction pathways for estrogenic activities promoting proliferation and differentiation of NS/PCs via well known nuclear estrogen receptors (ERs or putative membrane-associated ERs. NS/PCs were cultured from the telencephalon of 15-day-old rat embryos. In order to confirm the involvement of nuclear ERs for estrogenic activities, their specific antagonist, ICI-182,780, was used. The presence of putative membrane-associated ER was functionally examined as to whether E2 can activate rapid intracellular signaling mechanism. In order to confirm the involvement of membrane-associated ERs for estrogenic activities, a cell-impermeable E2, bovine serum albumin-conjugated E2 (E2-BSA was used. We showed that E2 could rapidly activate extracellular signal-regulated kinases 1/2 (ERK 1/2, which was not inhibited by ICI-182,780. ICI-182,780 abrogated the stimulatory effect of these estrogens (E2 and BPA on the proliferation of NS/PCs, but not their effect on the differentiation of the NS/PCs into oligodendroglia. Furthermore, E2-BSA mimicked the activity of differentiation from NS/PCs into oligodendroglia, but not the activity of proliferation. Our study suggests that (1 the estrogen induced proliferation of NS/PCs is mediated via nuclear ERs; (2 the oligodendroglial generation from NS/PCs is likely to be stimulated via putative membrane‑associated ERs.

  1. Neural predictors of individual differences in response to math tutoring in primary-grade school children

    National Research Council Canada - National Science Library

    Kaustubh Supekar; Anna G. Swigart; Caitlin Tenison; Dietsje D. Jolles; Miriam Rosenberg-Lee; Lynn Fuchs; Vinod Menon

    2013-01-01

    ... some children to acquire these skills faster than others. Here we investigate the behavioral and neural predictors of individual differences in arithmetic skill acquisition in response to 8-wk of one-to-one math tutoring...

  2. Depression and sickness behavior are Janus-faced responses to shared inflammatory pathways

    Directory of Open Access Journals (Sweden)

    Maes Michael

    2012-06-01

    Full Text Available Abstract It is of considerable translational importance whether depression is a form or a consequence of sickness behavior. Sickness behavior is a behavioral complex induced by infections and immune trauma and mediated by pro-inflammatory cytokines. It is an adaptive response that enhances recovery by conserving energy to combat acute inflammation. There are considerable phenomenological similarities between sickness behavior and depression, for example, behavioral inhibition, anorexia and weight loss, and melancholic (anhedonia, physio-somatic (fatigue, hyperalgesia, malaise, anxiety and neurocognitive symptoms. In clinical depression, however, a transition occurs to sensitization of immuno-inflammatory pathways, progressive damage by oxidative and nitrosative stress to lipids, proteins, and DNA, and autoimmune responses directed against self-epitopes. The latter mechanisms are the substrate of a neuroprogressive process, whereby multiple depressive episodes cause neural tissue damage and consequent functional and cognitive sequelae. Thus, shared immuno-inflammatory pathways underpin the physiology of sickness behavior and the pathophysiology of clinical depression explaining their partially overlapping phenomenology. Inflammation may provoke a Janus-faced response with a good, acute side, generating protective inflammation through sickness behavior and a bad, chronic side, for example, clinical depression, a lifelong disorder with positive feedback loops between (neuroinflammation and (neurodegenerative processes following less well defined triggers.

  3. Neural circuitry at age 6 months associated with later repetitive behavior and sensory responsiveness in autism.

    Science.gov (United States)

    Wolff, Jason J; Swanson, Meghan R; Elison, Jed T; Gerig, Guido; Pruett, John R; Styner, Martin A; Vachet, Clement; Botteron, Kelly N; Dager, Stephen R; Estes, Annette M; Hazlett, Heather C; Schultz, Robert T; Shen, Mark D; Zwaigenbaum, Lonnie; Piven, Joseph

    2017-01-01

    Restricted and repetitive behaviors are defining features of autism spectrum disorder (ASD). Under revised diagnostic criteria for ASD, this behavioral domain now includes atypical responses to sensory stimuli. To date, little is known about the neural circuitry underlying these features of ASD early in life. Longitudinal diffusion tensor imaging data were collected from 217 infants at high familial risk for ASD. Forty-four of these infants were diagnosed with ASD at age 2. Targeted cortical, cerebellar, and striatal white matter pathways were defined and measured at ages 6, 12, and 24 months. Dependent variables included the Repetitive Behavior Scale-Revised and the Sensory Experiences Questionnaire. Among children diagnosed with ASD, repetitive behaviors and sensory response patterns were strongly correlated, even when accounting for developmental level or social impairment. Longitudinal analyses indicated that the genu and cerebellar pathways were significantly associated with both repetitive behaviors and sensory responsiveness but not social deficits. At age 6 months, fractional anisotropy in the genu significantly predicted repetitive behaviors and sensory responsiveness at age 2. Cerebellar pathways significantly predicted later sensory responsiveness. Exploratory analyses suggested a possible disordinal interaction based on diagnostic status for the association between fractional anisotropy and repetitive behavior. Our findings suggest that restricted and repetitive behaviors contributing to a diagnosis of ASD at age 2 years are associated with structural properties of callosal and cerebellar white matter pathways measured during infancy and toddlerhood. We further identified that repetitive behaviors and unusual sensory response patterns co-occur and share common brain-behavior relationships. These results were strikingly specific given the absence of association between targeted pathways and social deficits.

  4. Interaction Dynamics Determine Signaling and Output Pathway Responses

    Directory of Open Access Journals (Sweden)

    Klement Stojanovski

    2017-04-01

    Full Text Available The understanding of interaction dynamics in signaling pathways can shed light on pathway architecture and provide insights into targets for intervention. Here, we explored the relevance of kinetic rate constants of a key upstream osmosensor in the yeast high-osmolarity glycerol-mitogen-activated protein kinase (HOG-MAPK pathway to signaling output responses. We created mutant pairs of the Sln1-Ypd1 complex interface that caused major compensating changes in the association (kon and dissociation (koff rate constants (kinetic perturbations but only moderate changes in the overall complex affinity (Kd. Yeast cells carrying a Sln1-Ypd1 mutant pair with moderate increases in kon and koff displayed a lower threshold of HOG pathway activation than wild-type cells. Mutants with higher kon and koff rates gave rise to higher basal signaling and gene expression but impaired osmoadaptation. Thus, the kon and koff rates of the components in the Sln1 osmosensor determine proper signaling dynamics and osmoadaptation.

  5. Neural and response correlations to natural complex sounds in the auditory midbrain

    Directory of Open Access Journals (Sweden)

    Dominika Lyzwa

    2016-11-01

    Full Text Available How natural communication sounds are spatially represented across the inferior colliculus, the main center of convergence for auditory information in the midbrain, is not known. The neural representation of the acoustic stimuli results from the interplay of locally differing input and the organization of spectral and temporal neural preferences that change gradually across the nucleus. This raises the question how similar the neural representation of the communication sounds is across these gradients of neural preferences, and whether it also changes gradually. Analyzed neural recordings were multi-unit cluster spike trains from guinea pigs presented with a spectrotemporally rich set of eleven species-specific communication sounds. Using cross-correlation, we analyzed the response similarity of spiking activity across a broad frequency range for neurons of similar and different frequency tuning. Furthermore, we separated the contribution of the stimulus to the correlations to investigate whether similarity is only attributable to the stimulus, or, whether interactions exist between the multi-unit clusters that lead to neural correlations and whether these follow the same representation as the response correlations. We found that similarity of responses is dependent on the neurons' spatial distance for similarly and differently frequency-tuned neurons, and that similarity decreases gradually with spatial distance. Significant neural correlations exist, and contribute to the total response similarity. Our findings suggest that for multi-unit clusters in the mammalian inferior colliculus, the gradual response similarity with spatial distance to natural complex sounds is shaped by neural interactions and the gradual organization of neural preferences.

  6. Using Neural Response Telemetry to Monitor Physiological Responses to Acoustic Stimulation in Hybrid Cochlear Implant Users.

    Science.gov (United States)

    Abbas, Paul J; Tejani, Viral D; Scheperle, Rachel A; Brown, Carolyn J

    This report describes the results of a series of experiments where we use the neural response telemetry (NRT) system of the Nucleus cochlear implant (CI) to measure the response of the peripheral auditory system to acoustic stimulation in Nucleus Hybrid CI users. The objectives of this study were to determine whether they could separate responses from hair cells and neurons and to evaluate the stability of these measures over time. Forty-four CI users participated. They all had residual acoustic hearing and used a Nucleus Hybrid S8, S12, or L24 CI or the standard lateral wall CI422 implant. The NRT system of the CI was used to trigger an acoustic stimulus (500-Hz tone burst or click), which was presented at a low stimulation rate (10, 15, or 50 per second) to the implanted ear via an insert earphone and to record the cochlear microphonic, the auditory nerve neurophonic and the compound action potential (CAP) from an apical intracochlear electrode. To record acoustically evoked responses, a longer time window than is available with the commercial NRT software is required. This limitation was circumvented by making multiple recordings for each stimulus using different time delays between the onset of stimulation and the onset of averaging. These recordings were then concatenated off-line. Matched recordings elicited using positive and negative polarity stimuli were added off-line to emphasize neural potentials (SUM) and subtracted off-line to emphasize potentials primarily generated by cochlear hair cells (DIF). These assumptions regarding the origin of the SUM and DIF components were tested by comparing the magnitude of these derived responses recorded using various stimulation rates. Magnitudes of the SUM and DIF components were compared with each other and with behavioral thresholds. SUM and DIF components were identified for most subjects, consistent with both hair cell and neural responses to acoustic stimulation. For a subset of the study participants, the DIF

  7. Artificial Neural Networks for Nonlinear Dynamic Response Simulation in Mechanical Systems

    DEFF Research Database (Denmark)

    Christiansen, Niels Hørbye; Høgsberg, Jan Becker; Winther, Ole

    2011-01-01

    It is shown how artificial neural networks can be trained to predict dynamic response of a simple nonlinear structure. Data generated using a nonlinear finite element model of a simplified wind turbine is used to train a one layer artificial neural network. When trained properly the network is ab...... to perform accurate response prediction much faster than the corresponding finite element model. Initial result indicate a reduction in cpu time by two orders of magnitude.......It is shown how artificial neural networks can be trained to predict dynamic response of a simple nonlinear structure. Data generated using a nonlinear finite element model of a simplified wind turbine is used to train a one layer artificial neural network. When trained properly the network is able...

  8. Diminished neural responses predict enhanced intrinsic motivation and sensitivity to external incentive.

    Science.gov (United States)

    Marsden, Karen E; Ma, Wei Ji; Deci, Edward L; Ryan, Richard M; Chiu, Pearl H

    2015-06-01

    The duration and quality of human performance depend on both intrinsic motivation and external incentives. However, little is known about the neuroscientific basis of this interplay between internal and external motivators. Here, we used functional magnetic resonance imaging to examine the neural substrates of intrinsic motivation, operationalized as the free-choice time spent on a task when this was not required, and tested the neural and behavioral effects of external reward on intrinsic motivation. We found that increased duration of free-choice time was predicted by generally diminished neural responses in regions associated with cognitive and affective regulation. By comparison, the possibility of additional reward improved task accuracy, and specifically increased neural and behavioral responses following errors. Those individuals with the smallest neural responses associated with intrinsic motivation exhibited the greatest error-related neural enhancement under the external contingency of possible reward. Together, these data suggest that human performance is guided by a "tonic" and "phasic" relationship between the neural substrates of intrinsic motivation (tonic) and the impact of external incentives (phasic).

  9. Neural correlates of inhibition and contextual cue processing related to treatment response in PTSD

    NARCIS (Netherlands)

    van Rooij, Sanne J H; Geuze, Elbert; Kennis, Mitzy; Rademaker, Arthur R|info:eu-repo/dai/nl/304836427; Vink, Matthijs

    Thirty to fifty percent of posttraumatic stress disorder (PTSD) patients do not respond to treatment. Understanding the neural mechanisms underlying treatment response could contribute to improve response rates. PTSD is often associated with decreased inhibition of fear responses in a safe

  10. Different neural pathways to negative affect in youth with pediatric bipolar disorder and severe mood dysregulation

    Science.gov (United States)

    Rich, Brendan A.; Carver, Frederick W.; Holroyd, Tom; Rosen, Heather R.; Mendoza, Jennifer K.; Cornwell, Brian R.; Fox, Nathan A.; Pine, Daniel S.; Coppola, Richard; Leibenluft, Ellen

    2011-01-01

    Questions persist regarding the presentation of bipolar disorder (BD) in youth and the nosological significance of irritability. Of particular interest is whether severe mood dysregulation (SMD), characterized by severe non-episodic irritability, hyperarousal, and hyper-reactivity to negative emotional stimuli, is a developmental presentation of pediatric BD and, therefore, whether the two conditions are pathophysiologically similar. We administered the affective Posner paradigm, an attentional task with a condition involving blocked goal attainment via rigged feedback. The sample included 60 youth (20 BD, 20 SMD, and 20 controls) ages 8–17. Magnetoencephalography (MEG) examined neuronal activity (4–50 Hz) following negative versus positive feedback. We also examined reaction time (RT), response accuracy, and self-reported affect. Both BD and SMD youth reported being less happy than controls during the rigged condition. Also, SMD youth reported greater arousal following negative feedback than both BD and controls, and they responded to negative feedback with significantly greater activation of the anterior cingulate cortex (ACC) and medial frontal gyrus (MFG) than controls. Compared to SMD and controls, BD youth displayed greater superior frontal gyrus (SFG) activation and decreased insula activation following negative feedback. Data suggest a greater negative affective response to blocked goal attainment in SMD versus BD and control youth. This occurs in tandem with hyperactivation of medial frontal regions in SMD youth, while BD youth show dysfunction in the SFG and insula. Data add to a growing empirical base that differentiates pediatric BD and SMD and begin to elucidate potential neural mechanisms of irritability. PMID:21561628

  11. Different neural pathways to negative affect in youth with pediatric bipolar disorder and severe mood dysregulation.

    Science.gov (United States)

    Rich, Brendan A; Carver, Frederick W; Holroyd, Tom; Rosen, Heather R; Mendoza, Jennifer K; Cornwell, Brian R; Fox, Nathan A; Pine, Daniel S; Coppola, Richard; Leibenluft, Ellen

    2011-10-01

    Questions persist regarding the presentation of bipolar disorder (BD) in youth and the nosological significance of irritability. Of particular interest is whether severe mood dysregulation (SMD), characterized by severe non-episodic irritability, hyper-arousal, and hyper-reactivity to negative emotional stimuli, is a developmental presentation of pediatric BD and, therefore, whether the two conditions are pathophysiologically similar. We administered the affective Posner paradigm, an attentional task with a condition involving blocked goal attainment via rigged feedback. The sample included 60 youth (20 BD, 20 SMD, and 20 controls) ages 8-17. Magnetoencephalography (MEG) examined neuronal activity (4-50 Hz) following negative versus positive feedback. We also examined reaction time (RT), response accuracy, and self-reported affect. Both BD and SMD youth reported being less happy than controls during the rigged condition. Also, SMD youth reported greater arousal following negative feedback than both BD and controls, and they responded to negative feedback with significantly greater activation of the anterior cingulate cortex (ACC) and medial frontal gyrus (MFG) than controls. Compared to SMD and controls, BD youth displayed greater superior frontal gyrus (SFG) activation and decreased insula activation following negative feedback. Data suggest a greater negative affective response to blocked goal attainment in SMD versus BD and control youth. This occurs in tandem with hyperactivation of medial frontal regions in SMD youth, while BD youth show dysfunction in the SFG and insula. Data add to a growing empirical base that differentiates pediatric BD and SMD and begin to elucidate potential neural mechanisms of irritability. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Socioeconomic disadvantage, neural responses to infant emotions, and emotional availability among first-time new mothers.

    Science.gov (United States)

    Kim, Pilyoung; Capistrano, Christian G; Erhart, Andrew; Gray-Schiff, Rachel; Xu, Nanxi

    2017-05-15

    During the early postpartum period, mothers exhibit increased amygdala responses to positive infant expressions, which are important for positive mother-infant relationships. Socioeconomic disadvantage is associated with altered amygdala response to emotional stimuli as well as more negative mother-infant relationships. However, little is known about the role of socioeconomic disadvantage in neural responses specifically to infants. Thus, we examined whether socioeconomic disadvantage (indexed by lower income-to-needs ratio) is associated with neural responses to infant emotions and parenting behaviors among new mothers. Using fMRI, neural responses to infants' emotional expressions (positive, negative, and neutral faces) were assessed among 39 low- and middle-income first-time mothers during 0-6 postpartum months. Lower income-to-needs ratio was associated with dampened amygdala responses to positive infant faces, but increased amygdala responses to negative infant faces. An indirect effect of socioeconomic disadvantage on emotional availability via amygdala activation suggests that socioeconomic disadvantage is associated with heightened neural sensitivity to infants' negative emotions, which is further associated with mothers' intrusiveness observed during interactions with their own infant. The findings suggest that low-income mothers may be more vulnerable to altered neural processing of infants' emotional expressions which may further influence mothers' emotional availability during interactions with their own infants. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Internal representation of task rules by recurrent dynamics: the importance of the diversity of neural responses

    Directory of Open Access Journals (Sweden)

    Mattia Rigotti

    2010-10-01

    Full Text Available Neural activity of behaving animals, especially in the prefrontal cortex, is highly heterogeneous, with selective responses to diverse aspects of the executed task. We propose a general model of recurrent neural networks that perform complex rule-based tasks, and we show that the diversity of neuronal responses plays a fundamental role when the behavioral responses are context dependent. Specifically, we found that when the inner mental states encoding the task rules are represented by stable patterns of neural activity (attractors of the neural dynamics, the neurons must be selective for combinations of sensory stimuli and inner mental states. Such mixed selectivity is easily obtained by neurons that connect with random synaptic strengths both to the recurrent network and to neurons encoding sensory inputs. The number of randomly connected neurons needed to solve a task is on average only three times as large as the number of neurons needed in a network designed ad hoc. Moreover, the number of needed neurons grows only linearly with the number of task-relevant events and mental states, provided that each neuron responds to a large proportion of events (dense/distributed coding. A biologically realistic implementation of the model captures several aspects of the activity recorded from monkeys performing context dependent tasks. Our findings explain the importance of the diversity of neural responses and provide us with simple and general principles for designing attractor neural networks that perform complex computation.

  14. Integrating resource defence theory with a neural nonapeptide pathway to explain territory-based mating systems.

    Science.gov (United States)

    Oldfield, Ronald G; Harris, Rayna M; Hofmann, Hans A

    2015-01-01

    The ultimate-level factors that drive the evolution of mating systems have been well studied, but an evolutionarily conserved neural mechanism involved in shaping behaviour and social organization across species has remained elusive. Here, we review studies that have investigated the role of neural arginine vasopressin (AVP), vasotocin (AVT), and their receptor V1a in mediating variation in territorial behaviour. First, we discuss how aggression and territoriality are a function of population density in an inverted-U relationship according to resource defence theory, and how territoriality influences some mating systems. Next, we find that neural AVP, AVT, and V1a expression, especially in one particular neural circuit involving the lateral septum of the forebrain, are associated with territorial behaviour in males of diverse species, most likely due to their role in enhancing social cognition. Then we review studies that examined multiple species and find that neural AVP, AVT, and V1a expression is associated with territory size in mammals and fishes. Because territoriality plays an important role in shaping mating systems in many species, we present the idea that neural AVP, AVT, and V1a expression that is selected to mediate territory size may also influence the evolution of different mating systems. Future research that interprets proximate-level neuro-molecular mechanisms in the context of ultimate-level ecological theory may provide deep insight into the brain-behaviour relationships that underlie the diversity of social organization and mating systems seen across the animal kingdom.

  15. Design and implementation of in vivo imaging of neural injury responses in the adult Drosophila wing.

    Science.gov (United States)

    Fang, Yanshan; Soares, Lorena; Bonini, Nancy M

    2013-04-01

    Live-imaging technology has markedly advanced in the field of neural injury and axon degeneration; however, studies are still predominantly performed in in vitro settings such as cultured neuronal cells or in model organisms such as Caenorhabditis elegans in which axons lack glial wrappings. We recently developed a new in vivo model for adult-stage neural injury in Drosophila melanogaster, using the highly accessible wing of the animal. Because the Drosophila wing is translucent and dispensable for survival, it allows clear and direct visualization of injury-induced progressive responses of axons and glia highlighted by fluorescent protein (FP) markers in live animals over time. Moreover, unlike previous Drosophila models of neural injury, this procedure does not require dissection of the CNS. Thus, the key preparation steps for in vivo imaging of the neural injury response described in this protocol can be completed within 30 min.

  16. Retinal metric: a stimulus distance measure derived from population neural responses.

    Science.gov (United States)

    Tkačik, Gašper; Granot-Atedgi, Einat; Segev, Ronen; Schneidman, Elad

    2013-02-01

    The ability of an organism to distinguish between various stimuli is limited by the structure and noise in the population code of its sensory neurons. Here we infer a distance measure on the stimulus space directly from the recorded activity of 100 neurons in the salamander retina. In contrast to previously used measures of stimulus similarity, this "neural metric" tells us how distinguishable a pair of stimulus clips is to the retina, based on the similarity between the induced distributions of population responses. We show that the retinal distance strongly deviates from Euclidean, or any static metric, yet has a simple structure: we identify the stimulus features that the neural population is jointly sensitive to, and show the support-vector-machine-like kernel function relating the stimulus and neural response spaces. We show that the non-Euclidean nature of the retinal distance has important consequences for neural decoding.

  17. Neural network connectivity and response latency modelled by stochastic processes

    DEFF Research Database (Denmark)

    Tamborrino, Massimiliano

    is connected to thousands of other neurons. The rst question is: how to model neural networks through stochastic processes? A multivariate Ornstein-Uhlenbeck process, obtained as a diffusion approximation of a jump process, is the proposed answer. Obviously, dependencies between neurons imply dependencies......Stochastic processes and their rst passage times have been widely used to describe the membrane potential dynamics of single neurons and to reproduce neuronal spikes, respectively.However, cerebral cortex in human brains is estimated to contain 10-20 billions of neurons and each of them...... between their spike times. Therefore, the second question is: how to detect neural network connectivity from simultaneously recorded spike trains? Answering this question corresponds to investigate the joint distribution of sequences of rst passage times. A non-parametric method based on copulas...

  18. The Neural Feedback Response to Error As a Teaching Signal for the Motor Learning System

    Science.gov (United States)

    Shadmehr, Reza

    2016-01-01

    When we experience an error during a movement, we update our motor commands to partially correct for this error on the next trial. How does experience of error produce the improvement in the subsequent motor commands? During the course of an erroneous reaching movement, proprioceptive and visual sensory pathways not only sense the error, but also engage feedback mechanisms, resulting in corrective motor responses that continue until the hand arrives at its goal. One possibility is that this feedback response is co-opted by the learning system and used as a template to improve performance on the next attempt. Here we used electromyography (EMG) to compare neural correlates of learning and feedback to test the hypothesis that the feedback response to error acts as a template for learning. We designed a task in which mixtures of error-clamp and force-field perturbation trials were used to deconstruct EMG time courses into error-feedback and learning components. We observed that the error-feedback response was composed of excitation of some muscles, and inhibition of others, producing a complex activation/deactivation pattern during the reach. Despite this complexity, across muscles the learning response was consistently a scaled version of the error-feedback response, but shifted 125 ms earlier in time. Across people, individuals who produced a greater feedback response to error, also learned more from error. This suggests that the feedback response to error serves as a teaching signal for the brain. Individuals who learn faster have a better teacher in their feedback control system. SIGNIFICANCE STATEMENT Our sensory organs transduce errors in behavior. To improve performance, we must generate better motor commands. How does the nervous system transform an error in sensory coordinates into better motor commands in muscle coordinates? Here we show that when an error occurs during a movement, the reflexes transform the sensory representation of error into motor

  19. Pathway switching explains the sharp response characteristic of hypoxia response network.

    Directory of Open Access Journals (Sweden)

    Yihai Yu

    2007-08-01

    Full Text Available Hypoxia induces the expression of genes that alter metabolism through the hypoxia-inducible factor (HIF. A theoretical model based on differential equations of the hypoxia response network has been previously proposed in which a sharp response to changes in oxygen concentration was observed but not quantitatively explained. That model consisted of reactions involving 23 molecular species among which the concentrations of HIF and oxygen were linked through a complex set of reactions. In this paper, we analyze this previous model using a combination of mathematical tools to draw out the key components of the network and explain quantitatively how they contribute to the sharp oxygen response. We find that the switch-like behavior is due to pathway-switching wherein HIF degrades rapidly under normoxia in one pathway, while the other pathway accumulates HIF to trigger downstream genes under hypoxia. The analytic technique is potentially useful in studying larger biomedical networks.

  20. A neural circuit model of emotional learning using two pathways with different granularity and speed of information processing.

    Science.gov (United States)

    Murakoshi, Kazushi; Saito, Mayuko

    2009-02-01

    We propose a neural circuit model of emotional learning using two pathways with different granularity and speed of information processing. In order to derive a precise time process, we utilized a spiking model neuron proposed by Izhikevich and spike-timing-dependent synaptic plasticity (STDP) of both excitatory and inhibitory synapses. We conducted computer simulations to evaluate the proposed model. We demonstrate some aspects of emotional learning from the perspective of the time process. The agreement of the results with the previous behavioral experiments suggests that the structure and learning process of the proposed model are appropriate.

  1. A gene expression signature of RAS pathway dependence predicts response to PI3K and RAS pathway inhibitors and expands the population of RAS pathway activated tumors

    Directory of Open Access Journals (Sweden)

    Paweletz Cloud

    2010-06-01

    Full Text Available Abstract Background Hyperactivation of the Ras signaling pathway is a driver of many cancers, and RAS pathway activation can predict response to targeted therapies. Therefore, optimal methods for measuring Ras pathway activation are critical. The main focus of our work was to develop a gene expression signature that is predictive of RAS pathway dependence. Methods We used the coherent expression of RAS pathway-related genes across multiple datasets to derive a RAS pathway gene expression signature and generate RAS pathway activation scores in pre-clinical cancer models and human tumors. We then related this signature to KRAS mutation status and drug response data in pre-clinical and clinical datasets. Results The RAS signature score is predictive of KRAS mutation status in lung tumors and cell lines with high (> 90% sensitivity but relatively low (50% specificity due to samples that have apparent RAS pathway activation in the absence of a KRAS mutation. In lung and breast cancer cell line panels, the RAS pathway signature score correlates with pMEK and pERK expression, and predicts resistance to AKT inhibition and sensitivity to MEK inhibition within both KRAS mutant and KRAS wild-type groups. The RAS pathway signature is upregulated in breast cancer cell lines that have acquired resistance to AKT inhibition, and is downregulated by inhibition of MEK. In lung cancer cell lines knockdown of KRAS using siRNA demonstrates that the RAS pathway signature is a better measure of dependence on RAS compared to KRAS mutation status. In human tumors, the RAS pathway signature is elevated in ER negative breast tumors and lung adenocarcinomas, and predicts resistance to cetuximab in metastatic colorectal cancer. Conclusions These data demonstrate that the RAS pathway signature is superior to KRAS mutation status for the prediction of dependence on RAS signaling, can predict response to PI3K and RAS pathway inhibitors, and is likely to have the most clinical

  2. A gene expression signature of RAS pathway dependence predicts response to PI3K and RAS pathway inhibitors and expands the population of RAS pathway activated tumors

    Science.gov (United States)

    2010-01-01

    Background Hyperactivation of the Ras signaling pathway is a driver of many cancers, and RAS pathway activation can predict response to targeted therapies. Therefore, optimal methods for measuring Ras pathway activation are critical. The main focus of our work was to develop a gene expression signature that is predictive of RAS pathway dependence. Methods We used the coherent expression of RAS pathway-related genes across multiple datasets to derive a RAS pathway gene expression signature and generate RAS pathway activation scores in pre-clinical cancer models and human tumors. We then related this signature to KRAS mutation status and drug response data in pre-clinical and clinical datasets. Results The RAS signature score is predictive of KRAS mutation status in lung tumors and cell lines with high (> 90%) sensitivity but relatively low (50%) specificity due to samples that have apparent RAS pathway activation in the absence of a KRAS mutation. In lung and breast cancer cell line panels, the RAS pathway signature score correlates with pMEK and pERK expression, and predicts resistance to AKT inhibition and sensitivity to MEK inhibition within both KRAS mutant and KRAS wild-type groups. The RAS pathway signature is upregulated in breast cancer cell lines that have acquired resistance to AKT inhibition, and is downregulated by inhibition of MEK. In lung cancer cell lines knockdown of KRAS using siRNA demonstrates that the RAS pathway signature is a better measure of dependence on RAS compared to KRAS mutation status. In human tumors, the RAS pathway signature is elevated in ER negative breast tumors and lung adenocarcinomas, and predicts resistance to cetuximab in metastatic colorectal cancer. Conclusions These data demonstrate that the RAS pathway signature is superior to KRAS mutation status for the prediction of dependence on RAS signaling, can predict response to PI3K and RAS pathway inhibitors, and is likely to have the most clinical utility in lung and breast

  3. Compensatory Neural Activity in Response to Cognitive Fatigue.

    Science.gov (United States)

    Wang, Chao; Trongnetrpunya, Amy; Samuel, Immanuel Babu Henry; Ding, Mingzhou; Kluger, Benzi M

    2016-04-06

    Prolonged continuous performance of a cognitively demanding task induces cognitive fatigue and is associated with a time-related deterioration of objective performance, the degree of which is referred to cognitive fatigability. Although the neural underpinnings of cognitive fatigue are poorly understood, prior studies report changes in neural activity consistent with deterioration of task-related networks over time. While compensatory brain activity is reported to maintain motor task performance in the face of motor fatigue and cognitive performance in the face of other stressors (e.g., aging) and structural changes, there are no studies to date demonstrating compensatory activity for cognitive fatigue. High-density electroencephalography was recorded from human subjects during a 160 min continuous performance of a cognitive control task. While most time-varying neural activity showed a linear decline over time, we identified an evoked potential over the anterior frontal region which demonstrated an inverted U-shaped time-on-task profile. This evoked brain activity peaked between 60 and 100 min into the task and was positively associated with better behavioral performance only during this interval. Following the peak and during subsequent decline of this anterior frontal activity, the rate of performance decline also accelerated. These findings demonstrate that this anterior frontal brain activity, which is not part of the primary task-related activity at baseline, is recruited to compensate for fatigue-induced impairments in the primary task-related network, and that this compensation terminates as cognitive fatigue further progresses. These findings may be relevant to understanding individual differences in cognitive fatigability and developing interventions for clinical conditions afflicted by fatigue. Fatigue refers to changes in objective performance and subjective effort induced by continuous task performance. We examined the neural underpinnings of cognitive

  4. Maternal dietary uridine causes, and deoxyuridine prevents, neural tube closure defects in a mouse model of folate-responsive neural tube defects.

    Science.gov (United States)

    Martiniova, Lucia; Field, Martha S; Finkelstein, Julia L; Perry, Cheryll A; Stover, Patrick J

    2015-04-01

    Folic acid prevents neural tube closure defects (NTDs), but the causal metabolic pathways have not been established. Serine hydroxymethyltransferase 1 (SHMT1) is an essential scaffold protein in folate-dependent de novo thymidylate synthesis in the nucleus. SHMT1-deficient mice provide a model to investigate folic acid-responsive NTDs wherein disruption of de novo thymidylate synthesis impairs neural tube closure. We examined the effects of maternal supplementation with the pyrimidine nucleosides uridine, thymidine, or deoxyuridine with and without folate deficiency on NTD incidence in the Shmt1 mouse model. Shmt1(+/+) and Shmt1(-/-) female mice fed folate-replete or folate-deficient diets and supplemented with uridine, thymidine, or deoxyuridine were bred, and litters (n = 10-23 per group) were examined for the presence of NTDs. Biomarkers of impaired folate status and metabolism were measured, including plasma nucleosides, hepatic uracil content, maternal plasma folate concentrations, and incorporation of nucleoside precursors into DNA. Shmt1(+/-) and Shmt1(-/-) embryos from dams fed the folate-deficient diet were susceptible to NTDs. No NTDs were observed in litters from dams fed the folate-deficient diet supplemented with deoxyuridine. Surprisingly, uridine supplementation increased NTD incidence, independent of embryo genotype and dietary folic acid. These dietary nucleosides did not affect maternal hepatic uracil accumulation in DNA but did affect plasma folate concentrations. Maternal deoxyuridine supplementation prevented NTDs in dams fed the folate-deficient diet, whereas maternal uridine supplementation increased NTD incidence, independent of folate and embryo genotype. These findings provide new insights into the metabolic impairments and mechanisms of folate-responsive NTDs resulting from decreased Shmt1 expression. © 2015 American Society for Nutrition.

  5. Kalman filtering for neural prediction of response spectra from mining tremors

    Energy Technology Data Exchange (ETDEWEB)

    Krok, A.; Waszczyszyn, Z. [Cracow University of Technology, Krakow (Poland)

    2007-08-15

    Acceleration response spectra (ARS) for mining tremors in the Upper Silesian Coalfield, Poland are generated using neural networks trained by means of Kalman filtering. The target ARS were computed on the base of measured accelerograms. It was proved that the standard feed-forward, layered neural network, trained by the DEFK (decoupled extended Kalman filter) algorithm is numerically much less efficient than the standard recurrent NN learnt by Recurrent DEKF, cf. (Haykin S, (editor). Kalman filtering and neural networks. New York: John Wiley & Sons; 2001). It is also shown that the studied KF algorithms are better than the traditional Resilient-Propagation learning method. The improvement of the training process and neural prediction due to introduction of an autoregressive input is also discussed in the paper.

  6. The ROCK/GGTase Pathway Are Essential to the Proliferation and Differentiation of Neural Stem Cells Mediated by Simvastatin.

    Science.gov (United States)

    Zhang, Chan; Wu, Jian-Min; Liao, Min; Wang, Jun-Ling; Xu, Chao-Jin

    2016-12-01

    Simvastatin, a lipophilic and fermentation-derived natural statin, is reported to treat neurological disorders, such as traumatic brain injury, Parkinson's disease (PD), Alzheimer disease (AD), etc. Recently, research also indicated that simvastatin could promote regeneration in the dentate gyrus of adult mice by Wnt/β-catenin signaling (Robin et al. in Stem Cell Reports 2:9-17, 2014). However, the effect and mechanisms by which simvastatin may affect the neural stem cells (NSCs; from the embryonic day 14.5 (E14.5) SD rat brain) are not fully understood. Here, we investigated the effects of different doses of simvastatin on the survival, proliferation, differentiation, migration, and cell cycle of NSCs as well as underlying intracellular signaling pathways. The results showed that simvastatin not only inhibits the proliferation of NSCs but also enhances the βIII-tubulin(+) neuron differentiation rate. Additionally, we find that simvastatin could also promote NSC migration and induce cell cycle arrest at M2 phrase. All these effects of simvastatin on NSCs were mimicked with an inhibitor of Rho kinase (ROCK) and a specific inhibitor of geranylgeranyl transferase (GGTase). In conclusion, these data indicate that simvastatin could promote neurogenesis of neural stem cells, and these effects were mediated through the ROCK/GGTase pathway.

  7. Neuron's eye view: Inferring features of complex stimuli from neural responses.

    Directory of Open Access Journals (Sweden)

    Xin Chen

    2017-08-01

    Full Text Available Experiments that study neural encoding of stimuli at the level of individual neurons typically choose a small set of features present in the world-contrast and luminance for vision, pitch and intensity for sound-and assemble a stimulus set that systematically varies along these dimensions. Subsequent analysis of neural responses to these stimuli typically focuses on regression models, with experimenter-controlled features as predictors and spike counts or firing rates as responses. Unfortunately, this approach requires knowledge in advance about the relevant features coded by a given population of neurons. For domains as complex as social interaction or natural movement, however, the relevant feature space is poorly understood, and an arbitrary a priori choice of features may give rise to confirmation bias. Here, we present a Bayesian model for exploratory data analysis that is capable of automatically identifying the features present in unstructured stimuli based solely on neuronal responses. Our approach is unique within the class of latent state space models of neural activity in that it assumes that firing rates of neurons are sensitive to multiple discrete time-varying features tied to the stimulus, each of which has Markov (or semi-Markov dynamics. That is, we are modeling neural activity as driven by multiple simultaneous stimulus features rather than intrinsic neural dynamics. We derive a fast variational Bayesian inference algorithm and show that it correctly recovers hidden features in synthetic data, as well as ground-truth stimulus features in a prototypical neural dataset. To demonstrate the utility of the algorithm, we also apply it to cluster neural responses and demonstrate successful recovery of features corresponding to monkeys and faces in the image set.

  8. Distinct neural pathways mediate alpha7 nicotinic acetylcholine receptor-dependent activation of the forebrain

    DEFF Research Database (Denmark)

    Thomsen, Morten S; Hay-Schmidt, Anders; Hansen, Henrik H

    2010-01-01

    important for cognitive function. However, the neural substrates involved in these effects remain elusive. Here we identify cortically projecting cholinergic neurons in the horizontal limb of the diagonal band of Broca (HDB) in the basal forebrain (BF) as important targets for alpha(7) nAChR activation...

  9. Behavioral and Physiological Neural Network Analyses: A Common Pathway toward Pattern Recognition and Prediction

    Science.gov (United States)

    Ninness, Chris; Lauter, Judy L.; Coffee, Michael; Clary, Logan; Kelly, Elizabeth; Rumph, Marilyn; Rumph, Robin; Kyle, Betty; Ninness, Sharon K.

    2012-01-01

    Using 3 diversified datasets, we explored the pattern-recognition ability of the Self-Organizing Map (SOM) artificial neural network as applied to diversified nonlinear data distributions in the areas of behavioral and physiological research. Experiment 1 employed a dataset obtained from the UCI Machine Learning Repository. Data for this study…

  10. Developmental Pathway Genes and Neural Plasticity Underlying Emotional Learning and Stress-Related Disorders

    Science.gov (United States)

    Maheau, Marissa E.; Ressler, Kerry J.

    2017-01-01

    The manipulation of neural plasticity as a means of intervening in the onset and progression of stress-related disorders retains its appeal for many researchers, despite our limited success in translating such interventions from the laboratory to the clinic. Given the challenges of identifying individual genetic variants that confer increased risk…

  11. Gaze Direction Modulates the Relation between Neural Responses to Faces and Visual Awareness.

    Science.gov (United States)

    Madipakkam, Apoorva Rajiv; Rothkirch, Marcus; Guggenmos, Matthias; Heinz, Andreas; Sterzer, Philipp

    2015-09-30

    Gaze direction and especially direct gaze is a powerful nonverbal cue that plays an important role in social interactions. Here we studied the neural mechanisms underlying the privileged access of direct gaze to visual awareness. We performed functional magnetic resonance imaging in healthy human volunteers who were exposed to faces with direct or averted gaze under continuous flash suppression, thereby manipulating their awareness of the faces. A gaze processing network comprising fusiform face area (FFA), superior temporal sulcus, amygdala, and intraparietal sulcus showed overall reduced neural responses when participants reported to be unaware of the faces. Interestingly, direct gaze elicited greater responses than averted gaze when participants were aware of the faces, but smaller responses when they were unaware. Additional between-subject correlation and single-trial analyses indicated that this pattern of results was due to a modulation of the relationship between neural responses and awareness by gaze direction: with increasing neural activation in the FFA, direct-gaze faces entered awareness more readily than averted-gaze faces. These findings suggest that for direct gaze, lower levels of neural activity are sufficient to give rise to awareness than for averted gaze, thus providing a neural basis for privileged access of direct gaze to awareness. Significance statement: Another person's eye gaze directed at oneself is a powerful social signal acting as a catalyst for further communication. Here, we studied the neural mechanisms underlying the prioritized access of direct gaze to visual awareness in healthy human volunteers and show that with increasing neural activation, direct-gaze faces enter awareness more readily than averted-gaze faces. This suggests that for a socially highly relevant cue like direct gaze, lower levels of neural activity are sufficient to give rise to awareness compared with averted gaze, possibly because the human brain is attuned

  12. [Retinoic acid signal pathway regulation of zebra fish tooth development through manipulation of the differentiation of neural crest].

    Science.gov (United States)

    Liu, Xin; Huang, Xing; Xu, Zhiyun; Yang, Deqin

    2016-04-01

    To investigate the mechanism of retinoic acid (RA) signal in dental evolution, RA is used to explore the influence of the mechanism on neural crest's migration during the early stage of zebra fish embryos. We divided embryos of wild type and transgenic line zebra fish into three groups. 1 x 10(-7) to 6 x 10(-7) mol x L(-1) RA and 1 x 10(-7) mo x L(-1) 4-diethylaminobenzaldehyde (DEAB) were added into egg water at 24 hpf for 9 h. Dimethyl sulfoxid (DMSO) with the concentration was used as control group. Then, antisense probes of dlx2a, dlx2b, and barxl were formulated to perform whole-mount in situ hybridization to check the expressions of the genes in 48 hpf to 72 hpf embryos. We observed fluorescence of transgenic line in 4 dpf embryos. We obtained three mRNA probes successfully. Compared with DMSO control group, a low concentration (1 x 10(-7) mol x L(-1)) of RA could up-regulate the expression of mRNA (barx1, dlx2a) in neural crest. Obvious migration trend was observed toward the pharyngeal arch in which teeth adhered. Transgenic fish had spreading fluorescence tendency in pharyngeal arch. However, a high concentration (4 x 10(-7) mol x L(-1)) of RA malformed the embryos and killed them after treatment. One third of the embryos of middle concentration (3 x 10(-7) mo x L(-1)) exhibited delayed development. DEAB resulted in neural crest dysplasia. The expression of barxl and dlx2a were suppressed, and the appearance of dlx2b in tooth was delayed. RA signal pathway can regulate the progenitors of tooth by controlling the growth of the neural crest and manipulating tooth development

  13. Response of neural reward regions to food cues in autism spectrum disorders

    Directory of Open Access Journals (Sweden)

    Cascio Carissa J

    2012-05-01

    Full Text Available Abstract Background One hypothesis for the social deficits that characterize autism spectrum disorders (ASD is diminished neural reward response to social interaction and attachment. Prior research using established monetary reward paradigms as a test of non-social reward to compare with social reward may involve confounds in the ability of individuals with ASD to utilize symbolic representation of money and the abstraction required to interpret monetary gains. Thus, a useful addition to our understanding of neural reward circuitry in ASD includes a characterization of the neural response to primary rewards. Method We asked 17 children with ASD and 18 children without ASD to abstain from eating for at least four hours before an MRI scan in which they viewed images of high-calorie foods. We assessed the neural reward network for increases in the blood oxygenation level dependent (BOLD signal in response to the food images Results We found very similar patterns of increased BOLD signal to these images in the two groups; both groups showed increased BOLD signal in the bilateral amygdala, as well as in the nucleus accumbens, orbitofrontal cortex, and insula. Direct group comparisons revealed that the ASD group showed a stronger response to food cues in bilateral insula along the anterior-posterior gradient and in the anterior cingulate cortex than the control group, whereas there were no neural reward regions that showed higher activation for controls than for ASD. Conclusion These results suggest that neural response to primary rewards is not diminished but in fact shows an aberrant enhancement in children with ASD.

  14. Subjective and Neural Responses to Intravenous Alcohol in Young Adults with Light and Heavy Drinking Patterns

    OpenAIRE

    Gilman, Jodi M; Ramchandani, Vijay A.; Crouss, Tess; Hommer, Daniel W.

    2011-01-01

    Heavy alcohol consumption during young adulthood is a risk factor for the development of serious alcohol use disorders. Research has shown that individual differences in subjective responses to alcohol may affect individuals' vulnerability to developing alcoholism. Studies comparing the subjective and objective response to alcohol between light and heavy drinkers (HDs), however, have yielded inconsistent results, and neural responses to alcohol in these groups have not been characterized. We ...

  15. The influence of cochlear traveling wave and neural adaptation on auditory brainstem responses

    DEFF Research Database (Denmark)

    Junius, D.; Dau, Torsten

    2005-01-01

    ), disparities occurred between the responses, reflecting a nonlinearity in the processing when neural activity is integrated across frequency. In the third experiment, the effect of within-train rate on wave-V response was investigated. The response to the chirp presented at a within-train rate of 95 Hz...... processing in the human auditory system. The findings might also be useful for the development of effective stimulation paradigms in clinical applications....

  16. Yeast signaling pathways in the oxidative stress response

    Energy Technology Data Exchange (ETDEWEB)

    Ikner, Aminah [Section of Microbiology, Division of Biological Sciences, University of California, Davis, CA 95616 (United States); Shiozaki, Kazuhiro [Section of Microbiology, Division of Biological Sciences, University of California, Davis, CA 95616 (United States)]. E-mail: kshiozaki@ucdavis.edu

    2005-01-06

    Oxidative stress that generates the reactive oxygen species (ROS) is one of the major causes of DNA damage and mutations. The 'DNA damage checkpoint' that arrests cell cycle and repairs damaged DNA has been a focus of recent studies, and the genetically amenable model systems provided by yeasts have been playing a leading role in the eukaryotic checkpoint research. However, means to eliminate ROS are likely to be as important as the DNA repair mechanisms in order to suppress mutations in the chromosomal DNA, and yeasts also serve as excellent models to understand how eukaryotes combat oxidative stress. In this article, we present an overview of the signaling pathways that sense oxidative stress and induce expression of various anti-oxidant genes in the budding yeast Saccharomyces cerevisiae, the fission yeast Schizosaccharomyces pombe and the pathogenic yeast Candida albicans. Three conserved signaling modules have been identified in the oxidative stress response of these diverse yeast species: the stress-responsive MAP kinase cascade, the multistep phosphorelay and the AP-1-like transcription factor. The structure and function of these signaling modules are discussed.

  17. The primary nitrate response: a multifaceted signalling pathway.

    Science.gov (United States)

    Medici, Anna; Krouk, Gabriel

    2014-10-01

    Nitrate (NO3(-)) application strongly affects gene expression in plants. This regulation is thought to be crucial for their adaptation in response to a changing nutritional environment. Depending on the conditions preceding or concomitant with nitrate provision, the treatment can affect up to a 10th of genome expression in Arabidopsis thaliana. The early events occurring after NO3(-) provision are often called the Primary Nitrate Response (PNR). Despite this simple definition, PNR is a complex process that is difficult to properly delineate. Here we report the different concepts related to PNR, review the different molecular components known to control it, and show, using meta-analysis, that this concept/pathway is not monolithic. We especially bring our attention to the genome-wide effects of LBD37 and LBD38 overexpression, NLP7, and CHL1/NRT1.1 mutations. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  18. Differential neural responses to child and sexual stimuli in human fathers and non-fathers and their hormonal correlates

    OpenAIRE

    Mascaro, Jennifer S.; Hackett, Patrick D.; Rilling, James K.

    2014-01-01

    Despite the well-documented importance of paternal caregiving for positive child development, little is known about the neural changes that accompany the transition to fatherhood in humans, or about how changes in hormone levels affect paternal brain function. We compared fathers of children aged 1–2 with non-fathers in terms of hormone levels (oxytocin and testosterone), neural responses to child picture stimuli, and neural responses to visual sexual stimuli. Compared to non-fathers, fathers...

  19. Assessing Basal and Acute Autophagic Responses in the Adult Drosophila Nervous System: The Impact of Gender, Genetics and Diet on Endogenous Pathway Profiles.

    Directory of Open Access Journals (Sweden)

    Eric P Ratliff

    Full Text Available The autophagy pathway is critical for the long-term homeostasis of cells and adult organisms and is often activated during periods of stress. Reduced pathway efficacy plays a central role in several progressive neurological disorders that are associated with the accumulation of cytotoxic peptides and protein aggregates. Previous studies have shown that genetic and transgenic alterations to the autophagy pathway impacts longevity and neural aggregate profiles of adult Drosophila. In this study, we have identified methods to measure the acute in vivo induction of the autophagy pathway in the adult fly CNS. Our findings indicate that the genotype, age, and gender of adult flies can influence pathway responses. Further, we demonstrate that middle-aged male flies exposed to intermittent fasting (IF had improved neuronal autophagic profiles. IF-treated flies also had lower neural aggregate profiles, maintained more youthful behaviors and longer lifespans, when compared to ad libitum controls. In summary, we present methodology to detect dynamic in vivo changes that occur to the autophagic profiles in the adult Drosophila CNS and that a novel IF-treatment protocol improves pathway response in the aging nervous system.

  20. Electrosensory neural responses to natural electro-communication stimuli are distributed along a continuum.

    Science.gov (United States)

    Sproule, Michael K J; Chacron, Maurice J

    2017-01-01

    Neural heterogeneities are seen ubiquitously within the brain and greatly complicate classification efforts. Here we tested whether the responses of an anatomically well-characterized sensory neuron population to natural stimuli could be used for functional classification. To do so, we recorded from pyramidal cells within the electrosensory lateral line lobe (ELL) of the weakly electric fish Apteronotus leptorhynchus in response to natural electro-communication stimuli as these cells can be anatomically classified into six different types. We then used two independent methodologies to functionally classify responses: one relies of reducing the dimensionality of a feature space while the other directly compares the responses themselves. Both methodologies gave rise to qualitatively similar results: while ON and OFF-type cells could easily be distinguished from one another, ELL pyramidal neuron responses are actually distributed along a continuum rather than forming distinct clusters due to heterogeneities. We discuss the implications of our results for neural coding and highlight some potential advantages.

  1. Gender differences in the neural response to acupuncture: Clinical implications

    NARCIS (Netherlands)

    Yeo, S.; Rosen, B.; Bosch, M.P.C.; Noort, M.W.M.L. van den; Lim, S.

    2016-01-01

    Objective: To examine gender differences and similarities in the psychophysical and brain responses to acupuncture at GB34, a point that is frequently used to treat motor function issues in Traditional Chinese Medicine. Methods: Functional MRI (fMRI) was used to measure brain activation in response

  2. Concurrent OCT imaging of stimulus evoked retinal neural activation and hemodynamic responses

    Science.gov (United States)

    Son, Taeyoon; Wang, Benquan; Lu, Yiming; Chen, Yanjun; Cao, Dingcai; Yao, Xincheng

    2017-02-01

    It is well established that major retinal diseases involve distortions of the retinal neural physiology and blood vascular structures. However, the details of distortions in retinal neurovascular coupling associated with major eye diseases are not well understood. In this study, a multi-modal optical coherence tomography (OCT) imaging system was developed to enable concurrent imaging of retinal neural activity and vascular hemodynamics. Flicker light stimulation was applied to mouse retinas to evoke retinal neural responses and hemodynamic changes. The OCT images were acquired continuously during the pre-stimulation, light-stimulation, and post-stimulation phases. Stimulus-evoked intrinsic optical signals (IOSs) and hemodynamic changes were observed over time in blood-free and blood regions, respectively. Rapid IOSs change occurred almost immediately after stimulation. Both positive and negative signals were observed in adjacent retinal areas. The hemodynamic changes showed time delays after stimulation. The signal magnitudes induced by light stimulation were observed in blood regions and did not show significant changes in blood-free regions. These differences may arise from different mechanisms in blood vessels and neural tissues in response to light stimulation. These characteristics agreed well with our previous observations in mouse retinas. Further development of the multimodal OCT may provide a new imaging method for studying how retinal structures and metabolic and neural functions are affected by age-related macular degeneration (AMD), glaucoma, diabetic retinopathy (DR), and other diseases, which promises novel noninvasive biomarkers for early disease detection and reliable treatment evaluations of eye diseases.

  3. Parametric characterization of neural activity in the locus coeruleus in response to vagus nerve stimulation.

    Science.gov (United States)

    Hulsey, Daniel R; Riley, Jonathan R; Loerwald, Kristofer W; Rennaker, Robert L; Kilgard, Michael P; Hays, Seth A

    2017-03-01

    Vagus nerve stimulation (VNS) has emerged as a therapy to treat a wide range of neurological disorders, including epilepsy, depression, stroke, and tinnitus. Activation of neurons in the locus coeruleus (LC) is believed to mediate many of the effects of VNS in the central nervous system. Despite the importance of the LC, there is a dearth of direct evidence characterizing neural activity in response to VNS. A detailed understanding of the brain activity evoked by VNS across a range of stimulation parameters may guide selection of stimulation regimens for therapeutic use. In this study, we recorded neural activity in the LC and the mesencephalic trigeminal nucleus (Me5) in response to VNS over a broad range of current amplitudes, pulse frequencies, train durations, inter-train intervals, and pulse widths. Brief 0.5s trains of VNS drive rapid, phasic firing of LC neurons at 0.1mA. Higher current intensities and longer pulse widths drive greater increases in LC firing rate. Varying the pulse frequency substantially affects the timing, but not the total amount, of phasic LC activity. VNS drives pulse-locked neural activity in the Me5 at current levels above 1.2mA. These results provide insight into VNS-evoked phasic neural activity in multiple neural structures and may be useful in guiding the selection of VNS parameters to enhance clinical efficacy. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Early Brain Response to Low-Dose Radiation Exposure Involves Molecular Networks and Pathways Associated with Cognitive Functions, Advanced Aging and Alzheimer's Disease

    Energy Technology Data Exchange (ETDEWEB)

    Lowe, Xiu R; Bhattacharya, Sanchita; Marchetti, Francesco; Wyrobek, Andrew J.

    2008-06-06

    Understanding the cognitive and behavioral consequences of brain exposures to low-dose ionizing radiation has broad relevance for health risks from medical radiation diagnostic procedures, radiotherapy, environmental nuclear contamination, as well as earth orbit and space missions. Analyses of transcriptome profiles of murine brain tissue after whole-body radiation showed that low-dose exposures (10 cGy) induced genes not affected by high dose (2 Gy), and low-dose genes were associated with unique pathways and functions. The low-dose response had two major components: pathways that are consistently seen across tissues, and pathways that were brain tissue specific. Low-dose genes clustered into a saturated network (p < 10{sup -53}) containing mostly down-regulated genes involving ion channels, long-term potentiation and depression, vascular damage, etc. We identified 9 neural signaling pathways that showed a high degree of concordance in their transcriptional response in mouse brain tissue after low-dose radiation, in the aging human brain (unirradiated), and in brain tissue from patients with Alzheimer's disease. Mice exposed to high-dose radiation did not show these effects and associations. Our findings indicate that the molecular response of the mouse brain within a few hours after low-dose irradiation involves the down-regulation of neural pathways associated with cognitive dysfunctions that are also down regulated in normal human aging and Alzheimer's disease.

  5. Attenuated neural response to emotional cues in cocaine-dependence: a preliminary analysis of gender differences.

    Science.gov (United States)

    Canterberry, Melanie; Peltier, MacKenzie R; Brady, Kathleen T; Hanlon, Colleen A

    2016-09-01

    Cocaine users often report a loss of arousal for nondrug-related stimuli, which may contribute to their response to drug-related rewards. However, little is known about users' neural reactivity to emotional nondrug-related stimuli and the potential influence of gender. Test the hypotheses that cocaine-dependent individuals have an attenuated neural response to arousing stimuli relative to controls and that this difference is amplified in women. The brain response to typically arousing positive and negative images as well as neutral images from the International Affective Picture System was measured in 40 individuals (20 non-treatment seeking cocaine-dependent and 20 age- and gender-matched control participants; 50% of whom were women). Images were displayed for 4 s each in blocks of five across two 270-second runs. General linear models assessed within and between group activation differences for the emotional images. Cocaine-dependent individuals had a significantly lower response to typically arousing positive and negative images than controls, with attenuated neural activity present in the medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC). Analyses by gender revealed less mPFC/ACC activation among female users, but not males, for both positive and negative images. The dampened neural response to typically arousing stimuli among cocaine-dependent polydrug users suggests decreased salience processing for nondrug stimuli, particularly among female users. This decreased responding is consistent with data from other substance using populations and suggests that this may be a general feature of addiction. Amplifying the neural response to naturally arousing nondrug-related reinforcers may present an opportunity for unique behavioral and brain stimulation therapies.

  6. Larger Neural Responses Produce BOLD Signals That Begin Earlier in Time

    Directory of Open Access Journals (Sweden)

    Serena eThompson

    2014-06-01

    Full Text Available Functional MRI analyses commonly rely on the assumption that the temporal dynamics of hemodynamic response functions (HRFs are independent of the amplitude of the neural signals that give rise to them. The validity of this assumption is particularly important for techniques that use fMRI to resolve sub-second timing distinctions between responses, in order to make inferences about the ordering of neural processes. Whether or not the detailed shape of the HRF is independent of neural response amplitude remains an open question, however. We performed experiments in which we measured responses in primary visual cortex (V1 to large, contrast-reversing checkerboards at a range of contrast levels, which should produce varying amounts of neural activity. Ten subjects (ages 22-52 were studied in each of two experiments using 3 Tesla scanners. We used rapid, 250 msec, temporal sampling (repetition time, or TR and both short and long inter-stimulus interval (ISI stimulus presentations. We tested for a systematic relationship between the onset of the HRF and its amplitude across conditions, and found a strong negative correlation between the two measures when stimuli were separated in time (long- and medium-ISI experiments, but not the short-ISI experiment. Thus, stimuli that produce larger neural responses, as indexed by HRF amplitude, also produced HRFs with shorter onsets. The relationship between amplitude and latency was strongest in voxels with lowest mean-normalized variance (i.e., parenchymal voxels. The onset differences observed in the longer-ISI experiments are likely attributable to mechanisms of neurovascular coupling, since they are substantially larger than reported differences in the onset of action potentials in V1 as a function of response amplitude.

  7. Neural Responses to Peer Rejection in Anxious Adolescents: Contributions from the Amygdala-Hippocampal Complex

    Science.gov (United States)

    Lau, Jennifer Y. F.; Guyer, Amanda E.; Tone, Erin B.; Jenness, Jessica; Parrish, Jessica M.; Pine, Daniel S.; Nelson, Eric E.

    2012-01-01

    Peer rejection powerfully predicts adolescent anxiety. While cognitive differences influence anxious responses to social feedback, little is known about neural contributions. Twelve anxious and twelve age-, gender- and IQ-matched, psychiatrically healthy adolescents received "not interested" and "interested" feedback from unknown peers during a…

  8. Neural networks in high-performance liquid chromatography optimization : Response surface modeling

    NARCIS (Netherlands)

    Metting, H.J; Coenegracht, P.M J

    1996-01-01

    The usefulness of artificial neural networks for response surface modeling in HPLC optimization is compared with (non-)linear regression methods. The number of hidden nodes is optimized by a lateral inhibition method. Overfitting is controlled by cross-validation using the leave one out method

  9. Chronic childhood peer rejection is associated with heightened neural responses to social exclusion during adolescence.

    NARCIS (Netherlands)

    Will, G.J.; Van, Lier P.A.; Crone, E.A.; Guroglu, B.

    2016-01-01

    This functional Magnetic Resonance Imaging (fMRI) study examined subjective and neural responses to social exclusion in adolescents (age 12-15) who either had a stable accepted (n = 27; 14 males) or a chronic rejected (n = 19; 12 males) status among peers from age 6 to 12. Both groups of adolescents

  10. Sex differences in neural responses to disgusting visual stimuli: implications for disgust-related psychiatric disorders.

    NARCIS (Netherlands)

    Caseras, X.; Mataix-Cols, D.; An, S.K.; Lawrence, N.S.; Speckens, A.E.M.; Giampietro, V.; Brammer, M.J.; Phillips, M.L.

    2007-01-01

    BACKGROUND: A majority of patients with disgust-related psychiatric disorders such as animal phobias and contamination-related obsessive-compulsive disorder are women. The aim of this functional magnetic resonance imaging (fMRI) study was to examine possible sex differences in neural responses to

  11. Associations among Pubertal Development, Empathic Ability, and Neural Responses While Witnessing Peer Rejection in Adolescence

    Science.gov (United States)

    Masten, Carrie L.; Eisenberger, Naomi I.; Pfeifer, Jennifer H.; Colich, Natalie L.; Dapretto, Mirella

    2013-01-01

    Links among concurrent and longitudinal changes in pubertal development and empathic ability from ages 10 to 13 and neural responses while witnessing peer rejection at age 13 were examined in 16 participants. More advanced pubertal development at age 13, and greater longitudinal increases in pubertal development, related to increased activity in…

  12. Enhanced food anticipatory activity associated with enhanced activation of extrahypothalamic neural pathways in serotonin2C receptor null mutant mice.

    Directory of Open Access Journals (Sweden)

    Jennifer L Hsu

    Full Text Available The ability to entrain circadian rhythms to food availability is important for survival. Food-entrained circadian rhythms are characterized by increased locomotor activity in anticipation of food availability (food anticipatory activity. However, the molecular components and neural circuitry underlying the regulation of food anticipatory activity remain unclear. Here we show that serotonin(2C receptor (5-HT2CR null mutant mice subjected to a daytime restricted feeding schedule exhibit enhanced food anticipatory activity compared to wild-type littermates, without phenotypic differences in the impact of restricted feeding on food consumption, body weight loss, or blood glucose levels. Moreover, we show that the enhanced food anticipatory activity in 5-HT2CR null mutant mice develops independent of external light cues and persists during two days of total food deprivation, indicating that food anticipatory activity in 5-HT2CR null mutant mice reflects the locomotor output of a food-entrainable oscillator. Whereas restricted feeding induces c-fos expression to a similar extent in hypothalamic nuclei of wild-type and null mutant animals, it produces enhanced expression in the nucleus accumbens and other extrahypothalamic regions of null mutant mice relative to wild-type subjects. These data suggest that 5-HT2CRs gate food anticipatory activity through mechanisms involving extrahypothalamic neural pathways.

  13. Learning by experience? Visceral pain-related neural and behavioral responses in a classical conditioning paradigm.

    Science.gov (United States)

    Icenhour, A; Labrenz, F; Ritter, C; Theysohn, N; Forsting, M; Bingel, U; Elsenbruch, S

    2017-06-01

    Studies investigating mechanisms underlying nocebo responses in pain have mainly focused on negative expectations induced by verbal suggestions. Herein, we addressed neural and behavioral correlates of nocebo responses induced by classical conditioning in a visceral pain model. In two independent studies, a total of 40 healthy volunteers underwent classical conditioning, consisting of repeated pairings of one visual cue (CS High ) with rectal distensions of high intensity, while a second cue (CS Low ) was always followed by low-intensity distensions. During subsequent test, only low-intensity distensions were delivered, preceded by either CS High or CS Low . Distension intensity ratings were assessed in both samples and functional magnetic resonance imaging data were available from one study (N=16). As a consequence of conditioning, we hypothesized CS High -cued distensions to be perceived as more intense and expected enhanced cue- and distension-related neural responses in regions encoding sensory and affective dimensions of pain and in structures associated with pain-related fear memory. During test, distension intensity ratings did not differ depending on preceding cue. Greater distension-induced neural activation was observed in somatosensory, prefrontal, and cingulate cortices and caudate when preceded by CS High . Analysis of cue-related responses revealed strikingly similar activation patterns. We report changes in neural activation patterns during anticipation and visceral stimulation induced by prior conditioning. In the absence of behavioral effects, markedly altered neural responses may indicate conditioning with visceral signals to induce hypervigilance rather than hyperalgesia, involving altered attention, reappraisal, and perceptual acuity as processes contributing to the pathophysiology of visceral pain. © 2017 John Wiley & Sons Ltd.

  14. The trait of sensory processing sensitivity and neural responses to changes in visual scenes

    OpenAIRE

    Jagiellowicz, Jadzia; Xu, Xiaomeng; Aron, Arthur; Aron, Elaine; Cao, Guikang; Feng, Tingyong; Weng, Xuchu

    2010-01-01

    This exploratory study examined the extent to which individual differences in sensory processing sensitivity (SPS), a temperament/personality trait characterized by social, emotional and physical sensitivity, are associated with neural response in visual areas in response to subtle changes in visual scenes. Sixteen participants completed the Highly Sensitive Person questionnaire, a standard measure of SPS. Subsequently, they were tested on a change detection task while undergoing functional m...

  15. Neural correlates of adaptive social responses to real-life frustrating situations: a functional MRI study

    OpenAIRE

    Sekiguchi, Atsushi; Sugiura, Motoaki; Yokoyama, Satoru; Sassa, Yuko; Horie, Kaoru; Sato, Shigeru; Kawashima, Ryuta

    2013-01-01

    Background Frustrating situations are encountered daily, and it is necessary to respond in an adaptive fashion. A psychological definition states that adaptive social behaviors are ?self-performing? and ?contain a solution.? The present study investigated the neural correlates of adaptive social responses to frustrating situations by assessing the dimension of causal attribution. Based on attribution theory, internal causality refers to one?s aptitudes that cause natural responses in real-lif...

  16. Language and the Newborn Brain: Does Prenatal Language Experience Shape the Neonate Neural Response to Speech?

    OpenAIRE

    Lillian eMay; Krista eByers-Heinlein; Judit eGervain; Werker, Janet F.

    2011-01-01

    Previous research has shown that by the time of birth, the neonate brain responds specially to the native language when compared to acoustically similar non-language stimuli. In the current study, we use Near Infrared Spectroscopy to ask how prenatal language experience might shape the brain response to language in newborn infants. To do so, we examine the neural response of neonates when listening to familiar versus unfamiliar language, as well as to non-linguistic backwards language. Twenty...

  17. Differences in Neural Response to Romantic Stimuli in Monogamous and Non-Monogamous Men.

    Science.gov (United States)

    Hamilton, Lisa Dawn; Meston, Cindy M

    2017-11-01

    In non-human animal research, studies comparing socially monogamous and promiscuous species of voles (Microtus) have identified some key neural differences related to monogamy and non-monogamy. Specifically, densities of the vasopressin V1a receptor and dopamine D2 receptors in subcortical reward-related and limbic areas of the brain have been linked to monogamous behavior in prairie voles (Microtus ochrogaster). Similar brain areas have been shown to be correlated with feelings of romantic love in monogamously pair-bonded humans. Humans vary in the degree to which they engage in (non-)monogamous behaviors. The present study examined the differences in neural activation in response to sexual and romantic stimuli in monogamous (n = 10) and non-monogamous (n = 10) men. Results indicated that monogamous men showed more reward-related neural activity when viewing romantic pictures compared to non-monogamous men. Areas with increased activation for monogamous men were all in the right hemisphere and included the thalamus, accumbens, striatum, pallidum, insula, and orbitofrontal cortex. There were no significant differences between groups in activation to sexual stimuli. These results demonstrate that the neural processing of romantic images is different for monogamous and non-monogamous men. There is some overlap in the neural areas showing increased activation in monogamous men in the present study and the neural areas that show differences in the vole models of monogamy and affiliation. Future research will be needed to clarify whether similar factors are contributing to the neural differences seen in monogamous and non-monogamous humans and voles.

  18. Overlapping neural response to the pain or harm of people, animals, and nature.

    Science.gov (United States)

    Mathur, Vani A; Cheon, Bobby K; Harada, Tokiko; Scimeca, Jason M; Chiao, Joan Y

    2016-01-29

    Interpersonal pain perception is a fundamental and evolutionarily beneficial social process. While critical for navigating the social world, whether or not people rely on similar processes to perceive and respond to the harm of the non-human biological world remains largely unknown. Here we investigate whether neural reactivity toward the suffering of other people is distinct from or overlapping with the neural response to pain and harm inflicted upon non-human entities, specifically animals and nature. We used fMRI to measure neural activity while participants (n=15) perceived and reported how badly they felt for the pain or harm of humans, animals, and nature, relative to neutral situations. Neural regions associated with perceiving the pain of other people (e.g. dorsal anterior cingulate cortex, bilateral anterior insula) were similarly recruited when perceiving and responding to painful scenes across people, animals, and nature. These results suggest that similar brain responses are relied upon when perceiving the harm of social and non-social biological entities, broadly construed, and that activity within the dorsal anterior cingulate cortex and bilateral anterior insula in response to pain-relevant stimuli is not uniquely specific to humans. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Acupuncture stimulation on GB34 activates neural responses associated with Parkinson's disease.

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    Yeo, Sujung; Lim, Sabina; Choe, Il-Hwan; Choi, Yeong-Gon; Chung, Kyung-Cheon; Jahng, Geon-Ho; Kim, Sung-Hoon

    2012-09-01

    Parkinson's disease (PD) is a degenerative brain disorder that is caused by neural defects in the substantia nigra. Numerous studies have reported that acupuncture treatment on GB34 (Yanglingquan) leads to significant improvements in patients with PD and in PD animal models. Studies using functional magnetic resonance imaging (fMRI) have shown that patients with PD, compared to healthy participants, have lower neural responses in extensive brain regions including the putamen, thalamus, and the supplementary motor area. This study investigated the reported association between acupuncture point GB34 and PD. Using fMRI, neural responses of 12 patients with PD and 12 healthy participants were examined before and after acupuncture stimulation. Acupuncture stimulation increased neural responses in regions including the substantia nigra, caudate, thalamus, and putamen, which are impaired caused by PD. Areas associated with PD were activated by the acupuncture stimulation on GB34. This shows that acupuncture treatment on GB34 may be effective in improving the symptoms of PD. Although more randomized controlled trials on the topic will be needed, this study shows that acupuncture may be helpful in the treatment of symptoms involving PD. © 2012 Blackwell Publishing Ltd.

  20. Mortality salience enhances racial in-group bias in empathic neural responses to others' suffering.

    Science.gov (United States)

    Li, Xiaoyang; Liu, Yi; Luo, Siyang; Wu, Bing; Wu, Xinhuai; Han, Shihui

    2015-09-01

    Behavioral research suggests that mortality salience (MS) leads to increased in-group identification and in-group favoritism in prosocial behavior. What remains unknown is whether and how MS influences brain activity that mediates emotional resonance with in-group and out-group members and is associated with in-group favoritism in helping behavior. The current work investigated MS effects on empathic neural responses to racial in-group and out-group members' suffering. Experiments 1 and 2 respectively recorded event related potentials (ERPs) and blood oxygen level dependent signals to pain/neutral expressions of Asian and Caucasian faces from Chinese adults who had been primed with MS or negative affect (NA). Experiment 1 found that an early frontal/central activity (P2) was more strongly modulated by pain vs. neutral expressions of Asian than Caucasian faces, but this effect was not affected by MS vs. NA priming. However, MS relative to NA priming enhanced racial in-group bias in long-latency neural response to pain expressions over the central/parietal regions (P3). Experiment 2 found that MS vs. NA priming increased racial in-group bias in empathic neural responses to pain expression in the anterior and mid-cingulate cortex. Our findings indicate that reminding mortality enhances brain activity that differentiates between racial in-group and out-group members' emotional states and suggest a neural basis of in-group favoritism under mortality threat. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Neural responses to emotional faces in women recovered from anorexia nervosa.

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    Cowdrey, Felicity A; Harmer, Catherine J; Park, Rebecca J; McCabe, Ciara

    2012-03-31

    Impairments in emotional processing have been associated with anorexia nervosa. However, it is unknown whether neural and behavioural differences in the processing of emotional stimuli persist following recovery. The aim of this study was to investigate the neural processing of emotional faces in individuals recovered from anorexia nervosa compared with healthy controls. Thirty-two participants (16 recovered anorexia nervosa, 16 healthy controls) underwent a functional magnetic resonance imaging (fMRI) scan. Participants viewed fearful and happy emotional faces and indicated the gender of the face presented. Whole brain analysis revealed no significant differences between the groups to the contrasts of fear versus happy and vice versa. Region of interest analysis demonstrated no significant differences in the neural response to happy or fearful stimuli between the groups in the amygdala or fusiform gyrus. These results suggest that processing of emotional faces may not be aberrant after recovery from anorexia nervosa. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  2. Associations between proprioceptive neural pathway structural connectivity and balance in people with multiple sclerosis

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    Brett W Fling

    2014-10-01

    Full Text Available Mobility and balance impairments are a hallmark of multiple sclerosis (MS, affecting nearly half of patients at presentation and resulting in decreased activity and participation, falls, injuries, and reduced quality of life. A growing body of work suggests that balance impairments in people with mild MS are primarily the result of deficits in proprioception, the ability to determine body position in space in the absence of vision. A better understanding of the pathophysiology of balance disturbances in MS is needed to develop evidence-based rehabilitation approaches. The purpose of the current study was to 1 map the cortical proprioceptive pathway in-vivo using diffusion weighted imaging and 2 assess associations between proprioceptive pathway white matter microstructural integrity and performance on clinical and behavioral balance tasks. We hypothesized that people with MS (PwMS would have reduced integrity of cerebral proprioceptive pathways, and that reduced white matter microstructure within these tracts would be strongly related to proprioceptive-based balance deficits. We found poorer balance control on proprioceptive-based tasks and reduced white matter microstructural integrity of the cortical proprioceptive tracts in PwMS compared with age-matched healthy controls. Microstructural integrity of this pathway in the right hemisphere was also strongly associated with proprioceptive-based balance control in PwMS and controls. Conversely, while white matter integrity of the right hemisphere’s proprioceptive pathway was significantly correlated with overall balance performance in healthy controls, there was no such relationship in PwMS. These results augment existing literature suggesting that balance control in PwMS may become more dependent upon 1 cerebellar-regulated proprioceptive control, 2 the vestibular system, and/or 3 the visual system.

  3. Neural correlates of adaptive social responses to real-life frustrating situations: a functional MRI study.

    Science.gov (United States)

    Sekiguchi, Atsushi; Sugiura, Motoaki; Yokoyama, Satoru; Sassa, Yuko; Horie, Kaoru; Sato, Shigeru; Kawashima, Ryuta

    2013-03-13

    Frustrating situations are encountered daily, and it is necessary to respond in an adaptive fashion. A psychological definition states that adaptive social behaviors are "self-performing" and "contain a solution." The present study investigated the neural correlates of adaptive social responses to frustrating situations by assessing the dimension of causal attribution. Based on attribution theory, internal causality refers to one's aptitudes that cause natural responses in real-life situations, whereas external causality refers to environmental factors, such as experimental conditions, causing such responses. To investigate the issue, we developed a novel approach that assesses causal attribution under experimental conditions. During fMRI scanning, subjects were required to engage in virtual frustrating situations and play the role of protagonists by verbalizing social responses, which were socially adaptive or non-adaptive. After fMRI scanning, the subjects reported their causal attribution index of the psychological reaction to the experimental condition. We performed a correlation analysis between the causal attribution index and brain activity. We hypothesized that the brain region whose activation would have a positive and negative correlation with the self-reported index of the causal attributions would be regarded as neural correlates of internal and external causal attribution of social responses, respectively. We found a significant negative correlation between external causal attribution and neural responses in the right anterior temporal lobe for adaptive social behaviors. This region is involved in the integration of emotional and social information. These results suggest that, particularly in adaptive social behavior, the social demands of frustrating situations, which involve external causality, may be integrated by a neural response in the right anterior temporal lobe.

  4. Abnormal regional spontaneous neural activity in visual pathway in retinal detachment patients: a resting-state functional MRI study

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    Huang X

    2017-11-01

    Full Text Available Xin Huang,1,2,* Dan Li,3,* Hai-Jun Li,3 Yu-Lin Zhong,1 Shelby Freeberg,4 Jing Bao,1 Xian-Jun Zeng,3 Yi Shao1 1Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Jiangxi Province Clinical Ophthalmology Institute, Nanchang, Jiangxi, People’s Republic of China; 2Department of Ophthalmology, Eye Center, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, Hubei, People’s Republic of China; 3Department of Radiology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 4Department of Ophthalmology, University of Florida, Gainesville, FL, USA *These authors contributed equally to this work Objective: The aim of the study was to investigate changes of brain neural homogeneity in retinal detachment (RD patients using the regional homogeneity (ReHo method to understand their relationships with clinical features. Materials and methods: A total of 30 patients with RD (16 men and 14 women, and 30 healthy controls (HCs (16 men and 14 women closely matched in age and sex were recruited. Resting-state functional magnetic resonance imaging scans were performed for all subjects. The ReHo method was used to investigate the brain regional neural homogeneity. Patients with RD were distinguished from HCs by receiver operating characteristic curve. The relationships between the mean ReHo signal values in many brain regions and clinical features in RD patients were calculated by Pearson correlation analysis. Results: Compared with HCs, RD patients had significantly decreased ReHo values in the right occipital lobe, right superior temporal gyrus, bilateral cuneus and left middle frontal gyrus. Moreover, we found that the mean ReHo signal of the bilateral cuneus showed positive relationships with the duration of the RD (r=0.392, P=0.032. Conclusion: The RD patients showed brain neural homogeneity dysfunction in the visual pathway, which may underline the pathological mechanism

  5. Differential Contribution of the Guanylyl Cyclase-Cyclic GMP-Protein Kinase G Pathway to the Proliferation of Neural Stem Cells Stimulated by Nitric Oxide

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    Bruno P. Carreira

    2012-02-01

    Full Text Available Nitric oxide (NO is an important inflammatory mediator involved in the initial boost in the proliferation of neural stem cells following brain injury. However, the mechanisms underlying the proliferative effect of NO are still unclear. The aim of this work was to investigate whether cyclic GMP (cGMP and the cGMP-dependent kinase (PKG are involved in the proliferative effect triggered by NO in neural stem cells. For this purpose, cultures of neural stem cells isolated from the mouse subventricular zone (SVZ were used. We observed that long-term exposure to the NO donor (24 h, NOC-18, increased the proliferation of SVZ cells in a cGMP-dependent manner, since the guanylate cyclase inhibitor, ODQ, prevented cell proliferation. Similarly to NOC-18, the cGMP analogue, 8-Br-cGMP, also increased cell proliferation. Interestingly, shorter exposures to NO (6 h increased cell proliferation in a cGMP-independent manner via the ERK/MAP kinase pathway. The selective inhibitor of PKG, KT5823, prevented the proliferative effect induced by NO at 24 h but not at 6 h. In conclusion, the proliferative effect of NO is initially mediated by the ERK/MAPK pathway, and at later stages by the GC/cGMP/PKG pathway. Thus, our work shows that NO induces neural stem cell proliferation by targeting these two pathways in a biphasic manner.

  6. Comparison of IT Neural Response Statistics with Simulations

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    Qiulei Dong

    2017-07-01

    Full Text Available Lehky et al. (2011 provided a statistical analysis on the responses of the recorded 674 neurons to 806 image stimuli in anterior inferotemporalm (AIT cortex of two monkeys. In terms of kurtosis and Pareto tail index, they observed that the population sparseness of both unnormalized and normalized responses is always larger than their single-neuron selectivity, hence concluded that the critical features for individual neurons in primate AIT cortex are not very complex, but there is an indefinitely large number of them. In this work, we explore an “inverse problem” by simulation, that is, by simulating each neuron indeed only responds to a very limited number of stimuli among a very large number of neurons and stimuli, to assess whether the population sparseness is always larger than the single-neuron selectivity. Our simulation results show that the population sparseness exceeds the single-neuron selectivity in most cases even if the number of neurons and stimuli are much larger than several hundreds, which confirms the observations in Lehky et al. (2011. In addition, we found that the variances of the computed kurtosis and Pareto tail index are quite large in some cases, which reveals some limitations of these two criteria when used for neuron response evaluation.

  7. The neural response to maternal stimuli: an ERP study.

    Directory of Open Access Journals (Sweden)

    Lili Wu

    Full Text Available Mothers are important to all humans. Research has established that maternal information affects individuals' cognition, emotion, and behavior. We measured event-related potentials (ERPs to examine attentional and evaluative processing of maternal stimuli while participants completed a Go/No-go Association Task that paired mother or others words with good or bad evaluative words. Behavioral data showed that participants responded faster to mother words paired with good than the mother words paired with bad but showed no difference in response to these others across conditions, reflecting a positive evaluation of mother. ERPs showed larger P200 and N200 in response to mother than in response to others, suggesting that mother attracted more attention than others. In the subsequent time window, mother in the mother + bad condition elicited a later and larger late positive potential (LPP than it did in the mother + good condition, but this was not true for others, also suggesting a positive evaluation of mother. These results suggest that people differentiate mother from others during initial attentional stage, and evaluative mother positively during later stage.

  8. Placebo-Activated Neural Systems are Linked to Antidepressant Responses

    Science.gov (United States)

    Peciña, Marta; Bohnert, Amy S. B.; Sikora, Magdalena; Avery, Erich T.; Langenecker, Scott A.; Mickey, Brian J.; Zubieta, Jon-Kar

    2016-01-01

    Importance High placebo responses have been observed across a wide range of pathologies, severely impacting drug development. Objective Here we examined neurochemical mechanisms underlying the formation of placebo effects in patients with Major Depressive Disorder (MDD). Participants Thirty-five medication-free MDD patients. Design and Intervention We performed a single-blinded two-week cross-over randomized controlled trial of two identical oral placebos (described as having either “active” or “inactive” fast-acting antidepressant-like effects) followed by a 10-week open-label treatment with a selective serotonin reuptake inhibitor (SSRI) or in some cases, another agent as clinically indicated. The volunteers were studied with PET and the μ-opioid receptor (MOR)-selective radiotracer [11C]carfentanil after each 1-week “inactive” and “active” oral placebo treatment. In addition, 1 mL of isotonic saline was administered intravenously (i.v.) within sight of the volunteer during PET scanning every 4 min over 20 min only after the 1-week active placebo treatment, with instructions that the compound may be associated with the activation of brain systems involved in mood improvement. This challenge stimulus was utilized to test the individual capacity to acutely activate endogenous opioid neurotransmision under expectations of antidepressant effect. Setting A University Health System. Main Outcomes and Measures Changes in depressive symptoms in response to “active” placebo and antidepressant. Baseline and activation measures of MOR binding. Results Higher baseline MOR binding in the nucleus accumbens (NAc) was associated with better response to antidepressant treatment (r=0.48; p=0.02). Reductions in depressive symptoms after 1-week of “active” placebo treatment, compared to the “inactive”, were associated with increased placebo-induced μ-opioid neurotransmission in a network of regions implicated in emotion, stress regulation, and the

  9. Visual Working Memory Enhances the Neural Response to Matching Visual Input.

    Science.gov (United States)

    Gayet, Surya; Guggenmos, Matthias; Christophel, Thomas B; Haynes, John-Dylan; Paffen, Chris L E; Van der Stigchel, Stefan; Sterzer, Philipp

    2017-07-12

    Visual working memory (VWM) is used to maintain visual information available for subsequent goal-directed behavior. The content of VWM has been shown to affect the behavioral response to concurrent visual input, suggesting that visual representations originating from VWM and from sensory input draw upon a shared neural substrate (i.e., a sensory recruitment stance on VWM storage). Here, we hypothesized that visual information maintained in VWM would enhance the neural response to concurrent visual input that matches the content of VWM. To test this hypothesis, we measured fMRI BOLD responses to task-irrelevant stimuli acquired from 15 human participants (three males) performing a concurrent delayed match-to-sample task. In this task, observers were sequentially presented with two shape stimuli and a retro-cue indicating which of the two shapes should be memorized for subsequent recognition. During the retention interval, a task-irrelevant shape (the probe) was briefly presented in the peripheral visual field, which could either match or mismatch the shape category of the memorized stimulus. We show that this probe stimulus elicited a stronger BOLD response, and allowed for increased shape-classification performance, when it matched rather than mismatched the concurrently memorized content, despite identical visual stimulation. Our results demonstrate that VWM enhances the neural response to concurrent visual input in a content-specific way. This finding is consistent with the view that neural populations involved in sensory processing are recruited for VWM storage, and it provides a common explanation for a plethora of behavioral studies in which VWM-matching visual input elicits a stronger behavioral and perceptual response. SIGNIFICANCE STATEMENT Humans heavily rely on visual information to interact with their environment and frequently must memorize such information for later use. Visual working memory allows for maintaining such visual information in the mind

  10. Astroglial Pentose Phosphate Pathway Rates in Response to High-Glucose Environments

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    Shinichi Takahashi

    2012-02-01

    Full Text Available ROS (reactive oxygen species play an essential role in the pathophysiology of diabetes, stroke and neurodegenerative disorders. Hyperglycaemia associated with diabetes enhances ROS production and causes oxidative stress in vascular endothelial cells, but adverse effects of either acute or chronic high-glucose environments on brain parenchymal cells remain unclear. The PPP (pentose phosphate pathway and GSH participate in a major defence mechanism against ROS in brain, and we explored the role and regulation of the astroglial PPP in response to acute and chronic high-glucose environments. PPP activity was measured in cultured neurons and astroglia by determining the difference in rate of 14CO2 production from [1-14C]glucose and [6-14C]glucose. ROS production, mainly H2O2, and GSH were also assessed. Acutely elevated glucose concentrations in the culture media increased PPP activity and GSH level in astroglia, decreasing ROS production. Chronically elevated glucose environments also induced PPP activation. Immunohistochemical analyses revealed that chronic high-glucose environments induced ER (endoplasmic reticulum stress (presumably through increased hexosamine biosynthetic pathway flux. Nuclear translocation of Nrf2 (nuclear factor-erythroid 2 p45 subunit-related factor 2, which regulates G6PDH (glyceraldehyde-6-phosphate dehydrogenase by enhancing transcription, was also observed in association with BiP (immunoglobulin heavy-chain-binding protein expression. Acute and chronic high-glucose environments activated the PPP in astroglia, preventing ROS elevation. Therefore a rapid decrease in glucose level seems to enhance ROS toxicity, perhaps contributing to neural damage when insulin levels given to diabetic patients are not properly calibrated and plasma glucose levels are not adequately maintained. These findings may also explain the lack of evidence for clinical benefits from strict glycaemic control during the acute phase of stroke.

  11. Application of artificial neural networks for response surface modelling in HPLC method development

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    Mohamed A. Korany

    2012-01-01

    Full Text Available This paper discusses the usefulness of artificial neural networks (ANNs for response surface modelling in HPLC method development. In this study, the combined effect of pH and mobile phase composition on the reversed-phase liquid chromatographic behaviour of a mixture of salbutamol (SAL and guaiphenesin (GUA, combination I, and a mixture of ascorbic acid (ASC, paracetamol (PAR and guaiphenesin (GUA, combination II, was investigated. The results were compared with those produced using multiple regression (REG analysis. To examine the respective predictive power of the regression model and the neural network model, experimental and predicted response factor values, mean of squares error (MSE, average error percentage (Er%, and coefficients of correlation (r were compared. It was clear that the best networks were able to predict the experimental responses more accurately than the multiple regression analysis.

  12. Bilingualism increases neural response consistency and attentional control: Evidence for sensory and cognitive coupling

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    Krizman, Jennifer; Skoe, Erika; Marian, Viorica; Kraus, Nina

    2014-01-01

    Auditory processing is presumed to be influenced by cognitive processes – including attentional control – in a top-down manner. In bilinguals, activation of both languages during daily communication hones inhibitory skills, which subsequently bolster attentional control. We hypothesize that the heightened attentional demands of bilingual communication strengthens connections between cognitive (i.e., attentional control) and auditory processing, leading to greater across-trial consistency in the auditory evoked response (i.e., neural consistency) in bilinguals. To assess this, we collected passively-elicited auditory evoked responses to the syllable [da] and separately obtained measures of attentional control and language ability in adolescent Spanish-English bilinguals and English monolinguals. Bilinguals demonstrated enhanced attentional control and more consistent brainstem and cortical responses. In bilinguals, but not monolinguals, brainstem consistency tracked with language proficiency and attentional control. We interpret these enhancements in neural consistency as the outcome of strengthened attentional control that emerged from experience communicating in two languages. PMID:24413593

  13. Morphological covariance in anatomical MRI scans can identify discrete neural pathways in the brain and their disturbances in persons with neuropsychiatric disorders.

    Science.gov (United States)

    Bansal, Ravi; Hao, Xuejun; Peterson, Bradley S

    2015-05-01

    We hypothesize that coordinated functional activity within discrete neural circuits induces morphological organization and plasticity within those circuits. Identifying regions of morphological covariation that are independent of morphological covariation in other regions therefore may therefore allow us to identify discrete neural systems within the brain. Comparing the magnitude of these variations in individuals who have psychiatric disorders with the magnitude of variations in healthy controls may allow us to identify aberrant neural pathways in psychiatric illnesses. We measured surface morphological features by applying nonlinear, high-dimensional warping algorithms to manually defined brain regions. We transferred those measures onto the surface of a unit sphere via conformal mapping and then used spherical wavelets and their scaling coefficients to simplify the data structure representing these surface morphological features of each brain region. We used principal component analysis (PCA) to calculate covariation in these morphological measures, as represented by their scaling coefficients, across several brain regions. We then assessed whether brain subregions that covaried in morphology, as identified by large eigenvalues in the PCA, identified specific neural pathways of the brain. To do so, we spatially registered the subnuclei for each eigenvector into the coordinate space of a Diffusion Tensor Imaging dataset; we used these subnuclei as seed regions to track and compare fiber pathways with known fiber pathways identified in neuroanatomical atlases. We applied these procedures to anatomical MRI data in a cohort of 82 healthy participants (42 children, 18 males, age 10.5 ± 2.43 years; 40 adults, 22 males, age 32.42 ± 10.7 years) and 107 participants with Tourette's Syndrome (TS) (71 children, 59 males, age 11.19 ± 2.2 years; 36 adults, 21 males, age 37.34 ± 10.9 years). We evaluated the construct validity of the identified covariation in morphology

  14. Relation of obesity to neural activation in response to food commercials

    Science.gov (United States)

    Yokum, Sonja; Stice, Eric; Harris, Jennifer L.; Brownell, Kelly D.

    2014-01-01

    Adolescents view thousands of food commercials annually, but the neural response to food advertising and its association with obesity is largely unknown. This study is the first to examine how neural response to food commercials differs from other stimuli (e.g. non-food commercials and television show) and to explore how this response may differ by weight status. The blood oxygen level-dependent functional magnetic resonance imaging activation was measured in 30 adolescents ranging from lean to obese in response to food and non-food commercials imbedded in a television show. Adolescents exhibited greater activation in regions implicated in visual processing (e.g. occipital gyrus), attention (e.g. parietal lobes), cognition (e.g. temporal gyrus and posterior cerebellar lobe), movement (e.g. anterior cerebellar cortex), somatosensory response (e.g. postcentral gyrus) and reward [e.g. orbitofrontal cortex and anterior cingulate cortex (ACC)] during food commercials. Obese participants exhibited less activation during food relative to non-food commercials in neural regions implicated in visual processing (e.g. cuneus), attention (e.g. posterior cerebellar lobe), reward (e.g. ventromedial prefrontal cortex and ACC) and salience detection (e.g. precuneus). Obese participants did exhibit greater activation in a region implicated in semantic control (e.g. medial temporal gyrus). These findings may inform current policy debates regarding the impact of food advertising to minors. PMID:23576811

  15. Relation of obesity to neural activation in response to food commercials.

    Science.gov (United States)

    Gearhardt, Ashley N; Yokum, Sonja; Stice, Eric; Harris, Jennifer L; Brownell, Kelly D

    2014-07-01

    Adolescents view thousands of food commercials annually, but the neural response to food advertising and its association with obesity is largely unknown. This study is the first to examine how neural response to food commercials differs from other stimuli (e.g. non-food commercials and television show) and to explore how this response may differ by weight status. The blood oxygen level-dependent functional magnetic resonance imaging activation was measured in 30 adolescents ranging from lean to obese in response to food and non-food commercials imbedded in a television show. Adolescents exhibited greater activation in regions implicated in visual processing (e.g. occipital gyrus), attention (e.g. parietal lobes), cognition (e.g. temporal gyrus and posterior cerebellar lobe), movement (e.g. anterior cerebellar cortex), somatosensory response (e.g. postcentral gyrus) and reward [e.g. orbitofrontal cortex and anterior cingulate cortex (ACC)] during food commercials. Obese participants exhibited less activation during food relative to non-food commercials in neural regions implicated in visual processing (e.g. cuneus), attention (e.g. posterior cerebellar lobe), reward (e.g. ventromedial prefrontal cortex and ACC) and salience detection (e.g. precuneus). Obese participants did exhibit greater activation in a region implicated in semantic control (e.g. medial temporal gyrus). These findings may inform current policy debates regarding the impact of food advertising to minors. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  16. Prospero-related homeobox 1 (Prox1) at the crossroads of diverse pathways during adult neural fate specification.

    Science.gov (United States)

    Stergiopoulos, Athanasios; Elkouris, Maximilianos; Politis, Panagiotis K

    2014-01-01

    Over the last decades, adult neurogenesis in the central nervous system (CNS) has emerged as a fundamental process underlying physiology and disease. Recent evidence indicates that the homeobox transcription factor Prox1 is a critical intrinsic regulator of neurogenesis in the embryonic CNS and adult dentate gyrus (DG) of the hippocampus, acting in multiple ways and instructed by extrinsic cues and intrinsic factors. In the embryonic CNS, Prox1 is mechanistically involved in the regulation of proliferation vs. differentiation decisions of neural stem cells (NSCs), promoting cell cycle exit and neuronal differentiation, while inhibiting astrogliogenesis. During the complex differentiation events in adult hippocampal neurogenesis, Prox1 is required for maintenance of intermediate progenitors (IPs), differentiation and maturation of glutamatergic interneurons, as well as specification of DG cell identity over CA3 pyramidal fate. The mechanism by which Prox1 exerts multiple functions involves distinct signaling pathways currently not fully highlighted. In this mini-review, we thoroughly discuss the Prox1-dependent phenotypes and molecular pathways in adult neurogenesis in relation to different upstream signaling cues and cell fate determinants. In addition, we discuss the possibility that Prox1 may act as a cross-talk point between diverse signaling cascades to achieve specific outcomes during adult neurogenesis.

  17. Variances handling method of clinical pathways based on T-S fuzzy neural networks with novel hybrid learning algorithm.

    Science.gov (United States)

    Du, Gang; Jiang, Zhibin; Diao, Xiaodi; Ye, Yan; Yao, Yang

    2012-06-01

    Clinical pathways' variances present complex, fuzzy, uncertain and high-risk characteristics. They could cause complicating diseases or even endanger patients' life if not handled effectively. In order to improve the accuracy and efficiency of variances handling by Takagi-Sugeno (T-S) fuzzy neural networks (FNNs), a new variances handling method for clinical pathways (CPs) is proposed in this study, which is based on T-S FNNs with novel hybrid learning algorithm. And the optimal structure and parameters can be achieved simultaneously by integrating the random cooperative decomposing particle swarm optimization algorithm (RCDPSO) and discrete binary version of PSO (DPSO) algorithm. Finally, a case study on liver poisoning of osteosarcoma preoperative chemotherapy CP is used to validate the proposed method. The result demonstrates that T-S FNNs based on the proposed algorithm achieves superior performances in efficiency, precision, and generalization ability to standard T-S FNNs, Mamdani FNNs and T-S FNNs based on other algorithms (CPSO and PSO) for variances handling of CPs.

  18. Neural pathways for language in autism: the potential for music-based treatments

    Science.gov (United States)

    Wan, Catherine Y; Schlaug, Gottfried

    2010-01-01

    Language deficits represent the core diagnostic characteristics of autism, and some of these individuals never develop functional speech. The language deficits in autism may be due to structural and functional abnormalities in certain language regions (e.g., frontal and temporal), or due to altered connectivity between these brain regions. In particular, a number of anatomical pathways that connect auditory and motor brain regions (e.g., the arcuate fasciculus, the uncinate fasciculus and the extreme capsule) may be altered in individuals with autism. These pathways may also provide targets for experimental treatments to facilitate communication skills in autism. We propose that music-based interventions (e.g., auditory–motor mapping training) would take advantage of the musical strengths of these children, and are likely to engage, and possibly strengthen, the connections between frontal and temporal regions bilaterally. Such treatments have important clinical potential in facilitating expressive language in nonverbal children with autism. PMID:21197137

  19. Neural pathways for language in autism: the potential for music-based treatments

    OpenAIRE

    Wan, Catherine Y; Schlaug, Gottfried

    2010-01-01

    Language deficits represent the core diagnostic characteristics of autism, and some of these individuals never develop functional speech. The language deficits in autism may be due to structural and functional abnormalities in certain language regions (e.g., frontal and temporal), or due to altered connectivity between these brain regions. In particular, a number of anatomical pathways that connect auditory and motor brain regions (e.g., the arcuate fasciculus, the uncinate fasciculus and the...

  20. Neural Responses to Heartbeats in the Default Network Encode the Self in Spontaneous Thoughts.

    Science.gov (United States)

    Babo-Rebelo, Mariana; Richter, Craig G; Tallon-Baudry, Catherine

    2016-07-27

    The default network (DN) has been consistently associated with self-related cognition, but also to bodily state monitoring and autonomic regulation. We hypothesized that these two seemingly disparate functional roles of the DN are functionally coupled, in line with theories proposing that selfhood is grounded in the neural monitoring of internal organs, such as the heart. We measured with magnetoencephalograhy neural responses evoked by heartbeats while human participants freely mind-wandered. When interrupted by a visual stimulus at random intervals, participants scored the self-relatedness of the interrupted thought. They evaluated their involvement as the first-person perspective subject or agent in the thought ("I"), and on another scale to what degree they were thinking about themselves ("Me"). During the interrupted thought, neural responses to heartbeats in two regions of the DN, the ventral precuneus and the ventromedial prefrontal cortex, covaried, respectively, with the "I" and the "Me" dimensions of the self, even at the single-trial level. No covariation between self-relatedness and peripheral autonomic measures (heart rate, heart rate variability, pupil diameter, electrodermal activity, respiration rate, and phase) or alpha power was observed. Our results reveal a direct link between selfhood and neural responses to heartbeats in the DN and thus directly support theories grounding selfhood in the neural monitoring of visceral inputs. More generally, the tight functional coupling between self-related processing and cardiac monitoring observed here implies that, even in the absence of measured changes in peripheral bodily measures, physiological and cognitive functions have to be considered jointly in the DN. The default network (DN) has been consistently associated with self-processing but also with autonomic regulation. We hypothesized that these two functions could be functionally coupled in the DN, inspired by theories according to which selfhood is

  1. Adolescent girls' neural response to reward mediates the relation between childhood financial disadvantage and depression.

    Science.gov (United States)

    Romens, Sarah E; Casement, Melynda D; McAloon, Rose; Keenan, Kate; Hipwell, Alison E; Guyer, Amanda E; Forbes, Erika E

    2015-11-01

    Children who experience socioeconomic disadvantage are at heightened risk for developing depression; however, little is known about neurobiological mechanisms underlying this association. Low socioeconomic status (SES) during childhood may confer risk for depression through its stress-related effects on the neural circuitry associated with processing monetary rewards. In a prospective study, we examined the relationships among the number of years of household receipt of public assistance from age 5-16 years, neural activation during monetary reward anticipation and receipt at age 16, and depression symptoms at age 16 in 123 girls. Number of years of household receipt of public assistance was positively associated with heightened response in the medial prefrontal cortex during reward anticipation, and this heightened neural response mediated the relationship between socioeconomic disadvantage and current depression symptoms, controlling for past depression. Chronic exposure to socioeconomic disadvantage in childhood may alter neural circuitry involved in reward anticipation in adolescence, which in turn may confer risk for depression. © 2015 Association for Child and Adolescent Mental Health.

  2. Adolescent girls’ neural response to reward mediates the relation between childhood financial disadvantage and depression

    Science.gov (United States)

    Romens, Sarah E.; Casement, Melynda D.; McAloon, Rose; Keenan, Kate; Hipwell, Alison E.; Guyer, Amanda E.; Forbes, Erika E.

    2015-01-01

    Background Children who experience socioeconomic disadvantage are at heightened risk for developing depression; however, little is known about neurobiological mechanisms underlying this association. Low socioeconomic status (SES) during childhood may confer risk for depression through its stress-related effects on the neural circuitry associated with processing monetary rewards. Methods In a prospective study, we examined the relationships among the number of years of household receipt of public assistance from age 5–16 years, neural activation during monetary reward anticipation and receipt at age 16, and depression symptoms at age 16 in 123 girls. Results Number of years of household receipt of public assistance was positively associated with heightened response in the medial prefrontal cortex during reward anticipation, and this heightened neural response mediated the relationship between socioeconomic disadvantage and current depression symptoms, controlling for past depression. Conclusions Chronic exposure to socioeconomic disadvantage in childhood may alter neural circuitry involved in reward anticipation in adolescence, which in turn may confer risk for depression. PMID:25846746

  3. Neural Responses to Kindness and Malevolence Differ in Illness and Recovery in Women With Anorexia Nervosa

    Science.gov (United States)

    McAdams, Carrie J.; Lohrenz, Terry; Montague, P. Read

    2015-01-01

    In anorexia nervosa, problems with social relationships contribute to illness, and improvements in social support are associated with recovery. Using the multiround trust game and 3T MRI, we compare neural responses in a social relationship in three groups of women: women with anorexia nervosa, women in long-term weight recovery from anorexia nervosa, and healthy comparison women. Surrogate markers related to social signals in the game were computed each round to assess whether the relationship was improving (benevolence) or deteriorating (malevolence) for each subject. Compared with healthy women, neural responses to benevolence were diminished in the precuneus and right angular gyrus in both currently-ill and weight-recovered subjects with anorexia, but neural responses to malevolence differed in the left fusiform only in currently-ill subjects. Next, using a whole-brain regression, we identified an office assessment, the positive personalizing bias, that was inversely correlated with neural activity in the occipital lobe, the precuneus and posterior cingulate, the bilateral temporoparietal junctions, and dorsal anterior cingulate, during benevolence for all groups of subjects. The positive personalizing bias is a self-report measure that assesses the degree with which a person attributes positive experiences to other people. These data suggest that problems in perceiving kindness may be a consistent trait related to the development of anorexia nervosa, whereas recognizing malevolence may be related to recovery. Future work on social brain function, in both healthy and psychiatric populations, should consider positive personalizing biases as a possible marker of neural differences related to kindness perception. PMID:26416161

  4. Neural responses to kindness and malevolence differ in illness and recovery in women with anorexia nervosa.

    Science.gov (United States)

    McAdams, Carrie J; Lohrenz, Terry; Montague, P Read

    2015-12-01

    In anorexia nervosa, problems with social relationships contribute to illness, and improvements in social support are associated with recovery. Using the multiround trust game and 3T MRI, we compare neural responses in a social relationship in three groups of women: women with anorexia nervosa, women in long-term weight recovery from anorexia nervosa, and healthy comparison women. Surrogate markers related to social signals in the game were computed each round to assess whether the relationship was improving (benevolence) or deteriorating (malevolence) for each subject. Compared with healthy women, neural responses to benevolence were diminished in the precuneus and right angular gyrus in both currently-ill and weight-recovered subjects with anorexia, but neural responses to malevolence differed in the left fusiform only in currently-ill subjects. Next, using a whole-brain regression, we identified an office assessment, the positive personalizing bias, that was inversely correlated with neural activity in the occipital lobe, the precuneus and posterior cingulate, the bilateral temporoparietal junctions, and dorsal anterior cingulate, during benevolence for all groups of subjects. The positive personalizing bias is a self-report measure that assesses the degree with which a person attributes positive experiences to other people. These data suggest that problems in perceiving kindness may be a consistent trait related to the development of anorexia nervosa, whereas recognizing malevolence may be related to recovery. Future work on social brain function, in both healthy and psychiatric populations, should consider positive personalizing biases as a possible marker of neural differences related to kindness perception. © 2015 Wiley Periodicals, Inc.

  5. Nanoscale Properties of Neural Cell Prosthetic and Astrocyte Response

    Science.gov (United States)

    Flowers, D. A.; Ayres, V. M.; Delgado-Rivera, R.; Ahmed, I.; Meiners, S. A.

    2009-03-01

    Preliminary data from in-vivo investigations (rat model) suggest that a nanofiber prosthetic device of fibroblast growth factor-2 (FGF-2)-modified nanofibers can correctly guide regenerating axons across an injury gap with aligned functional recovery. Scanning Probe Recognition Microscopy (SPRM) with auto-tracking of individual nanofibers is used for investigation of the key nanoscale properties of the nanofiber prosthetic device for central nervous system tissue engineering and repair. The key properties under SPRM investigation include nanofiber stiffness and surface roughness, nanofiber curvature, nanofiber mesh density and porosity, and growth factor presentation and distribution. Each of these factors has been demonstrated to have global effects on cell morphology, function, proliferation, morphogenesis, migration, and differentiation. The effect of FGF-2 modification on the key nanoscale properties is investigated. Results from the nanofiber prosthetic properties investigations are correlated with astrocyte response to unmodified and FGF-2 modified scaffolds, using 2D planar substrates as a control.

  6. Inhibition and impulsivity: behavioral and neural basis of response control.

    Science.gov (United States)

    Bari, Andrea; Robbins, Trevor W

    2013-09-01

    In many circumstances alternative courses of action and thoughts have to be inhibited to allow the emergence of goal-directed behavior. However, this has not been the accepted view in the past and only recently has inhibition earned its own place in the neurosciences as a fundamental cognitive function. In this review we first introduce the concept of inhibition from early psychological speculations based on philosophical theories of the human mind. The broad construct of inhibition is then reduced to its most readily observable component which necessarily is its behavioral manifestation. The study of 'response inhibition' has the advantage of dealing with a relatively simple and straightforward process, the overriding of a planned or already initiated action. Deficient inhibitory processes profoundly affect everyday life, causing impulsive conduct which is generally detrimental for the individual. Impulsivity has been consistently linked to several types of addiction, attention deficit/hyperactivity disorder, mania and other psychiatric conditions. Our discussion of the behavioral assessment of impulsivity will focus on objective laboratory tasks of response inhibition that have been implemented in parallel for humans and other species with relatively few qualitative differences. The translational potential of these measures has greatly improved our knowledge of the neurobiological basis of behavioral inhibition and impulsivity. We will then review the current models of behavioral inhibition along with their expression via underlying brain regions, including those involved in the activation of the brain's emergency 'brake' operation, those engaged in more controlled and sustained inhibitory processes and other ancillary executive functions. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Pattern of neural responses to verbal fluency shows diagnostic specificity for schizophrenia and bipolar disorder

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    Walshe Muriel

    2011-01-01

    Full Text Available Abstract Background Impairments in executive function and language processing are characteristic of both schizophrenia and bipolar disorder. Their functional neuroanatomy demonstrate features that are shared as well as specific to each disorder. Determining the distinct pattern of neural responses in schizophrenia and bipolar disorder may provide biomarkers for their diagnoses. Methods 104 participants underwent functional magnetic resonance imaging (fMRI scans while performing a phonological verbal fluency task. Subjects were 32 patients with schizophrenia in remission, 32 patients with bipolar disorder in an euthymic state, and 40 healthy volunteers. Neural responses to verbal fluency were examined in each group, and the diagnostic potential of the pattern of the neural responses was assessed with machine learning analysis. Results During the verbal fluency task, both patient groups showed increased activation in the anterior cingulate, left dorsolateral prefrontal cortex and right putamen as compared to healthy controls, as well as reduced deactivation of precuneus and posterior cingulate. The magnitude of activation was greatest in patients with schizophrenia, followed by patients with bipolar disorder and then healthy individuals. Additional recruitment in the right inferior frontal and right dorsolateral prefrontal cortices was observed in schizophrenia relative to both bipolar disorder and healthy subjects. The pattern of neural responses correctly identified individual patients with schizophrenia with an accuracy of 92%, and those with bipolar disorder with an accuracy of 79% in which mis-classification was typically of bipolar subjects as healthy controls. Conclusions In summary, both schizophrenia and bipolar disorder are associated with altered function in prefrontal, striatal and default mode networks, but the magnitude of this dysfunction is particularly marked in schizophrenia. The pattern of response to verbal fluency is highly

  8. Neural basis of individual differences in the response to mental stress: a magnetoencephalography study.

    Science.gov (United States)

    Yamano, Emi; Ishii, Akira; Tanaka, Masaaki; Nomura, Shusaku; Watanabe, Yasuyoshi

    2016-12-01

    Stress is a risk factor for the onset of mental disorders. Although stress response varies across individuals, the mechanism of individual differences remains unclear. Here, we investigated the neural basis of individual differences in response to mental stress using magnetoencephalography (MEG). Twenty healthy male volunteers completed the Temperament and Character Inventory (TCI). The experiment included two types of tasks: a non-stress-inducing task and a stress-inducing task. During these tasks, participants passively viewed non-stress-inducing images and stress-inducing images, respectively, and MEG was recorded. Before and after each task, MEG and electrocardiography were recorded and subjective ratings were obtained. We grouped participants according to Novelty seeking (NS) - tendency to be exploratory, and Harm avoidance (HA) - tendency to be cautious. Participants with high NS and low HA (n = 10) assessed by TCI had a different neural response to stress than those with low NS and high HA (n = 10). Event-related desynchronization (ERD) in the beta frequency band was observed only in participants with high NS and low HA in the brain region extending from Brodmann's area 31 (including the posterior cingulate cortex and precuneus) from 200 to 350 ms after the onset of picture presentation in the stress-inducing task. Individual variation in personality traits (NS and HA) was associated with the neural response to mental stress. These findings increase our understanding of the psychological and neural basis of individual differences in the stress response, and will contribute to development of the psychotherapeutic approaches to stress-related disorders.

  9. Auditory Responses to Electric and Infrared Neural Stimulation of the Rat Cochlear Nucleus

    Science.gov (United States)

    Verma, Rohit; Guex, Amelie A.; Hancock, Kenneth E.; Durakovic, Nedim; McKay, Colette M.; Slama, Michaël C. C.; Brown, M. Christian; Lee, Daniel J.

    2014-01-01

    In an effort to improve the auditory brainstem implant, a prosthesis in which user outcomes are modest, we applied electric and infrared neural stimulation (INS) to the cochlear nucleus in a rat animal model. Electric stimulation evoked regions of neural activation in the inferior colliculus and short-latency, multipeaked auditory brainstem responses (ABRs). Pulsed INS, delivered to the surface of the cochlear nucleus via an optical fiber, evoked broad neural activation in the inferior colliculus. Strongest responses were recorded when the fiber was placed at lateral positions on the cochlear nucleus, close to the temporal bone. INS-evoked ABRs were multipeaked but longer in latency than those for electric stimulation; they resembled the responses to acoustic stimulation. After deafening, responses to electric stimulation persisted, whereas those to INS disappeared, consistent with a reported “optophonic” effect, a laser-induced acoustic artifact. Thus, for deaf individuals who use the auditory brainstem implant, INS alone did not appear promising as a new approach. PMID:24508368

  10. Auditory responses to electric and infrared neural stimulation of the rat cochlear nucleus.

    Science.gov (United States)

    Verma, Rohit U; Guex, Amélie A; Hancock, Kenneth E; Durakovic, Nedim; McKay, Colette M; Slama, Michaël C C; Brown, M Christian; Lee, Daniel J

    2014-04-01

    In an effort to improve the auditory brainstem implant, a prosthesis in which user outcomes are modest, we applied electric and infrared neural stimulation (INS) to the cochlear nucleus in a rat animal model. Electric stimulation evoked regions of neural activation in the inferior colliculus and short-latency, multipeaked auditory brainstem responses (ABRs). Pulsed INS, delivered to the surface of the cochlear nucleus via an optical fiber, evoked broad neural activation in the inferior colliculus. Strongest responses were recorded when the fiber was placed at lateral positions on the cochlear nucleus, close to the temporal bone. INS-evoked ABRs were multipeaked but longer in latency than those for electric stimulation; they resembled the responses to acoustic stimulation. After deafening, responses to electric stimulation persisted, whereas those to INS disappeared, consistent with a reported "optophonic" effect, a laser-induced acoustic artifact. Thus, for deaf individuals who use the auditory brainstem implant, INS alone did not appear promising as a new approach. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Girls’ Challenging Social Experiences in Early Adolescence Predict Neural Response to Rewards and Depressive Symptoms1

    Science.gov (United States)

    Casement, Melynda D.; Guyer, Amanda E.; Hipwell, Alison; McAloon, Rose L.; Hoffmann, Amy M.; Keenan, Kathryn; Forbes, Erika E.

    2014-01-01

    Developmental models of psychopathology posit that exposure to social stressors may confer risk for depression in adolescent girls by disrupting neural reward circuitry. The current study tested this hypothesis by examining the relationship between early adolescent social stressors and later neural reward processing and depressive symptoms. Participants were 120 girls from an ongoing longitudinal study of precursors to depression across adolescent development. Low parental warmth, peer victimization, and depressive symptoms were assessed when the girls were 11 and 12 years old, and participants completed a monetary reward guessing fMRI task and assessment of depressive symptoms at age 16. Results indicate that low parental warmth was associated with increased response to potential rewards in the medial prefrontal cortex (mPFC), striatum, and amygdala, whereas peer victimization was associated with decreased response to potential rewards in the mPFC. Furthermore, concurrent depressive symptoms were associated with increased reward anticipation response in mPFC and striatal regions that were also associated with early adolescent psychosocial stressors, with mPFC and striatal response mediating the association between social stressors and depressive symptoms. These findings are consistent with developmental models that emphasize the adverse impact of early psychosocial stressors on neural reward processing and risk for depression in adolescence. PMID:24397999

  12. Girls' challenging social experiences in early adolescence predict neural response to rewards and depressive symptoms.

    Science.gov (United States)

    Casement, Melynda D; Guyer, Amanda E; Hipwell, Alison E; McAloon, Rose L; Hoffmann, Amy M; Keenan, Kathryn E; Forbes, Erika E

    2014-04-01

    Developmental models of psychopathology posit that exposure to social stressors may confer risk for depression in adolescent girls by disrupting neural reward circuitry. The current study tested this hypothesis by examining the relationship between early adolescent social stressors and later neural reward processing and depressive symptoms. Participants were 120 girls from an ongoing longitudinal study of precursors to depression across adolescent development. Low parental warmth, peer victimization, and depressive symptoms were assessed when the girls were 11 and 12 years old, and participants completed a monetary reward guessing fMRI task and assessment of depressive symptoms at age 16. Results indicate that low parental warmth was associated with increased response to potential rewards in the medial prefrontal cortex (mPFC), striatum, and amygdala, whereas peer victimization was associated with decreased response to potential rewards in the mPFC. Furthermore, concurrent depressive symptoms were associated with increased reward anticipation response in mPFC and striatal regions that were also associated with early adolescent psychosocial stressors, with mPFC and striatal response mediating the association between social stressors and depressive symptoms. These findings are consistent with developmental models that emphasize the adverse impact of early psychosocial stressors on neural reward processing and risk for depression in adolescence. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  13. Girls’ challenging social experiences in early adolescence predict neural response to rewards and depressive symptoms

    Directory of Open Access Journals (Sweden)

    Melynda D. Casement

    2014-04-01

    Full Text Available Developmental models of psychopathology posit that exposure to social stressors may confer risk for depression in adolescent girls by disrupting neural reward circuitry. The current study tested this hypothesis by examining the relationship between early adolescent social stressors and later neural reward processing and depressive symptoms. Participants were 120 girls from an ongoing longitudinal study of precursors to depression across adolescent development. Low parental warmth, peer victimization, and depressive symptoms were assessed when the girls were 11 and 12 years old, and participants completed a monetary reward guessing fMRI task and assessment of depressive symptoms at age 16. Results indicate that low parental warmth was associated with increased response to potential rewards in the medial prefrontal cortex (mPFC, striatum, and amygdala, whereas peer victimization was associated with decreased response to potential rewards in the mPFC. Furthermore, concurrent depressive symptoms were associated with increased reward anticipation response in mPFC and striatal regions that were also associated with early adolescent psychosocial stressors, with mPFC and striatal response mediating the association between social stressors and depressive symptoms. These findings are consistent with developmental models that emphasize the adverse impact of early psychosocial stressors on neural reward processing and risk for depression in adolescence.

  14. Associations between maternal negative affect and adolescent's neural response to peer evaluation

    Directory of Open Access Journals (Sweden)

    Patricia Z. Tan

    2014-04-01

    Full Text Available Parenting is often implicated as a potential source of individual differences in youths’ emotional information processing. The present study examined whether parental affect is related to an important aspect of adolescent emotional development, response to peer evaluation. Specifically, we examined relations between maternal negative affect, observed during parent–adolescent discussion of an adolescent-nominated concern with which s/he wants parental support, and adolescent neural responses to peer evaluation in 40 emotionally healthy and depressed adolescents. We focused on a network of ventral brain regions involved in affective processing of social information: the amygdala, anterior insula, nucleus accumbens, and subgenual anterior cingulate, as well as the ventrolateral prefrontal cortex. Maternal negative affect was not associated with adolescent neural response to peer rejection. However, longer durations of maternal negative affect were associated with decreased responsivity to peer acceptance in the amygdala, left anterior insula, subgenual anterior cingulate, and left nucleus accumbens. These findings provide some of the first evidence that maternal negative affect is associated with adolescents’ neural processing of social rewards. Findings also suggest that maternal negative affect could contribute to alterations in affective processing, specifically, dampening the saliency and/or reward of peer interactions during adolescence.

  15. Intranasal oxytocin increases neural responses to social reward in post-traumatic stress disorder.

    Science.gov (United States)

    Nawijn, Laura; van Zuiden, Mirjam; Koch, Saskia B J; Frijling, Jessie L; Veltman, Dick J; Olff, Miranda

    2017-02-01

    Therapeutic alliance and perceived social support are important predictors of treatment response for post-traumatic stress disorder (PTSD). Intranasal oxytocin administration may enhance treatment response by increasing sensitivity for social reward and thereby therapeutic alliance and perceived social support. As a first step to investigate this therapeutical potential, we investigated whether intranasal oxytocin enhances neural sensitivity to social reward in PTSD patients. Male and female police officers with (n = 35) and without PTSD (n = 37) were included in a double-blind, randomized, placebo-controlled cross-over fMRI study. After intranasal oxytocin (40 IU) and placebo administration, a social incentive delay task was conducted to investigate neural responses during social reward and punishment anticipation and feedback. Under placebo, PTSD patients showed reduced left anterior insula (AI) responses to social rewards (i.e. happy faces) compared with controls. Oxytocin administration increased left AI responses during social reward in PTSD patients, such that PTSD patients no longer differed from controls under placebo. Furthermore, in PTSD patients, oxytocin increased responses to social reward in the right putamen. By normalizing abberant insula responses and increasing putamen responses to social reward, oxytocin administration may enhance sensitivity for social support and therapeutic alliance in PTSD patients. Future studies are needed to investigate clinical effects of oxytocin. © The Author (2016). Published by Oxford University Press.

  16. Neural responses to complex auditory rhythms: the role of attending

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    Heather L Chapin

    2010-12-01

    Full Text Available The aim of this study was to explore the role of attention in pulse and meter perception using complex rhythms. We used a selective attention paradigm in which participants attended to either a complex auditory rhythm or a visually presented word list. Performance on a reproduction task was used to gauge whether participants were attending to the appropriate stimulus. We hypothesized that attention to complex rhythms – which contain no energy at the pulse frequency – would lead to activations in motor areas involved in pulse perception. Moreover, because multiple repetitions of a complex rhythm are needed to perceive a pulse, activations in pulse related areas would be seen only after sufficient time had elapsed for pulse perception to develop. Selective attention was also expected to modulate activity in sensory areas specific to the modality. We found that selective attention to rhythms led to increased BOLD responses in basal ganglia, and basal ganglia activity was observed only after the rhythms had cycled enough times for a stable pulse percept to develop. These observations suggest that attention is needed to recruit motor activations associated with the perception of pulse in complex rhythms. Moreover, attention to the auditory stimulus enhanced activity in an attentional sensory network including primary auditory, insula, anterior cingulate, and prefrontal cortex, and suppressed activity in sensory areas associated with attending to the visual stimulus.

  17. Encoding neural and synaptic functionalities in electron spin: A pathway to efficient neuromorphic computing

    Science.gov (United States)

    Sengupta, Abhronil; Roy, Kaushik

    2017-12-01

    Present day computers expend orders of magnitude more computational resources to perform various cognitive and perception related tasks that humans routinely perform every day. This has recently resulted in a seismic shift in the field of computation where research efforts are being directed to develop a neurocomputer that attempts to mimic the human brain by nanoelectronic components and thereby harness its efficiency in recognition problems. Bridging the gap between neuroscience and nanoelectronics, this paper attempts to provide a review of the recent developments in the field of spintronic device based neuromorphic computing. Description of various spin-transfer torque mechanisms that can be potentially utilized for realizing device structures mimicking neural and synaptic functionalities is provided. A cross-layer perspective extending from the device to the circuit and system level is presented to envision the design of an All-Spin neuromorphic processor enabled with on-chip learning functionalities. Device-circuit-algorithm co-simulation framework calibrated to experimental results suggest that such All-Spin neuromorphic systems can potentially achieve almost two orders of magnitude energy improvement in comparison to state-of-the-art CMOS implementations.

  18. Spatially pooled contrast responses predict neural and perceptual similarity of naturalistic image categories.

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    Iris I A Groen

    Full Text Available The visual world is complex and continuously changing. Yet, our brain transforms patterns of light falling on our retina into a coherent percept within a few hundred milliseconds. Possibly, low-level neural responses already carry substantial information to facilitate rapid characterization of the visual input. Here, we computationally estimated low-level contrast responses to computer-generated naturalistic images, and tested whether spatial pooling of these responses could predict image similarity at the neural and behavioral level. Using EEG, we show that statistics derived from pooled responses explain a large amount of variance between single-image evoked potentials (ERPs in individual subjects. Dissimilarity analysis on multi-electrode ERPs demonstrated that large differences between images in pooled response statistics are predictive of more dissimilar patterns of evoked activity, whereas images with little difference in statistics give rise to highly similar evoked activity patterns. In a separate behavioral experiment, images with large differences in statistics were judged as different categories, whereas images with little differences were confused. These findings suggest that statistics derived from low-level contrast responses can be extracted in early visual processing and can be relevant for rapid judgment of visual similarity. We compared our results with two other, well- known contrast statistics: Fourier power spectra and higher-order properties of contrast distributions (skewness and kurtosis. Interestingly, whereas these statistics allow for accurate image categorization, they do not predict ERP response patterns or behavioral categorization confusions. These converging computational, neural and behavioral results suggest that statistics of pooled contrast responses contain information that corresponds with perceived visual similarity in a rapid, low-level categorization task.

  19. Differentiation-Dependent Motility-Responses of Developing Neural Progenitors to Optogenetic Stimulation

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    Tímea Köhidi

    2017-12-01

    Full Text Available During neural tissue genesis, neural stem/progenitor cells are exposed to bioelectric stimuli well before synaptogenesis and neural circuit formation. Fluctuations in the electrochemical potential in the vicinity of developing cells influence the genesis, migration and maturation of neuronal precursors. The complexity of the in vivo environment and the coexistence of various progenitor populations hinder the understanding of the significance of ionic/bioelectric stimuli in the early phases of neuronal differentiation. Using optogenetic stimulation, we investigated the in vitro motility responses of radial glia-like neural stem/progenitor populations to ionic stimuli. Radial glia-like neural stem cells were isolated from CAGloxpStoploxpChR2(H134-eYFP transgenic mouse embryos. After transfection with Cre-recombinase, ChR2(channelrhodopsin-2-expressing and non-expressing cells were separated by eYFP fluorescence. Expression of light-gated ion channels were checked by patch clamp and fluorescence intensity assays. Neurogenesis by ChR2-expressing and non-expressing cells was induced by withdrawal of EGF from the medium. Cells in different (stem cell, migrating progenitor and maturing precursor stages of development were illuminated with laser light (λ = 488 nm; 1.3 mW/mm2; 300 ms in every 5 min for 12 h. The displacement of the cells was analyzed on images taken at the end of each light pulse. Results demonstrated that the migratory activity decreased with the advancement of neuronal differentiation regardless of stimulation. Light-sensitive cells, however, responded on a differentiation-dependent way. In non-differentiated ChR2-expressing stem cell populations, the motility did not change significantly in response to light-stimulation. The displacement activity of migrating progenitors was enhanced, while the motility of differentiating neuronal precursors was markedly reduced by illumination.

  20. Temperament and Parenting Styles in Early Childhood Differentially Influence Neural Response to Peer Evaluation in Adolescence

    OpenAIRE

    Guyer, Amanda E.; Jarcho, Johanna M.; Pérez-Edgar, Koraly; Degnan, Kathryn A.; Pine, Daniel S.; Fox, Nathan A.; Nelson, Eric E.

    2015-01-01

    Behavioral inhibition (BI) is a temperament characterized by social reticence and withdrawal from unfamiliar or novel contexts and conveys risk for social anxiety disorder. Developmental outcomes associated with this temperament can be influenced by children’s caregiving context. The convergence of a child’s temperamental disposition and rearing environment is ultimately expressed at both the behavioral and neural levels in emotional and cognitive response patterns to social challenges. The p...

  1. Maternal neural responses to infant cries and faces: relationships with substance use

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    Nicole eLandi

    2011-06-01

    Full Text Available Substance abuse in pregnant and recently postpartum women is a major public health concern because of effects on the infant and on the ability of the adult to care for the infant. In addition to the negative health effects of teratogenic substances on fetal development, substance use can contribute to difficulties associated with the social and behavioral aspects of parenting. Neural circuits associated with parenting behavior overlap with circuits involved in addiction (e.g., frontal, striatal and limbic systems and thus may be co-opted for the craving/reward cycle associated with substance use and abuse and be less available for parenting. The current study investigates the degree to which neural circuits associated with parenting are disrupted in mothers who are substance-using. Specifically, we used functional magnetic resonance imaging to examine the neural response to emotional infant cues (faces and cries in substance-using compared to non-using mothers. In response to both faces (of varying emotional valence and cries (of varying distress levels, substance-using mothers evidenced reduced neural activation in regions that have been previously implicated in reward and motivation as well as regions involved in cognitive control. Specifically, in response to faces, substance users showed reduced activation in prefrontal regions, including the dorsolateral and ventromedial prefrontal cortex, as well as visual processing (occipital lobes and limbic regions (parahippocampus and amygdala. Similarly, in response to infant cries substance-using mothers showed reduced activation relative to non-using mothers in prefrontal regions, auditory sensory processing regions, insula and limbic regions (parahippocampus and amygdala. These findings suggest that infant stimuli may be less salient for substance-using mothers, and such reduced saliency may impair developing infant-caregiver attachment and the ability of mothers to respond appropriately to their

  2. Effects of Acute Alcohol Intoxication on Empathic Neural Responses for Pain

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    Yang Hu

    2018-01-01

    Full Text Available The questions whether and how empathy for pain can be modulated by acute alcohol intoxication in the non-dependent population remain unanswered. To address these questions, a double-blind, placebo-controlled, within-subject study design was adopted in this study, in which healthy social drinkers were asked to complete a pain-judgment task using pictures depicting others' body parts in painful or non-painful situations during fMRI scanning, either under the influence of alcohol intoxication or placebo conditions. Empathic neural activity for pain was reduced by alcohol intoxication only in the dorsal anterior cingulate cortex (dACC. More interestingly, we observed that empathic neural activity for pain in the right anterior insula (rAI was significantly correlated with trait empathy only after alcohol intoxication, along with impaired functional connectivity between the rAI and the fronto-parietal attention network. Our results reveal that alcohol intoxication not only inhibits empathic neural responses for pain but also leads to trait empathy inflation, possibly via impaired top-down attentional control. These findings help to explain the neural mechanism underlying alcohol-related social problems.

  3. Infants' somatotopic neural responses to seeing human actions: I've got you under my skin.

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    Joni N Saby

    Full Text Available Human infants rapidly learn new skills and customs via imitation, but the neural linkages between action perception and production are not well understood. Neuroscience studies in adults suggest that a key component of imitation-identifying the corresponding body part used in the acts of self and other-has an organized neural signature. In adults, perceiving someone using a specific body part (e.g., hand vs. foot is associated with activation of the corresponding area of the sensory and/or motor strip in the observer's brain-a phenomenon called neural somatotopy. Here we examine whether preverbal infants also exhibit somatotopic neural responses during the observation of others' actions. 14-month-old infants were randomly assigned to watch an adult reach towards and touch an object using either her hand or her foot. The scalp electroencephalogram (EEG was recorded and event-related changes in the sensorimotor mu rhythm were analyzed. Mu rhythm desynchronization was greater over hand areas of sensorimotor cortex during observation of hand actions and was greater over the foot area for observation of foot actions. This provides the first evidence that infants' observation of someone else using a particular body part activates the corresponding areas of sensorimotor cortex. We hypothesize that this somatotopic organization in the developing brain supports imitation and cultural learning. The findings connect developmental cognitive neuroscience, adult neuroscience, action representation, and behavioral imitation.

  4. Tympanal mechanics and neural responses in the ears of a noctuid moth.

    Science.gov (United States)

    ter Hofstede, Hannah M; Goerlitz, Holger R; Montealegre-Z, Fernando; Robert, Daniel; Holderied, Marc W

    2011-12-01

    Ears evolved in many groups of moths to detect the echolocation calls of predatory bats. Although the neurophysiology of bat detection has been intensively studied in moths for decades, the relationship between sound-induced movement of the noctuid tympanic membrane and action potentials in the auditory sensory cells (A1 and A2) has received little attention. Using laser Doppler vibrometry, we measured the velocity and displacement of the tympanum in response to pure tone pulses for moths that were intact or prepared for neural recording. When recording from the auditory nerve, the displacement of the tympanum at the neural threshold remained constant across frequencies, whereas velocity varied with frequency. This suggests that the key biophysical parameter for triggering action potentials in the sensory cells of noctuid moths is tympanum displacement, not velocity. The validity of studies on the neurophysiology of moth hearing rests on the assumption that the dissection and recording procedures do not affect the biomechanics of the ear. There were no consistent differences in tympanal velocity or displacement when moths were intact or prepared for neural recordings for sound levels close to neural threshold, indicating that this and other neurophysiological studies provide good estimates of what intact moths hear at threshold.

  5. Differential neural responses to food images in women with bulimia versus anorexia nervosa.

    Directory of Open Access Journals (Sweden)

    Samantha J Brooks

    Full Text Available BACKGROUND: Previous fMRI studies show that women with eating disorders (ED have differential neural activation to viewing food images. However, despite clinical differences in their responses to food, differential neural activation to thinking about eating food, between women with anorexia nervosa (AN and bulimia nervosa (BN is not known. METHODS: We compare 50 women (8 with BN, 18 with AN and 24 age-matched healthy controls [HC] while they view food images during functional Magnetic Resonance Imaging (fMRI. RESULTS: In response to food (vs non-food images, women with BN showed greater neural activation in the visual cortex, right dorsolateral prefrontal cortex, right insular cortex and precentral gyrus, women with AN showed greater activation in the right dorsolateral prefrontal cortex, cerebellum and right precuneus. HC women activated the cerebellum, right insular cortex, right medial temporal lobe and left caudate. Direct comparisons revealed that compared to HC, the BN group showed relative deactivation in the bilateral superior temporal gyrus/insula, and visual cortex, and compared to AN had relative deactivation in the parietal lobe and dorsal posterior cingulate cortex, but greater activation in the caudate, superior temporal gyrus, right insula and supplementary motor area. CONCLUSIONS: Women with AN and BN activate top-down cognitive control in response to food images, yet women with BN have increased activation in reward and somatosensory regions, which might impinge on cognitive control over food consumption and binge eating.

  6. Enhanced neural response to anticipation, effort and consummation of reward and aversion during bupropion treatment.

    Science.gov (United States)

    Dean, Z; Horndasch, S; Giannopoulos, P; McCabe, C

    2016-08-01

    We have previously shown that the selective serotonergic reuptake inhibitor, citalopram, reduces the neural response to reward and aversion in healthy volunteers. We suggest that this inhibitory effect might underlie the emotional blunting reported by patients on these medications. Bupropion is a dopaminergic and noradrenergic reuptake inhibitor and has been suggested to have more therapeutic effects on reward-related deficits. However, how bupropion affects the neural responses to reward and aversion is unclear. Seventeen healthy volunteers (9 female, 8 male) received 7 days bupropion (150 mg/day) and 7 days placebo treatment, in a double-blind crossover design. Our functional magnetic resonance imaging task consisted of three phases; an anticipatory phase (pleasant or unpleasant cue), an effort phase (button presses to achieve a pleasant taste or to avoid an unpleasant taste) and a consummatory phase (pleasant or unpleasant tastes). Volunteers also rated wanting, pleasantness and intensity of the tastes. Relative to placebo, bupropion increased activity during the anticipation phase in the ventral medial prefrontal cortex (vmPFC) and caudate. During the effort phase, bupropion increased activity in the vmPFC, striatum, dorsal anterior cingulate cortex and primary motor cortex. Bupropion also increased medial orbitofrontal cortex, amygdala and ventral striatum activity during the consummatory phase. Our results are the first to show that bupropion can increase neural responses during the anticipation, effort and consummation of rewarding and aversive stimuli. This supports the notion that bupropion might be beneficial for depressed patients with reward-related deficits and blunted affect.

  7. NEURAL REACTIVITY TO REWARD AS A PREDICTOR OF COGNITIVE BEHAVIORAL THERAPY RESPONSE IN ANXIETY AND DEPRESSION.

    Science.gov (United States)

    Burkhouse, Katie L; Kujawa, Autumn; Kennedy, Amy E; Shankman, Stewart A; Langenecker, Scott A; Phan, K Luan; Klumpp, Heide

    2016-04-01

    Cognitive behavioral therapy (CBT) is a well-established treatment for anxiety and depression; however, response to CBT is heterogeneous across patients and many remain symptomatic after therapy, raising the need to identify prospective predictors for treatment planning. Altered neural processing of reward has been implicated in both depression and anxiety, and improving hedonic capacity is a goal of CBT. However, little is known about how neural response to reward relates to CBT outcomes in depression and anxiety. The current study used the reward positivity (RewP) event-related potential (ERP) component to examine whether neural reactivity to reward would predict CBT response in a sample of patients with anxiety without depression (n = 30) and comorbid anxiety and depression (CAD, n = 22). Participants completed a guessing reward ERP paradigm before completing 12 weeks of standard CBT. The majority of the sample (68%; 35 out of 52 patients) responded to treatment, and those with a reduced RewP at baseline were more likely to respond to treatment. A reduced RewP was also associated with a greater pre-to-post CBT reduction in depressive symptoms among individuals with CAD, but not among individuals with pure anxiety. CBT may be most beneficial in reducing depressive symptoms for individuals who demonstrate decreased reward reactivity prior to treatment. CBT may target reward brain function, leading to greater improvement in symptoms. These effects may be strongest, and therefore most meaningful, for individuals with reward-processing deficits prior to treatment. © 2016 Wiley Periodicals, Inc.

  8. Evidence of Rapid Modulation by Social Information of Subjective, Physiological, and Neural Responses to Emotional Expressions

    Directory of Open Access Journals (Sweden)

    Martial Mermillod

    2018-01-01

    Full Text Available Recent research suggests that conceptual or emotional factors could influence the perceptual processing of stimuli. In this article, we aimed to evaluate the effect of social information (positive, negative, or no information related to the character of the target on subjective (perceived and felt valence and arousal, physiological (facial mimicry as well as on neural (P100 and N170 responses to dynamic emotional facial expressions (EFE that varied from neutral to one of the six basic emotions. Across three studies, the results showed reduced ratings of valence and arousal of EFE associated with incongruent social information (Study 1, increased electromyographical responses (Study 2, and significant modulation of P100 and N170 components (Study 3 when EFE were associated with social (positive and negative information (vs. no information. These studies revealed that positive or negative social information reduces subjective responses to incongruent EFE and produces a similar neural and physiological boost of the early perceptual processing of EFE irrespective of their congruency. In conclusion, the article suggests that the presence of positive or negative social context modulates early physiological and neural activity preceding subsequent behavior.

  9. Differential Neural Responses to Food Images in Women with Bulimia versus Anorexia Nervosa

    Science.gov (United States)

    Brooks, Samantha J.; O′Daly, Owen G.; Uher, Rudolf; Friederich, Hans-Christoph; Giampietro, Vincent; Brammer, Michael; Williams, Steven C. R.; Schiöth, Helgi B.; Treasure, Janet; Campbell, Iain C.

    2011-01-01

    Background Previous fMRI studies show that women with eating disorders (ED) have differential neural activation to viewing food images. However, despite clinical differences in their responses to food, differential neural activation to thinking about eating food, between women with anorexia nervosa (AN) and bulimia nervosa (BN) is not known. Methods We compare 50 women (8 with BN, 18 with AN and 24 age-matched healthy controls [HC]) while they view food images during functional Magnetic Resonance Imaging (fMRI). Results In response to food (vs non-food) images, women with BN showed greater neural activation in the visual cortex, right dorsolateral prefrontal cortex, right insular cortex and precentral gyrus, women with AN showed greater activation in the right dorsolateral prefrontal cortex, cerebellum and right precuneus. HC women activated the cerebellum, right insular cortex, right medial temporal lobe and left caudate. Direct comparisons revealed that compared to HC, the BN group showed relative deactivation in the bilateral superior temporal gyrus/insula, and visual cortex, and compared to AN had relative deactivation in the parietal lobe and dorsal posterior cingulate cortex, but greater activation in the caudate, superior temporal gyrus, right insula and supplementary motor area. Conclusions Women with AN and BN activate top-down cognitive control in response to food images, yet women with BN have increased activation in reward and somatosensory regions, which might impinge on cognitive control over food consumption and binge eating. PMID:21799807

  10. Differential neural responses to food images in women with bulimia versus anorexia nervosa.

    Science.gov (United States)

    Brooks, Samantha J; O'Daly, Owen G; Uher, Rudolf; Friederich, Hans-Christoph; Giampietro, Vincent; Brammer, Michael; Williams, Steven C R; Schiöth, Helgi B; Treasure, Janet; Campbell, Iain C

    2011-01-01

    Previous fMRI studies show that women with eating disorders (ED) have differential neural activation to viewing food images. However, despite clinical differences in their responses to food, differential neural activation to thinking about eating food, between women with anorexia nervosa (AN) and bulimia nervosa (BN) is not known. We compare 50 women (8 with BN, 18 with AN and 24 age-matched healthy controls [HC]) while they view food images during functional Magnetic Resonance Imaging (fMRI). In response to food (vs non-food) images, women with BN showed greater neural activation in the visual cortex, right dorsolateral prefrontal cortex, right insular cortex and precentral gyrus, women with AN showed greater activation in the right dorsolateral prefrontal cortex, cerebellum and right precuneus. HC women activated the cerebellum, right insular cortex, right medial temporal lobe and left caudate. Direct comparisons revealed that compared to HC, the BN group showed relative deactivation in the bilateral superior temporal gyrus/insula, and visual cortex, and compared to AN had relative deactivation in the parietal lobe and dorsal posterior cingulate cortex, but greater activation in the caudate, superior temporal gyrus, right insula and supplementary motor area. Women with AN and BN activate top-down cognitive control in response to food images, yet women with BN have increased activation in reward and somatosensory regions, which might impinge on cognitive control over food consumption and binge eating.

  11. Spatiotemporal reconstruction of auditory steady-state responses to acoustic amplitude modulations: Potential sources beyond the auditory pathway.

    Science.gov (United States)

    Farahani, Ehsan Darestani; Goossens, Tine; Wouters, Jan; van Wieringen, Astrid

    2017-03-01

    Investigating the neural generators of auditory steady-state responses (ASSRs), i.e., auditory evoked brain responses, with a wide range of screening and diagnostic applications, has been the focus of various studies for many years. Most of these studies employed a priori assumptions regarding the number and location of neural generators. The aim of this study is to reconstruct ASSR sources with minimal assumptions in order to gain in-depth insight into the number and location of brain regions that are activated in response to low- as well as high-frequency acoustically amplitude modulated signals. In order to reconstruct ASSR sources, we applied independent component analysis with subsequent equivalent dipole modeling to single-subject EEG data (young adults, 20-30 years of age). These data were based on white noise stimuli, amplitude modulated at 4, 20, 40, or 80Hz. The independent components that exhibited a significant ASSR were clustered among all participants by means of a probabilistic clustering method based on a Gaussian mixture model. Results suggest that a widely distributed network of sources, located in cortical as well as subcortical regions, is active in response to 4, 20, 40, and 80Hz amplitude modulated noises. Some of these sources are located beyond the central auditory pathway. Comparison of brain sources in response to different modulation frequencies suggested that the identified brain sources in the brainstem, the left and the right auditory cortex show a higher responsiveness to 40Hz than to the other modulation frequencies. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Modulation of calcium-induced cell death in human neural stem cells by the novel peptidylarginine deiminase-AIF pathway.

    Science.gov (United States)

    U, Kin Pong; Subramanian, Venkataraman; Nicholas, Antony P; Thompson, Paul R; Ferretti, Patrizia

    2014-06-01

    PADs (peptidylarginine deiminases) are calcium-dependent enzymes that change protein-bound arginine to citrulline (citrullination/deimination) affecting protein conformation and function. PAD up-regulation following chick spinal cord injury has been linked to extensive tissue damage and loss of regenerative capability. Having found that human neural stem cells (hNSCs) expressed PAD2 and PAD3, we studied PAD function in these cells and investigated PAD3 as a potential target for neuroprotection by mimicking calcium-induced secondary injury responses. We show that PAD3, rather than PAD2 is a modulator of cell growth/death and that PAD activity is not associated with caspase-3-dependent cell death, but is required for AIF (apoptosis inducing factor)-mediated apoptosis. PAD inhibition prevents association of PAD3 with AIF and AIF cleavage required for its translocation to the nucleus. Finally, PAD inhibition also hinders calcium-induced cytoskeleton disassembly and association of PAD3 with vimentin, that we show to be associated also with AIF; together this suggests that PAD-dependent cytoskeleton disassembly may play a role in AIF translocation to the nucleus. This is the first study highlighting a role of PAD activity in balancing hNSC survival/death, identifying PAD3 as an important upstream regulator of calcium-induced apoptosis, which could be targeted to reduce neural loss, and shedding light on the mechanisms involved. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  13. Evidence from pupillometry and fMRI indicates reduced neural response during vicarious social pain but not physical pain in autism.

    Science.gov (United States)

    Krach, Sören; Kamp-Becker, Inge; Einhäuser, Wolfgang; Sommer, Jens; Frässle, Stefan; Jansen, Andreas; Rademacher, Lena; Müller-Pinzler, Laura; Gazzola, Valeria; Paulus, Frieder M

    2015-11-01

    Autism spectrum disorder (ASD) is characterized by substantial social deficits. The notion that dysfunctions in neural circuits involved in sharing another's affect explain these deficits is appealing, but has received only modest experimental support. Here we evaluated a complex paradigm on the vicarious social pain of embarrassment to probe social deficits in ASD as to whether it is more potent than paradigms currently in use. To do so we acquired pupillometry and fMRI in young adults with ASD and matched healthy controls. During a simple vicarious physical pain task no differences emerged between groups in behavior, pupillometry, and neural activation of the anterior insula (AIC) and anterior cingulate cortex (ACC). In contrast, processing complex vicarious social pain yielded reduced responses in ASD on all physiological measures of sharing another's affect. The reduced activity within the AIC was thereby explained by the severity of autistic symptoms in the social and affective domain. Additionally, behavioral responses lacked correspondence with the anterior cingulate and anterior insula cortex activity found in controls. Instead, behavioral responses in ASD were associated with hippocampal activity. The observed dissociation echoes the clinical observations that deficits in ASD are most pronounced in complex social situations and simple tasks may not probe the dysfunctions in neural pathways involved in sharing affect. Our results are highly relevant because individuals with ASD may have preserved abilities to share another's physical pain but still have problems with the vicarious representation of more complex emotions that matter in life. © 2015 Wiley Periodicals, Inc.

  14. Neural responsivity during soft drink intake, anticipation, and advertisement exposure in habitually consuming youth.

    Science.gov (United States)

    Burger, Kyle S; Stice, Eric

    2014-02-01

    Although soft drinks are heavily advertised, widely consumed, and have been associated with obesity, little is understood regarding neural responsivity to soft drink intake, anticipated intake, and advertisements. Functional MRI was used to assess examine neural response to carbonated soft drink intake, anticipated intake and advertisement exposure as well as milkshake intake in 27 adolescents that varied on soft drink consumer status. Intake and anticipated intake of carbonated Coke® activated regions implicated in gustatory, oral somatosensory, and reward processing, yet high-fat/sugar milkshake intake elicited greater activation in these regions vs. Coke intake. Advertisements highlighting the Coke product vs. nonfood control advertisements, but not the Coke logo, activated gustatory and visual brain regions. Habitual Coke consumers vs. nonconsumers showed greater posterior cingulate responsivity to Coke logo ads, suggesting that the logo is a conditioned cue. Coke consumers exhibited less ventrolateral prefrontal cortex responsivity during anticipated Coke intake relative to nonconsumers. Results indicate that soft drinks activate reward and gustatory regions, but are less potent in activating these regions than high-fat/sugar beverages, and imply that habitual soft drink intake promotes hyper-responsivity of regions encoding salience/attention toward brand specific cues and hypo-responsivity of inhibitory regions while anticipating intake. Copyright © 2013 The Obesity Society.

  15. Investigating the association between parity and the maternal neural response to infant cues.

    Science.gov (United States)

    Maupin, Angela N; Rutherford, Helena J V; Landi, Nicole; Potenza, Marc N; Mayes, Linda C

    2018-01-08

    Understanding the maternal neural response to infant affective cues has important implications for parent-child relationships. The current study employed event-related potentials (ERPs) to examine patterns in mothers' responses to infant affective cues, and evaluated the influence of maternal experience, defined by parity (i.e., the number of children a mother has) on ERP responses. Eighty-three mothers, three months postpartum, viewed photographs of displays of infant emotional faces (sad or happy) and listened to infant cries of different distress levels and a control tone. Maternal neural response was modulated by the emotional content of the auditory stimulus, as indexed by the N100 amplitude and latency. However, response to infant faces was not modulated by the emotional content of the stimuli as indexed by the N170. Neither N100 nor N170 were affected by parity. Maternal engagement with auditory stimuli, as indexed by the P300, was modulated by the emotional content of the cry and was affected by parity. A similar parity effect was observed for the P300 response to infant faces. Results suggest that parity may play an important role at later stages of maternal infant cue perception.

  16. Different neural and cognitive response to emotional faces in healthy monozygotic twins at risk of depression.

    Science.gov (United States)

    Miskowiak, K W; Glerup, L; Vestbo, C; Harmer, C J; Reinecke, A; Macoveanu, J; Siebner, H R; Kessing, L V; Vinberg, M

    2015-05-01

    Negative cognitive bias and aberrant neural processing of emotional faces are trait-marks of depression. Yet it is unclear whether these changes constitute an endophenotype for depression and are also present in healthy individuals with hereditary risk for depression. Thirty healthy, never-depressed monozygotic (MZ) twins with a co-twin history of depression (high risk group: n = 13) or without co-twin history of depression (low-risk group: n = 17) were enrolled in a functional magnetic resonance imaging (fMRI) study. During fMRI, participants viewed fearful and happy faces while performing a gender discrimination task. After the scan, they were given a faces dot-probe task, a facial expression recognition task and questionnaires assessing mood, personality traits and coping strategies. High-risk twins showed increased neural response to happy and fearful faces in dorsal anterior cingulate cortex (ACC), dorsomedial prefrontal cortex (dmPFC), pre-supplementary motor area and occipito-parietal regions compared to low-risk twins. They also displayed stronger negative coupling between amygdala and pregenual ACC, dmPFC and temporo-parietal regions during emotional face processing. These task-related changes in neural responses in high-risk twins were accompanied by impaired gender discrimination performance during face processing. They also displayed increased attention vigilance for fearful faces and were slower at recognizing facial expressions relative to low-risk controls. These effects occurred in the absence of differences between groups in mood, subjective state or coping. Different neural response and functional connectivity within fronto-limbic and occipito-parietal regions during emotional face processing and enhanced fear vigilance may be key endophenotypes for depression.

  17. kMEn: analyzing noisy and bidirectional transcriptional pathway responses in single subjects

    Science.gov (United States)

    Li, Qike; Schissler, A. Grant; Gardeux, Vincent; Berghout, Joanne; Achour, Ikbel; Kenost, Colleen

    2017-01-01

    Motivation Understanding dynamic, patient-level transcriptomic response to therapy is an important step forward for precision medicine. However, conventional transcriptome analysis aims to discover cohort-level change, lacking the capacity to unveil patient-specific response to therapy. To address this gap, we previously developed two N-of-1-pathways methods, Wilcoxon and Mahalanobis distance, to detect unidirectionally responsive transcripts within a pathway using a pair of samples from a single subject. Yet, these methods cannot recognize bidirectionally (up and down) responsive pathways. Further, our previous approaches have not been assessed in presence of background noise and are not designed to identify differentially expressed mRNAs between two samples of a patient taken in different contexts (e.g. cancer vs non cancer), which we termed responsive transcripts (RTs). Methods We propose a new N-of-1-pathways method, k-Means Enrichment (kMEn), that detects bidirection-ally responsive pathways, despite background noise, using a pair of transcriptomes from a single patient. kMEn identifies transcripts responsive to the stimulus through k-means clustering and then tests for an over-representation of the responsive genes within each pathway. The pathways identified by kMEn are mechanistically interpretable pathways significantly responding to a stimulus. Results In ~9000 simulations varying six parameters, superior performance of kMEn over previous single-subject methods is evident by: i) improved precision-recall at various levels of bidirectional response and ii) lower rates of false positives (1-specificity) when more than 10% of genes in the genome are differentially expressed (background noise). In a clinical proof-of-concept, personal treatment-specific pathways identified by kMEn correlate with therapeutic response (p-valuesingle-subject transcriptome dynamics of bidirectionally-regulated signals, kMEn provides a novel approach to identify mechanism

  18. A common oxytocin receptor gene (OXTR) polymorphism modulates intranasal oxytocin effects on the neural response to social cooperation in humans

    National Research Council Canada - National Science Library

    Feng, C; Lori, A; Waldman, I. D; Binder, E. B; Haroon, E; Rilling, J. K

    2015-01-01

    .... However, OT effects are often heterogeneous across individuals. Here we explore individual differences in OT effects on the neural response to social cooperation as a function of the rs53576 polymorphism of the oxytocin receptor gene ( OXTR...

  19. NEURAL PAIN PATHWAY TRACING OF RABBIT ISCHEMIC HEART BY DOUBLE-RETROGRADE NEUROTRACING

    Directory of Open Access Journals (Sweden)

    Theodorus Dapamede

    2015-01-01

    Full Text Available Background. Myocardial ischaemia occurs due to inadequate supply of oxygen to fulfill the myocardial tissue oxygen demand. This leads to angina pectoris or referred pain, whichhappens because of the inability of the brain to distinguish the visceral afferent inputs from the somatic afferent inputs since they run along a common pathway via the dorsal root ganglia. Aims. This study aims to distinguish specific areas of the rabbit heart that are projected to specific dorsal root ganglia, which then associates to its specific dermatomes. Methods. A double-retrograde neurotracing method was used, with True Blue and Nuclear Yellow as the neurotracers. Rabbits were divided into 3 groups, which the first and second groups were ligated at the left anterior descending artery and at the left circumflex artery, respectively.The third group acted as the control group, without ligation.True blue was injected at ischaemic sites following ligation. Nuclear yellowwas injected at the skin, dermatomes T1-T4. Dorsal root ganglia levels T1-T4 were then examined for both neurotracers at 3 days post injection. Results. There is significant association between the site of ligation to the projection of the neurotracers at specific dorsal root ganglia (p<0.05. The first group showed high tendency to be projected to T2 and the second group showed a high tendency to project to T1. Conclusion. This study shows that the rabbit heart can be specifically projected neuronally to specific dorsal root ganglia, following coronary artery ligation.

  20. Nitrosative Stress, Hypernitrosylation, and Autoimmune Responses to Nitrosylated Proteins: New Pathways in Neuroprogressive Disorders Including Depression and Chronic Fatigue Syndrome.

    Science.gov (United States)

    Morris, Gerwyn; Berk, Michael; Klein, Hans; Walder, Ken; Galecki, Piotr; Maes, Michael

    2017-08-01

    Nitric oxide plays an indispensable role in modulating cellular signaling and redox pathways. This role is mainly effected by the readily reversible nitrosylation of selective protein cysteine thiols. The reversibility and sophistication of this signaling system is enabled and regulated by a number of enzymes which form part of the thioredoxin, glutathione, and pyridoxine antioxidant systems. Increases in nitric oxide levels initially lead to a defensive increase in the number of nitrosylated proteins in an effort to preserve their function. However, in an environment of chronic oxidative and nitrosative stress (O&NS), nitrosylation of crucial cysteine groups within key enzymes of the thioredoxin, glutathione, and pyridoxine systems leads to their inactivation thereby disabling denitrosylation and transnitrosylation and subsequently a state described as "hypernitrosylation." This state leads to the development of pathology in multiple domains such as the inhibition of enzymes of the electron transport chain, decreased mitochondrial function, and altered conformation of proteins and amino acids leading to loss of immune tolerance and development of autoimmunity. Hypernitrosylation also leads to altered function or inactivation of proteins involved in the regulation of apoptosis, autophagy, proteomic degradation, transcription factor activity, immune-inflammatory pathways, energy production, and neural function and survival. Hypernitrosylation, as a consequence of chronically elevated O&NS and activated immune-inflammatory pathways, can explain many characteristic abnormalities observed in neuroprogressive disease including major depression and chronic fatigue syndrome/myalgic encephalomyelitis. In those disorders, increased bacterial translocation may drive hypernitrosylation and autoimmune responses against nitrosylated proteins.

  1. Antipsychotic dose modulates behavioral and neural responses to feedback during reinforcement learning in schizophrenia.

    Science.gov (United States)

    Insel, Catherine; Reinen, Jenna; Weber, Jochen; Wager, Tor D; Jarskog, L Fredrik; Shohamy, Daphna; Smith, Edward E

    2014-03-01

    Schizophrenia is characterized by an abnormal dopamine system, and dopamine blockade is the primary mechanism of antipsychotic treatment. Consistent with the known role of dopamine in reward processing, prior research has demonstrated that patients with schizophrenia exhibit impairments in reward-based learning. However, it remains unknown how treatment with antipsychotic medication impacts the behavioral and neural signatures of reinforcement learning in schizophrenia. The goal of this study was to examine whether antipsychotic medication modulates behavioral and neural responses to prediction error coding during reinforcement learning. Patients with schizophrenia completed a reinforcement learning task while undergoing functional magnetic resonance imaging. The task consisted of two separate conditions in which participants accumulated monetary gain or avoided monetary loss. Behavioral results indicated that antipsychotic medication dose was associated with altered behavioral approaches to learning, such that patients taking higher doses of medication showed increased sensitivity to negative reinforcement. Higher doses of antipsychotic medication were also associated with higher learning rates (LRs), suggesting that medication enhanced sensitivity to trial-by-trial feedback. Neuroimaging data demonstrated that antipsychotic dose was related to differences in neural signatures of feedback prediction error during the loss condition. Specifically, patients taking higher doses of medication showed attenuated prediction error responses in the striatum and the medial prefrontal cortex. These findings indicate that antipsychotic medication treatment may influence motivational processes in patients with schizophrenia.

  2. Asymmetries in behavioral and neural responses to spectral cues demonstrate the generality of auditory looming bias

    Science.gov (United States)

    Reed, Darrin K.; Tóth, Brigitta; Best, Virginia; Majdak, Piotr; Colburn, H. Steven; Shinn-Cunningham, Barbara

    2017-01-01

    Studies of auditory looming bias have shown that sources increasing in intensity are more salient than sources decreasing in intensity. Researchers have argued that listeners are more sensitive to approaching sounds compared with receding sounds, reflecting an evolutionary pressure. However, these studies only manipulated overall sound intensity; therefore, it is unclear whether looming bias is truly a perceptual bias for changes in source distance, or only in sound intensity. Here we demonstrate both behavioral and neural correlates of looming bias without manipulating overall sound intensity. In natural environments, the pinnae induce spectral cues that give rise to a sense of externalization; when spectral cues are unnatural, sounds are perceived as closer to the listener. We manipulated the contrast of individually tailored spectral cues to create sounds of similar intensity but different naturalness. We confirmed that sounds were perceived as approaching when spectral contrast decreased, and perceived as receding when spectral contrast increased. We measured behavior and electroencephalography while listeners judged motion direction. Behavioral responses showed a looming bias in that responses were more consistent for sounds perceived as approaching than for sounds perceived as receding. In a control experiment, looming bias disappeared when spectral contrast changes were discontinuous, suggesting that perceived motion in distance and not distance itself was driving the bias. Neurally, looming bias was reflected in an asymmetry of late event-related potentials associated with motion evaluation. Hence, both our behavioral and neural findings support a generalization of the auditory looming bias, representing a perceptual preference for approaching auditory objects. PMID:28827336

  3. Asymmetries in behavioral and neural responses to spectral cues demonstrate the generality of auditory looming bias.

    Science.gov (United States)

    Baumgartner, Robert; Reed, Darrin K; Tóth, Brigitta; Best, Virginia; Majdak, Piotr; Colburn, H Steven; Shinn-Cunningham, Barbara

    2017-09-05

    Studies of auditory looming bias have shown that sources increasing in intensity are more salient than sources decreasing in intensity. Researchers have argued that listeners are more sensitive to approaching sounds compared with receding sounds, reflecting an evolutionary pressure. However, these studies only manipulated overall sound intensity; therefore, it is unclear whether looming bias is truly a perceptual bias for changes in source distance, or only in sound intensity. Here we demonstrate both behavioral and neural correlates of looming bias without manipulating overall sound intensity. In natural environments, the pinnae induce spectral cues that give rise to a sense of externalization; when spectral cues are unnatural, sounds are perceived as closer to the listener. We manipulated the contrast of individually tailored spectral cues to create sounds of similar intensity but different naturalness. We confirmed that sounds were perceived as approaching when spectral contrast decreased, and perceived as receding when spectral contrast increased. We measured behavior and electroencephalography while listeners judged motion direction. Behavioral responses showed a looming bias in that responses were more consistent for sounds perceived as approaching than for sounds perceived as receding. In a control experiment, looming bias disappeared when spectral contrast changes were discontinuous, suggesting that perceived motion in distance and not distance itself was driving the bias. Neurally, looming bias was reflected in an asymmetry of late event-related potentials associated with motion evaluation. Hence, both our behavioral and neural findings support a generalization of the auditory looming bias, representing a perceptual preference for approaching auditory objects.

  4. Aβ-Induced Insulin Resistance and the Effects of Insulin on the Cholesterol Synthesis Pathway and Aβ Secretion in Neural Cells.

    Science.gov (United States)

    Najem, Dema; Bamji-Mirza, Michelle; Yang, Ze; Zhang, Wandong

    2016-06-01

    Alzheimer's disease (AD) is characterized by amyloid-β (Aβ) toxicity, tau pathology, insulin resistance, neuroinflammation, and dysregulation of cholesterol homeostasis, all of which play roles in neurodegeneration. Insulin has polytrophic effects on neurons and may be at the center of these pathophysiological changes. In this study, we investigated possible relationships among insulin signaling and cholesterol biosynthesis, along with the effects of Aβ42 on these pathways in vitro. We found that neuroblastoma 2a (N2a) cells transfected with the human gene encoding amyloid-β protein precursor (AβPP) (N2a-AβPP) produced Aβ and exhibited insulin resistance by reduced p-Akt and a suppressed cholesterol-synthesis pathway following insulin treatment, and by increased phosphorylation of insulin receptor subunit-1 at serine 612 (p-IRS-S612) as compared to parental N2a cells. Treatment of human neuroblastoma SH-SY5Y cells with Aβ42 also increased p-IRS-S612, suggesting that Aβ42 is responsible for insulin resistance. The insulin resistance was alleviated when N2a-AβPP cells were treated with higher insulin concentrations. Insulin increased Aβ release from N2a-AβPP cells, by which it may promote Aβ clearance. Insulin increased cholesterol-synthesis gene expression in SH-SY5Y and N2a cells, including 24-dehydrocholesterol reductase (DHCR24) and 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR) through sterol-regulatory element-binding protein-2 (SREBP2). While Aβ42-treated SH-SY5Y cells exhibited increased HMGCR expression and c-Jun phosphorylation as pro-inflammatory responses, they also showed down-regulation of neuro-protective/anti-inflammatory DHCR24. These results suggest that Aβ42 may cause insulin resistance, activate JNK for c-Jun phosphorylation, and lead to dysregulation of cholesterol homeostasis, and that enhancing insulin signaling may relieve the insulin-resistant phenotype and the dysregulated cholesterol-synthesis pathway to promote A

  5. Dynamic emotional and neural responses to music depend on performance expression and listener experience.

    Science.gov (United States)

    Chapin, Heather; Jantzen, Kelly; Kelso, J A Scott; Steinberg, Fred; Large, Edward

    2010-12-16

    Apart from its natural relevance to cognition, music provides a window into the intimate relationships between production, perception, experience, and emotion. Here, emotional responses and neural activity were observed as they evolved together with stimulus parameters over several minutes. Participants listened to a skilled music performance that included the natural fluctuations in timing and sound intensity that musicians use to evoke emotional responses. A mechanical performance of the same piece served as a control. Before and after fMRI scanning, participants reported real-time emotional responses on a 2-dimensional rating scale (arousal and valence) as they listened to each performance. During fMRI scanning, participants listened without reporting emotional responses. Limbic and paralimbic brain areas responded to the expressive dynamics of human music performance, and both emotion and reward related activations during music listening were dependent upon musical training. Moreover, dynamic changes in timing predicted ratings of emotional arousal, as well as real-time changes in neural activity. BOLD signal changes correlated with expressive timing fluctuations in cortical and subcortical motor areas consistent with pulse perception, and in a network consistent with the human mirror neuron system. These findings show that expressive music performance evokes emotion and reward related neural activations, and that music's affective impact on the brains of listeners is altered by musical training. Our observations are consistent with the idea that music performance evokes an emotional response through a form of empathy that is based, at least in part, on the perception of movement and on violations of pulse-based temporal expectancies.

  6. Neural substrates of treatment response to cognitive-behavioral therapy in panic disorder with agoraphobia.

    Science.gov (United States)

    Lueken, Ulrike; Straube, Benjamin; Konrad, Carsten; Wittchen, Hans-Ulrich; Ströhle, Andreas; Wittmann, André; Pfleiderer, Bettina; Uhlmann, Christina; Arolt, Volker; Jansen, Andreas; Kircher, Tilo

    2013-11-01

    Although exposure-based cognitive-behavioral therapy (CBT) is an effective treatment option for panic disorder with agoraphobia, the neural substrates of treatment response remain unknown. Evidence suggests that panic disorder with agoraphobia is characterized by dysfunctional safety signal processing. Using fear conditioning as a neurofunctional probe, the authors investigated neural baseline characteristics and neuroplastic changes after CBT that were associated with treatment outcome in patients with panic disorder with agoraphobia. Neural correlates of fear conditioning and extinction were measured using functional MRI before and after a manualized CBT program focusing on behavioral exposure in 49 medication-free patients with a primary diagnosis of panic disorder with agoraphobia. Treatment response was defined as a reduction exceeding 50% in Hamilton Anxiety Rating Scale scores. At baseline, nonresponders exhibited enhanced activation in the right pregenual anterior cingulate cortex, the hippocampus, and the amygdala in response to a safety signal. While this activation pattern partly resolved in nonresponders after CBT, successful treatment was characterized by increased right hippocampal activation when processing stimulus contingencies. Treatment response was associated with an inhibitory functional coupling between the anterior cingulate cortex and the amygdala that did not change over time. This study identified brain activation patterns associated with treatment response in patients with panic disorder with agoraphobia. Altered safety signal processing and anterior cingulate cortex-amygdala coupling may indicate individual differences among these patients that determine the effectiveness of exposure-based CBT and associated neuroplastic changes. Findings point to brain networks by which successful CBT in this patient population is mediated.

  7. Dynamic emotional and neural responses to music depend on performance expression and listener experience.

    Directory of Open Access Journals (Sweden)

    Heather Chapin

    2010-12-01

    Full Text Available Apart from its natural relevance to cognition, music provides a window into the intimate relationships between production, perception, experience, and emotion. Here, emotional responses and neural activity were observed as they evolved together with stimulus parameters over several minutes. Participants listened to a skilled music performance that included the natural fluctuations in timing and sound intensity that musicians use to evoke emotional responses. A mechanical performance of the same piece served as a control. Before and after fMRI scanning, participants reported real-time emotional responses on a 2-dimensional rating scale (arousal and valence as they listened to each performance. During fMRI scanning, participants listened without reporting emotional responses. Limbic and paralimbic brain areas responded to the expressive dynamics of human music performance, and both emotion and reward related activations during music listening were dependent upon musical training. Moreover, dynamic changes in timing predicted ratings of emotional arousal, as well as real-time changes in neural activity. BOLD signal changes correlated with expressive timing fluctuations in cortical and subcortical motor areas consistent with pulse perception, and in a network consistent with the human mirror neuron system. These findings show that expressive music performance evokes emotion and reward related neural activations, and that music's affective impact on the brains of listeners is altered by musical training. Our observations are consistent with the idea that music performance evokes an emotional response through a form of empathy that is based, at least in part, on the perception of movement and on violations of pulse-based temporal expectancies.

  8. Neural Reactivity to Angry Faces Predicts Treatment Response in Pediatric Anxiety.

    Science.gov (United States)

    Bunford, Nora; Kujawa, Autumn; Fitzgerald, Kate D; Swain, James E; Hanna, Gregory L; Koschmann, Elizabeth; Simpson, David; Connolly, Sucheta; Monk, Christopher S; Phan, K Luan

    2017-02-01

    Although cognitive-behavioral psychotherapy (CBT) and pharmacotherapy are evidence-based treatments for pediatric anxiety, many youth with anxiety disorders fail to respond to these treatments. Given limitations of clinical measures in predicting treatment response, identifying neural predictors is timely. In this study, 35 anxious youth (ages 7-19 years) completed an emotional face-matching task during which the late positive potential (LPP), an event-related potential (ERP) component that indexes sustained attention towards emotional stimuli, was measured. Following the ERP measurement, youth received CBT or selective serotonin reuptake inhibitor (SSRI) treatment, and the LPP was examined as a predictor of treatment response. Findings indicated that, accounting for pre-treatment anxiety severity, neural reactivity to emotional faces predicted anxiety severity post- CBT and SSRI treatment such that enhanced electrocortical response to angry faces was associated with better treatment response. An enhanced LPP to angry faces may predict treatment response insofar as it may reflect greater emotion dysregulation or less avoidance and/or enhanced engagement with environmental stimuli in general, including with treatment.

  9. Neural Network Model Of The PXIE RFQ Cooling System and Resonant Frequency Response

    Energy Technology Data Exchange (ETDEWEB)

    Edelen, Auralee [Fermilab; Biedron, Sandra [Colorado State U., Fort Collins; Bowring, Daniel [Fermilab; Chase, Brian [Fermilab; Edelen, Jonathan [Fermilab; Milton, Stephen [Colorado State U., Fort Collins; Steimel, Jim [Fermilab

    2016-06-01

    As part of the PIP-II Injector Experiment (PXIE) accel-erator, a four-vane radio frequency quadrupole (RFQ) accelerates a 30-keV, 1-mA to 10-mA H' ion beam to 2.1 MeV. It is designed to operate at a frequency of 162.5 MHz with arbitrary duty factor, including continuous wave (CW) mode. The resonant frequency is controlled solely by a water-cooling system. We present an initial neural network model of the RFQ frequency response to changes in the cooling system and RF power conditions during pulsed operation. A neural network model will be used in a model predictive control scheme to regulate the resonant frequency of the RFQ.

  10. Neural responses to multimodal ostensive signals in 5-month-old infants.

    Directory of Open Access Journals (Sweden)

    Eugenio Parise

    Full Text Available Infants' sensitivity to ostensive signals, such as direct eye contact and infant-directed speech, is well documented in the literature. We investigated how infants interpret such signals by assessing common processing mechanisms devoted to them and by measuring neural responses to their compounds. In Experiment 1, we found that ostensive signals from different modalities display overlapping electrophysiological activity in 5-month-old infants, suggesting that these signals share neural processing mechanisms independently of their modality. In Experiment 2, we found that the activation to ostensive signals from different modalities is not additive to each other, but rather reflects the presence of ostension in either stimulus stream. These data support the thesis that ostensive signals obligatorily indicate to young infants that communication is directed to them.

  11. Melodic pitch expectation interacts with neural responses to syntactic but not semantic violations.

    Science.gov (United States)

    Carrus, Elisa; Pearce, Marcus T; Bhattacharya, Joydeep

    2013-09-01

    Current behavioural and electrophysiological evidence suggests that music and language syntactic processing depends on at least partly shared neural resources. Existing studies using a simultaneous presentation paradigm are limited to the effects of violations of harmonic structure in Western tonal music on processing of single syntactic or semantic violations. Because melody is a universal property of music as it is emphasized also by non-western musical traditions, it is fundamental to investigate interactions between melodic expectation and language processing. The present study investigates the effect of melodically unexpected notes on neural responses elicited by linguistic violations. Sentences with or without a violation in the last word were presented on screen simultaneously with melodies whose last note had a high- or low-probability, as estimated by a computational model of melodic expectation. Violations in language could be syntactic, semantic or combined. The electroencephalogram (EEG) was recorded while participants occasionally responded to language stimuli. Confirming previous studies, low-probability notes elicited an enhanced N1 compared to high-probability notes. Further, syntactic violations elicited a left anterior negativity (LAN) and P600 component, and semantic violations elicited an N400. Combined violations elicited components which resembled neural responses to both syntactic and semantic incongruities. The LAN amplitude was decreased when language syntactic violations were presented simultaneously with low-probability notes compared to when they were presented with high-probability notes. The N400 was not influenced by the note-probability. These findings show support for the neural interaction between language and music processing, including novel evidence for melodic processing which can be incorporated in a computational framework of melodic expectation. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. AICAR induces astroglial differentiation of neural stem cells via activating the JAK/STAT3 pathway independently of AMP-activated protein kinase.

    Science.gov (United States)

    Zang, Yi; Yu, Li-Fang; Pang, Tao; Fang, Lei-Ping; Feng, Xu; Wen, Tie-Qiao; Nan, Fa-Jun; Feng, Lin-Yin; Li, Jia

    2008-03-07

    Neural stem cell differentiation and the determination of lineage decision between neuronal and glial fates have important implications in the study of developmental, pathological, and regenerative processes. Although small molecule chemicals with the ability to control neural stem cell fate are considered extremely useful tools in this field, few were reported. AICAR is an adenosine analog and extensively used to activate AMP-activated protein kinase (AMPK), a metabolic "fuel gauge" of the biological system. In the present study, we found an unrecognized astrogliogenic activity of AICAR on not only immortalized neural stem cell line C17.2 (C17.2-NSC), but also primary neural stem cells (NSCs) derived from post-natal (P0) rat hippocampus (P0-NSC) and embryonic day 14 (E14) rat embryonic cortex (E14-NSC). However, another AMPK activator, Metformin, did not alter either the C17.2-NSC or E14-NSC undifferentiated state although both Metformin and AICAR can activate the AMPK pathway in NSC. Furthermore, overexpression of dominant-negative mutants of AMPK in C17.2-NSC was unable to block the gliogenic effects of AICAR. We also found AICAR could activate the Janus kinase (JAK) STAT3 pathway in both C17.2-NSC and E14-NSC but Metformin fails. JAK inhibitor I abolished the gliogenic effects of AICAR. Taken together, these results suggest that the astroglial differentiation effect of AICAR on neural stem cells was acting independently of AMPK and that the JAK-STAT3 pathway is essential for the gliogenic effect of AICAR.

  13. Inverted Encoding Models of Human Population Response Conflate Noise and Neural Tuning Width.

    Science.gov (United States)

    Liu, Taosheng; Cable, Dylan; Gardner, Justin L

    2018-01-10

    Channel-encoding models offer the ability to bridge different scales of neuronal measurement by interpreting population responses, typically measured with BOLD imaging in humans, as linear sums of groups of neurons (channels) tuned for visual stimulus properties. Inverting these models to form predicted channel responses from population measurements in humans seemingly offers the potential to infer neuronal tuning properties. Here, we test the ability to make inferences about neural tuning width from inverted encoding models. We examined contrast invariance of orientation selectivity in human V1 (both sexes) and found that inverting the encoding model resulted in channel response functions that became broader with lower contrast, thus apparently violating contrast invariance. Simulations showed that this broadening could be explained by contrast-invariant single-unit tuning with the measured decrease in response amplitude at lower contrast. The decrease in response lowers the signal-to-noise ratio of population responses that results in poorer population representation of orientation. Simulations further showed that increasing signal to noise makes channel response functions less sensitive to underlying neural tuning width, and in the limit of zero noise will reconstruct the channel function assumed by the model regardless of the bandwidth of single units. We conclude that our data are consistent with contrast-invariant orientation tuning in human V1. More generally, our results demonstrate that population selectivity measures obtained by encoding models can deviate substantially from the behavior of single units because they conflate neural tuning width and noise and are therefore better used to estimate the uncertainty of decoded stimulus properties.SIGNIFICANCE STATEMENT It is widely recognized that perceptual experience arises from large populations of neurons, rather than a few single units. Yet, much theory and experiment have examined links between single

  14. Neural cell adhesion molecule-stimulated neurite outgrowth depends on activation of protein kinase C and the Ras-mitogen-activated protein kinase pathway

    DEFF Research Database (Denmark)

    Kolkova, K; Novitskaya, V; Pedersen, N

    2000-01-01

    The signal transduction pathways associated with neural cell adhesion molecule (NCAM)-induced neuritogenesis are only partially characterized. We here demonstrate that NCAM-induced neurite outgrowth depends on activation of p59(fyn), focal adhesion kinase (FAK), phospholipase Cgamma (PLCgamma......), protein kinase C (PKC), and the Ras-mitogen-activated protein (MAP) kinase pathway. This was done using a coculture system consisting of PC12-E2 cells grown on fibroblasts, with or without NCAM expression, allowing NCAM-NCAM interactions resulting in neurite outgrowth. PC12-E2 cells were transiently...... propose a model of NCAM signaling involving two pathways: NCAM-Ras-MAP kinase and NCAM-FGF receptor-PLCgamma-PKC, and we propose that PKC serves as the link between the two pathways activating Raf and thereby creating the sustained activity of the MAP kinases necessary for neuronal differentiation....

  15. Altered neural activation during prepotent response inhibition in breast cancer survivors treated with chemotherapy: an fMRI study.

    Science.gov (United States)

    Kam, Julia W Y; Boyd, Lara A; Hsu, Chun L; Liu-Ambrose, Teresa; Handy, Todd C; Lim, Howard J; Hayden, Sherri; Campbell, Kristin L

    2016-09-01

    While impairments in executive functions have been reported in breast cancer survivors (BCS) who have undergone adjuvant chemotherapy, only a limited number of functional neuroimaging studies have associated alterations in cerebral activity with executive functions deficits in BCS. Using fMRI, the current study assessed the neural basis underlying a specific facet of executive function, namely prepotent response inhibition. 12 BCS who self-reported cognitive problems up to 3 years following cancer treatment and 12 female healthy comparisons (HC) performed the Stroop task. We compared their neural activation between the incongruent and neutral experimental conditions. Relative to the HC group, BCS showed lower blood-oxygen level dependent signal in several frontal regions, including the anterior cingulate cortex, a region critical for response inhibition. Our data indicates reduced neural activation in BCS during a prepotent response inhibition task, providing support for the prevailing notion of neural alterations observed in BCS treated with chemotherapy.

  16. Artificial Neural Network-Based Early-Age Concrete Strength Monitoring Using Dynamic Response Signals.

    Science.gov (United States)

    Kim, Junkyeong; Lee, Chaggil; Park, Seunghee

    2017-06-07

    Concrete is one of the most common materials used to construct a variety of civil infrastructures. However, since concrete might be susceptible to brittle fracture, it is essential to confirm the strength of concrete at the early-age stage of the curing process to prevent unexpected collapse. To address this issue, this study proposes a novel method to estimate the early-age strength of concrete, by integrating an artificial neural network algorithm with a dynamic response measurement of the concrete material. The dynamic response signals of the concrete, including both electromechanical impedances and guided ultrasonic waves, are obtained from an embedded piezoelectric sensor module. The cross-correlation coefficient of the electromechanical impedance signals and the amplitude of the guided ultrasonic wave signals are selected to quantify the variation in dynamic responses according to the strength of the concrete. Furthermore, an artificial neural network algorithm is used to verify a relationship between the variation in dynamic response signals and concrete strength. The results of an experimental study confirm that the proposed approach can be effectively applied to estimate the strength of concrete material from the early-age stage of the curing process.

  17. Psychological, endocrine and neural responses to social evaluation in subclinical depression.

    Science.gov (United States)

    Dedovic, Katarina; Duchesne, Annie; Engert, Veronika; Lue, Sonja Damika; Andrews, Julie; Efanov, Simona I; Beaudry, Thomas; Pruessner, Jens C

    2014-10-01

    This study aimed to identify vulnerability patterns in psychological, physiological and neural responses to mild psychosocial challenge in a population that is at a direct risk of developing depression, but who has not as yet succumbed to the full clinical syndrome. A group of healthy and a group of subclinically depressed participants underwent a modified Montreal Imaging Stress task (MIST), a mild neuroimaging psychosocial task and completed state self-esteem and mood measures. Cortisol levels were assessed throughout the session. All participants showed a decrease in performance self-esteem levels following the MIST. Yet, the decline in performance self-esteem levels was associated with increased levels of anxiety and confusion in the healthy group, but increased levels of depression in the subclinical group, following the MIST. The subclinical group showed overall lower cortisol levels compared with the healthy group. The degree of change in activity in the subgenual anterior cingulate cortex in response to negative evaluation was associated with increased levels of depression in the whole sample. Findings suggest that even in response to a mild psychosocial challenge, those individuals vulnerable to depression already show important maladaptive response patterns at psychological and neural levels. The findings point to important targets for future interventions. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  18. Temperament and Parenting Styles in Early Childhood Differentially Influence Neural Response to Peer Evaluation in Adolescence.

    Science.gov (United States)

    Guyer, Amanda E; Jarcho, Johanna M; Pérez-Edgar, Koraly; Degnan, Kathryn A; Pine, Daniel S; Fox, Nathan A; Nelson, Eric E

    2015-07-01

    Behavioral inhibition (BI) is a temperament characterized by social reticence and withdrawal from unfamiliar or novel contexts and conveys risk for social anxiety disorder. Developmental outcomes associated with this temperament can be influenced by children's caregiving context. The convergence of a child's temperamental disposition and rearing environment is ultimately expressed at both the behavioral and neural levels in emotional and cognitive response patterns to social challenges. The present study used functional neuroimaging to assess the moderating effects of different parenting styles on neural response to peer rejection in two groups of adolescents characterized by their early childhood temperament (M(age) = 17.89 years, N = 39, 17 males, 22 females; 18 with BI; 21 without BI). The moderating effects of authoritarian and authoritative parenting styles were examined in three brain regions linked with social anxiety: ventrolateral prefrontal cortex (vlPFC), striatum, and amygdala. In youth characterized with BI in childhood, but not in those without BI, diminished responses to peer rejection in vlPFC were associated with higher levels of authoritarian parenting. In contrast, all youth showed decreased caudate response to peer rejection at higher levels of authoritative parenting. These findings indicate that BI in early life relates to greater neurobiological sensitivity to variance in parenting styles, particularly harsh parenting, in late adolescence. These results are discussed in relation to biopsychosocial models of development.

  19. Neural correlates of emotional response inhibition in obsessive-compulsive disorder: A preliminary study.

    Science.gov (United States)

    Berlin, Heather A; Schulz, Kurt P; Zhang, Sam; Turetzky, Rachel; Rosenthal, David; Goodman, Wayne

    2015-11-30

    Failure to inhibit recurrent anxiety-provoking thoughts is a central symptom of obsessive-compulsive disorder (OCD). Neuroimaging studies suggest inhibitory control and disgust processing abnormalities in patients with OCD. However, the emotional modulation of response inhibition deficits in OCD and their neural correlates remain to be elucidated. For this preliminary study we administered an adapted affective response inhibition paradigm, an emotional go/no-go task, during fMRI to characterize the neural systems underlying disgust-related and fear-related inhibition in nine adults with contamination-type OCD compared to ten matched healthy controls. Participants with OCD had significantly greater anterior insula cortex activation when inhibiting responses to both disgusting (bilateral), and fearful (right-sided) images, compared to healthy controls. They also had increased activation in several frontal, temporal, and parietal regions, but there was no evidence of amygdala activation in OCD or healthy participants and no significant between-group differences in performance on the emotion go/no-go task. The anterior insula appears to play a central role in the emotional modulation of response inhibition in contamination-type OCD to both fearful and disgusting images. The insula may serve as a potential treatment target for contamination-type OCD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. Hypoxia and the hypoxic response pathway protect against pore-forming toxins in C. elegans.

    Directory of Open Access Journals (Sweden)

    Audrey Bellier

    2009-12-01

    Full Text Available Pore-forming toxins (PFTs are by far the most abundant bacterial protein toxins and are important for the virulence of many important pathogens. As such, cellular responses to PFTs critically modulate host-pathogen interactions. Although many cellular responses to PFTs have been recorded, little is understood about their relevance to pathological or defensive outcomes. To shed light on this important question, we have turned to the only genetic system for studying PFT-host interactions-Caenorhabditis elegans intoxication by Crystal (Cry protein PFTs. We mutagenized and screened for C. elegans mutants resistant to a Cry PFT and recovered one mutant. Complementation, sequencing, transgenic rescue, and RNA interference data demonstrate that this mutant eliminates a gene normally involved in repression of the hypoxia (low oxygen response pathway. We find that up-regulation of the C. elegans hypoxia pathway via the inactivation of three different genes that normally repress the pathway results in animals resistant to Cry PFTs. Conversely, mutation in the central activator of the hypoxia response, HIF-1, suppresses this resistance and can result in animals defective in PFT defenses. These results extend to a PFT that attacks mammals since up-regulation of the hypoxia pathway confers resistance to Vibrio cholerae cytolysin (VCC, whereas down-regulation confers hypersusceptibility. The hypoxia PFT defense pathway acts cell autonomously to protect the cells directly under attack and is different from other hypoxia pathway stress responses. Two of the downstream effectors of this pathway include the nuclear receptor nhr-57 and the unfolded protein response. In addition, the hypoxia pathway itself is induced by PFT, and low oxygen is protective against PFT intoxication. These results demonstrate that hypoxia and induction of the hypoxia response protect cells against PFTs, and that the cellular environment can be modulated via the hypoxia pathway to

  1. JAK‐STAT pathway activation in response to spinal cord injury in regenerative and non‐regenerative stages of Xenopus laevis

    Science.gov (United States)

    Tapia, Victor S.; Herrera‐Rojas, Mauricio

    2017-01-01

    Abstract Xenopus laevis tadpoles can regenerate the spinal cord after injury but this capability is lost during metamorphosis. Comparative studies between pre‐metamorphic and metamorphic Xenopus stages can aid towards understanding the molecular mechanisms of spinal cord regeneration. Analysis of a previous transcriptome‐wide study suggests that, in response to injury, the JAK‐STAT pathway is differentially activated in regenerative and non‐regenerative stages. We characterized the activation of the JAK‐STAT pathway and found that regenerative tadpoles have an early and transient activation. In contrast, the non‐regenerative stages have a delayed and sustained activation of the pathway. We found that STAT3 is activated in response to injury mainly in Sox2/3+ ependymal cells, motoneurons and sensory neurons. Finally, to study the role of temporal activation we generated a transgenic line to express a constitutively active version of STAT3. The sustained activation of the JAK‐STAT pathway in regenerative tadpoles reduced the expression of pro‐neurogenic genes normally upregulated in response to spinal cord injury, suggesting that activation of the JAK‐STAT pathway modulates the fate of neural progenitors. PMID:28316792

  2. SINs and SOMs: Neural microcircuits for size tuning in the zebrafish and mouse visual pathway.

    Directory of Open Access Journals (Sweden)

    Alison J. Barker

    2013-05-01

    Full Text Available In many animals, a fast and reliable circuit for discriminating between predator-sized objects and edible (prey-sized objects is necessary for survival. How are receptive fields in visual brain areas organized to extract information about size? Recent studies from the zebrafish optic tectum and the mouse visual cortex suggest de novo shaping of receptive fields by subtypes of inhibitory neurons. Del Bene et al. (2010 describe a population of GABAergic neurons in the zebrafish optic tectum (Superficial Interneurons, SINs that are necessary for size filtering during prey capture. Adesnik et al. (2012 describe a somatostatin-expressing interneuron population (SOMs that confers surround suppression on layer II/III pyramidal cells in mouse V1. Strikingly both the SINs and the SOMs, display size-dependent response properties. Increasing visual stimulus size increases excitatory input to these neurons. Dampening SIN or SOM activity alters tuning of neighboring circuits such that they lose preference for small objects. Both results provide exciting evidence for mechanisms of size filtering in visual circuits. Here we review the roles of the SINs and the SOMs and speculate on the similarity of such spatial filters across species.

  3. DMPD: Convergence of the NF-kappaB and IRF pathways in the regulation of the innateantiviral response. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17706453 Convergence of the NF-kappaB and IRF pathways in the regulation of the innatea... (.png) (.svg) (.html) (.csml) Show Convergence of the NF-kappaB and IRF pathways in the regulation of the innatea... IRF pathways in the regulation of the innateantiviral response. Authors Hiscott J. Publication Cytokine Gro

  4. Variability of Neuronal Responses: Types and Functional Significance in Neuroplasticity and Neural Darwinism.

    Science.gov (United States)

    Chervyakov, Alexander V; Sinitsyn, Dmitry O; Piradov, Michael A

    2016-01-01

    HIGHLIGHTS We suggest classifying variability of neuronal responses as follows: false (associated with a lack of knowledge about the influential factors), "genuine harmful" (noise), "genuine neutral" (synonyms, repeats), and "genuine useful" (the basis of neuroplasticity and learning).The genuine neutral variability is considered in terms of the phenomenon of degeneracy.Of particular importance is the genuine useful variability that is considered as a potential basis for neuroplasticity and learning. This type of variability is considered in terms of the neural Darwinism theory. In many cases, neural signals detected under the same external experimental conditions significantly change from trial to trial. The variability phenomenon, which complicates extraction of reproducible results and is ignored in many studies by averaging, has attracted attention of researchers in recent years. In this paper, we classify possible types of variability based on its functional significance and describe features of each type. We describe the key adaptive significance of variability at the neural network level and the degeneracy phenomenon that may be important for learning processes in connection with the principle of neuronal group selection.

  5. Neural responses to social exclusion in adolescents: Effects of peer status.

    Science.gov (United States)

    de Water, Erik; Mies, Gabry W; Ma, Ili; Mennes, Maarten; Cillessen, Antonius H N; Scheres, Anouk

    2017-07-01

    We examined whether adolescents' neural responses to social exclusion and inclusion are influenced by their own popularity and acceptance and by the popularity of their excluders and includers. Accepted adolescents are highly prosocial. In contrast, popular adolescents, who are central and influential, show prosocial as well as antisocial behaviors, such as peer exclusion. Fifty-two 12-16 year-old adolescents underwent an functional magnetic resonance imaging (fMRI) scan while playing the ball-tossing game Cyberball in which they received or did not receive the ball from other virtual players. The other virtual players were described as either highly popular or average in popularity. Participants' own popularity and acceptance were assessed with peer nominations at school (n = 31). Participants' acceptance was positively correlated with activity of the dorsal anterior cingulate cortex (ACC) during exclusion. Participants' popularity was positively associated with ventral striatum and medial prefrontal cortex activity during exclusion, but only when the excluders were popular virtual players. Participants showed increased rostral ACC activation to inclusion by players who were average in popularity. These findings indicate that peer status plays an important role in adolescents' neural processing of social exclusion and inclusion. Moreover, these findings underscore that popularity and acceptance are distinct types of high peer status in adolescence, with not only distinct behavioral correlates, but also distinct neural correlates. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Spheroid growth in ovarian cancer alters transcriptome responses for stress pathways and epigenetic responses.

    Directory of Open Access Journals (Sweden)

    Trillitye Paullin

    Full Text Available Ovarian cancer is the most lethal gynecological cancer, with over 200,000 women diagnosed each year and over half of those cases leading to death. These poor statistics are related to a lack of early symptoms and inadequate screening techniques. This results in the cancer going undetected until later stages when the tumor has metastasized through a process that requires the epithelial to mesenchymal transition (EMT. In lieu of traditional monolayer cell culture, EMT and cancer progression in general is best characterized through the use of 3D spheroid models. In this study, we examine gene expression changes through microarray analysis in spheroid versus monolayer ovarian cancer cells treated with TGFβ to induce EMT. Transcripts that included Coiled-Coil Domain Containing 80 (CCDC80, Solute Carrier Family 6 (Neutral Amino Acid Transporter, Member 15 (SLC6A15, Semaphorin 3E (SEMA3E and PIF1 5'-To-3' DNA Helicase (PIF1 were downregulated more than 10-fold in the 3D cells while Inhibitor Of DNA Binding 2, HLH Protein (ID2, Regulator Of Cell Cycle (RGCC, Protease, Serine 35 (PRSS35, and Aldo-Keto Reductase Family 1, Member C1 (AKR1C1 were increased more than 50-fold. Interestingly, EMT factors, stress responses and epigenetic processes were significantly affected by 3D growth. The heat shock response and the oxidative stress response were also identified as transcriptome responses that showed significant changes upon 3D growth. Subnetwork enrichment analysis revealed that DNA integrity (e.g. DNA damage, genetic instability, nucleotide excision repair, and the DNA damage checkpoint pathway were altered in the 3D spheroid model. In addition, two epigenetic processes, DNA methylation and histone acetylation, were increased with 3D growth. These findings support the hypothesis that three dimensional ovarian cell culturing is physiologically different from its monolayer counterpart.

  7. Emotion regulation in social anxiety disorder: behavioral and neural responses to three socio-emotional tasks

    Science.gov (United States)

    2013-01-01

    Background Social anxiety disorder (SAD) is thought to involve deficits in emotion regulation, and more specifically, deficits in cognitive reappraisal. However, evidence for such deficits is mixed. Methods Using functional magnetic resonance imaging (fMRI) of blood oxygen-level dependent (BOLD) signal, we examined reappraisal-related behavioral and neural responses in 27 participants with generalized SAD and 27 healthy controls (HC) during three socio-emotional tasks: (1) looming harsh faces (Faces); (2) videotaped actors delivering social criticism (Criticism); and (3) written autobiographical negative self-beliefs (Beliefs). Results Behaviorally, compared to HC, participants with SAD had lesser reappraisal-related reduction in negative emotion in the Beliefs task. Neurally, compared to HC, participants with SAD had lesser BOLD responses in reappraisal-related brain regions when reappraising faces, in visual and attention related regions when reappraising criticism, and in the left superior temporal gyrus when reappraising beliefs. Examination of the temporal dynamics of BOLD responses revealed late reappraisal-related increased responses in HC, compared to SAD. In addition, the dorsomedial prefrontal cortex (DMPFC), which showed reappraisal-related increased activity in both groups, had similar temporal dynamics in SAD and HC during the Faces and Criticism tasks, but greater late response increases in HC, compared to SAD, during the Beliefs task. Reappraisal-related greater late DMPFC responses were associated with greater percent reduction in negative emotion ratings in SAD patients. Conclusions These results suggest a dysfunction of cognitive reappraisal in SAD patients, with overall reduced late brain responses in prefrontal regions, particularly when reappraising faces. Decreased late activity in the DMPFC might be associated with deficient reappraisal and greater negative reactivity. Trial registration ClinicalTrials.gov identifier: NCT00380731 PMID

  8. Neural response to catecholamine depletion in remitted bulimia nervosa: Relation to depression and relapse.

    Science.gov (United States)

    Mueller, Stefanie Verena; Mihov, Yoan; Federspiel, Andrea; Wiest, Roland; Hasler, Gregor

    2017-07-01

    Bulimia nervosa has been associated with a dysregulated catecholamine system. Nevertheless, the influence of this dysregulation on bulimic symptoms, on neural activity, and on the course of the illness is not clear yet. An instructive paradigm for directly investigating the relationship between catecholaminergic functioning and bulimia nervosa has involved the behavioral and neural responses to experimental catecholamine depletion. The purpose of this study was to examine the neural substrate of catecholaminergic dysfunction in bulimia nervosa and its relationship to relapse. In a randomized, double-blind and crossover study design, catecholamine depletion was achieved by using the oral administration of alpha-methyl-paratyrosine (AMPT) over 24 h in 18 remitted bulimic (rBN) and 22 healthy (HC) female participants. Cerebral blood flow (CBF) was measured using a pseudo continuous arterial spin labeling (pCASL) sequence. In a follow-up telephone interview, bulimic relapse was assessed. Following AMPT, rBN participants revealed an increased vigor reduction and CBF decreases in the pallidum and posterior midcingulate cortex (pMCC) relative to HC participants showing no CBF changes in these regions. These results indicated that the pallidum and the pMCC are the functional neural correlates of the dysregulated catecholamine system in bulimia nervosa. Bulimic relapse was associated with increased depressive symptoms and CBF reduction in the hippocampus/parahippocampal gyrus following catecholamine depletion. AMPT-induced increased CBF in this region predicted staying in remission. These findings demonstrated the importance of depressive symptoms and the stress system in the course of bulimia nervosa. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  9. Neural Correlates of the Binaural Masking Level Difference in Human Frequency-Following Responses.

    Science.gov (United States)

    Clinard, Christopher G; Hodgson, Sarah L; Scherer, Mary Ellen

    2017-04-01

    The binaural masking level difference (BMLD) is an auditory phenomenon where binaural tone-in-noise detection is improved when the phase of either signal or noise is inverted in one of the ears (SπNo or SoNπ, respectively), relative to detection when signal and noise are in identical phase at each ear (SoNo). Processing related to BMLDs and interaural time differences has been confirmed in the auditory brainstem of non-human mammals; in the human auditory brainstem, phase-locked neural responses elicited by BMLD stimuli have not been systematically examined across signal-to-noise ratio. Behavioral and physiological testing was performed in three binaural stimulus conditions: SoNo, SπNo, and SoNπ. BMLDs at 500 Hz were obtained from 14 young, normal-hearing adults (ages 21-26). Physiological BMLDs used the frequency-following response (FFR), a scalp-recorded auditory evoked potential dependent on sustained phase-locked neural activity; FFR tone-in-noise detection thresholds were used to calculate physiological BMLDs. FFR BMLDs were significantly smaller (poorer) than behavioral BMLDs, and FFR BMLDs did not reflect a physiological release from masking, on average. Raw FFR amplitude showed substantial reductions in the SπNo condition relative to SoNo and SoNπ conditions, consistent with negative effects of phase summation from left and right ear FFRs. FFR amplitude differences between stimulus conditions (e.g., SoNo amplitude-SπNo amplitude) were significantly predictive of behavioral SπNo BMLDs; individuals with larger amplitude differences had larger (better) behavioral B MLDs and individuals with smaller amplitude differences had smaller (poorer) behavioral B MLDs. These data indicate a role for sustained phase-locked neural activity in BMLDs of humans and are the first to show predictive relationships between behavioral BMLDs and human brainstem responses.

  10. Effects of Oxytocin on Neural Response to Facial Expressions in Patients with Schizophrenia.

    Science.gov (United States)

    Shin, Na Young; Park, Hye Yoon; Jung, Wi Hoon; Park, Jin Woo; Yun, Je-Yeon; Jang, Joon Hwan; Kim, Sung Nyun; Han, Hyun Jung; Kim, So-Yeon; Kang, Do-Hyung; Kwon, Jun Soo

    2015-07-01

    Impaired facial emotion recognition is a core deficit in schizophrenia. Oxytocin has been shown to improve social perception in patients with schizophrenia; however, the effect of oxytocin on the neural activity underlying facial emotion recognition has not been investigated. This study was aimed to assess the effect of a single dose of intranasal oxytocin on brain activity in patients with schizophrenia using an implicit facial emotion-recognition paradigm. Sixteen male patients with schizophrenia and 16 age-matched healthy male control subjects participated in a randomized, double-blind, placebo-controlled crossover trial at Seoul National University Hospital. Delivery of a single dose of 40 IU intranasal oxytocin and the placebo was separated by 1 week. Drug conditions were compared by performing a region of interest (ROI) analysis of the bilateral amygdala on responses to the emotion recognition test. It was found that nasal spray decreased amygdala activity for fearful emotion and increased activity for happy faces. Further, oxytocin elicited differential effects between the patient and control groups. Intranasal oxytocin attenuated amygdala activity for emotional faces in patients with schizophrenia, whereas intranasal oxytocin significantly increased amygdala activity in healthy controls. Oxytocin-induced BOLD signal changes in amygdala in response to happy faces was related to attachment style in the control group. Our result provides new evidence of a modulatory effect of oxytocin on neural response to emotional faces for patients with schizophrenia. Future studies are needed to investigate the effectiveness of long-term treatment with intranasal oxytocin on neural activity in patients with schizophrenia.

  11. Different neural and cognitive response to emotional faces in healthy monozygotic twins at risk of depression

    DEFF Research Database (Denmark)

    Miskowiak, K W; Glerup, L; Vestbo, C

    2015-01-01

    healthy, never-depressed monozygotic (MZ) twins with a co-twin history of depression (high risk group: n = 13) or without co-twin history of depression (low-risk group: n = 17) were enrolled in a functional magnetic resonance imaging (fMRI) study. During fMRI, participants viewed fearful and happy faces...... while performing a gender discrimination task. After the scan, they were given a faces dot-probe task, a facial expression recognition task and questionnaires assessing mood, personality traits and coping strategies. RESULTS: High-risk twins showed increased neural response to happy and fearful faces...

  12. Chronic Childhood Peer Rejection is Associated with Heightened Neural Responses to Social Exclusion During Adolescence

    OpenAIRE

    Will, G.J.; Van, Lier P.A.; Crone, E.A.; Guroglu, B.

    2015-01-01

    This functional Magnetic Resonance Imaging (fMRI) study examined subjective and neural responses to social exclusion in adolescents (age 12?15) who either had a stable accepted (n?=?27; 14 males) or a chronic rejected (n?=?19; 12 males) status among peers from age 6 to 12. Both groups of adolescents reported similar increases in distress after being excluded in a virtual ball-tossing game (Cyberball), but adolescents with a history of chronic peer rejection showed higher activity in brain reg...

  13. Bilingualism increases neural response consistency and attentional control: evidence for sensory and cognitive coupling.

    Science.gov (United States)

    Krizman, Jennifer; Skoe, Erika; Marian, Viorica; Kraus, Nina

    2014-01-01

    Auditory processing is presumed to be influenced by cognitive processes - including attentional control - in a top-down manner. In bilinguals, activation of both languages during daily communication hones inhibitory skills, which subsequently bolster attentional control. We hypothesize that the heightened attentional demands of bilingual communication strengthens connections between cognitive (i.e., attentional control) and auditory processing, leading to greater across-trial consistency in the auditory evoked response (i.e., neural consistency) in bilinguals. To assess this, we collected passively-elicited auditory evoked responses to the syllable [da] in adolescent Spanish-English bilinguals and English monolinguals and separately obtained measures of attentional control and language ability. Bilinguals demonstrated enhanced attentional control and more consistent brainstem and cortical responses. In bilinguals, but not monolinguals, brainstem consistency tracked with language proficiency and attentional control. We interpret these enhancements in neural consistency as the outcome of strengthened attentional control that emerged from experience communicating in two languages. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Bayesian Mapping Reveals That Attention Boosts Neural Responses to Predicted and Unpredicted Stimuli.

    Science.gov (United States)

    Garrido, Marta I; Rowe, Elise G; Halász, Veronika; Mattingley, Jason B

    2017-04-10

    Predictive coding posits that the human brain continually monitors the environment for regularities and detects inconsistencies. It is unclear, however, what effect attention has on expectation processes, as there have been relatively few studies and the results of these have yielded contradictory findings. Here, we employed Bayesian model comparison to adjudicate between 2 alternative computational models. The "Opposition" model states that attention boosts neural responses equally to predicted and unpredicted stimuli, whereas the "Interaction" model assumes that attentional boosting of neural signals depends on the level of predictability. We designed a novel, audiospatial attention task that orthogonally manipulated attention and prediction by playing oddball sequences in either the attended or unattended ear. We observed sensory prediction error responses, with electroencephalography, across all attentional manipulations. Crucially, posterior probability maps revealed that, overall, the Opposition model better explained scalp and source data, suggesting that attention boosts responses to predicted and unpredicted stimuli equally. Furthermore, Dynamic Causal Modeling showed that these Opposition effects were expressed in plastic changes within the mismatch negativity network. Our findings provide empirical evidence for a computational model of the opposing interplay of attention and expectation in the brain. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  15. Neural response suppression predicts repetition priming of spoken words and pseudowords.

    Science.gov (United States)

    Orfanidou, Eleni; Marslen-Wilson, William D; Davis, Matthew H

    2006-08-01

    An important method for studying how the brain processes familiar stimuli is to present the same item on more than one occasion and measure how responses change with repetition. Here we use repetition priming in a sparse functional magnetic resonance imaging (fMRI) study to probe the neuroanatomical basis of spoken word recognition and the representations of spoken words that mediate repetition priming effects. Participants made lexical decisions to words and pseudowords spoken by a male or female voice that were presented twice, with half of the repetitions in a different voice. Behavioral and neural priming was observed for both words and pseudowords and was not affected by voice changes. The fMRI data revealed an elevated response to words compared to pseudowords in both posterior and anterior temporal regions, suggesting that both contribute to word recognition. Both reduced and elevated activation for second presentations (repetition suppression and enhancement) were observed in frontal and posterior regions. Correlations between behavioral priming and neural repetition suppression were observed in frontal regions, suggesting that repetition priming effects for spoken words reflect changes within systems involved in generating behavioral responses. Based on the current results, these processes are sufficiently abstract to display priming despite changes in the physical form of the stimulus and operate equivalently for words and pseudowords.

  16. In vivo kinetic analysis of the penicillin biosynthesis pathway using PAA stimulus response experiments.

    Science.gov (United States)

    Deshmukh, Amit T; Verheijen, Peter J T; Maleki Seifar, Reza; Heijnen, Joseph J; van Gulik, Walter M

    2015-11-01

    In this study we combined experimentation with mathematical modeling to unravel the in vivo kinetic properties of the enzymes and transporters of the penicillin biosynthesis pathway in a high yielding Penicillium chrysogenum strain. The experiment consisted of a step response experiment with the side chain precursor phenyl acetic acid (PAA) in a glucose-limited chemostat. The metabolite data showed that in the absence of PAA all penicillin pathway enzymes were expressed, leading to the production of a significant amount of 6-aminopenicillanic acid (6APA) as end product. After the stepwise perturbation with PAA, the pathway produced PenG within seconds. From the extra- and intracellular metabolite measurements, hypotheses for the secretion mechanisms of penicillin pathway metabolites were derived. A dynamic model of the penicillin biosynthesis pathway was then constructed that included the formation and transport over the cytoplasmic membrane of pathway intermediates, PAA and the product penicillin-G (PenG). The model parameters and changes in the enzyme levels of the penicillin biosynthesis pathway under in vivo conditions were simultaneously estimated using experimental data obtained at three different timescales (seconds, minutes, hours). The model was applied to determine changes in the penicillin pathway enzymes in time, calculate fluxes and analyze the flux control of the pathway. This led to a reassessment of the in vivo behavior of the pathway enzymes and in particular Acyl-CoA:Isopenicillin N Acyltransferase (AT). Copyright © 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  17. Relationship between Parental Feeding Practices and Neural Responses to Food Cues in Adolescents.

    Directory of Open Access Journals (Sweden)

    Harriet A Allen

    response to parental teaching and modelling of behaviour. Parental restrictive feeding and parental teaching and modelling affected neural responses to food cues in different ways, depending on motivations and diagnoses, illustrating a social influence on neural responses to food cues.

  18. Relationship between Parental Feeding Practices and Neural Responses to Food Cues in Adolescents.

    Science.gov (United States)

    Allen, Harriet A; Chambers, Alison; Blissett, Jacqueline; Chechlacz, Magdalena; Barrett, Timothy; Higgs, Suzanne; Nouwen, Arie

    2016-01-01

    parental teaching and modelling of behaviour. Parental restrictive feeding and parental teaching and modelling affected neural responses to food cues in different ways, depending on motivations and diagnoses, illustrating a social influence on neural responses to food cues.

  19. Differential neural responses to child and sexual stimuli in human fathers and non-fathers and their hormonal correlates.

    Science.gov (United States)

    Mascaro, Jennifer S; Hackett, Patrick D; Rilling, James K

    2014-08-01

    Despite the well-documented importance of paternal caregiving for positive child development, little is known about the neural changes that accompany the transition to fatherhood in humans, or about how changes in hormone levels affect paternal brain function. We compared fathers of children aged 1-2 with non-fathers in terms of hormone levels (oxytocin and testosterone), neural responses to child picture stimuli, and neural responses to visual sexual stimuli. Compared to non-fathers, fathers had significantly higher levels of plasma oxytocin and lower levels of plasma testosterone. In response to child picture stimuli, fathers showed stronger activation than non-fathers within regions important for face emotion processing (caudal middle frontal gyrus [MFG]), mentalizing (temporo-parietal junction [TPJ]) and reward processing (medial orbitofrontal cortex [mOFC]). On the other hand, non-fathers had significantly stronger neural responses to sexually provocative images in regions important for reward and approach-related motivation (dorsal caudate and nucleus accumbens). Testosterone levels were negatively correlated with responses to child stimuli in the MFG. Surprisingly, neither testosterone nor oxytocin levels predicted neural responses to sexual stimuli. Our results suggest that the decline in testosterone that accompanies the transition to fatherhood may be important for augmenting empathy toward children. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Studying the glial cell response to biomaterials and surface topography for improving the neural electrode interface

    Science.gov (United States)

    Ereifej, Evon S.

    Neural electrode devices hold great promise to help people with the restoration of lost functions, however, research is lacking in the biomaterial design of a stable, long-term device. Current devices lack long term functionality, most have been found unable to record neural activity within weeks after implantation due to the development of glial scar tissue (Polikov et al., 2006; Zhong and Bellamkonda, 2008). The long-term effect of chronically implanted electrodes is the formation of a glial scar made up of reactive astrocytes and the matrix proteins they generate (Polikov et al., 2005; Seil and Webster, 2008). Scarring is initiated when a device is inserted into brain tissue and is associated with an inflammatory response. Activated astrocytes are hypertrophic, hyperplastic, have an upregulation of intermediate filaments GFAP and vimentin expression, and filament formation (Buffo et al., 2010; Gervasi et al., 2008). Current approaches towards inhibiting the initiation of glial scarring range from altering the geometry, roughness, size, shape and materials of the device (Grill et al., 2009; Kotov et al., 2009; Kotzar et al., 2002; Szarowski et al., 2003). Literature has shown that surface topography modifications can alter cell alignment, adhesion, proliferation, migration, and gene expression (Agnew et al., 1983; Cogan et al., 2005; Cogan et al., 2006; Merrill et al., 2005). Thus, the goals of the presented work are to study the cellular response to biomaterials used in neural electrode fabrication and assess surface topography effects on minimizing astrogliosis. Initially, to examine astrocyte response to various materials used in neural electrode fabrication, astrocytes were cultured on platinum, silicon, PMMA, and SU-8 surfaces, with polystyrene as the control surface. Cell proliferation, viability, morphology and gene expression was measured for seven days in vitro. Results determined the cellular characteristics, reactions and growth rates of astrocytes

  1. Suppression of TDO-mediated tryptophan catabolism in glioblastoma cells by a steroid-responsive FKBP52-dependent pathway.

    Science.gov (United States)

    Ott, Martina; Litzenburger, Ulrike M; Rauschenbach, Katharina J; Bunse, Lukas; Ochs, Katharina; Sahm, Felix; Pusch, Stefan; Opitz, Christiane A; Blaes, Jonas; von Deimling, Andreas; Wick, Wolfgang; Platten, Michael

    2015-01-01

    Tryptophan catabolism is increasingly recognized as a key and druggable molecular mechanism active in cancer, immune, and glioneural cells and involved in the modulation of antitumor immunity, autoimmunity and glioneural function. In addition to the pivotal rate limiting enzyme indoleamine-2,3-dioxygenase, expression of tryptophan-2,3-dioxygenase (TDO) has recently been described as an alternative pathway responsible for constitutive tryptophan degradation in malignant gliomas and other types of cancer. In addition, TDO has been implicated as a key regulator of neurotoxicity involved in neurodegenerative diseases and ageing. The pathways regulating TDO expression, however, are largely unknown. Here, a siRNA-based transcription factor profiling in human glioblastoma cells revealed that the expression of human TDO is suppressed by endogenous glucocorticoid signaling. Similarly, treatment of glioblastoma cells with the synthetic glucocorticoid dexamethasone led to a reduction of TDO expression and activity in vitro and in vivo. TDO inhibition was dependent on the immunophilin FKBP52, whose FK1 domain physically interacted with the glucocorticoid receptor as demonstrated by bimolecular fluorescence complementation and in situ proximity ligation assays. Accordingly, gene expression profile analyses revealed negative correlation of FKBP52 and TDO in glial and neural tumors and in normal brain. Knockdown of FKBP52 and treatment with the FK-binding immunosuppressant FK506 enhanced TDO expression and activity in glioblastoma cells. In summary, we identify a novel steroid-responsive FKBP52-dependent pathway suppressing the expression and activity of TDO, a central and rate-limiting enzyme in tryptophan metabolism, in human gliomas. © 2014 Wiley Periodicals, Inc.

  2. Transient Modulations of Neural Responses to Heartbeats Covary with Bodily Self-Consciousness.

    Science.gov (United States)

    Park, Hyeong-Dong; Bernasconi, Fosco; Bello-Ruiz, Javier; Pfeiffer, Christian; Salomon, Roy; Blanke, Olaf

    2016-08-10

    Recent research has investigated self-consciousness associated with the multisensory processing of bodily signals (e.g., somatosensory, visual, vestibular signals), a notion referred to as bodily self-consciousness, and these studies have shown that the manipulation of bodily inputs induces changes in bodily self-consciousness such as self-identification. Another line of research has highlighted the importance of signals from the inside of the body (e.g., visceral signals) and proposed that neural representations of internal bodily signals underlie self-consciousness, which to date has been based on philosophical inquiry, clinical case studies, and behavioral studies. Here, we investigated the relationship of bodily self-consciousness with the neural processing of internal bodily signals. By combining electrical neuroimaging, analysis of peripheral physiological signals, and virtual reality technology in humans, we show that transient modulations of neural responses to heartbeats in the posterior cingulate cortex covary with changes in bodily self-consciousness induced by the full-body illusion. Additional analyses excluded that measured basic cardiorespiratory parameters or interoceptive sensitivity traits could account for this finding. These neurophysiological data link experimentally the cortical mapping of the internal body to self-consciousness. What are the brain mechanisms of self-consciousness? Prominent views propose that the neural processing associated with signals from the internal organs (such as the heart and the lung) plays a critical role in self-consciousness. Although this hypothesis dates back to influential views in philosophy and psychology (e.g., William James), definitive experimental evidence supporting this idea is lacking despite its recent impact in neuroscience. In the present study, we show that posterior cingulate activities responding to heartbeat signals covary with changes in participants' conscious self-identification with a body

  3. Abnormal cardiovascular response to exercise in hypertension: contribution of neural factors.

    Science.gov (United States)

    Mitchell, Jere H

    2017-06-01

    During both dynamic (e.g., endurance) and static (e.g., strength) exercise there are exaggerated cardiovascular responses in hypertension. This includes greater increases in blood pressure, heart rate, and efferent sympathetic nerve activity than in normal controls. Two of the known neural factors that contribute to this abnormal cardiovascular response are the exercise pressor reflex (EPR) and functional sympatholysis. The EPR originates in contracting skeletal muscle and reflexly increases sympathetic efferent nerve activity to the heart and blood vessels as well as decreases parasympathetic efferent nerve activity to the heart. These changes in autonomic nerve activity cause an increase in blood pressure, heart rate, left ventricular contractility, and vasoconstriction in the arterial tree. However, arterial vessels in the contracting skeletal muscle have a markedly diminished vasoconstrictor response. The markedly diminished vasoconstriction in contracting skeletal muscle has been termed functional sympatholysis. It has been shown in hypertension that there is an enhanced EPR, including both its mechanoreflex and metaboreflex components, and an impaired functional sympatholysis. These conditions set up a positive feedback or vicious cycle situation that causes a progressively greater decrease in the blood flow to the exercising muscle. Thus these two neural mechanisms contribute significantly to the abnormal cardiovascular response to exercise in hypertension. In addition, exercise training in hypertension decreases the enhanced EPR, including both mechanoreflex and metaboreflex function, and improves the impaired functional sympatholysis. These two changes, caused by exercise training, improve the muscle blood flow to exercising muscle and cause a more normal cardiovascular response to exercise in hypertension. Copyright © 2017 the American Physiological Society.

  4. The impoverished brain: disparities in maternal education affect the neural response to sound.

    Science.gov (United States)

    Skoe, Erika; Krizman, Jennifer; Kraus, Nina

    2013-10-30

    Despite the prevalence of poverty worldwide, little is known about how early socioeconomic adversity affects auditory brain function. Socioeconomically disadvantaged children are underexposed to linguistically and cognitively stimulating environments and overexposed to environmental toxins, including noise pollution. This kind of sensory impoverishment, we theorize, has extensive repercussions on how the brain processes sound. To characterize how this impoverishment affects auditory brain function, we compared two groups of normal-hearing human adolescents who attended the same schools and who were matched in age, sex, and ethnicity, but differed in their maternal education level, a correlate of socioeconomic status (SES). In addition to lower literacy levels and cognitive abilities, adolescents from lower maternal education backgrounds were found to have noisier neural activity than their classmates, as reflected by greater activity in the absence of auditory stimulation. Additionally, in the lower maternal education group, the neural response to speech was more erratic over repeated stimulation, with lower fidelity to the input signal. These weaker, more variable, and noisier responses are suggestive of an inefficient auditory system. By studying SES within a neuroscientific framework, we have the potential to expand our understanding of how experience molds the brain, in addition to informing intervention research aimed at closing the achievement gap between high-SES and low-SES children.

  5. Branding and a child's brain: an fMRI study of neural responses to logos.

    Science.gov (United States)

    Bruce, Amanda S; Bruce, Jared M; Black, William R; Lepping, Rebecca J; Henry, Janice M; Cherry, Joseph Bradley C; Martin, Laura E; Papa, Vlad B; Davis, Ann M; Brooks, William M; Savage, Cary R

    2014-01-01

    Branding and advertising have a powerful effect on both familiarity and preference for products, yet no neuroimaging studies have examined neural response to logos in children. Food advertising is particularly pervasive and effective in manipulating choices in children. The purpose of this study was to examine how healthy children's brains respond to common food and other logos. A pilot validation study was first conducted with 32 children to select the most culturally familiar logos, and to match food and non-food logos on valence and intensity. A new sample of 17 healthy weight children were then scanned using functional magnetic resonance imaging. Food logos compared to baseline were associated with increased activation in orbitofrontal cortex and inferior prefrontal cortex. Compared to non-food logos, food logos elicited increased activation in posterior cingulate cortex. Results confirmed that food logos activate some brain regions in children known to be associated with motivation. This marks the first study in children to examine brain responses to culturally familiar logos. Considering the pervasiveness of advertising, research should further investigate how children respond at the neural level to marketing.

  6. Behavioral and neural responses to infant and adult tears: The impact of maternal love withdrawal.

    Science.gov (United States)

    Riem, Madelon M E; van IJzendoorn, Marinus H; De Carli, Pietro; Vingerhoets, Ad J J M; Bakermans-Kranenburg, Marian J

    2017-09-01

    The current study examined behavioral and neural responses to infant and adult tears, taking into account childhood experiences with parental love-withdrawal. With functional MRI (fMRI), we measured neural reactivity to pictures of infants and adults with and without tears on their faces in nulliparous women with varying childhood experiences of maternal use of love withdrawal. Behavioral responses to infant and adult tears were measured with an approach-avoidance task. We found that individuals with experiences of love withdrawal showed less amygdala and insula reactivity to adult tears, but love withdrawal did not affect amygdala and insula reactivity to infant tears. During the approach-avoidance task, individuals responded faster to adult tears in the approach condition compared with the avoidance condition, indicating that adult tears facilitate approach behavior. Individuals responded faster to infant tears than to adult tears, regardless of approach or avoidance condition. Our findings suggest that infant tears are highly salient and may, therefore, overrule the effects of contextual and personal characteristics that influence the perception of adult crying. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  7. Beyond emotions: A meta-analysis of neural response within face processing system in social anxiety.

    Science.gov (United States)

    Gentili, Claudio; Cristea, Ioana Alina; Angstadt, Mike; Klumpp, Heide; Tozzi, Leonardo; Phan, K Luan; Pietrini, Pietro

    2016-02-01

    Patients with social anxiety disorder (SAD) experience anxiety and avoidance in face-to-face interactions. We performed a meta-analysis of functional magnetic resonance imaging (fMRI) studies in SAD to provide a comprehensive understanding of the neural underpinnings of face perception in this disorder. To this purpose, we adopted an innovative approach, asking authors for unpublished data. This is a common procedure for behavioral meta-analyses, which, however has never been used in neuroimaging studies. We searched Pubmed with the key words "Social Anxiety AND faces" and "Social Phobia AND faces." Then, we selected those fMRI studies for which we were able to obtain data for the comparison between SAD and healthy controls (HC) in a face perception task, either from the published papers or from the authors themselves. In this way, we obtained 23 studies (totaling 449 SAD and 424 HC individuals). We identified significant clusters in which faces evoked a higher response in SAD in bilateral amygdala, globus pallidus, superior temporal sulcus, visual cortex, and prefrontal cortex. We also found a higher activity for HC in the lingual gyrus and in the posterior cingulate. Our findings show that altered neural response to face in SAD is not limited to emotional structures but involves a complex network. These results may have implications for the understanding of SAD pathophysiology, as they suggest that a dysfunctional face perception process may bias patient person-to-person interactions. © 2015 by the Society for Experimental Biology and Medicine.

  8. Chronic Childhood Peer Rejection is Associated with Heightened Neural Responses to Social Exclusion During Adolescence.

    Science.gov (United States)

    Will, Geert-Jan; van Lier, Pol A C; Crone, Eveline A; Güroğlu, Berna

    2016-01-01

    This functional Magnetic Resonance Imaging (fMRI) study examined subjective and neural responses to social exclusion in adolescents (age 12-15) who either had a stable accepted (n = 27; 14 males) or a chronic rejected (n = 19; 12 males) status among peers from age 6 to 12. Both groups of adolescents reported similar increases in distress after being excluded in a virtual ball-tossing game (Cyberball), but adolescents with a history of chronic peer rejection showed higher activity in brain regions previously linked to the detection of, and the distress caused by, social exclusion. Specifically, compared with stably accepted adolescents, chronically rejected adolescents displayed: 1) higher activity in the dorsal anterior cingulate cortex (dACC) during social exclusion and 2) higher activity in the dACC and anterior prefrontal cortex when they were incidentally excluded in a social interaction in which they were overall included. These findings demonstrate that chronic childhood peer rejection is associated with heightened neural responses to social exclusion during adolescence, which has implications for understanding the processes through which peer rejection may lead to adverse effects on mental health over time.

  9. Actor-recipient role affects neural responses to self in emotional situations.

    Science.gov (United States)

    Wang, Xiaoyan; Zheng, Li; Cheng, Xuemei; Li, Lin; Sun, Lining; Wang, Qianfeng; Guo, Xiuyan

    2015-01-01

    People often take either the role of an actor or that of recipient in positive and negative interpersonal events when they interact with others. The present study investigated how the actor-recipient role affected the neural responses to self in emotional situations. Twenty-five participants were scanned while they were presented with positive and negative interpersonal events and were asked to rate the degree to which the actor/the recipient was that kind of person who caused the interpersonal event. Half of the trials were self-relevant events and the other half were other-relevant events. Results showed that people were more likely to isolate self from negative events when they played the role of actor relative to recipient. Pregenual anterior cingulate cortex (pgACC) and posterior dorsal anterior cingulate cortex (pdACC) were more active for self than other only in negative events. More importantly, also in negative interpersonal events, dorsal medial prefrontal cortex (dmPFC) showed greater self-related activations (self-other) when participants played the role of recipient relative to actor, while activities in orbitofrontal cortex (OFC) were greater for self than other only when the evaluation target played the role of recipient. These results showed that the actor-recipient role affected neural responses to self in emotional situations, especially when a recipient role was played in negative situations.

  10. Like or dislike? Affective preference modulates neural response to others' gains and losses.

    Directory of Open Access Journals (Sweden)

    Yang Wang

    Full Text Available Previous studies have demonstrated that the brain responds differentially to others' gains and losses relative to one's own, moderated by social context factors such as competition and interpersonal relationships. In the current study, we tested the hypothesis that the neural response to others' outcomes could be modulated by a short-term induced affective preference. We engaged 17 men and 18 women in a social-exchange game, in which two confederates played fairly or unfairly. Both men and women rated the fair player as likable and the unfair players as unlikable. Afterwards, ERPs were recorded while participants observed each confederates playing a gambling game individually. This study examines feedback related negativity (FRN, an ERP component sensitive to negative feedback. ANOVA showed a significant interaction in which females but not males displayed stronger FRNs when observing likable players' outcomes compared to unlikable ones'. However, males did not respond differently under either circumstance. These findings suggest that, at least in females, the neural response is influenced by a short-term induced affective preference.

  11. Like or dislike? Affective preference modulates neural response to others' gains and losses.

    Science.gov (United States)

    Wang, Yang; Qu, Chen; Luo, Qiuling; Qu, Lulu; Li, Xuebing

    2014-01-01

    Previous studies have demonstrated that the brain responds differentially to others' gains and losses relative to one's own, moderated by social context factors such as competition and interpersonal relationships. In the current study, we tested the hypothesis that the neural response to others' outcomes could be modulated by a short-term induced affective preference. We engaged 17 men and 18 women in a social-exchange game, in which two confederates played fairly or unfairly. Both men and women rated the fair player as likable and the unfair players as unlikable. Afterwards, ERPs were recorded while participants observed each confederates playing a gambling game individually. This study examines feedback related negativity (FRN), an ERP component sensitive to negative feedback. ANOVA showed a significant interaction in which females but not males displayed stronger FRNs when observing likable players' outcomes compared to unlikable ones'. However, males did not respond differently under either circumstance. These findings suggest that, at least in females, the neural response is influenced by a short-term induced affective preference.

  12. ETHYLENE RESPONSE FACTOR1 Integrates Signals from Ethylene and Jasmonate Pathways in Plant DefenseW⃞

    Science.gov (United States)

    Lorenzo, Oscar; Piqueras, Raquel; Sánchez-Serrano, Jose J.; Solano, Roberto

    2003-01-01

    Cross-talk between ethylene and jasmonate signaling pathways determines the activation of a set of defense responses against pathogens and herbivores. However, the molecular mechanisms that underlie this cross-talk are poorly understood. Here, we show that ethylene and jasmonate pathways converge in the transcriptional activation of ETHYLENE RESPONSE FACTOR1 (ERF1), which encodes a transcription factor that regulates the expression of pathogen response genes that prevent disease progression. The expression of ERF1 can be activated rapidly by ethylene or jasmonate and can be activated synergistically by both hormones. In addition, both signaling pathways are required simultaneously to activate ERF1, because mutations that block any of them prevent ERF1 induction by any of these hormones either alone or in combination. Furthermore, 35S:ERF1 expression can rescue the defense response defects of coi1 (coronative insensitive1) and ein2 (ethylene insensitive2); therefore, it is a likely downstream component of both ethylene and jasmonate signaling pathways. Transcriptome analysis in Col;35S:ERF1 transgenic plants and ethylene/jasmonate-treated wild-type plants further supports the notion that ERF1 regulates in vivo the expression of a large number of genes responsive to both ethylene and jasmonate. These results suggest that ERF1 acts downstream of the intersection between ethylene and jasmonate pathways and suggest that this transcription factor is a key element in the integration of both signals for the regulation of defense response genes. PMID:12509529

  13. A Ferroxidase, Cfo1, Regulates Diverse Environmental Stress Responses of Cryptococcus neoformans through the HOG Pathway.

    Science.gov (United States)

    Lee, Kyung-Tae; Lee, Jang-Won; Lee, Dohyun; Jung, Won-Hee; Bahn, Yong-Sun

    2014-06-01

    The iron uptake and utilization pathways play a critical role in allowing human pathogens, including Cryptococcus neoformans, the causative agent of fatal meningoencephalitis, to survive within the mammalian body by competing with the host for iron. Here we show that the iron regulon is also required for diverse environmental stress responses and that in C. neoformans, it is regulated by the high-osmolarity glycerol response (HOG) pathway. Between CFO1 and CFO2, two ferroxidase genes in the iron regulon, CFO1 but not CFO2 was induced during oxidative and osmotic stress. Interestingly, we found that the HOG pathway repressed basal expression of both CFO1 and CFO2. Furthermore, when the HOG pathway was blocked, CFO2 also responded to oxidative and osmotic stress and the response of CFO1 was increased. We also established that CFO1 plays a major role in responding and adapting to diverse environmental stresses, including oxidative and genotoxic damage, osmotic fluctuations, heavy metal stress, and stress induced by cell membrane destabilizers. Therefore, our findings indicate that in C. neoformans, the iron uptake and utilization pathways are not only required for iron acquisition and survival, but also play a significant role in the environmental stress response through crosstalk with the HOG pathway.

  14. Neural responses to maternal praise and criticism: Relationship to depression and anxiety symptoms in high-risk adolescent girls

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    Robin L. Aupperle

    2016-01-01

    Conclusions: Results support a relationship between anxiety and depressive symptoms and prefrontal-amygdala responses to maternal feedback. The lateralization of amygdala findings suggests separate neural targets for interventions reducing reactivity to negative feedback or increasing salience of positive feedback. Exploratory analyses suggest that parents' OXTR genetic profile influences parent-child interactions and related adolescent brain responses.

  15. Reciprocal Pathways between American and Chinese Early Adolescents' Sense of Responsibility and Disclosure to Parents

    Science.gov (United States)

    Qin, Lili; Pomerantz, Eva M.

    2013-01-01

    This research examined the reciprocal pathways between youth's sense of responsibility to parents and disclosure to them during early adolescence in the United States and China. Four times over the seventh and eighth grades, 825 American and Chinese youth (M[subscript age] = 12.73 years) reported on their sense of responsibility to parents and…

  16. Differential effects of neural inactivation of the dorsolateral striatum on response and latent extinction.

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    Goodman, Jarid; Gabriele, Amanda; Packard, Mark G

    2017-04-01

    The present study examined the role of the dorsolateral striatum (DLS) in extinction behavior. Male Long-Evans rats were initially trained on the straight alley maze, in which they were reinforced to traverse a straight runway and retrieve food reward at the opposite end of the maze. After initial acquisition, animals were given extinction training using 1 of 2 distinct protocols: response extinction or latent extinction. For response extinction, the animal was released from the same starting position and had the opportunity to perform the originally reinforced approach response to the goal end of the maze, which no longer contained food. For latent extinction, the animal was confined to the original goal location without food, allowing the animal to form a new cognitive expectation (i.e., that the goal location is no longer reinforced). Immediately before response or latent extinction training, animals received bilateral intra-DLS administration of the sodium channel blocker bupivacaine or control injections of physiological saline. Results indicated that neural inactivation of the DLS with bupivacaine impaired response extinction, but did not influence latent extinction. The dissociation observed indicates that the DLS selectively mediates extinction mechanisms involving suppression of the original response, as opposed to cognitive mechanisms involving a change in expectation. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  17. An ATM-independent S-phase checkpoint response involves CHK1 pathway

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    Zhou, Xiang-Yang; Wang, Xiang; Hu, Baocheng; Guan, Jun; Iliakis, George; Wang, Ya

    2002-01-01

    After exposure to genotoxic stress, proliferating cells actively slow down the DNA replication through a S-phase checkpoint to provide time for repair. We report that in addition to the ataxia-telangiectasia mutated (ATM)-dependent pathway that controls the fast response, there is an ATM-independent pathway that controls the slow response to regulate the S-phase checkpoint after ionizing radiation in mammalian cells. The slow response of S-phase checkpoint, which is resistant to wortmannin, sensitive to caffeine and UCN-01, and related to cyclin-dependent kinase phosphorylation, is much stronger in CHK1 overexpressed cells, and it could be abolished by Chk1 antisense oligonucleotides. These results provide evidence that the ATM-independent slow response of S-phase checkpoint involves CHK1 pathway.

  18. Neural responses to smoking stimuli are influenced by smokers' attitudes towards their own smoking behaviour.

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    Bastian Stippekohl

    Full Text Available An important feature of addiction is the high drug craving that may promote the continuation of consumption. Environmental stimuli classically conditioned to drug-intake have a strong motivational power for addicts and can elicit craving. However, addicts differ in the attitudes towards their own consumption behavior: some are content with drug taking (consonant users whereas others are discontent (dissonant users. Such differences may be important for clinical practice because the experience of dissonance might enhance the likelihood to consider treatment. This fMRI study investigated in smokers whether these different attitudes influence subjective and neural responses to smoking stimuli. Based on self-characterization, smokers were divided into consonant and dissonant smokers. These two groups were presented smoking stimuli and neutral stimuli. Former studies have suggested differences in the impact of smoking stimuli depending on the temporal stage of the smoking ritual they are associated with. Therefore, we used stimuli associated with the beginning (BEGIN-smoking-stimuli and stimuli associated with the terminal stage (END-smoking-stimuli of the smoking ritual as distinct stimulus categories. Stimulus ratings did not differ between both groups. Brain data showed that BEGIN-smoking-stimuli led to enhanced mesolimbic responses (amygdala, hippocampus, insula in dissonant compared to consonant smokers. In response to END-smoking-stimuli, dissonant smokers showed reduced mesocortical responses (orbitofrontal cortex, subcallosal cortex compared to consonant smokers. These results suggest that smoking stimuli with a high incentive value (BEGIN-smoking-stimuli are more appetitive for dissonant than consonant smokers at least on the neural level. To the contrary, smoking stimuli with low incentive value (END-smoking-stimuli seem to be less appetitive for dissonant smokers than consonant smokers. These differences might be one reason why dissonant

  19. The presence of a culturally similar or dissimilar social partner affects neural responses to emotional stimuli

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    Kate A. Woodcock

    2013-06-01

    Full Text Available Background: Emotional responding is sensitive to social context; however, little emphasis has been placed on the mechanisms by which social context effects changes in emotional responding. Objective: We aimed to investigate the effects of social context on neural responses to emotional stimuli to inform on the mechanisms underpinning context-linked changes in emotional responding. Design: We measured event-related potential (ERP components known to index specific emotion processes and self-reports of explicit emotion regulation strategies and emotional arousal. Female Chinese university students observed positive, negative, and neutral photographs, whilst alone or accompanied by a culturally similar (Chinese or dissimilar researcher (British. Results: There was a reduction in the positive versus neutral differential N1 amplitude (indexing attentional capture by positive stimuli in the dissimilar relative to alone context. In this context, there was also a corresponding increase in amplitude of a frontal late positive potential (LPP component (indexing engagement of cognitive control resources. In the similar relative to alone context, these effects on differential N1 and frontal LPP amplitudes were less pronounced, but there was an additional decrease in the amplitude of a parietal LPP component (indexing motivational relevance in response to positive stimuli. In response to negative stimuli, the differential N1 component was increased in the similar relative to dissimilar and alone (trend context. Conclusion: These data suggest that neural processes engaged in response to emotional stimuli are modulated by social context. Possible mechanisms for the social-context-linked changes in attentional capture by emotional stimuli include a context-directed modulation of the focus of attention, or an altered interpretation of the emotional stimuli based on additional information proportioned by the context.

  20. Burst firing in a motion-sensitive neural pathway correlates with expansion properties of looming objects that evoke avoidance behaviours

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    Glyn Allan McMillan

    2015-12-01

    Full Text Available The locust visual system contains a well-defined motion-sensitive pathway that transfers visual input to motor centers involved in predator evasion and collision avoidance. One interneuron in this pathway, the descending contralateral movement detector (DCMD, is typically described as using rate coding; edge expansion of approaching objects causes an increased rate of neuronal firing that peaks after a certain retinal threshold angle is exceeded. However, evidence of intrinsic DCMD bursting properties combined with observable oscillations in mean firing rates and tight clustering of spikes in raw traces, suggest that bursting may be important for motion detection. Sensory neuron bursting provides important timing information about dynamic stimuli in many model systems, yet no studies have rigorously investigated if bursting occurs in the locust DCMD during object approach. We presented repetitions of 30 looming stimuli known to generate behavioural responses to each of 20 locusts in order to identify and quantify putative bursting activity in the DCMD. Overall, we found a bimodal distribution of inter-spike intervals (ISI with peaks of more frequent and shorter ISIs occurring from 1-8 ms and longer less frequent ISIs occurring from 40-50 ms. Subsequent analysis identified bursts and isolated single spikes from the responses. Bursting frequency increased in the latter phase of an approach and peaked at the time of collision, while isolated spiking was predominant during the beginning of stimulus approach. We also found that the majority of inter-burst intervals occurred at 40-50 ms (or 20-25 bursts/s. Bursting also occurred across varied stimulus parameters and suggests that burst timing may be a key component of looming detection. Our findings suggest that the DCMD uses two modes of coding to transmit information about looming stimuli and that these modes change dynamically with a changing stimulus at a behaviourally-relevant time.

  1. Burst Firing in a Motion-Sensitive Neural Pathway Correlates with Expansion Properties of Looming Objects that Evoke Avoidance Behaviors.

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    McMillan, Glyn A; Gray, John R

    2015-01-01

    The locust visual system contains a well-defined motion-sensitive pathway that transfers visual input to motor centers involved in predator evasion and collision avoidance. One interneuron in this pathway, the descending contralateral movement detector (DCMD), is typically described as using rate coding; edge expansion of approaching objects causes an increased rate of neuronal firing that peaks after a certain retinal threshold angle is exceeded. However, evidence of intrinsic DCMD bursting properties combined with observable oscillations in mean firing rates and tight clustering of spikes in raw traces, suggest that bursting may be important for motion detection. Sensory neuron bursting provides important timing information about dynamic stimuli in many model systems, yet no studies have rigorously investigated if bursting occurs in the locust DCMD during object approach. We presented repetitions of 30 looming stimuli known to generate behavioral responses to each of 20 locusts in order to identify and quantify putative bursting activity in the DCMD. Overall, we found a bimodal distribution of inter-spike intervals (ISI) with peaks of more frequent and shorter ISIs occurring from 1-8 ms and longer less frequent ISIs occurring from 40-50 ms. Subsequent analysis identified bursts and isolated single spikes from the responses. Bursting frequency increased in the latter phase of an approach and peaked at the time of collision, while isolated spiking was predominant during the beginning of stimulus approach. We also found that the majority of inter-burst intervals (IBIs) occurred at 40-50 ms (or 20-25 bursts/s). Bursting also occurred across varied stimulus parameters and suggests that burst timing may be a key component of looming detection. Our findings suggest that the DCMD uses two modes of coding to transmit information about looming stimuli and that these modes change dynamically with a changing stimulus at a behaviorally-relevant time.

  2. Neural patterning of human induced pluripotent stem cells in 3-D cultures for studying biomolecule-directed differential cellular responses.

    Science.gov (United States)

    Yan, Yuanwei; Bejoy, Julie; Xia, Junfei; Guan, Jingjiao; Zhou, Yi; Li, Yan

    2016-09-15

    Appropriate neural patterning of human induced pluripotent stem cells (hiPSCs) is critical to generate specific neural cells/tissues and even mini-brains that are physiologically relevant to model neurological diseases. However, the capacity of signaling factors that regulate 3-D neural tissue patterning in vitro and differential responses of the resulting neural populations to various biomolecules have not yet been fully understood. By tuning neural patterning of hiPSCs with small molecules targeting sonic hedgehog (SHH) signaling, this study generated different 3-D neuronal cultures that were mainly comprised of either cortical glutamatergic neurons or motor neurons. Abundant glutamatergic neurons were observed following the treatment with an antagonist of SHH signaling, cyclopamine, while Islet-1 and HB9-expressing motor neurons were enriched by an SHH agonist, purmorphamine. In neurons derived with different neural patterning factors, whole-cell patch clamp recordings showed similar voltage-gated Na(+)/K(+) currents, depolarization-evoked action potentials and spontaneous excitatory post-synaptic currents. Moreover, these different neuronal populations exhibited differential responses to three classes of biomolecules, including (1) matrix metalloproteinase inhibitors that affect extracellular matrix remodeling; (2) N-methyl-d-aspartate that induces general neurotoxicity; and (3) amyloid β (1-42) oligomers that cause neuronal subtype-specific neurotoxicity. This study should advance our understanding of hiPSC self-organization and neural tissue development and provide a transformative approach to establish 3-D models for neurological disease modeling and drug discovery. Appropriate neural patterning of human induced pluripotent stem cells (hiPSCs) is critical to generate specific neural cells, tissues and even mini-brains that are physiologically relevant to model neurological diseases. However, the capability of sonic hedgehog-related small molecules to tune

  3. Improved system identification using artificial neural networks and analysis of individual differences in responses of an identified neuron.

    Science.gov (United States)

    Costalago Meruelo, Alicia; Simpson, David M; Veres, Sandor M; Newland, Philip L

    2016-03-01

    Mathematical modelling is used routinely to understand the coding properties and dynamics of responses of neurons and neural networks. Here we analyse the effectiveness of Artificial Neural Networks (ANNs) as a modelling tool for motor neuron responses. We used ANNs to model the synaptic responses of an identified motor neuron, the fast extensor motor neuron, of the desert locust in response to displacement of a sensory organ, the femoral chordotonal organ, which monitors movements of the tibia relative to the femur of the leg. The aim of the study was threefold: first to determine the potential value of ANNs as tools to model and investigate neural networks, second to understand the generalisation properties of ANNs across individuals and to different input signals and third, to understand individual differences in responses of an identified neuron. A metaheuristic algorithm was developed to design the ANN architectures. The performance of the models generated by the ANNs was compared with those generated through previous mathematical models of the same neuron. The results suggest that ANNs are significantly better than LNL and Wiener models in predicting specific neural responses to Gaussian White Noise, but not significantly different when tested with sinusoidal inputs. They are also able to predict responses of the same neuron in different individuals irrespective of which animal was used to develop the model, although notable differences between some individuals were evident. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. Simultaneous contribution of two rod pathways to AII amacrine and cone bipolar cell light responses.

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    Trexler, E Brady; Li, Wei; Massey, Stephen C

    2005-03-01

    Rod signals traverse several synapses en route to cone bipolar cells. In one pathway, rods communicate directly with cones via gap junctions. In a second pathway, signals flow rods-rod bipolars-AII amacrines-cone bipolars. The relative contribution of each pathway to retinal function is not well understood. Here we have examined this question from the perspective of the AII amacrine. AIIs form bidirectional electrical synapses with on cone bipolars. Consequently, as on cone bipolars are activated by outer plexiform inputs, they too should contribute to the AII response. Rod bipolar inputs to AIIs were blocked by AMPA receptor antagonists, revealing a smaller, non-AMPA component of the light response. This small residual response did not reverse between -70 and +70 mV and was blocked by carbenoxolone, suggesting that the current arose in on cone bipolars and was transmitted to AIIs via gap junctions. The residual component was evident for stimuli 2 log units below cone threshold and was prolonged for bright stimuli, demonstrating that it was rod driven. Because the rod bipolar-AII pathway was blocked, the rod-driven residual current likely was generated via the rod-cone pathway activation of on cone bipolars. Thus for a large range of intensities, rod signals reach the inner retina by both rod bipolar-AII and rod-cone coupling pathways.

  5. Auditory and multisensory responses in the tectofugal pathway of the barn owl.

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    Reches, Amit; Gutfreund, Yoram

    2009-07-29

    A common visual pathway in all amniotes is the tectofugal pathway connecting the optic tectum with the forebrain. The tectofugal pathway has been suggested to be involved in tasks such as orienting and attention, tasks that may benefit from integrating information across senses. Nevertheless, previous research has characterized the tectofugal pathway as strictly visual. Here we recorded from two stations along the tectofugal pathway of the barn owl: the thalamic nucleus rotundus (nRt) and the forebrain entopallium (E). We report that neurons in E and nRt respond to auditory stimuli as well as to visual stimuli. Visual tuning to the horizontal position of the stimulus and auditory tuning to the corresponding spatial cue (interaural time difference) were generally broad, covering a large portion of the contralateral space. Responses to spatiotemporally coinciding multisensory stimuli were mostly enhanced above the responses to the single modality stimuli, whereas spatially misaligned stimuli were not. Results from inactivation experiments suggest that the auditory responses in E are of tectal origin. These findings support the notion that the tectofugal pathway is involved in multisensory processing. In addition, the findings suggest that the ascending auditory information to the forebrain is not as bottlenecked through the auditory thalamus as previously thought.

  6. The Effects of Experimental Manipulation of Sleep Duration on Neural Response to Food Cues.

    Science.gov (United States)

    Demos, Kathryn E; Sweet, Lawrence H; Hart, Chantelle N; McCaffery, Jeanne M; Williams, Samantha E; Mailloux, Kimberly A; Trautvetter, Jennifer; Owens, Max M; Wing, Rena R

    2017-11-01

    Despite growing literature on neural food cue responsivity in obesity, little is known about how the brain processes food cues following partial sleep deprivation and whether short sleep leads to changes similar to those observed in obesity. We used functional magnetic resonance imaging (fMRI) to test the hypothesis that short sleep leads to increased reward-related and decreased inhibitory control-related processing of food cues.In a within-subject design, 30 participants (22 female, mean age = 36.7 standard deviation = 10.8 years, body mass index range 20.4-40.7) completed four nights of 6 hours/night time-in-bed (TIB; short sleep) and four nights of 9 hours/night TIB (long sleep) in random counterbalanced order in their home environments. Following each sleep condition, participants completed an fMRI scan while viewing food and nonfood images.A priori region of interest analyses revealed increased activity to food in short versus long sleep in regions of reward processing (eg, nucleus accumbens/putamen) and sensory/motor signaling (ie, right paracentral lobule, an effect that was most pronounced in obese individuals). Contrary to the hypothesis, whole brain analyses indicated greater food cue responsivity during short sleep in an inhibitory control region (right inferior frontal gyrus) and ventral medial prefrontal cortex, which has been implicated in reward coding and decision-making (false discovery rate corrected q = 0.05).These findings suggest that sleep restriction leads to both greater reward and control processing in response to food cues. Future research is needed to understand the dynamic functional connectivity between these regions during short sleep and whether the interplay between these neural processes determines if one succumbs to food temptation. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

  7. The effect of surface wave propagation on neural responses to vibration in primate glabrous skin.

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    Louise R Manfredi

    Full Text Available Because tactile perception relies on the response of large populations of receptors distributed across the skin, we seek to characterize how a mechanical deformation of the skin at one location affects the skin at another. To this end, we introduce a novel non-contact method to characterize the surface waves produced in the skin under a variety of stimulation conditions. Specifically, we deliver vibrations to the fingertip using a vibratory actuator and measure, using a laser Doppler vibrometer, the surface waves at different distances from the locus of stimulation. First, we show that a vibration applied to the fingertip travels at least the length of the finger and that the rate at which it decays is dependent on stimulus frequency. Furthermore, the resonant frequency of the skin matches the frequency at which a subpopulation of afferents, namely Pacinian afferents, is most sensitive. We show that this skin resonance can lead to a two-fold increase in the strength of the response of a simulated afferent population. Second, the rate at which vibrations propagate across the skin is dependent on the stimulus frequency and plateaus at 7 m/s. The resulting delay in neural activation across locations does not substantially blur the temporal patterning in simulated populations of afferents for frequencies less than 200 Hz, which has important implications about how vibratory frequency is encoded in the responses of somatosensory neurons. Third, we show that, despite the dependence of decay rate and propagation speed on frequency, the waveform of a complex vibration is well preserved as it travels across the skin. Our results suggest, then, that the propagation of surface waves promotes the encoding of spectrally complex vibrations as the entire neural population is exposed to essentially the same stimulus. We also discuss the implications of our results for biomechanical models of the skin.

  8. Predicting Response to Neoadjuvant Chemotherapy with PET Imaging Using Convolutional Neural Networks.

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    Petros-Pavlos Ypsilantis

    Full Text Available Imaging of cancer with 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET has become a standard component of diagnosis and staging in oncology, and is becoming more important as a quantitative monitor of individual response to therapy. In this article we investigate the challenging problem of predicting a patient's response to neoadjuvant chemotherapy from a single 18F-FDG PET scan taken prior to treatment. We take a "radiomics" approach whereby a large amount of quantitative features is automatically extracted from pretherapy PET images in order to build a comprehensive quantification of the tumor phenotype. While the dominant methodology relies on hand-crafted texture features, we explore the potential of automatically learning low- to high-level features directly from PET scans. We report on a study that compares the performance of two competing radiomics strategies: an approach based on state-of-the-art statistical classifiers using over 100 quantitative imaging descriptors, including texture features as well as standardized uptake values, and a convolutional neural network, 3S-CNN, trained directly from PET scans by taking sets of adjacent intra-tumor slices. Our experimental results, based on a sample of 107 patients with esophageal cancer, provide initial evidence that convolutional neural networks have the potential to extract PET imaging representations that are highly predictive of response to therapy. On this dataset, 3S-CNN achieves an average 80.7% sensitivity and 81.6% specificity in predicting non-responders, and outperforms other competing predictive models.

  9. Neural response in obsessive-compulsive washers depends on individual fit of triggers

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    Ali eBaioui

    2013-04-01

    Full Text Available BackgroundPatients with obsessive-compulsive disorder (OCD have highly idiosyncratic triggers. To fully understand which role this idiosyncrasy plays in the neurobiological mechanisms behind OCD, it is necessary to elucidate the impact of individualization regarding the applied investigation methods.This functional magnetic resonance imaging (fMRI study explores the neural correlates of contamination/washing-related OCD with a highly individualized symptom provocation paradigm. Additionally, it is the first study to directly compare individualized and standardized symptom provocation. MethodsNineteen patients with washing compulsions created individual OCD hierarchies, which later served as instructions to photograph their own individualized stimulus sets. The patients and 19 case-by-case matched healthy controls participated in a symptom provocation fMRI experiment with individualized and standardized stimulus sets created for each patient. ResultsOCD patients compared to healthy controls displayed stronger activation in the basal ganglia (nucleus accumbens, nucleus caudatus, pallidum for individualized symptom provocation. Using standardized symptom provocation, this group comparison led to stronger activation in the nucleus caudatus. The direct comparison of between-group effects for both symptom provocation approaches revealed stronger activation of the orbitofronto-striatal network for individualized symptom provocation.ConclusionsThe present study provides insight into the differential impact of individualized and standardized symptom provocation on the orbitofronto-striatal network of OCD washers. Behavioral and neural responses imply a higher symptom-specificity of individualized symptom provocation.

  10. Efficient Simulation of Wing Modal Response: Application of 2nd Order Shape Sensitivities and Neural Networks

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    Kapania, Rakesh K.; Liu, Youhua

    2000-01-01

    At the preliminary design stage of a wing structure, an efficient simulation, one needing little computation but yielding adequately accurate results for various response quantities, is essential in the search of optimal design in a vast design space. In the present paper, methods of using sensitivities up to 2nd order, and direct application of neural networks are explored. The example problem is how to decide the natural frequencies of a wing given the shape variables of the structure. It is shown that when sensitivities cannot be obtained analytically, the finite difference approach is usually more reliable than a semi-analytical approach provided an appropriate step size is used. The use of second order sensitivities is proved of being able to yield much better results than the case where only the first order sensitivities are used. When neural networks are trained to relate the wing natural frequencies to the shape variables, a negligible computation effort is needed to accurately determine the natural frequencies of a new design.

  11. Neural Network Based Response Prediction of rTMS in Major Depressive Disorder Using QEEG Cordance.

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    Erguzel, Turker Tekin; Ozekes, Serhat; Gultekin, Selahattin; Tarhan, Nevzat; Hizli Sayar, Gokben; Bayram, Ali

    2015-01-01

    The combination of repetitive transcranial magnetic stimulation (rTMS), a non-pharmacological form of therapy for treating major depressive disorder (MDD), and electroencephalogram (EEG) is a valuable tool for investigating the functional connectivity in the brain. This study aims to explore whether pre-treating frontal quantitative EEG (QEEG) cordance is associated with response to rTMS treatment among MDD patients by using an artificial intelligence approach, artificial neural network (ANN). The artificial neural network using pre-treatment cordance of frontal QEEG classification was carried out to identify responder or non-responder to rTMS treatment among 55 MDD subjects. The classification performance was evaluated using k-fold cross-validation. The ANN classification identified responders to rTMS treatment with a sensitivity of 93.33%, and its overall accuracy reached to 89.09%. Area under Receiver Operating Characteristic (ROC) curve (AUC) value for responder detection using 6, 8 and 10 fold cross validation were 0.917, 0.823 and 0.894 respectively. Potential utility of ANN approach method can be used as a clinical tool in administering rTMS therapy to a targeted group of subjects suffering from MDD. This methodology is more potentially useful to the clinician as prediction is possible using EEG data collected before this treatment process is initiated. It is worth using feature selection algorithms to raise the sensitivity and accuracy values.

  12. Enhanced neural responses to rule violation in children with autism: a comparison to social exclusion.

    Science.gov (United States)

    Bolling, Danielle Z; Pitskel, Naomi B; Deen, Ben; Crowley, Michael J; McPartland, James C; Kaiser, Martha D; Wyk, Brent C Vander; Wu, Jia; Mayes, Linda C; Pelphrey, Kevin A

    2011-07-01

    The present study aimed to explore the neural correlates of two characteristic deficits in autism spectrum disorders (ASD); social impairment and restricted, repetitive behavior patterns. To this end, we used comparable experiences of social exclusion and rule violation to probe potentially atypical neural networks in ASD. In children and adolescents with and without ASD, we used the interactive ball-toss game (Cyberball) to elicit social exclusion and a comparable game (Cybershape) to elicit a non-exclusive rule violation. Using functional magnetic resonance imaging (fMRI), we identified group differences in brain responses to social exclusion and rule violation. Though both groups reported equal distress following exclusion, the right insula and ventral anterior cingulate cortex were hypoactive during exclusion in children with ASD. In rule violation, right insula and dorsal prefrontal cortex were hyperactive in ASD. Right insula showed a dissociation in activation; it was hypoactive to social exclusion and hyperactive to rule violation in the ASD group. Further probed, different regions of right insula were modulated in each game, highlighting differences in regional specificity for which subsequent analyses revealed differences in patterns of functional connectivity. These results demonstrate neurobiological differences in processing social exclusion and rule violation in children with ASD.

  13. Structured chaos shapes spike-response noise entropy in balanced neural networks

    Directory of Open Access Journals (Sweden)

    Guillaume eLajoie

    2014-10-01

    Full Text Available Large networks of sparsely coupled, excitatory and inhibitory cells occur throughout the brain. For many models of these networks, a striking feature is that their dynamics are chaotic and thus, are sensitive to small perturbations. How does this chaos manifest in the neural code? Specifically, how variable are the spike patterns that such a network produces in response to an input signal? To answer this, we derive a bound for a general measure of variability -- spike-train entropy. This leads to important insights on the variability of multi-cell spike pattern distributions in large recurrent networks of spiking neurons responding to fluctuating inputs. The analysis is based on results from random dynamical systems theory and is complemented by detailed numerical simulations. We find that the spike pattern entropy is an order of magnitude lower than what would be extrapolated from single cells. This holds despite the fact that network coupling becomes vanishingly sparse as network size grows -- a phenomenon that depends on ``extensive chaos, as previously discovered for balanced networks without stimulus drive. Moreover, we show how spike pattern entropy is controlled by temporal features of the inputs. Our findings provide insight into how neural networks may encode stimuli in the presence of inherently chaotic dynamics.

  14. Reduced neural responses to vocal fear: a potential biomarker for callous-uncaring traits in early childhood.

    Science.gov (United States)

    Hoyniak, Caroline P; Bates, John E; Petersen, Isaac T; Yang, Chung-Lin; Darcy, Isabelle; Fontaine, Nathalie M G

    2017-11-08

    Callous-unemotional (CU) traits are characterized by a lack of guilt and empathy, and low responsiveness to distress and fear in others. Children with CU traits are at-risk for engaging in early and persistent conduct problems. Individuals showing CU traits have been shown to have reduced neural responses to others' distress (e.g., fear). However, the neural components of distress responses in children with CU traits have not been investigated in early childhood. In the current study, we examined neural responses that underlie the processing of emotionally valenced vocal stimuli using the event-related potential technique in a group of preschoolers. Participants between 2 and 5 years old took part in an auditory oddball task containing English-based pseudowords spoken with either a fearful, happy, or a neutral prosody while electroencephalography data were collected. The mismatch negativity (MMN) component, an index of the automatic detection of deviant stimuli within a series of stimuli, was examined in association with two dimensions of CU traits (i.e., callousness-uncaring and unemotional dimensions) reported by primary caregivers. Findings suggest that the callousness-uncaring dimension of CU traits in early childhood is associated with reduced responses to fearful vocal stimuli. Reduced neural responses to vocal fear could be a biomarker for callous-uncaring traits in early childhood. These findings are relevant for clinicians and researchers attempting to identify risk factors for early callous-uncaring traits. © 2017 John Wiley & Sons Ltd.

  15. Cold atmospheric plasma (CAP), a novel physicochemical source, induces neural differentiation through cross-talk between the specific RONS cascade and Trk/Ras/ERK signaling pathway.

    Science.gov (United States)

    Jang, Ja-Young; Hong, Young June; Lim, Junsup; Choi, Jin Sung; Choi, Eun Ha; Kang, Seongman; Rhim, Hyangshuk

    2018-02-01

    Plasma, formed by ionization of gas molecules or atoms, is the most abundant form of matter and consists of highly reactive physicochemical species. In the physics and chemistry fields, plasma has been extensively studied; however, the exact action mechanisms of plasma on biological systems, including cells and humans, are not well known. Recent evidence suggests that cold atmospheric plasma (CAP), which refers to plasma used in the biomedical field, may regulate diverse cellular processes, including neural differentiation. However, the mechanism by which these physicochemical signals, elicited by reactive oxygen and nitrogen species (RONS), are transmitted to biological system remains elusive. In this study, we elucidated the physicochemical and biological (PCB) connection between the CAP cascade and Trk/Ras/ERK signaling pathway, which resulted in neural differentiation. Excited atomic oxygen in the plasma phase led to the formation of RONS in the PCB network, which then interacted with reactive atoms in the extracellular liquid phase to form nitric oxide (NO). Production of large amounts of superoxide radical (O2-) in the mitochondria of cells exposed to CAP demonstrated that extracellular NO induced the reversible inhibition of mitochondrial complex IV. We also demonstrated that cytosolic hydrogen peroxide, formed by O2- dismutation, act as an intracellular messenger to specifically activate the Trk/Ras/ERK signaling pathway. This study is the first to elucidate the mechanism linking physicochemical signals from the CAP cascade to the intracellular neural differentiation signaling pathway, providing physical, chemical and biological insights into the development of therapeutic techniques to treat neurological diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Large-scale functional neural network correlates of response inhibition: an fMRI meta-analysis.

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    Zhang, Ruibin; Geng, Xiujuan; Lee, Tatia M C

    2017-12-01

    An influential hypothesis from the last decade proposed that regions within the right inferior frontal cortex of the human brain were dedicated to supporting response inhibition. There is growing evidence, however, to support an alternative model, which proposes that neural areas associated with specific inhibitory control tasks co-exist as common network mechanisms, supporting diverse cognitive processes. This meta-analysis of 225 studies comprising 323 experiments examined the common and distinct neural correlates of cognitive processes for response inhibition, namely interference resolution, action withholding, and action cancellation. Activation coordinates for each subcategory were extracted using multilevel kernel density analysis (MKDA). The extracted activity patterns were then mapped onto the brain functional network atlas to derive the common (i.e., process-general) and distinct (i.e., domain-oriented) neural network correlates of these processes. Independent of the task types, activation of the right hemispheric regions (inferior frontal gyrus, insula, median cingulate, and paracingulate gyri) and superior parietal gyrus was common across the cognitive processes studied. Mapping the activation patterns to a brain functional network atlas revealed that the fronto-parietal and ventral attention networks were the core neural systems that were commonly engaged in different processes of response inhibition. Subtraction analyses elucidated the distinct neural substrates of interference resolution, action withholding, and action cancellation, revealing stronger activation in the ventral attention network for interference resolution than action inhibition. On the other hand, action withholding/cancellation primarily engaged the fronto-striatal circuit. Overall, our results suggest that response inhibition is a multidimensional cognitive process involving multiple neural regions and networks for coordinating optimal performance. This finding has significant

  17. Empathic neural responses are modulated by the perceived fairness of others

    Science.gov (United States)

    Singer, Tania; Seymour, Ben; O'Doherty, John P.; Stephan, Klaas E.; Dolan, Raymond J.; Frith, Chris D.

    2009-01-01

    The neural processes underlying empathy are a subject of intense interest within the social neurosciences1-3. However, very little is known about how brain empathic responses are modulated by the affective link between individuals. We show here that empathic responses are modulated by learned preferences, a result consistent with economic models of social preferences4-7. We engaged male and female volunteers in an economic game, in which two confederates played fairly or unfairly, and then measured brain activity with functional magnetic resonance imaging while these same volunteers observed the confederates receiving pain. Both sexes exhibited empathy-related activation in pain-related brain areas (fronto-insular and anterior cingulate cortices) towards fair players. However, these empathy-related responses were significantly reduced in males when observing an unfair person receiving pain. This effect was accompanied by increased activation in reward-related areas, correlated with an expressed desire for revenge. We conclude that in men (at least) empathic responses are shaped by valuation of other people's social behaviour, such that they empathize with fair opponents while favouring the physical punishment of unfair opponents, a finding that echoes recent evidence for altruistic punishment. PMID:16421576

  18. Modeling forest ecosystem responses to elevated carbon dioxide and ozone using artificial neural networks.

    Science.gov (United States)

    Larsen, Peter E; Cseke, Leland J; Miller, R Michael; Collart, Frank R

    2014-10-21

    Rising atmospheric levels of carbon dioxide and ozone will impact productivity and carbon sequestration in forest ecosystems. The scale of this process and the potential economic consequences provide an incentive for the development of models to predict the types and rates of ecosystem responses and feedbacks that result from and influence of climate change. In this paper, we use phenotypic and molecular data derived from the Aspen Free Air CO2 Enrichment site (Aspen-FACE) to evaluate modeling approaches for ecosystem responses to changing conditions. At FACE, it was observed that different aspen clones exhibit clone-specific responses to elevated atmospheric levels of carbon dioxide and ozone. To identify the molecular basis for these observations, we used artificial neural networks (ANN) to examine above and below-ground community phenotype responses to elevated carbon dioxide, elevated ozone and gene expression profiles. The aspen community models generated using this approach identified specific genes and subnetworks of genes associated with variable sensitivities for aspen clones. The ANN model also predicts specific co-regulated gene clusters associated with differential sensitivity to elevated carbon dioxide and ozone in aspen species. The results suggest ANN is an effective approach to predict relevant gene expression changes resulting from environmental perturbation and provides useful information for the rational design of future biological experiments. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Novel transformation-based response prediction of shear building using interval neural network

    Science.gov (United States)

    Chakraverty, S.; Sahoo, Deepti Moyi

    2017-04-01

    Present paper uses powerful technique of interval neural network (INN) to simulate and estimate structural response of multi-storey shear buildings subject to earthquake motion. The INN is first trained for a real earthquake data, viz., the ground acceleration as input and the numerically generated responses of different floors of multi-storey buildings as output. Till date, no model exists to handle positive and negative data in the INN. As such here, the bipolar data in [ -1, 1] are converted first to unipolar form, i.e., to [0, 1] by means of a novel transformation for the first time to handle the above training patterns in normalized form. Once the training is done, again the unipolar data are converted back to its bipolar form by using the inverse transformation. The trained INN architecture is then used to simulate and test the structural response of different floors for various intensity earthquake data and it is found that the predicted responses given by INN model are good for practical purposes.

  20. Relief as a reward: hedonic and neural responses to safety from pain.

    Directory of Open Access Journals (Sweden)

    Siri Leknes

    2011-04-01

    Full Text Available Relief fits the definition of a reward. Unlike other reward types the pleasantness of relief depends on the violation of a negative expectation, yet this has not been investigated using neuroimaging approaches. We hypothesized that the degree of negative expectation depends on state (dread and trait (pessimism sensitivity. Of the brain regions that are involved in mediating pleasure, the nucleus accumbens also signals unexpected reward and positive prediction error. We hypothesized that accumbens activity reflects the level of negative expectation and subsequent pleasant relief. Using fMRI and two purpose-made tasks, we compared hedonic and BOLD responses to relief with responses during an appetitive reward task in 18 healthy volunteers. We expected some similarities in task responses, reflecting common neural substrates implicated across reward types. However, we also hypothesized that relief responses would differ from appetitive rewards in the nucleus accumbens, since only relief pleasantness depends on negative expectations. The results confirmed these hypotheses. Relief and appetitive reward task activity converged in the ventromedial prefrontal cortex, which also correlated with appetitive reward pleasantness ratings. In contrast, dread and pessimism scores correlated with relief but not with appetitive reward hedonics. Moreover, only relief pleasantness covaried with accumbens activation. Importantly, the accumbens signal appeared to specifically reflect individual differences in anticipation of the adverse event (dread, pessimism but was uncorrelated to appetitive reward hedonics. In conclusion, relief differs from appetitive rewards due to its reliance on negative expectations, the violation of which is reflected in relief-related accumbens activation.

  1. Homeostatic response to hypoxia is regulated by the N-end rule pathway in plants

    Science.gov (United States)

    Gibbs, Daniel J.; Lee, Seung Cho; Isa, Nurulhikma Md; Gramuglia, Silvia; Fukao, Takeshi; Bassel, George W.; Correia, Cristina Sousa; Corbineau, Françoise; Theodoulou, Frederica L.; Bailey-Serres, Julia; Holdsworth, Michael J.

    2011-01-01

    Plants and animals are obligate aerobes, requiring oxygen for mitochondrial respiration and energy production. In plants, an unanticipated decline in oxygen availability (hypoxia), as caused by root waterlogging or foliage submergence, triggers changes in gene transcription and mRNA translation that promote anaerobic metabolism and thus sustain substrate-level ATP production1. In contrast to animals2, oxygen sensing has not been ascribed to a mechanism of gene regulation in response to oxygen deprivation in plants. Here we show that the N-end rule pathway of targeted proteolysis acts as a homeostatic sensor of severe low oxygen in Arabidopsis, through its regulation of key hypoxia response transcription factors. We found that plants lacking components of the N-end rule pathway constitutively express core hypoxia response genes and are more tolerant of hypoxic stress. We identify the hypoxia-associated Ethylene Response Factor (ERF) Group VII transcription factors of Arabidopsis as substrates of this pathway. Regulation of these proteins by the N-end rule pathway occurs through a characteristic conserved motif at the N-terminus initiating with MetCys- (MC-). Enhanced stability of one of these proteins, HRE2, under low oxygen conditions improves hypoxia survival and reveals a molecular mechanism for oxygen sensing in plants via the evolutionarily conserved N-end rule pathway. SUB1A-1, a major determinant of submergence tolerance in rice3, was shown not to be a substrate for the N-end rule pathway despite containing the N-terminal motif, suggesting that it is uncoupled from N-end rule pathway regulation, and that enhanced stability may relate to the superior tolerance of Sub1 rice varieties to multiple abiotic stresses4. PMID:22020279

  2. Longitudinal Analysis of the Absence of Intraoperative Neural Response Telemetry in Children using Cochlear Implants

    Directory of Open Access Journals (Sweden)

    Moura, Amanda Christina Gomes de

    2014-07-01

    Full Text Available Introduction Currently the cochlear implant allows access to sounds in individuals with profound hearing loss. The objective methods used to verify the integrity of the cochlear device and the electrophysiologic response of users have noted these improvements. Objective To establish whether the evoked compound action potential of the auditory nerve can appear after electrical stimulation when it is absent intraoperatively. Methods The clinical records of children implanted with the Nucleus Freedom (Cochlear Ltd., Australia (CI24RE cochlear implant between January 2009 and January 2010 with at least 6 months of use were evaluated. The neural response telemetry (NRT thresholds of electrodes 1, 6, 11, 16, and 22 during surgery and after at least 3 months of implant use were analyzed and correlated with etiology, length of auditory deprivation, and chronological age. These data were compared between a group of children exhibiting responses in all of the tested electrodes and a group of children who had at least one absent response. Results The sample was composed of clinical records of 51 children. From these, 21% (11 showed no NRT in at least one of the tested electrodes. After an average of 4.9 months of stimulation, the number of individuals exhibiting absent responses decreased from 21 to 11% (n = 6. Conclusion It is feasible that absent responses present after a period of electrical stimulation. In our sample, 45% (n = 5 of the patients with intraoperative absence exhibited a positive response after an average of 4.9 months of continued electrical stimulation.

  3. Attenuated neural response to gamble outcomes in drug-naive patients with Parkinson’s disease

    DEFF Research Database (Denmark)

    van der Vegt, Joyce P M; Hulme, Oliver J; Zittel, Simone

    2013-01-01

    resulting in impulse control disorders. To circumvent this treatment confound, we assayed the neural basis of reward processing in a group of newly diagnosed patients with Parkinson's disease that had never been treated with dopaminergic drugs. Thirteen drug-naive patients with Parkinson's disease and 12......Parkinson's disease results from the degeneration of dopaminergic neurons in the substantia nigra, manifesting as a spectrum of motor, cognitive and affective deficits. Parkinson's disease also affects reward processing, but disease-related deficits in reinforcement learning are thought to emerge...... at a slower pace than motor symptoms as the degeneration progresses from dorsal to ventral striatum. Dysfunctions in reward processing are difficult to study in Parkinson's disease as most patients have been treated with dopaminergic drugs, which sensitize reward responses in the ventral striatum, commonly...

  4. Does a single session of electroconvulsive therapy alter the neural response to emotional faces in depression?

    DEFF Research Database (Denmark)

    Miskowiak, Kamilla W; Kessing, Lars V; Ott, Caroline V

    2017-01-01

    Negative neurocognitive bias is a core feature of major depressive disorder that is reversed by pharmacological and psychological treatments. This double-blind functional magnetic resonance imaging study investigated for the first time whether electroconvulsive therapy modulates negative neurocog......Negative neurocognitive bias is a core feature of major depressive disorder that is reversed by pharmacological and psychological treatments. This double-blind functional magnetic resonance imaging study investigated for the first time whether electroconvulsive therapy modulates negative...... to fearful versus happy faces as well as in fear-specific functional connectivity between amygdala and occipito-temporal regions. Across all patients, greater fear-specific amygdala - occipital coupling correlated with lower fear vigilance. Despite no statistically significant shift in neural response...

  5. Different neural responses to stranger and personally familiar faces in shy and bold adults.

    Science.gov (United States)

    Beaton, Elliott A; Schmidt, Louis A; Schulkin, Jay; Antony, Martin M; Swinson, Richard P; Hall, Geoffrey B

    2008-06-01

    The shy-bold continuum is a fundamental behavioral trait conserved across human and nonhuman animals. Individual differences along the shy-bold continuum are presumed to arise from, and are maintained by, differences in the excitability of forebrain limbic areas involved in the evaluation of stimulus saliency. To test this hypothesis, the authors conducted an event-related functional MRI (fMRI) study in which brain scans were acquired on shy and bold adults during the presentation of neutral stranger and personally familiar faces. Shy adults exhibited greater bilateral amygdala activation during the presentation of stranger faces and greater left amygdala activation during personally familiar faces than their bold counterparts. Bold adults exhibited greater bilateral nucleus accumbens activation in response to stranger and personally familiar faces than shy adults. Findings suggest that there are distinct neural substrates underlying and maintaining individual differences along a shy-bold continuum in humans. (Copyright) 2008 APA, all rights reserved.

  6. A CREB-Sirt1-Hes1 Circuitry Mediates Neural Stem Cell Response to Glucose Availability

    Directory of Open Access Journals (Sweden)

    Salvatore Fusco

    2016-02-01

    Full Text Available Adult neurogenesis plays increasingly recognized roles in brain homeostasis and repair and is profoundly affected by energy balance and nutrients. We found that the expression of Hes-1 (hairy and enhancer of split 1 is modulated in neural stem and progenitor cells (NSCs by extracellular glucose through the coordinated action of CREB (cyclic AMP responsive element binding protein and Sirt-1 (Sirtuin 1, two cellular nutrient sensors. Excess glucose reduced CREB-activated Hes-1 expression and results in impaired cell proliferation. CREB-deficient NSCs expanded poorly in vitro and did not respond to glucose availability. Elevated glucose also promoted Sirt-1-dependent repression of the Hes-1 promoter. Conversely, in low glucose, CREB replaced Sirt-1 on the chromatin associated with the Hes-1 promoter enhancing Hes-1 expression and cell proliferation. Thus, the glucose-regulated antagonism between CREB and Sirt-1 for Hes-1 transcription participates in the metabolic regulation of neurogenesis.

  7. Anxiety and neural responses to infant and adult faces during pregnancy.

    Science.gov (United States)

    Rutherford, Helena J V; Byrne, Simon P; Austin, Grace M; Lee, Jonathan D; Crowley, Michael J; Mayes, Linda C

    2017-04-01

    Women are vulnerable to anxiety during pregnancy and postpartum. However, little is known about antenatal anxiety and neural processing of infant-relevant information. In this experiment, the N170, P300, and LPP (late positive potential) event-related potentials were measured from 43 pregnant women as they viewed infant and adult faces, which were either neutral or distressed in expression. Mother's self-reported anxiety levels were also assessed. The N170 was comparable across face conditions and was not associated with anxiety. However, our central finding was that greater levels of antenatal anxiety were associated with a larger LPP, but only for neutral infant faces. Results suggest that antenatal anxiety may result in deeper processing of neutral, emotionally ambiguous, infant faces during pregnancy. These findings are discussed in light of other work indicating an interpretive bias toward threat in response to neutral stimuli in anxiety. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. The Imd pathway is involved in antiviral immune responses in Drosophila.

    Directory of Open Access Journals (Sweden)

    Alexandre Costa

    2009-10-01

    Full Text Available Cricket Paralysis virus (CrPV is a member of the Dicistroviridae family of RNA viruses, which infect a broad range of insect hosts, including the fruit fly Drosophila melanogaster. Drosophila has emerged as an effective system for studying innate immunity because of its powerful genetic techniques and the high degree of gene and pathway conservation. Intra-abdominal injection of CrPV into adult flies causes a lethal infection that provides a robust assay for the identification of mutants with altered sensitivity to viral infection. To gain insight into the interactions between viruses and the innate immune system, we injected wild type flies with CrPV and observed that antimicrobial peptides (AMPs were not induced and hemocytes were depleted in the course of infection. To investigate the contribution of conserved immune signaling pathways to antiviral innate immune responses, CrPV was injected into isogenic mutants of the Immune Deficiency (Imd pathway, which resembles the mammalian Tumor Necrosis Factor Receptor (TNFR pathway. Loss-of-function mutations in several Imd pathway genes displayed increased sensitivity to CrPV infection and higher CrPV loads. Our data show that antiviral innate immune responses in flies infected with CrPV depend upon hemocytes and signaling through the Imd pathway.

  9. Neural predictors of individual differences in response to math tutoring in primary-grade school children.

    Science.gov (United States)

    Supekar, Kaustubh; Swigart, Anna G; Tenison, Caitlin; Jolles, Dietsje D; Rosenberg-Lee, Miriam; Fuchs, Lynn; Menon, Vinod

    2013-05-14

    Now, more than ever, the ability to acquire mathematical skills efficiently is critical for academic and professional success, yet little is known about the behavioral and neural mechanisms that drive some children to acquire these skills faster than others. Here we investigate the behavioral and neural predictors of individual differences in arithmetic skill acquisition in response to 8-wk of one-to-one math tutoring. Twenty-four children in grade 3 (ages 8-9 y), a critical period for acquisition of basic mathematical skills, underwent structural and resting-state functional MRI scans pretutoring. A significant shift in arithmetic problem-solving strategies from counting to fact retrieval was observed with tutoring. Notably, the speed and accuracy of arithmetic problem solving increased with tutoring, with some children improving significantly more than others. Next, we examined whether pretutoring behavioral and brain measures could predict individual differences in arithmetic performance improvements with tutoring. No behavioral measures, including intelligence quotient, working memory, or mathematical abilities, predicted performance improvements. In contrast, pretutoring hippocampal volume predicted performance improvements. Furthermore, pretutoring intrinsic functional connectivity of the hippocampus with dorsolateral and ventrolateral prefrontal cortices and the basal ganglia also predicted performance improvements. Our findings provide evidence that individual differences in morphometry and connectivity of brain regions associated with learning and memory, and not regions typically involved in arithmetic processing, are strong predictors of responsiveness to math tutoring in children. More generally, our study suggests that quantitative measures of brain structure and intrinsic brain organization can provide a more sensitive marker of skill acquisition than behavioral measures.

  10. Strength training-induced responses in older adults: attenuation of descending neural drive with age.

    Science.gov (United States)

    Unhjem, Runar; Lundestad, Raymond; Fimland, Marius Steiro; Mosti, Mats Peder; Wang, Eivind

    2015-06-01

    Although reductions in resting H-reflex responses and maximal firing frequency suggest that reduced efferent drive may limit muscle strength in elderly, there are currently no reports of V-wave measurements in elderly, reflecting the magnitude of efferent output to the muscle during maximal contraction. Furthermore, it is uncertain whether potential age-related neural deficiencies can be restored by resistance training. We assessed evoked reflex recordings in the triceps surae muscles during rest and maximal voluntary contraction (MVC), rate of force development (RFD), and muscle mass in seven elderly (74 ± 6 years) males before and after 8 weeks of heavy resistance training, contrasted by seven young (24 ± 4 years) male controls. At baseline, m. soleus (SOL) V/M ratio (0.124 ± 0.082 vs. 0.465 ± 0.197, p elderly compared to young. Also, SOL H-reflex latency (33.29 ± 2.41 vs. 30.29 ± 0.67 ms, p elderly. The reduced neural drive was, despite similar leg muscle mass (10.7 ± 1.2 vs. 11.5 ± 1.4 kg), mirrored by lower MVC (158 ± 48 vs. 240 ± 54 Nm, p elderly. In response to training SOL V/M ratio (0.184 ± 0.092, p elderly, yet only to a level ~40 % of the young. This was accompanied by increased MVC (190 ± 70 Nm, p muscle strength. Furthermore, this motor system impairment can to some extent be improved by heavy resistance training.

  11. BIOMARKER IDENTIFICATION IN BREAST CANCER: BETA-ADRENERGIC RECEPTOR SIGNALING AND PATHWAYS TO THERAPEUTIC RESPONSE

    Directory of Open Access Journals (Sweden)

    Liana E. Kafetzopoulou

    2013-03-01

    Full Text Available Recent preclinical studies have associated beta-adrenergic receptor (β-AR signaling with breast cancer pathways such as progression and metastasis. These findings have been supported by clinical and epidemiological studies which examined the effect of beta-blocker therapy on breast cancer metastasis, recurrence and mortality. Results from these studies have provided initial evidence for the inhibition of cell migration in breast cancer by beta-blockers and have introduced the beta-adrenergic receptor pathways as a target for therapy. This paper analyzes gene expression profiles in breast cancer patients, utilising Artificial Neural Networks (ANNs to identify molecular signatures corresponding to possible disease management pathways and biomarker treatment strategies associated with beta-2-adrenergic receptor (ADRB2 cell signaling. The adrenergic receptor relationship to cancer is investigated in order to validate the results of recent studies that suggest the use of beta-blockers for breast cancer therapy. A panel of genes is identified which has previously been reported to play an important role in cancer and also to be involved in the beta-adrenergic receptor signaling.

  12. Biomarker identification in breast cancer: Beta-adrenergic receptor signaling and pathways to therapeutic response.

    Science.gov (United States)

    Kafetzopoulou, Liana E; Boocock, David J; Dhondalay, Gopal Krishna R; Powe, Desmond G; Ball, Graham R

    2013-01-01

    Recent preclinical studies have associated beta-adrenergic receptor (β-AR) signaling with breast cancer pathways such as progression and metastasis. These findings have been supported by clinical and epidemiological studies which examined the effect of beta-blocker therapy on breast cancer metastasis, recurrence and mortality. Results from these studies have provided initial evidence for the inhibition of cell migration in breast cancer by beta-blockers and have introduced the beta-adrenergic receptor pathways as a target for therapy. This paper analyzes gene expression profiles in breast cancer patients, utilising Artificial Neural Networks (ANNs) to identify molecular signatures corresponding to possible disease management pathways and biomarker treatment strategies associated with beta-2-adrenergic receptor (ADRB2) cell signaling. The adrenergic receptor relationship to cancer is investigated in order to validate the results of recent studies that suggest the use of beta-blockers for breast cancer therapy. A panel of genes is identified which has previously been reported to play an important role in cancer and also to be involved in the beta-adrenergic receptor signaling.

  13. Monocyte / macrophage inflammatory response pathways to combat Francisella infection: possible therapeutic targets?

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    Devyn D Gillette

    2014-02-01

    Full Text Available Francisella tularensis can bypass and suppress host immune responses, even to the point of manipulating immune cell phenotypes and intercellular inflammatory networks. Strengthening these responses such that immune cells more readily identify and destroy the bacteria is likely to become a viable (and perhaps necessary strategy for combating infections with Francisella, especially given the likelihood of antibiotic resistance in the foreseeable future. Monocytes and macrophages offer a niche wherein Francisella can invade and replicate, resulting in substantially higher bacterial load that can overcome the host. As such, understanding their responses to Francisella may uncover potential avenues of therapy that could promote a lowering of bacterial burden and clearance of infection. These response pathways include Toll-like Receptor 2 (TLR2, the caspase-1 inflammasome, Interferons, NADPH oxidase, Phosphatidylinositide 3-kinase (PI3K and the Ras pathway. In this review we summarize the literature pertaining to the roles of these pathways during Francisella infection, with an emphasis on monocyte / macrophage responses. The therapeutic targeting of one or more such pathways may ultimately become a valuable tool for the treatment of tularemia, and several possibilities are discussed.

  14. Aging causes decreased resistance to multiple stresses and a failure to activate specific stress response pathways

    Science.gov (United States)

    Bergsma, Alexis L.; Senchuk, Megan M.; Van Raamsdonk, Jeremy M.

    2016-01-01

    In this work, we examine the relationship between stress resistance and aging. We find that resistance to multiple types of stress peaks during early adulthood and then declines with age. To dissect the underlying mechanisms, we use C. elegans transcriptional reporter strains that measure the activation of different stress responses including: the heat shock response, mitochondrial unfolded protein response, endoplasmic reticulum unfolded protein response, hypoxia response, SKN-1-mediated oxidative stress response, and the DAF-16-mediated stress response. We find that the decline in stress resistance with age is at least partially due to a decreased ability to activate protective mechanisms in response to stress. In contrast, we find that any baseline increase in stress caused by the advancing age is too mild to detectably upregulate any of the stress response pathways. Further exploration of how worms respond to stress with increasing age revealed that the ability to mount a hormetic response to heat stress is also lost with increasing age. Overall, this work demonstrates that resistance to all types of stress declines with age. Based on our data, we speculate that the decrease in stress resistance with advancing age results from a genetically-programmed inactivation of stress response pathways, not accumulation of damage. PMID:27053445

  15. Neural mechanisms underlying the conditioned diminution of the unconditioned fear response.

    Science.gov (United States)

    Wood, Kimberly H; Ver Hoef, Lawrence W; Knight, David C

    2012-03-01

    Recognizing cues that predict an aversive event allows one to react more effectively under threatening conditions, and minimizes the reaction to the threat itself. This is demonstrated during Pavlovian fear conditioning when the unconditioned response (UCR) to a predictable unconditioned stimulus (UCS) is diminished compared to the UCR to an unpredictable UCS. The present study investigated the functional magnetic resonance imaging (fMRI) signal response associated with Pavlovian conditioned UCR diminution to better understand the relationship between individual differences in behavior and the neural mechanisms of the threat-related emotional response. Healthy volunteers participated in a fear conditioning study in which trait anxiety, skin conductance response (SCR), UCS expectancy, and the fMRI signal were assessed. During acquisition trials, a tone (CS+) was paired with a white noise UCS and a second tone (CS-) was presented without the UCS. Test trials consisted of the CS+ paired with the UCS, CS- paired with the UCS, and presentations of the UCS alone to assess conditioned UCR diminution. UCR diminution was observed within the dorsolateral PFC, dorsomedial PFC, cingulate cortex, inferior parietal lobule (IPL), anterior insula, and amygdala. The threat-related activity within the dorsolateral PFC, dorsomedial PFC, posterior cingulate cortex, and IPL varied with individual differences in trait anxiety. In addition, anticipatory (i.e. CS elicited) activity within the PFC showed an inverse relationship with threat-related (i.e. UCS elicited) activity within the PFC, IPL, and amygdala. Further, the emotional response (indexed via SCR) elicited by the threat was closely linked to amygdala activity. These findings are consistent with the view that the amygdala and PFC support learning-related processes that influence the emotional response evoked by a threat. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. Neural Hyperactivity of the Central Auditory System in Response to Peripheral Damage

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    Yi Zhao

    2016-01-01

    Full Text Available It is increasingly appreciated that cochlear pathology is accompanied by adaptive responses in the central auditory system. The cause of cochlear pathology varies widely, and it seems that few commonalities can be drawn. In fact, despite intricate internal neuroplasticity and diverse external symptoms, several classical injury models provide a feasible path to locate responses to different peripheral cochlear lesions. In these cases, hair cell damage may lead to considerable hyperactivity in the central auditory pathways, mediated by a reduction in inhibition, which may underlie some clinical symptoms associated with hearing loss, such as tinnitus. Homeostatic plasticity, the most discussed and acknowledged mechanism in recent years, is most likely responsible for excited central activity following cochlear damage.

  17. Molecular Responses to Aphid Feeding in Arabidopsis in Relation to Plant Defense Pathways1

    Science.gov (United States)

    Moran, Patrick J.; Thompson, Gary A.

    2001-01-01

    Little is known about molecular responses in plants to phloem feeding by insects. The induction of genes associated with wound and pathogen response pathways was investigated following green peach aphid (Myzus persicae) feeding on Arabidopsis. Aphid feeding on rosette leaves induced transcription of two genes associated with salicylic acid (SA)-dependent responses to pathogens (PR-1 and BGL2) 10- and 23-fold, respectively. Induction of PR-1 and BGL2 mRNA was reduced in npr1 mutant plants, which are deficient in SA signaling. Application of the SA analog benzothiadiazole led to decreases in aphid reproduction on leaves of both wild-type plants and mutant plants deficient in responsiveness to SA, suggesting that wild-type SA-dependent responses do not influence resistance to aphids. Two-fold increases occurred in mRNA levels of PDF1.2, which encodes defensin, a peptide involved in the jasmonate (JA)-/ethylene-dependent response pathway. Transcripts encoding JA-inducible lipoxygenase (LOX2) and SA/JA-inducible Phe-ammonia lyase increased 1.5- to 2-fold. PDF1.2 and LOX2 induction by aphids did not occur in infested leaves of the JA-resistant coi1-1 mutant. Aphid feeding induced 10-fold increases in mRNA levels of a stress-related monosaccharide symporter gene, STP4. Phloem feeding on Arabidopsis leads to stimulation of response pathways associated with both pathogen infection and wounding. PMID:11161062

  18. A translational study on looming-evoked defensive response and the underlying subcortical pathway in autism.

    Science.gov (United States)

    Hu, Yu; Chen, Zhuoming; Huang, Lu; Xi, Yue; Li, Bingxiao; Wang, Hong; Yan, Jiajian; Lee, Tatia M C; Tao, Qian; So, Kwok-Fai; Ren, Chaoran

    2017-11-07

    Rapidly approaching objects indicating threats can induce defensive response through activating a subcortical pathway comprising superior colliculus (SC), lateral posterior nucleus (LP), and basolateral amygdala (BLA). Abnormal defensive response has been reported in autism, and impaired synaptic connections could be the underlying mechanism. Whether the SC-LP-BLA pathway processes looming stimuli abnormally in autism is not clear. Here, we found that looming-evoked defensive response is impaired in a subgroup of the valproic acid (VPA) mouse model of autism. By combining the conventional neurotracer and transneuronal rabies virus tracing techniques, we demonstrated that synaptic connections in the SC-LP-BLA pathway were abnormal in VPA mice whose looming-evoked defensive responses were absent. Importantly, we further translated the finding to children with autism and observed that they did not present looming-evoked defensive response. Furthermore, the findings of the DTI with the probabilistic tractography showed that the structural connections of SC-pulvinar-amygdala in autism children were weak. The pulvinar is parallel to the LP in a mouse. Because looming-evoked defensive response is innate in humans and emerges much earlier than do social and language functions, the absence of defensive response could be an earlier sign of autism in children.

  19. Neural correlates of fast stimulus discrimination and response selection in top-level fencers.

    Science.gov (United States)

    Di Russo, Francesco; Taddei, Francesco; Apnile, Teresa; Spinelli, Donatella

    2006-11-13

    Flexible adaptation of behaviour is highly required in some sports, such as fencing. In particular, stimulus discrimination and motor response selection and inhibition processes are crucial. We investigated the neural mechanisms responsible for fencers' fast and flexible behaviour recording event-related potentials (ERPs) in discriminative reaction task (DRT, Go/No-go task) and simple reaction task (SRT) to visual stimuli. In the DRT, in addition to faster RTs measured in fencers with respect to control subjects, three main electrophysiological differences were found. First, attentional modulation of the visual processing taking place in the occipital lobes and reaching a peak at 170 ms was enhanced in the athletes group. Second, the activity in the posterior cingulate gyrus, associated with the stimulus discrimination stage, started earlier in fencers than controls (150 ms versus 200 ms) and the peak had larger amplitude. Third, the activity at the level of the prefrontal cortex (time range: 250-350 ms), associated with response selection stage and particularly with motor inhibition process, was stronger in fencers. No differences between athletes and controls were found in the SRT for both ERPs and RTs. Concluding, the fencers' ability to cope to the opponent feint switching quickly from an intended action to a new more appropriate action is likely due to a faster stimulus discrimination facilitated by higher attention and by stronger inhibition activity in prefrontal cortex.

  20. Blunted feelings: alexithymia is associated with a diminished neural response to speech prosody.

    Science.gov (United States)

    Goerlich-Dobre, Katharina Sophia; Witteman, Jurriaan; Schiller, Niels O; van Heuven, Vincent J P; Aleman, André; Martens, Sander

    2014-08-01

    How we perceive emotional signals from our environment depends on our personality. Alexithymia, a personality trait characterized by difficulties in emotion regulation has been linked to aberrant brain activity for visual emotional processing. Whether alexithymia also affects the brain's perception of emotional speech prosody is currently unknown. We used functional magnetic resonance imaging to investigate the impact of alexithymia on hemodynamic activity of three a priori regions of the prosody network: the superior temporal gyrus (STG), the inferior frontal gyrus and the amygdala. Twenty-two subjects performed an explicit task (emotional prosody categorization) and an implicit task (metrical stress evaluation) on the same prosodic stimuli. Irrespective of task, alexithymia was associated with a blunted response of the right STG and the bilateral amygdalae to angry, surprised and neutral prosody. Individuals with difficulty describing feelings deactivated the left STG and the bilateral amygdalae to a lesser extent in response to angry compared with neutral prosody, suggesting that they perceived angry prosody as relatively more salient than neutral prosody. In conclusion, alexithymia may be associated with a generally blunted neural response to speech prosody. Such restricted prosodic processing may contribute to problems in social communication associated with this personality trait. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  1. Corticostriatal response selection in sentence production: Insights from neural network simulation with reservoir computing.

    Science.gov (United States)

    Hinaut, Xavier; Lance, Florian; Droin, Colas; Petit, Maxime; Pointeau, Gregoire; Dominey, Peter Ford

    2015-11-01

    Language production requires selection of the appropriate sentence structure to accommodate the communication goal of the speaker - the transmission of a particular meaning. Here we consider event meanings, in terms of predicates and thematic roles, and we address the problem that a given event can be described from multiple perspectives, which poses a problem of response selection. We present a model of response selection in sentence production that is inspired by the primate corticostriatal system. The model is implemented in the context of reservoir computing where the reservoir - a recurrent neural network with fixed connections - corresponds to cortex, and the readout corresponds to the striatum. We demonstrate robust learning, and generalization properties of the model, and demonstrate its cross linguistic capabilities in English and Japanese. The results contribute to the argument that the corticostriatal system plays a role in response selection in language production, and to the stance that reservoir computing is a valid potential model of corticostriatal processing. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Concise Review: Reprogramming, Behind the Scenes: Noncanonical Neural Stem Cell Signaling Pathways Reveal New, Unseen Regulators of Tissue Plasticity With Therapeutic Implications.

    Science.gov (United States)

    Poser, Steven W; Chenoweth, Josh G; Colantuoni, Carlo; Masjkur, Jimmy; Chrousos, George; Bornstein, Stefan R; McKay, Ronald D; Androutsellis-Theotokis, Andreas

    2015-11-01

    Interest is great in the new molecular concepts that explain, at the level of signal transduction, the process of reprogramming. Usually, transcription factors with developmental importance are used, but these approaches give limited information on the signaling networks involved, which could reveal new therapeutic opportunities. Recent findings involving reprogramming by genetic means and soluble factors with well-studied downstream signaling mechanisms, including signal transducer and activator of transcription 3 (STAT3) and hairy and enhancer of split 3 (Hes3), shed new light into the molecular mechanisms that might be involved. We examine the appropriateness of common culture systems and their ability to reveal unusual (noncanonical) signal transduction pathways that actually operate in vivo. We then discuss such novel pathways and their importance in various plastic cell types, culminating in their emerging roles in reprogramming mechanisms. We also discuss a number of reprogramming paradigms (mouse induced pluripotent stem cells, direct conversion to neural stem cells, and in vivo conversion of acinar cells to β-like cells). Specifically for acinar-to-β-cell reprogramming paradigms, we discuss the common view of the underlying mechanism (involving the Janus kinase-STAT pathway that leads to STAT3-tyrosine phosphorylation) and present alternative interpretations that implicate STAT3-serine phosphorylation alone or serine and tyrosine phosphorylation occurring in sequential order. The implications for drug design and therapy are important given that different phosphorylation sites on STAT3 intercept different signaling pathways. We introduce a new molecular perspective in the field of reprogramming with broad implications in basic, biotechnological, and translational research. Reprogramming is a powerful approach to change cell identity, with implications in both basic and applied biology. Most efforts involve the forced expression of key transcription

  3. Behavioral and neural responses of toads to salt solutions correlate with basolateral membrane potential of epidermal cells of the skin

    DEFF Research Database (Denmark)

    Hillyard, Stanley D; Baula, Victor; Tuttle, Wendy

    2007-01-01

    low, V(b) transiently hyperpolarized to values near the equilibrium potential for K(+) and corresponded with the reduced neural response. These results support the hypothesis that chemosensory function of the skin is analogous to that of mammalian taste cells but utilizes paracellular ion transport...

  4. The Pentose Phosphate Pathway Is a Metabolic Redox Sensor and Regulates Transcription During the Antioxidant Response

    NARCIS (Netherlands)

    Kruger, A.; Gruning, N.M.; Wamelink, M.M.C.; Kerick, M.; Kirpy, A.; Parkhomchuk, D.; Bluemlein, K.; Schweiger, M.R.; Soldatov, A.; Lehrach, H.; Jakobs, C.A.J.M.; Ralser, M.

    2011-01-01

    Aims: A shift in primary carbon metabolism is the fastest response to oxidative stress. Induced within seconds, it precedes transcriptional regulation, and produces reducing equivalents in form of NADPH within the pentose phosphate pathway (PPP). Results: Here, we provide evidence for a regulatory

  5. Phytohormone signaling pathway analysis method for comparing hormone responses in plant-pest interactions

    Directory of Open Access Journals (Sweden)

    Studham Matthew E

    2012-07-01

    Full Text Available Abstract Background Phytohormones mediate plant defense responses to pests and pathogens. In particular, the hormones jasmonic acid, ethylene, salicylic acid, and abscisic acid have been shown to dictate and fine-tune defense responses, and identification of the phytohormone components of a particular defense response is commonly used to characterize it. Identification of phytohormone regulation is particularly important in transcriptome analyses. Currently there is no computational tool to determine the relative activity of these hormones that can be applied to transcriptome analyses in soybean. Findings We developed a pathway analysis method that provides a broad measure of the activation or suppression of individual phytohormone pathways based on changes in transcript expression of pathway-related genes. The magnitude and significance of these changes are used to determine a pathway score for a phytohormone for a given comparison in a microarray experiment. Scores for individual hormones can then be compared to determine the dominant phytohormone in a given defense response. To validate this method, it was applied to publicly available data from previous microarray experiments that studied the response of soybean plants to Asian soybean rust and soybean cyst nematode. The results of the analyses for these experiments agreed with our current understanding of the role of phytohormones in these defense responses. Conclusions This method is useful in providing a broad measure of the relative induction and suppression of soybean phytohormones during a defense response. This method could be used as part of microarray studies that include individual transcript analysis, gene set analysis, and other methods for a comprehensive defense response characterization.

  6. Platelet-rich plasma for regeneration of neural feedback pathways around dental implants: a concise review and outlook on future possibilities

    Science.gov (United States)

    Huang, Yan; Bornstein, Michael M; Lambrichts, Ivo; Yu, Hai-Yang; Politis, Constantinus; Jacobs, Reinhilde

    2017-01-01

    Along with the development of new materials, advanced medical imaging and surgical techniques, osseointegrated dental implants are considered a successful and constantly evolving treatment modality for the replacement of missing teeth in patients with complete or partial edentulism. The importance of restoring the peripheral neural feedback pathway and thus repairing the lack of periodontal mechanoreceptors after tooth extraction has been highlighted in the literature. Nevertheless, regenerating the nerve fibers and reconstructing the neural feedback pathways around osseointegrated implants remain a challenge. Recent studies have provided evidence that platelet-rich plasma (PRP) therapy is a promising treatment for musculoskeletal injuries. Because of its high biological safety, convenience and usability, PRP therapy has gradually gained popularity in the clinical field. Although much remains to be learned, the growth factors from PRP might play key roles in peripheral nerve repair mechanisms. This review presents known growth factors contributing to the biological efficacy of PRP and illustrates basic and (pre-)clinical evidence regarding the use of PRP and its relevant products in peripheral nerve regeneration. In addition, the potential of local application of PRP for structural and functional recovery of injured peripheral nerves around dental implants is discussed. PMID:28282030

  7. Ebola Virus Altered Innate and Adaptive Immune Response Signalling Pathways: Implications for Novel Therapeutic Approaches.

    Science.gov (United States)

    Kumar, Anoop

    2016-01-01

    Ebola virus (EBOV) arise attention for their impressive lethality by the poor immune response and high inflammatory reaction in the patients. It causes a severe hemorrhagic fever with case fatality rates of up to 90%. The mechanism underlying this lethal outcome is poorly understood. In 2014, a major outbreak of Ebola virus spread amongst several African countries, including Leone, Sierra, and Guinea. Although infections only occur frequently in Central Africa, but the virus has the potential to spread globally. Presently, there is no vaccine or treatment is available to counteract Ebola virus infections due to poor understanding of its interaction with the immune system. Accumulating evidence indicates that the virus actively alters both innate and adaptive immune responses and triggers harmful inflammatory responses. In the literature, some reports have shown that alteration of immune signaling pathways could be due to the ability of EBOV to interfere with dendritic cells (DCs), which link innate and adaptive immune responses. On the other hand, some reports have demonstrated that EBOV, VP35 proteins act as interferon antagonists. So, how the Ebola virus altered the innate and adaptive immune response signaling pathways is still an open question for the researcher to be explored. Thus, in this review, I try to summarize the mechanisms of the alteration of innate and adaptive immune response signaling pathways by Ebola virus which will be helpful for designing effective drugs or vaccines against this lethal infection. Further, potential targets, current treatment and novel therapeutic approaches have also been discussed.

  8. Neural responses in songbird forebrain reflect learning rates, acquired salience, and stimulus novelty after auditory discrimination training

    Science.gov (United States)

    Phan, Mimi L.; Vicario, David S.

    2014-01-01

    How do social interactions form and modulate the neural representations of specific complex signals? This question can be addressed in the songbird auditory system. Like humans, songbirds learn to vocalize by imitating tutors heard during development. These learned vocalizations are important in reproductive and social interactions and in individual recognition. As a model for the social reinforcement of particular songs, male zebra finches were trained to peck for a food reward in response to one song stimulus (GO) and to withhold responding for another (NoGO). After performance reached criterion, single and multiunit neural responses to both trained and novel stimuli were obtained from multiple electrodes inserted bilaterally into two songbird auditory processing areas [caudomedial mesopallium (CMM) and caudomedial nidopallium (NCM)] of awake, restrained birds. Neurons in these areas undergo stimulus-specific adaptation to repeated song stimuli, and responses to familiar stimuli adapt more slowly than to novel stimuli. The results show that auditory responses differed in NCM and CMM for trained (GO and NoGO) stimuli vs. novel song stimuli. When subjects were grouped by the number of training days required to reach criterion, fast learners showed larger neural responses and faster stimulus-specific adaptation to all stimuli than slow learners in both areas. Furthermore, responses in NCM of fast learners were more strongly left-lateralized than in slow learners. Thus auditory responses in these sensory areas not only encode stimulus familiarity, but also reflect behavioral reinforcement in our paradigm, and can potentially be modulated by social interactions. PMID:25475353

  9. Second language processing shows increased native-like neural responses after months of no exposure.

    Science.gov (United States)

    Morgan-Short, Kara; Finger, Ingrid; Grey, Sarah; Ullman, Michael T

    2012-01-01

    Although learning a second language (L2) as an adult is notoriously difficult, research has shown that adults can indeed attain native language-like brain processing and high proficiency levels. However, it is important to then retain what has been attained, even in the absence of continued exposure to the L2--particularly since periods of minimal or no L2 exposure are common. This event-related potential (ERP) study of an artificial language tested performance and neural processing following a substantial period of no exposure. Adults learned to speak and comprehend the artificial language to high proficiency with either explicit, classroom-like, or implicit, immersion-like training, and then underwent several months of no exposure to the language. Surprisingly, proficiency did not decrease during this delay. Instead, it remained unchanged, and there was an increase in native-like neural processing of syntax, as evidenced by several ERP changes--including earlier, more reliable, and more left-lateralized anterior negativities, and more robust P600s, in response to word-order violations. Moreover, both the explicitly and implicitly trained groups showed increased native-like ERP patterns over the delay, indicating that such changes can hold independently of L2 training type. The results demonstrate that substantial periods with no L2 exposure are not necessarily detrimental. Rather, benefits may ensue from such periods of time even when there is no L2 exposure. Interestingly, both before and after the delay the implicitly trained group showed more native-like processing than the explicitly trained group, indicating that type of training also affects the attainment of native-like processing in the brain. Overall, the findings may be largely explained by a combination of forgetting and consolidation in declarative and procedural memory, on which L2 grammar learning appears to depend. The study has a range of implications, and suggests a research program with

  10. Vocal and Neural Responses to Unexpected Changes in Voice Pitch Auditory Feedback During Register Transitions.

    Science.gov (United States)

    Patel, Sona; Lodhavia, Anjli; Frankford, Saul; Korzyukov, Oleg; Larson, Charles R

    2016-11-01

    It is known that singers are able to control their voice to maintain a relatively constant vocal quality while transitioning between vocal registers; however, the neural mechanisms underlying this effect are not understood. It was hypothesized that greater attention to the acoustical feedback of the voice and increased control of the vocal musculature during register transitions compared with singing within a register would be represented as neurological differences in event-related potentials. Nine singers sang musical notes at the high end of the modal register (the boundary between the modal and the head/falsetto registers) and at the low end (the boundary between the modal and the fry/pulse registers). While singing, the pitch of the voice auditory feedback was unexpectedly shifted either into the adjacent register ("toward" the register boundary) or within the modal register ("away from" the boundary). Singers were instructed to maintain a constant pitch and ignore any changes to their voice feedback. Vocal response latencies and magnitude of the accompanying N1 and P2 event-related potentials were greatest at the lower (modal-to-fry) boundary when the pitch shift carried the subjects' voices into the fry register as opposed to remaining within the modal register. These findings suggest that when a singer lowers the pitch of his or her voice such that it enters the fry register from the modal register, there is increased sensory-motor control of the voice, reflected as increased magnitude of the neural potentials to help minimize qualitative changes in the voice. Copyright © 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  11. Second language processing shows increased native-like neural responses after months of no exposure.

    Directory of Open Access Journals (Sweden)

    Kara Morgan-Short

    Full Text Available Although learning a second language (L2 as an adult is notoriously difficult, research has shown that adults can indeed attain native language-like brain processing and high proficiency levels. However, it is important to then retain what has been attained, even in the absence of continued exposure to the L2--particularly since periods of minimal or no L2 exposure are common. This event-related potential (ERP study of an artificial language tested performance and neural processing following a substantial period of no exposure. Adults learned to speak and comprehend the artificial language to high proficiency with either explicit, classroom-like, or implicit, immersion-like training, and then underwent several months of no exposure to the language. Surprisingly, proficiency did not decrease during this delay. Instead, it remained unchanged, and there was an increase in native-like neural processing of syntax, as evidenced by several ERP changes--including earlier, more reliable, and more left-lateralized anterior negativities, and more robust P600s, in response to word-order violations. Moreover, both the explicitly and implicitly trained groups showed increased native-like ERP patterns over the delay, indicating that such changes can hold independently of L2 training type. The results demonstrate that substantial periods with no L2 exposure are not necessarily detrimental. Rather, benefits may ensue from such periods of time even when there is no L2 exposure. Interestingly, both before and after the delay the implicitly trained group showed more native-like processing than the explicitly trained group, indicating that type of training also affects the attainment of native-like processing in the brain. Overall, the findings may be largely explained by a combination of forgetting and consolidation in declarative and procedural memory, on which L2 grammar learning appears to depend. The study has a range of implications, and suggests a research

  12. Vocal and neural responses to unexpected changes in voice pitch auditory feedback during register transitions

    Science.gov (United States)

    Patel, Sona; Lodhavia, Anjli; Frankford, Saul; Korzyukov, Oleg; Larson, Charles R.

    2016-01-01

    Objective/Hypothesis It is known that singers are able to control their voice to maintain a relatively constant vocal quality while transitioning between vocal registers; however, the neural mechanisms underlying this effect are not understood. It was hypothesized that greater attention to the acoustical feedback of the voice and increased control of the vocal musculature during register transitions compared to singing within a register would be represented as neurological differences in event-related potentials (ERPs). Study Design/Methods Nine singers sang musical notes at the high end of the modal register (the boundary between the modal and head/falsetto registers) and at the low end (the boundary between the modal and fry/pulse registers). While singing, the pitch of the voice auditory feedback was unexpectedly shifted either into the adjacent register (“toward” the register boundary) or within the modal register (“away from” the boundary). Singers were instructed to maintain a constant pitch and ignore any changes to their voice feedback. Results Vocal response latencies and magnitude of the accompanying N1 and P2 ERPs were greatest at the lower (modal-fry) boundary when the pitch shift carried the subjects’ voices into the fry register as opposed to remaining within the modal register. Conclusions These findings suggest that when a singer lowers the pitch of their voice such that it enters the fry register from the modal register, there is increased sensory-motor control of the voice, reflected as increased magnitude of the neural potentials to help minimize qualitative changes in the voice. PMID:26739860

  13. Neural responses during social and self-knowledge tasks in bulimia nervosa

    Directory of Open Access Journals (Sweden)

    Carrie J Mcadams

    2013-09-01

    Full Text Available Self-evaluation closely dependent upon body shape and weight is one of the defining criteria for bulimia nervosa. We studied 53 adult women, 17 with bulimia nervosa, 18 with a recent history of anorexia nervosa, and 18 healthy comparison women, using three different fMRI tasks that required thinking about self-knowledge and social interactions: the Social Identity task, the Physical Identity task, and the Social Attribution task. Previously, we identified regions of interest (ROI in the same tasks using whole brain voxel-wise comparisons of the healthy comparison women and women with a recent history of anorexia nervosa. Here, we report on the neural activations in those ROIs in subjects with bulimia nervosa. In the Social Attribution task, we examined activity in the right temporoparietal junction, an area frequently associated with mentalization. In the Social Identity task, we examined activity in the precuneus and dorsal anterior cingulate. In the Physical Identity task, we examined activity in a ventral region of the dorsal anterior cingulate. Interestingly, in all tested regions, the average activation in subjects with bulimia was more than the average activation levels seen in the subjects with a history of anorexia but less than that seen in healthy subjects. In three regions, the right temporoparietal junction, the precuneus, and the dorsal anterior cingulate, group responses in the subjects with bulimia were significantly different from healthy subjects but not subjects with anorexia. The neural activations of people with bulimia nervosa performing fMRI tasks engaging social processing are more similar to people with anorexia nervosa than healthy people. This suggests biological measures of social processes may be helpful in characterizing individuals with eating disorders.

  14. The neural cell adhesion molecule

    DEFF Research Database (Denmark)

    Berezin, V; Bock, E; Poulsen, F M

    2000-01-01

    During the past year, the understanding of the structure and function of neural cell adhesion has advanced considerably. The three-dimensional structures of several of the individual modules of the neural cell adhesion molecule (NCAM) have been determined, as well as the structure of the complex...... between two identical fragments of the NCAM. Also during the past year, a link between homophilic cell adhesion and several signal transduction pathways has been proposed, connecting the event of cell surface adhesion to cellular responses such as neurite outgrowth. Finally, the stimulation of neurite...

  15. Cellular stress response and innate immune signaling: integrating pathways in host defense and inflammation

    Science.gov (United States)

    Muralidharan, Sujatha; Mandrekar, Pranoti

    2013-01-01

    Extensive research in the past decade has identified innate immune recognition receptors and intracellular signaling pathways that culminate in inflammatory responses. Besides its role in cytoprotection, the importance of cell stress in inflammation and host defense against pathogens is emerging. Recent studies have shown that proteins in cellular stress responses, including the heat shock response, ER stress response, and DNA damage response, interact with and regulate signaling intermediates involved in the activation of innate and adaptive immune responses. The effect of such regulation by cell stress proteins may dictate the inflammatory profile of the immune response during infection and disease. In this review, we describe the regulation of innate immune cell activation by cell stress pathways, present detailed descriptions of the types of stress response proteins and their crosstalk with immune signaling intermediates that are essential in host defense, and illustrate the relevance of these interactions in diseases characteristic of aberrant immune responses, such as chronic inflammatory diseases, autoimmune disorders, and cancer. Understanding the crosstalk between cellular stress proteins and immune signaling may have translational implications for designing more effective regimens to treat immune disorders. PMID:23990626

  16. The CWI Pathway: Regulation of the Transcriptional Adaptive Response to Cell Wall Stress in Yeast

    Directory of Open Access Journals (Sweden)

    Ana Belén Sanz

    2017-12-01

    Full Text Available Fungi are surrounded by an essential structure, the cell wall, which not only confers cell shape but also protects cells from environmental stress. As a consequence, yeast cells growing under cell wall damage conditions elicit rescue mechanisms to provide maintenance of cellular integrity and fungal survival. Through transcriptional reprogramming, yeast modulate the expression of genes important for cell wall biogenesis and remodeling, metabolism and energy generation, morphogenesis, signal transduction and stress. The yeast cell wall integrity (CWI pathway, which is very well conserved in other fungi, is the key pathway for the regulation of this adaptive response. In this review, we summarize the current knowledge of the yeast transcriptional program elicited to counterbalance cell wall stress situations, the role of the CWI pathway in the regulation of this program and the importance of the transcriptional input received by other pathways. Modulation of this adaptive response through the CWI pathway by positive and negative transcriptional feedbacks is also discussed. Since all these regulatory mechanisms are well conserved in pathogenic fungi, improving our knowledge about them will have an impact in the developing of new antifungal therapies.

  17. Association genetics and transcriptome analysis reveal a gibberellin-responsive pathway involved in regulating photosynthesis.

    Science.gov (United States)

    Xie, Jianbo; Tian, Jiaxing; Du, Qingzhang; Chen, Jinhui; Li, Ying; Yang, Xiaohui; Li, Bailian; Zhang, Deqiang

    2016-05-01

    Gibberellins (GAs) regulate a wide range of important processes in plant growth and development, including photosynthesis. However, the mechanism by which GAs regulate photosynthesis remains to be understood. Here, we used multi-gene association to investigate the effect of genes in the GA-responsive pathway, as constructed by RNA sequencing, on photosynthesis, growth, and wood property traits, in a population of 435 Populus tomentosa By analyzing changes in the transcriptome following GA treatment, we identified many key photosynthetic genes, in agreement with the observed increase in measurements of photosynthesis. Regulatory motif enrichment analysis revealed that 37 differentially expressed genes related to photosynthesis shared two essential GA-related cis-regulatory elements, the GA response element and the pyrimidine box. Thus, we constructed a GA-responsive pathway consisting of 47 genes involved in regulating photosynthesis, including GID1, RGA, GID2, MYBGa, and 37 photosynthetic differentially expressed genes. Single nucleotide polymorphism (SNP)-based association analysis showed that 142 SNPs, representing 40 candidate genes in this pathway, were significantly associated with photosynthesis, growth, and wood property traits. Epistasis analysis uncovered interactions between 310 SNP-SNP pairs from 37 genes in this pathway, revealing possible genetic interactions. Moreover, a structural gene-gene matrix based on a time-course of transcript abundances provided a better understanding of the multi-gene pathway affecting photosynthesis. The results imply a functional role for these genes in mediating photosynthesis, growth, and wood properties, demonstrating the potential of combining transcriptome-based regulatory pathway construction and genetic association approaches to detect the complex genetic networks underlying quantitative traits. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights

  18. Contributions of DNA repair and damage response pathways to the non-linear genotoxic responses of alkylating agents

    Science.gov (United States)

    Klapacz, Joanna; Pottenger, Lynn H.; Engelward, Bevin P.; Heinen, Christopher D.; Johnson, George E.; Clewell, Rebecca A.; Carmichael, Paul L.; Adeleye, Yeyejide; Andersen, Melvin E.

    2016-01-01

    From a risk assessment perspective, DNA-reactive agents are conventionally assumed to have genotoxic risks at all exposure levels, thus applying a linear extrapolation for low-dose responses. New approaches discussed here, including more diverse and sensitive methods for assessing DNA damage and DNA repair, strongly support the existence of measurable regions where genotoxic responses with increasing doses are insignificant relative to control. Model monofunctional alkylating agents have in vitro and in vivo datasets amenable to determination of points of departure (PoDs) for genotoxic effects. A session at the 2013 Society of Toxicology meeting provided an opportunity to survey the progress in understanding the biological basis of empirically-observed PoDs for DNA alkylating agents. Together with the literature published since, this review discusses cellular pathways activated by endogenous and exogenous alkylation DNA damage. Cells have evolved conserved processes that monitor and counteract a spontaneous steady-state level of DNA damage. The ubiquitous network of DNA repair pathways serves as the first line of defense for clearing of the DNA damage and preventing mutation. Other biological pathways discussed here that are activated by genotoxic stress include post-translational activation of cell cycle networks and transcriptional networks for apoptosis/cell death. The interactions of various DNA repair and DNA damage response pathways provide biological bases for the observed PoD behaviors seen with genotoxic compounds. Thus, after formation of DNA adducts, the activation of cellular pathways can lead to the avoidance a mutagenic outcome. The understanding of the cellular mechanisms acting within the low-dose region will serve to better characterize risks from exposures to DNA-reactive agents at environmentally-relevant concentrations. PMID:27036068

  19. Oxytocin receptor gene variations predict neural and behavioral response to oxytocin in autism

    Science.gov (United States)

    Watanabe, Takamitsu; Otowa, Takeshi; Abe, Osamu; Kuwabara, Hitoshi; Aoki, Yuta; Natsubori, Tatsunobu; Takao, Hidemasa; Kakiuchi, Chihiro; Kondo, Kenji; Ikeda, Masashi; Iwata, Nakao; Kasai, Kiyoto; Sasaki, Tsukasa

    2017-01-01

    Abstract Oxytocin appears beneficial for autism spectrum disorder (ASD), and more than 20 single-nucleotide polymorphisms (SNPs) in oxytocin receptor (OXTR) are relevant to ASD. However, neither biological functions of OXTR SNPs in ASD nor critical OXTR SNPs that determine oxytocin’s effects on ASD remains known. Here, using a machine-learning algorithm that was designed to evaluate collective effects of multiple SNPs and automatically identify most informative SNPs, we examined relationships between 27 representative OXTR SNPs and six types of behavioral/neural response to oxytocin in ASD individuals. The oxytocin effects were extracted from our previous placebo-controlled within-participant clinical trial administering single-dose intranasal oxytocin to 38 high-functioning adult Japanese ASD males. Consequently, we identified six different SNP sets that could accurately predict the six different oxytocin efficacies, and confirmed the robustness of these SNP selections against variations of the datasets and analysis parameters. Moreover, major alleles of several prominent OXTR SNPs—including rs53576 and rs2254298—were found to have dissociable effects on the oxytocin efficacies. These findings suggest biological functions of the OXTR SNP variants on autistic oxytocin responses, and implied that clinical oxytocin efficacy may be genetically predicted before its actual administration, which would contribute to establishment of future precision medicines for ASD. PMID:27798253

  20. Adolescent neural response to reward is related to participant sex and task motivation.

    Science.gov (United States)

    Alarcón, Gabriela; Cservenka, Anita; Nagel, Bonnie J

    2017-02-01

    Risky decision making is prominent during adolescence, perhaps contributed to by heightened sensation seeking and ongoing maturation of reward and dopamine systems in the brain, which are, in part, modulated by sex hormones. In this study, we examined sex differences in the neural substrates of reward sensitivity during a risky decision-making task and hypothesized that compared with girls, boys would show heightened brain activation in reward-relevant regions, particularly the nucleus accumbens, during reward receipt. Further, we hypothesized that testosterone and estradiol levels would mediate this sex difference. Moreover, we predicted boys would make more risky choices on the task. While boys showed increased nucleus accumbens blood oxygen level-dependent (BOLD) response relative to girls, sex hormones did not mediate this effect. As predicted, boys made a higher percentage of risky decisions during the task. Interestingly, boys also self-reported more motivation to perform well and earn money on the task, while girls self-reported higher state anxiety prior to the scan session. Motivation to earn money partially mediated the effect of sex on nucleus accumbens activity during reward. Previous research shows that increased motivation and salience of reinforcers is linked with more robust striatal BOLD response, therefore psychosocial factors, in addition to sex, may play an important role in reward sensitivity. Elucidating neurobiological mechanisms that support adolescent sex differences in risky decision making has important implications for understanding individual differences that lead to advantageous and adverse behaviors that affect health outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. From Agents to Objects: Sexist Attitudes and Neural Responses to Sexualized Targets

    Science.gov (United States)

    Cikara, Mina; Eberhardt, Jennifer L.; Fiske, Susan T.

    2013-01-01

    Agency attribution is a hallmark of mind perception; thus, diminished attributions of agency may disrupt social-cognition processes typically elicited by human targets. The current studies examine the effect of perceivers’ sexist attitudes on associations of agency with, and neural responses to, images of sexualized and clothed men and women. In study 1, male (but not female) participants with higher hostile sexism scores more quickly associated sexualized women with first-person action verbs (“handle”) and clothed women with third-person action verbs (“handles”) than the inverse, as compared to their less sexist peers. In study 2, hostile sexism correlated negatively with activation of regions associated with mental state attribution—mPFC, posterior cingulate, temporal poles—but only when viewing sexualized women. Heterosexual men best recognized images of sexualized female bodies (but not faces), as compared with other targets’ bodies; however, neither face nor body recognition were related to hostile sexism, suggesting the fMRI findings are not explained by more or less attention to sexualized female targets. Diminished mental-state attribution is not unique to targets that people prefer to avoid, as in dehumanization of stigmatized people. The current studies demonstrate that appetitive social targets may elicit a similar response depending on perceivers’ attitudes toward them. PMID:20350187

  2. From agents to objects: sexist attitudes and neural responses to sexualized targets.

    Science.gov (United States)

    Cikara, Mina; Eberhardt, Jennifer L; Fiske, Susan T

    2011-03-01

    Agency attribution is a hallmark of mind perception; thus, diminished attributions of agency may disrupt social-cognition processes typically elicited by human targets. The current studies examine the effect of perceivers' sexist attitudes on associations of agency with, and neural responses to, images of sexualized and clothed men and women. In Study 1, male (but not female) participants with higher hostile sexism scores more quickly associated sexualized women with first-person action verbs ("handle") and clothed women with third-person action verbs ("handles") than the inverse, as compared to their less sexist peers. In Study 2, hostile sexism correlated negatively with activation of regions associated with mental state attribution-medial prefrontal cortex, posterior cingulate, temporal poles-but only when viewing sexualized women. Heterosexual men best recognized images of sexualized female bodies (but not faces), as compared with other targets' bodies; however, neither face nor body recognition was related to hostile sexism, suggesting that the fMRI findings are not explained by more or less attention to sexualized female targets. Diminished mental state attribution is not unique to targets that people prefer to avoid, as in dehumanization of stigmatized people. The current studies demonstrate that appetitive social targets may elicit a similar response depending on perceivers' attitudes toward them.

  3. Psychogenic and neural visual-cue response in PD dopamine dysregulation syndrome.

    Science.gov (United States)

    Loane, Clare; Wu, Kit; O'Sullivan, Sean S; Lawrence, Andrew D; Woodhead, Zoe; Lees, Andrew J; Piccini, Paola; Politis, Marios

    2015-11-01

    Dopamine dysregulation syndrome (DDS) in Parkinson's disease (PD) patients refers to the compulsive use of dopaminergic replacement therapy and has serious psycho-social consequences. Mechanisms underlying DDS are not clear although has been linked to dysfunctional brain reward networks. With fMRI, we investigate behavioral and neural response to drug-cues in six PD DDS patients and 12 PD control patients in both the ON and OFF medication state. Behavioral measures of liking, wanting and subjectively 'feeling ON medication' were also collected. Behaviorally, PD DDS patients feel less ON and want their drugs more at baseline compared to PD controls. Following drug-cue exposure, PD DDS patients feel significantly more ON medication, which correlates with significant increases in reward related regions. The results demonstrate that exposure to drug-cues increases the subjective feeling of being 'ON' medication which corresponds to dysfunctional activation in reward related regions in PD DDS patients. These findings should be extended in future studies. Visual stimuli being sufficient to elicit behavioral response through neuroadaptations could have direct implications to the management of addictive behavior. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Neural Responses to Truth Telling and Risk Propensity under Asymmetric Information.

    Science.gov (United States)

    Suzuki, Hideo; Misaki, Masaya; Krueger, Frank; Bodurka, Jerzy

    2015-01-01

    Trust is multi-dimensional because it can be characterized by subjective trust, trust antecedent, and behavioral trust. Previous research has investigated functional brain responses to subjective trust (e.g., a judgment of trustworthiness) or behavioral trust (e.g., decisions to trust) in perfect information, where all relevant information is available to all participants. In contrast, we conducted a novel examination of the patterns of functional brain activity to a trust antecedent, specifically truth telling, in asymmetric information, where one individual has more information than others, with the effect of varying risk propensity. We used functional magnetic resonance imaging (fMRI) and recruited 13 adults, who played the Communication Game, where they served as the "Sender" and chose either truth telling (true advice) or lie telling (false advice) regarding the best payment allocation for their partner. Our behavioral results revealed that subjects with recreational high risk tended to choose true advice. Moreover, fMRI results yielded that the choices of true advice were associated with increased cortical activation in the anterior rostral medial and frontopolar prefrontal cortices, middle frontal cortex, temporoparietal junction, and precuneus. Furthermore, when we specifically evaluated a role of the bilateral amygdala as the region of interest (ROI), decreased amygdala response was associated with high risk propensity, regardless of truth telling or lying. In conclusion, our results have implications for how differential functions of the cortical areas may contribute to the neural processing of truth telling.

  5. Neural and cortisol responses during play with human and computer partners in children with autism.

    Science.gov (United States)

    Edmiston, Elliot Kale; Merkle, Kristen; Corbett, Blythe A

    2015-08-01

    Children with autism spectrum disorder (ASD) exhibit impairment in reciprocal social interactions, including play, which can manifest as failure to show social preference or discrimination between social and nonsocial stimuli. To explore mechanisms underlying these deficits, we collected salivary cortisol from 42 children 8-12 years with ASD or typical development during a playground interaction with a confederate child. Participants underwent functional MRI during a prisoner's dilemma game requiring cooperation or defection with a human (confederate) or computer partner. Search region of interest analyses were based on previous research (e.g. insula, amygdala, temporal parietal junction-TPJ). There were significant group differences in neural activation based on partner and response pattern. When playing with a human partner, children with ASD showed limited engagement of a social salience brain circuit during defection. Reduced insula activation during defection in the ASD children relative to TD children, regardless of partner type, was also a prominent finding. Insula and TPJ BOLD during defection was also associated with stress responsivity and behavior in the ASD group under playground conditions. Children with ASD engage social salience networks less than TD children during conditions of social salience, supporting a fundamental disturbance of social engagement. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  6. Oxytocin receptor gene variations predict neural and behavioral response to oxytocin in autism.

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    Watanabe, Takamitsu; Otowa, Takeshi; Abe, Osamu; Kuwabara, Hitoshi; Aoki, Yuta; Natsubori, Tatsunobu; Takao, Hidemasa; Kakiuchi, Chihiro; Kondo, Kenji; Ikeda, Masashi; Iwata, Nakao; Kasai, Kiyoto; Sasaki, Tsukasa; Yamasue, Hidenori

    2017-03-01

    Oxytocin appears beneficial for autism spectrum disorder (ASD), and more than 20 single-nucleotide polymorphisms (SNPs) in oxytocin receptor (OXTR) are relevant to ASD. However, neither biological functions of OXTR SNPs in ASD nor critical OXTR SNPs that determine oxytocin's effects on ASD remains known. Here, using a machine-learning algorithm that was designed to evaluate collective effects of multiple SNPs and automatically identify most informative SNPs, we examined relationships between 27 representative OXTR SNPs and six types of behavioral/neural response to oxytocin in ASD individuals. The oxytocin effects were extracted from our previous placebo-controlled within-participant clinical trial administering single-dose intranasal oxytocin to 38 high-functioning adult Japanese ASD males. Consequently, we identified six different SNP sets that could accurately predict the six different oxytocin efficacies, and confirmed the robustness of these SNP selections against variations of the datasets and analysis parameters. Moreover, major alleles of several prominent OXTR SNPs-including rs53576 and rs2254298-were found to have dissociable effects on the oxytocin efficacies. These findings suggest biological functions of the OXTR SNP variants on autistic oxytocin responses, and implied that clinical oxytocin efficacy may be genetically predicted before its actual administration, which would contribute to establishment of future precision medicines for ASD. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  7. Menstrual cycle alters sympathetic neural responses to orthostatic stress in young, eumenorrheic women.

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    Carter, Jason R; Lawrence, Johnathan E; Klein, Jenna C

    2009-07-01

    Sympathetic baroreflex sensitivity (BRS) and muscle sympathetic nerve activity (MSNA) responses during early follicular (EF) and midluteal (ML) phases of the menstrual cycle are controversial. We hypothesize an augmented sympathetic BRS and MSNA response to orthostatic stress during the ML phase of the menstrual cycle. MSNA, mean arterial pressure (MAP), and heart rate (HR) were recorded during progressive lower body negative pressure (LBNP) (-5, -10, -15, -20, -30, and -40 mmHg; 3 min/stage) in 13 healthy, eumenorrheic women (age 21 +/- 1 yr). Sympathetic BRS was assessed by examining relations between spontaneous fluctuations of diastolic arterial pressure and MSNA at rest and during progressive LBNP. Plasma estradiol (42 +/- 6 vs. 112 +/- 12 pg/ml; P menstrual cycle. These findings suggest that hormonal fluctuations of eumenorrheic women may influence sympathoexcitation during an orthostatic challenge, but not through sympathetic baroreflex-mediated pathways.

  8. A model of the ethylene signaling pathway and its gene response in Arabidopsis thaliana: Pathway cross-talk and noise-filtering properties

    Science.gov (United States)

    Díaz, José; Álvarez-Buylla, Elena R.

    2006-06-01

    Dynamic models of molecular networks and pathways enable in silico evaluations of the consistency of proposed interactions and the outcomes of perturbations as well as of hypotheses on system-level structure and function. We postulate a continuous model of the activation dynamics of the ethylene response factor 1 (ERF1) gene in response to ethylene signaling. This activation elicits the response of the plant defensin 1 (PDF1) gene, which also responds to jasmonic acid, and the inhibition of the putative auxin responsive factor 2 (ARF2) gene, that also responds to auxin. Our model allows the effect of different ethylene concentrations in eliciting contrasting genetic and phenotypic responses to be evaluated allows the effect of different ethylene concentrations in eliciting contrasting genetic and phenotypic responses to be evaluated and seems to consider key components of the ethylene pathway because the ERF1 dose-response curve that we predict has the same qualitative form as the phenotypic dose-response curves obtained experimentally. Therefore, our model suggests that the phenotypic dose-response curves obtained experimentally could be due, at least in part, to ERF1 changes to different ethylene concentrations. Stability analyses show that the model's results are robust to parameter estimates. Of interest is that our model predicts that the ethylene pathway may filter stochastic and rapid chaotic fluctuations in ethylene availability. This novel approach may be applied to any cellular signaling and response pathway in plants and animals.

  9. Exact Bayesian bin classification: a fast alternative to Bayesian classification and its application to neural response analysis.

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    Endres, D; Földiák, P

    2008-02-01

    We investigate the general problem of signal classification and, in particular, that of assigning stimulus labels to neural spike trains recorded from single cortical neurons. Finding efficient ways of classifying neural responses is especially important in experiments involving rapid presentation of stimuli. We introduce a fast, exact alternative to Bayesian classification. Instead of estimating the class-conditional densities p(x|y) (where x is a scalar function of the feature[s], y the class label) and converting them to P(y|x) via Bayes' theorem, this probability is evaluated directly and without the need for approximations. This is achieved by integrating over all possible binnings of x with an upper limit on the number of bins. Computational time is quadratic in both the number of observed data points and the number of bins. The algorithm also allows for the computation of feedback signals, which can be used as input to subsequent stages of inference, e.g. neural network training. Responses of single neurons from high-level visual cortex (area STSa) to rapid sequences of complex visual stimuli are analysed. Information latency and response duration increase nonlinearly with presentation duration, suggesting that neural processing speeds adapt to presentation speeds.

  10. Stress Response Pathways in Ameloblasts: Implications for Amelogenesis and Dental Fluorosis

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    John D. Bartlett

    2012-08-01

    Full Text Available Human enamel development of the permanent teeth takes place during childhood and stresses encountered during this period can have lasting effects on the appearance and structural integrity of the enamel. One of the most common examples of this is the development of dental fluorosis after childhood exposure to excess fluoride, an elemental agent used to increase enamel hardness and prevent dental caries. Currently the molecular mechanism responsible for dental fluorosis remains unknown; however, recent work suggests dental fluorosis may be the result of activated stress response pathways in ameloblasts during the development of permanent teeth. Using fluorosis as an example, the role of stress response pathways during enamel maturation is discussed.

  11. rsfMRI effects of KB220Z™ on Neural Pathways in Reward Circuitry of Abstinent Genotyped Heroin Addicts

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    Blum, Kenneth; Liu, Yijun; Wang, Wei; Wang, Yarong; Zhang, Yi; Oscar-Berman, Marlene; Smolen, Andrew; Febo, Marcelo; Han, David; Simpatico, Thomas; Cronjé, Frans J; Demetrovics, Zsolt; Gold, Mark S.

    2016-01-01

    Recently Willuhn et al. reported that cocaine use and even non-substance related addictive behavior, increases, as dopaminergic function is reduced. Chronic cocaine exposure has been associated with decreases in D2/D3 receptors, also associated with lower activation to cues in occipital cortex and cerebellum in a recent PET study from Volkow’s group. Therefore, treatment strategies, like dopamine agonist therapy, that might conserve dopamine function may be an interesting approach to relapse prevention in psychoactive drug and behavioral addictions. To this aim, we evaluated the effect of KB220Z™ on reward circuitry of ten heroin addicts undergoing protracted abstinence, an average 16.9 months. In a randomized placebo-controlled crossover study of KB220Z™ five subjects completed a triple blinded–experiment in which the subject, the person administering the treatment and the person evaluating the response to treatment were blinded as to which treatment any particular subject was receiving. In addition, nine subjects total were genotyped utilizing the GARSRX™ test. We preliminarily report that KB220Z ™ induced an increase in BOLD activation in caudate-accumbens-dopaminergic pathways compared to placebo following one-hour acute administration. Furthermore, KB220Z™ also reduced resting state activity in the putamen of abstinent heroin addicts. In the second phase of this pilot study of all ten abstinent heroin-dependent subjects, three brain regions of interest (ROIs) we observed to be significantly activated from resting state by KB220Z compared to placebo (P addiction by direct or indirect dopaminergic interaction. Due to small sample size, we caution definitive interpretation of these preliminary results and confirmation with additional research and ongoing rodent and human studies of KB220Z, is required. PMID:25526228

  12. DIFFERENTIAL PATHWAY DEPENDENCY DISCOVERY ASSOCIATED WITH DRUG RESPONSE ACROSS CANCER CELL LINES.

    Science.gov (United States)

    Speyer, Gil; Mahendra, Divya; Tran, Hai J; Kiefer, Jeff; Schreiber, Stuart L; Clemons, Paul A; Dhruv, Harshil; Berens, Michael; Kim, Seungchan

    2017-01-01

    The effort to personalize treatment plans for cancer patients involves the identification of drug treatments that can effectively target the disease while minimizing the likelihood of adverse reactions. In this study, the gene-expression profile of 810 cancer cell lines and their response data to 368 small molecules from the Cancer Therapeutics Research Portal (CTRP) are analyzed to identify pathways with significant rewiring between genes, or differential gene dependency, between sensitive and non-sensitive cell lines. Identified pathways and their corresponding differential dependency networks are further analyzed to discover essentiality and specificity mediators of cell line response to drugs/compounds. For analysis we use the previously published method EDDY (Evaluation of Differential DependencY). EDDY first constructs likelihood distributions of gene-dependency networks, aided by known genegene interaction, for two given conditions, for example, sensitive cell lines vs. non-sensitive cell lines. These sets of networks yield a divergence value between two distributions of network likelihoods that can be assessed for significance using permutation tests. Resulting differential dependency networks are then further analyzed to identify genes, termed mediators, which may play important roles in biological signaling in certain cell lines that are sensitive or non-sensitive to the drugs. Establishing statistical correspondence between compounds and mediators can improve understanding of known gene dependencies associated with drug response while also discovering new dependencies. Millions of compute hours resulted in thousands of these statistical discoveries. EDDY identified 8,811 statistically significant pathways leading to 26,822 compound-pathway-mediator triplets. By incorporating STITCH and STRING databases, we could construct evidence networks for 14,415 compound-pathway-mediator triplets for support. The results of this analysis are presented in a

  13. Muscles provide protection during microbial infection by activating innate immune response pathways in Drosophila and zebrafish

    Directory of Open Access Journals (Sweden)

    Arunita Chatterjee

    2016-06-01

    Full Text Available Muscle contraction brings about movement and locomotion in animals. However, muscles have also been implicated in several atypical physiological processes including immune response. The role of muscles in immunity and the mechanism involved has not yet been deciphered. In this paper, using Drosophila indirect flight muscles (IFMs as a model, we show that muscles are immune-responsive tissues. Flies with defective IFMs are incapable of mounting a potent humoral immune response. Upon immune challenge, the IFMs produce anti-microbial peptides (AMPs through the activation of canonical signaling pathways, and these IFM-synthesized AMPs are essential for survival upon infection. The trunk muscles of zebrafish, a vertebrate model system, also possess the capacity to mount an immune response against bacterial infections, thus establishing that immune responsiveness of muscles is evolutionarily conserved. Our results suggest that physiologically fit muscles might boost the innate immune response of an individual.

  14. How right is left? Handedness modulates neural responses during morphosyntactic processing.

    Science.gov (United States)

    Grey, Sarah; Tanner, Darren; van Hell, Janet G

    2017-08-15

    Most neurocognitive models of language processing generally assume population-wide homogeneity in the neural mechanisms used during language comprehension, yet individual differences are known to influence these neural mechanisms. In this study, we focus on handedness as an individual difference hypothesized to affect language comprehension. Left-handers and right-handers with a left-handed blood relative, or familial sinistrals, are hypothesized to process language differently than right-handers with no left-handed relatives (Hancock and Bever, 2013; Ullman, 2004). Yet, left-handers are often excluded from neurocognitive language research, and familial sinistrality in right-handers is often not taken into account. In the current study we used event-related potentials to test morphosyntactic processing in three groups that differed in their handedness profiles: left-handers (LH), right-handers with a left-handed blood relative (RH FS+), and right-handers with no reported left-handed blood relative (RH FS-; both right-handed groups were previously tested by Tanner and Van Hell, 2014). Results indicated that the RH FS- group showed only P600 responses during morphosyntactic processing whereas the LH and RH FS+ groups showed biphasic N400-P600 patterns. N400s in LH and RH FS+ groups are consistent with theories that associate left-handedness (self or familial) with increased reliance on lexical/semantic mechanisms during language processing. Inspection of individual-level results illustrated that variability in RH FS- individuals' morphosyntactic processing was remarkably low: most individuals were P600-dominant. In contrast, LH and RH FS+ individuals showed marked variability in brain responses, which was similar for both groups: half of individuals were N400-dominant and half were P600-dominant. Our findings have implications for neurocognitive models of language that have been largely formulated around data from only right-handers without accounting for familial

  15. Neural and behavioral responses to attractiveness in adult and infant faces.

    Science.gov (United States)

    Hahn, Amanda C; Perrett, David I

    2014-10-01

    Facial attractiveness provides a very powerful motivation for sexual and parental behavior. We therefore review the importance of faces to the study of neurobiological control of human reproductive motivations. For heterosexual individuals there is a common brain circuit involving the nucleus accumbens, the medial prefrontal, dorsal anterior cingulate and the orbitofrontal cortices that is activated more by attractive than unattractive faces, particularly for faces of the opposite sex. Behavioral studies indicate parallel effects of attractiveness on incentive salience or willingness to work to see faces. There is some evidence that the reward value of opposite sex attractiveness is more pronounced in men than women, perhaps reflecting the greater importance assigned to physical attractiveness by men when evaluating a potential mate. Sex differences and similarities in response to facial attractiveness are reviewed. Studies comparing heterosexual and homosexual observers indicate the orbitofrontal cortex and mediodorsal thalamus are more activated by faces of the desired sex than faces of the less-preferred sex, independent of observer gender or sexual orientation. Infant faces activate brain regions that partially overlap with those responsive to adult faces. Infant faces provide a powerful stimulus, which also elicits sex differences in behavior and brain responses that appear dependent on sex hormones. There are many facial dimensions affecting perceptions of attractiveness that remain unexplored in neuroimaging, and we conclude by suggesting that future studies combining parametric manipulation of face images, brain imaging, hormone assays and genetic polymorphisms in receptor sensitivity are needed to understand the neural and hormonal mechanisms underlying reproductive drives. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Negative affect and neural response to palatable food intake in bulimia nervosa.

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    Bohon, Cara; Stice, Eric

    2012-06-01

    Binge eating is often preceded by reports of negative affect, but the mechanism by which affect may lead to binge eating is unclear. This study evaluated the effect of negative affect on neural response to anticipation and receipt of palatable food in women with bulimia nervosa (BN) versus healthy controls. We also evaluated connectivity between the amygdala and reward-related brain regions. Females with and without BN (n=26) underwent functional magnetic resonance imaging (fMRI) during receipt and anticipated receipt of chocolate milkshake and a tasteless solution. We measured negative affect just prior to the scan. Women with BN showed a positive correlation between negative affect and activity in the putamen, caudate, and pallidum during anticipated receipt of milkshake (versus tasteless solution). There were no significant relations between negative affect and receipt of milkshake. Connectivity analyses revealed a greater relation of amygdala activity to activation in the left putamen and insula during anticipated receipt of milkshake in the bulimia group relative to the control group. The opposite pattern was found for the taste of milkshake; the control group showed a greater relation of amygdala activity to activation in the left putamen and insula in response to milkshake receipt than the bulimia group. Results show that as negative affect increases, so does responsivity of reward regions to anticipated intake of palatable food, implying that negative affect may increase the reward value of food for individuals with bulimia nervosa or that negative affect has become a conditioned cue due to a history of binge eating in a negative mood. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. Comparative Effects of Methylphenidate, Modafinil, and MDMA on Response Inhibition Neural Networks in Healthy Subjects.

    Science.gov (United States)

    Schmidt, André; Müller, Felix; Dolder, Patrick C; Schmid, Yasmin; Zanchi, Davide; Liechti, Matthias E; Borgwardt, Stefan

    2017-09-01

    Psychostimulants such as methylphenidate and modafinil are increasingly used by healthy people for cognitive enhancement purposes, whereas the acute effect of 3,4-methylenedioxymethamphetamine (ecstasy) on cognitive functioning in healthy subjects remains unclear. This study directly compared the acute effects of methylphenidate, modafinil, and 3,4-methylenedioxymethamphetamine on the neural mechanisms underlying response inhibition in healthy subjects. Using a double-blind, within-subject, placebo-controlled, cross-over design, methylphenidate, modafinil, and 3,4-methylenedioxymethamphetamine were administrated to 21 healthy subjects while performing a go/no-go event-related functional magnetic resonance imaging task to assess brain activation during motor response inhibition. Relative to placebo, methylphenidate and modafinil but not 3,4-methylenedioxymethamphetamine improved inhibitory performance. Methylphenidate significantly increased activation in the right middle frontal gyrus, middle/superior temporal gyrus, inferior parietal lobule, presupplementary motor area, and anterior cingulate cortex compared with placebo. Methylphenidate also induced significantly higher activation in the anterior cingulate cortex and presupplementary motor area and relative to modafinil. Relative to placebo, modafinil significantly increased activation in the right middle frontal gyrus and superior/inferior parietal lobule, while 3,4-methylenedioxymethamphetamine significantly increased activation in the right middle/inferior frontal gyrus and superior parietal lobule. Direct comparison of methylphenidate, modafinil, and 3,4-methylenedioxymethamphetamine revealed broad recruitment of fronto-parietal regions but specific effects of methylphenidate on middle/superior temporal gyrus, anterior cingulate cortex, and presupplementary motor area activation, suggesting dissociable modulations of response inhibition networks and potentially the superiority of methylphenidate in the

  18. A Preliminary Investigation of Pathways to Inflated Responsibility Beliefs in Children with Obsessive Compulsive Disorder.

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    Collins, Lindsey M; Coles, Meredith E

    2018-01-17

    Cognitive theorists posit that inflated responsibility beliefs contribute to the development of obsessive compulsive disorder (OCD). Salkovskis et al. (1999) proposed that experiencing heightened responsibility, overprotective parents and rigid rules, and thinking one influenced or caused a negative life event act as 'pathways' to the development of inflated responsibility beliefs, thereby increasing risk for OCD. Studies in adults with OCD and non-clinical adolescents support the link between these experiences and responsibility beliefs (Coles et al., 2015; Halvaiepour and Nosratabadi, 2015), but the theory has never been tested in youth with current OCD. We provided an initial test of the theory by Salkovskis et al. (1999) in youth with OCD. We predicted that childhood experiences proposed by Salkovskis et al. (1999) would correlate positively with responsibility and harm beliefs and OCD symptom severity. Twenty youth with OCD (age 9‒16 years) completed a new child-report measure of the experiences hypothesized by Salkovskis et al. (1999), the Pathways to Inflated Responsibility Beliefs Scale-Child Version (PIRBS-CV). Youth also completed the Obsessive Beliefs Questionnaire-Child Version (Coles et al., 2010) and the Obsessive Compulsive Inventory-Child Version (Foa et al., 2010). Consistent with hypotheses, the PIRBS-CV was significantly related to responsibility and harm beliefs and OCD symptom severity. Results provide initial support for the theory proposed by Salkovskis et al. (1999) as applied to youth with OCD. Future studies are needed to further assess the model in early-onset OCD.

  19. Neural Responses to Visual Food Cues According to Weight Status: A Systematic Review of Functional Magnetic Resonance Imaging Studies

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    Kirrilly ePursey

    2014-07-01

    Full Text Available Emerging evidence from recent neuroimaging studies suggests specific food related behaviours contribute to the development of obesity. The aim of this review was to report the neural responses to visual food cues, as assessed by functional magnetic resonance imaging (fMRI, in humans of differing weight status. Published studies to 2014 were retrieved and included if they: used visual food cues, studied humans >18 years old, reported weight status, and included fMRI outcomes. Sixty studies were identified that investigated the neural responses of healthy weight participants (n=26, healthy weight compared to obese participants (n=17, and weight loss interventions (n=12. High calorie food images were used in the majority of studies (n=36, however, image selection justification was only provided in 19 studies. Obese individuals had increased activation of reward-related brain areas including the insula and orbitofrontal cortex in response to visual food cues compared to healthy weight individuals, and this was particularly evident in response to energy dense cues. Additionally, obese individuals were more responsive to food images when satiated. Meta-analysis of changes in neural activation post- weight loss revealed small areas of convergence of activation across studies in brain areas related to emotion, memory and learning such as the cingulate gyrus, lentiform nucleus and precuneus.Differential activation patterns to visual food cues were observed between obese, healthy weight and weight loss populations. Future studies require standardisation of dietetic variables and fMRI outcomes to enable more direct comparisons between studies.

  20. Variants in TNIP1, a regulator of the NF-kB pathway, found in two patients with neural tube defects.

    Science.gov (United States)

    Francesca, La Carpia; Claudia, Rendeli; Molinario, Clelia; Annamaria, Milillo; Chiara, Farroni; Natalia, Cannelli; Emanuele, Ausili; Valentina, Paolucci; Giovanni, Neri; Costantino, Romagnoli; Eugenio, Sangiorgi; Fiorella, Gurrieri

    2016-06-01

    Neural tube defects (NTDs) occur in 1:1000 births. The etiology is complex, with the influence of environmental and genetic factors. Environmental factors, such as folate deficiency, diabetes, or hypoxia strongly contribute to the occurrence of NTD. Also, there is a strong genetic contribution to NTD, as highlighted by the number of genes so far identified in several different developmental pathways usually altered in NTD. Each gene identified so far accounts for a small percentage of all NTD cases, indicating a very high heterogeneity. Exome sequencing was performed in seven sporadic patients with severe mielomeningocele. Novel coding variants shared by two or more patients were selected for further analysis. We identified in two unrelated patients two different variants in TNIP1, a gene not previously involved in NTD whose main role is downregulation of the NF-kB pathway. One variant, c.1089T>G (p.Phe363Leu), is de novo, whereas the c.1781C>T (p.Pro594Leu) is absent in the mother, but could not be tested in the father, as he was unavailable. The latter variant is a very rare variant in the ExAC database. These findings suggest that TNIP1 is a new potential predisposing gene to spina bifida (SB) and its pathway needs to be investigated in human NTD in order to confirm its role and to plan appropriate counseling to families.

  1. IGF-1 promotes Brn-4 expression and neuronal differentiation of neural stem cells via the PI3K/Akt pathway.

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    Xinhua Zhang

    Full Text Available Our previous studies indicated that transcription factor Brn-4 is upregulated in the surgically denervated hippocampus in vivo, promoting neuronal differentiation of hippocampal neural stem cells (NSCs in vitro. The molecules mediating Brn-4 upregulation in the denervated hippocampus remain unknown. In this study we examined the levels of insulin-like growth factor-1 (IGF-1 in hippocampus following denervation. Surgical denervation led to a significant increase in IGF-1 expression in vivo. We also report that IGF-1 treatment on NSCs in vitro led to a marked acceleration of Brn-4 expression and cell differentiation down neuronal pathways. The promotion effects were blocked by PI3K-specific inhibitor (LY294002, but not MAPK inhibitor (PD98059; levels of phospho-Akt were increased by IGF-1 treatment. In addition, inhibition of IGF-1 receptor (AG1024 and mTOR (rapamycin both attenuated the increased expression of Brn-4 induced by IGF-1. Together, the results demonstrated that upregulation of IGF-1 induced by hippocampal denervation injury leads to activation of the PI3K/Akt signaling pathway, which in turn gives rise to upregulation of the Brn-4 and subsequent stem cell differentiation down neuronal pathways.

  2. Neural response during the activation of the attachment system in patients with borderline personality disorder: An fMRI study

    Directory of Open Access Journals (Sweden)

    Anna Buchheim

    2016-08-01

    Full Text Available Individuals with borderline personality disorder (BPD are characterized by emotional instability, impaired emotion regulation and unresolved attachment patterns associated with abusive childhood experiences. We investigated the neural response during the activation of the attachment system in BPD patients compared to healthy controls using functional magnetic resonance imaging. Eleven female patients with BPD without posttraumatic stress disorder and seventeen healthy female controls matched for age and education were telling stories in the scanner in response to the Adult Attachment Projective Picture System, an eight-picture set assessment of adult attachment. The picture set includes theoretically-derived attachment scenes, such as separation, death, threat and potential abuse. The picture presentation order is designed to gradually increase the activation of the attachment system. Each picture stimulus was presented for two minutes. Analyses examine group differences in attachment classifications and neural activation patterns over the course of the task. Unresolved attachment was associated with increasing amygdala activation over the course of the attachment task in patients as well as controls. Unresolved controls, but not patients, showed activation in the right dorsolateral prefrontal cortex and the rostral cingulate zone. We interpret this as a neural signature of BPD patients’ inability to exert top-down control under conditions of attachment distress. These findings point to possible neural mechanisms for underlying affective dysregulation in BPD in the context of attachment trauma and fear.

  3. Dissecting complex transcriptional responses using pathway-level scores based on prior information

    Directory of Open Access Journals (Sweden)

    Ward Lucas D

    2007-09-01

    Full Text Available Abstract Background The genomewide pattern of changes in mRNA expression measured using DNA microarrays is typically a complex superposition of the response of multiple regulatory pathways to changes in the environment of the cells. The use of prior information, either about the function of the protein encoded by each gene, or about the physical interactions between regulatory factors and the sequences controlling its expression, has emerged as a powerful approach for dissecting complex transcriptional responses. Results We review two different approaches for combining the noisy expression levels of multiple individual genes into robust pathway-level differential expression scores. The first is based on a comparison between the distribution of expression levels of genes within a predefined gene set and those of all other genes in the genome. The second starts from an estimate of the strength of genomewide regulatory network connectivities based on sequence information or direct measurements of protein-DNA interactions, and uses regression analysis to estimate the activity of gene regulatory pathways. The statistical methods used are explained in detail. Conclusion By avoiding the thresholding of individual genes, pathway-level analysis of differential expression based on prior information can be considerably more sensitive to subtle changes in gene expression than gene-level analysis. The methods are technically straightforward and yield results that are easily interpretable, both biologically and statistically.

  4. The Neural Crest in Cardiac Congenital Anomalies

    Science.gov (United States)

    Keyte, Anna; Hutson, Mary Redmond

    2012-01-01

    This review discusses the function of neural crest as they relate to cardiovascular defects. The cardiac neural crest cells are a subpopulation of cranial neural crest discovered nearly 30 years ago by ablation of premigratory neural crest. The cardiac neural crest cells are necessary for normal cardiovascular development. We begin with a description of the crest cells in normal development, including their function in remodeling the pharyngeal arch arteries, outflow tract septation, valvulogenesis, and development of the cardiac conduction system. The cells are also responsible for modulating signaling in the caudal pharynx, including the second heart field. Many of the molecular pathways that are known to influence specification, migration, patterning and final targeting of the cardiac neural crest cells are reviewed. The cardiac neural crest cells play a critical role in the pathogenesis of various human cardiocraniofacial syndromes such as DiGeorge, Velocardiofacial, CHARGE, Fetal Alcohol, Alagille, LEOPARD, and Noonan syndromes, as well as Retinoic Acid Embryopathy. The loss of neural crest cells or their dysfunction may not always directly cause abnormal cardiovascular development, but are involved secondarily because crest cells represent a major component in the complex tissue interactions in the head, pharynx and outflow tract. Thus many of the human syndromes linking defects in the heart, face and brain can be better understood when considered within the context of a single cardiocraniofacial developmental module with the neural crest being a key cell type that interconnects the regions. PMID:22595346

  5. Development of a stimuli-responsive polymer nanocomposite toward biologically optimized, MEMS-based neural probes

    Science.gov (United States)

    Hess, A. E.; Capadona, J. R.; Shanmuganathan, K.; Hsu, L.; Rowan, S. J.; Weder, C.; Tyler, D. J.; Zorman, C. A.

    2011-05-01

    This paper reports the development of micromachining processes and mechanical evaluation of a stimuli-responsive, mechanically dynamic polymer nanocomposite for biomedical microsystems. This nanocomposite consists of a cellulose nanofiber network encased in a polyvinyl acetate matrix. Micromachined tensile testing structures fabricated from the nanocomposite displayed a reversible and switchable stiffness comparable to bulk samples, with a Young's modulus of 3420 MPa when dry, reducing to ~20 MPa when wet, and a stiff-to-flexible transition time of ~300 s. This mechanically dynamic behavior is particularly attractive for the development of adaptive intracortical probes that are sufficiently stiff to insert into the brain without buckling, but become highly compliant upon insertion. Along these lines, a micromachined neural probe incorporating parylene insulating/moisture barrier layers and Ti/Au electrodes was fabricated from the nanocomposite using a fabrication process designed specifically for this chemical- and temperature-sensitive material. It was found that the parylene layers only slightly increased the stiffness of the probe in the wet state in spite of its much higher Young's modulus. Furthermore, the Ti/Au electrodes exhibited impedance comparable to Au electrodes on conventional substrates. Swelling of the nanocomposite was highly anisotropic favoring the thickness dimension by a factor of 8 to 12, leading to excellent adhesion between the nanocomposite and parylene layers and no discernable deformation of the probes when deployed in deionized water.

  6. Response surface and neural network based predictive models of cutting temperature in hard turning

    Directory of Open Access Journals (Sweden)

    Mozammel Mia

    2016-11-01

    Full Text Available The present study aimed to develop the predictive models of average tool-workpiece interface temperature in hard turning of AISI 1060 steels by coated carbide insert. The Response Surface Methodology (RSM and Artificial Neural Network (ANN were employed to predict the temperature in respect of cutting speed, feed rate and material hardness. The number and orientation of the experimental trials, conducted in both dry and high pressure coolant (HPC environments, were planned using full factorial design. The temperature was measured by using the tool-work thermocouple. In RSM model, two quadratic equations of temperature were derived from experimental data. The analysis of variance (ANOVA and mean absolute percentage error (MAPE were performed to suffice the adequacy of the models. In ANN model, 80% data were used to train and 20% data were employed for testing. Like RSM, herein, the error analysis was also conducted. The accuracy of the RSM and ANN model was found to be ⩾99%. The ANN models exhibit an error of ∼5% MAE for testing data. The regression coefficient was found to be greater than 99.9% for both dry and HPC. Both these models are acceptable, although the ANN model demonstrated a higher accuracy. These models, if employed, are expected to provide a better control of cutting temperature in turning of hardened steel.

  7. Motor and mental training in older people: Transfer, interference, and associated functional neural responses.

    Science.gov (United States)

    Boraxbekk, C J; Hagkvist, Filip; Lindner, Philip

    2016-08-01

    Learning new motor skills may become more difficult with advanced age. In the present study, we randomized 56 older individuals, including 30 women (mean age 70.6 years), to 6 weeks of motor training, mental (motor imagery) training, or a combination of motor and mental training of a finger tapping sequence. Performance improvements and post-training functional magnetic resonance imaging (fMRI) were used to investigate performance gains and associated underlying neural processes. Motor-only training and a combination of motor and mental training improved performance in the trained task more than mental-only training. The fMRI data showed that motor training was associated with a representation in the premotor cortex and mental training with a representation in the secondary visual cortex. Combining motor and mental training resulted in both premotor and visual cortex representations. During fMRI scanning, reduced performance was observed in the combined motor and mental training group, possibly indicating interference between the two training methods. We concluded that motor and motor imagery training in older individuals is associated with different functional brain responses. Furthermore, adding mental training to motor training did not result in additional performance gains compared to motor-only training and combining training methods may result in interference between representations, reducing performance. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Differential Responses of Human Fetal Brain Neural Stem Cells to Zika Virus Infection

    Directory of Open Access Journals (Sweden)

    Erica L. McGrath

    2017-03-01

    Full Text Available Zika virus (ZIKV infection causes microcephaly in a subset of infants born to infected pregnant mothers. It is unknown whether human individual differences contribute to differential susceptibility of ZIKV-related neuropathology. Here, we use an Asian-lineage ZIKV strain, isolated from the 2015 Mexican outbreak (Mex1-7, to infect primary human neural stem cells (hNSCs originally derived from three individual fetal brains. All three strains of hNSCs exhibited similar rates of Mex1-7 infection and reduced proliferation. However, Mex1-7 decreased neuronal differentiation in only two of the three stem cell strains. Correspondingly, ZIKA-mediated transcriptome alterations were similar in these two strains but significantly different from that of the third strain with no ZIKV-induced neuronal reduction. This study thus confirms that an Asian-lineage ZIKV strain infects primary hNSCs and demonstrates a cell-strain-dependent response of hNSCs to ZIKV infection.

  9. Differential Responses of Human Fetal Brain Neural Stem Cells to Zika Virus Infection.

    Science.gov (United States)

    McGrath, Erica L; Rossi, Shannan L; Gao, Junling; Widen, Steven G; Grant, Auston C; Dunn, Tiffany J; Azar, Sasha R; Roundy, Christopher M; Xiong, Ying; Prusak, Deborah J; Loucas, Bradford D; Wood, Thomas G; Yu, Yongjia; Fernández-Salas, Ildefonso; Weaver, Scott C; Vasilakis, Nikos; Wu, Ping

    2017-03-14

    Zika virus (ZIKV) infection causes microcephaly in a subset of infants born to infected pregnant mothers. It is unknown whether human individual differences contribute to differential susceptibility of ZIKV-related neuropathology. Here, we use an Asian-lineage ZIKV strain, isolated from the 2015 Mexican outbreak (Mex1-7), to infect primary human neural stem cells (hNSCs) originally derived from three individual fetal brains. All three strains of hNSCs exhibited similar rates of Mex1-7 infection and reduced proliferation. However, Mex1-7 decreased neuronal differentiation in only two of the three stem cell strains. Correspondingly, ZIKA-mediated transcriptome alterations were similar in these two strains but significantly different from that of the third strain with no ZIKV-induced neuronal reduction. This study thus confirms that an Asian-lineage ZIKV strain infects primary hNSCs and demonstrates a cell-strain-dependent response of hNSCs to ZIKV infection. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Neural responses to unfairness and fairness depend on self-contribution to the income

    Science.gov (United States)

    Guo, Xiuyan; Zheng, Li; Cheng, Xuemei; Chen, Menghe; Li, Jianqi; Chen, Luguang; Yang, Zhiliang

    2014-01-01

    Self-contribution to the income (individual achievement) was an important factor which needs to be taken into individual’s fairness considerations. This study aimed at elucidating the modulation of self-contribution to the income, on recipient’s responses to unfairness in the Ultimatum Game. Eighteen participants were scanned while they were playing an adapted version of the Ultimatum Game as responders. Before splitting money, the proposer and the participant (responder) played the ball-guessing game. The responder’s contribution to the income was manipulated by both the participant’s and the proposer’s accuracy in the ball-guessing game. It turned out that the participants more often rejected unfair offers and gave lower fairness ratings when they played a more important part in the earnings. At the neural level, anterior insula, anterior cingulate cortex, dorsolateral prefrontal cortex and temporoparietal junction showed greater activities to unfairness when self-contribution increased, whereas ventral striatum and medial orbitofrontal gyrus showed higher activations to fair (vs unfair) offers in the other-contributed condition relative to the other two. Besides, the activations of right dorsolateral prefrontal cortex during unfair offers showed positive correlation with rejection rates in the self-contributed condition. These findings shed light on the significance of self-contribution in fairness-related social decision-making processes. PMID:23946001

  11. Difference in neural response to social exclusion observation and subsequent altruism between adolescents and adults.

    Science.gov (United States)

    Tousignant, Béatrice; Eugène, Fanny; Sirois, Katia; Jackson, Philip L

    2017-04-13

    Empathy and prosocial behaviors toward peers promote successful social development and creation of significant long-term relationships, but surprisingly little is known about the maturation of these skills during the period of adolescence. As the majority of studies have used questionnaires or pain observation paradigms, it remains unknown whether the empathic response of adolescents differs from that of adults in a paradigm that is closer to everyday life. In the current study, fMRI was used to examine the neural correlates of social exclusion observation and subsequent prosocial behavior in 20 adolescents (aged 12-17 years) and 20 adults (aged 22-30 years) while playing a ball-tossing game with what they believed to be real individuals. Observing someone being excluded compared to observing equal inclusion of all players elicited a significantly higher activation of the IFG (pars triangularis) in adults compared to adolescents. When given the opportunity to directly help the excluded player during the game, adolescents showed significantly less prosocial behavior than adults, which was underpinned by a significantly lower activity in the right temporoparietal junction, medial/dorsomedial prefrontal cortex and fusiform face area. These findings might indicate that adolescents have a lower propensity to take the victim's perspective and share his or her distress when witnessing social exclusion, which leads to a lower altruistic motivation to help. The factors that could generate what can be interpreted as a downward modulation of empathy during adolescence are discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Response surface and artificial neural network prediction model and optimization for surface roughness in machining

    Directory of Open Access Journals (Sweden)

    Ashok Kumar Sahoo

    2015-04-01

    Full Text Available The present paper deals with the development of prediction model using response surface methodology and artificial neural network and optimizes the process parameter using 3D surface plot. The experiment has been conducted using coated carbide insert in machining AISI 1040 steel under dry environment. The coefficient of determination value for RSM model is found to be high (R2 = 0.99 close to unity. It indicates the goodness of fit for the model and high significance of the model. The percentage of error for RSM model is found to be only from -2.63 to 2.47. The maximum error between ANN model and experimental lies between -1.27 and 0.02 %, which is significantly less than the RSM model. Hence, both the proposed RSM and ANN prediction model sufficiently predict the surface roughness, accurately. However, ANN prediction model seems to be better compared with RSM model. From the 3D surface plots, the optimal parametric combination for the lowest surface roughness is d1-f1-v3 i.e. depth of cut of 0.1 mm, feed of 0.04 mm/rev and cutting speed of 260 m/min respectively.

  13. Response surface and neural network based predictive models of cutting temperature in hard turning.

    Science.gov (United States)

    Mia, Mozammel; Dhar, Nikhil R

    2016-11-01

    The present study aimed to develop the predictive models of average tool-workpiece interface temperature in hard turning of AISI 1060 steels by coated carbide insert. The Response Surface Methodology (RSM) and Artificial Neural Network (ANN) were employed to predict the temperature in respect of cutting speed, feed rate and material hardness. The number and orientation of the experimental trials, conducted in both dry and high pressure coolant (HPC) environments, were planned using full factorial design. The temperature was measured by using the tool-work thermocouple. In RSM model, two quadratic equations of temperature were derived from experimental data. The analysis of variance (ANOVA) and mean absolute percentage error (MAPE) were performed to suffice the adequacy of the models. In ANN model, 80% data were used to train and 20% data were employed for testing. Like RSM, herein, the error analysis was also conducted. The accuracy of the RSM and ANN model was found to be ⩾99%. The ANN models exhibit an error of ∼5% MAE for testing data. The regression coefficient was found to be greater than 99.9% for both dry and HPC. Both these models are acceptable, although the ANN model demonstrated a higher accuracy. These models, if employed, are expected to provide a better control of cutting temperature in turning of hardened steel.

  14. Perceptual and neural responses to sweet taste in humans and rodents.

    Science.gov (United States)

    Lemon, Christian H

    2015-08-01

    This mini-review discusses some of the parallels between rodent neurophysiological and human psychophysical data concerning temperature effects on sweet taste. "Sweet" is an innately rewarding taste sensation that is associated in part with foods that contain calories in the form of sugars. Humans and other mammals can show unconditioned preference for select sweet stimuli. Such preference is poised to influence diet selection and, in turn, nutritional status, which underscores the importance of delineating the physiological mechanisms for sweet taste with respect to their influence on human health. Advances in our knowledge of the biology of sweet taste in humans have arisen in part through studies on mechanisms of gustatory processing in rodent models. Along this line, recent work has revealed there are operational parallels in neural systems for sweet taste between mice and humans, as indexed by similarities in the effects of temperature on central neurophysiological and psychophysical responses to sucrose in these species. Such association strengthens the postulate that rodents can serve as effective models of particular mechanisms of appetitive taste processing. Data supporting this link are discussed here, as are rodent and human data that shed light on relationships between mechanisms for sweet taste and ingestive disorders, such as alcohol abuse. Rodent models have utility for understanding mechanisms of taste processing that may pertain to human flavor perception. Importantly, there are limitations to generalizing data from rodents, albeit parallels across species do exist.

  15. Secure attachment partners attenuate neural responses to social exclusion: an fMRI investigation.

    Science.gov (United States)

    Karremans, Johan C; Heslenfeld, Dirk J; van Dillen, Lotte F; Van Lange, Paul A M

    2011-07-01

    Research has shown that social exclusion has devastating psychological, physiological, and behavioral consequences. However, little is known about possible ways to shield individuals from the detrimental effects of social exclusion. The present study, in which participants were excluded during a ball-tossing game, examined whether (reminders of) secure attachment relationships could attenuate neurophysiological pain- and stress-related responses to social exclusion. Social exclusion was associated with activation in brain areas implicated in the regulation and experience of social distress, including areas in the lateral and medial prefrontal cortex, ventral anterior cingulate cortex, and hypothalamus. However, less activation in these areas was found to the extent that participants felt more securely attached to their attachment figure. Moreover, the psychological presence (i.e., salience) of an attachment figure attenuated hypothalamus activation during episodes of social exclusion, thereby providing insight into the neural mechanisms by which attachment relationships may help in coping with social stress. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. Roles of Response Inhibition and Gene-Environment Interplay in Pathways to Adolescents' Externalizing Problems.

    Science.gov (United States)

    Wang, Frances L; Chassin, Laurie; Lee, Matthew; Haller, Moira; King, Kevin

    2017-06-01

    This study used two waves of data to investigate pathways through which adolescents' response inhibition related to later externalizing problems. A polygenic risk score indexed genetic risk for poor response inhibition. Adolescents' performance on a response inhibition task mediated the relation between adolescents' polygenic risk scores and mother's inconsistent parenting (i.e., evocative rGE), even after controlling for mothers' genetic risk (i.e., passive rGE). Mothers' inconsistent parenting subsequently prospectively predicted adolescents' externalizing problems. Adolescents' response inhibition also prospectively predicted later externalizing behaviors. These findings were subgroup-specific, with greater risk for non-Hispanic Caucasian boys with substance-disordered parents. Results suggest that poor response inhibition may increase risk for adolescents' externalizing problems both directly and by evoking certain environmental conditions. © 2016 The Authors. Journal of Research on Adolescence © 2016 Society for Research on Adolescence.

  17. Skin Conductance Responses and Neural Activations During Fear Conditioning and Extinction Recall Across Anxiety Disorders.

    Science.gov (United States)

    Marin, Marie-France; Zsido, Rachel G; Song, Huijin; Lasko, Natasha B; Killgore, William D S; Rauch, Scott L; Simon, Naomi M; Milad, Mohammed R

    2017-06-01

    The fear conditioning and extinction neurocircuitry has been extensively studied in healthy and clinical populations, with a particular focus on posttraumatic stress disorder. Despite significant overlap of symptoms between posttraumatic stress disorder and anxiety disorders, the latter has received less attention. Given that dysregulated fear levels characterize anxiety disorders, examining the neural correlates of fear and extinction learning may shed light on the pathogenesis of underlying anxiety disorders. To investigate the psychophysiological and neural correlates of fear conditioning and extinction recall in anxiety disorders and to document how these features differ as a function of multiple diagnoses or anxiety severity. This investigation was a cross-sectional, case-control, functional magnetic resonance imaging study at an academic medical center. Participants were healthy controls and individuals with at least 1 of the following anxiety disorders: generalized anxiety disorder, social anxiety disorder, specific phobia, and panic disorder. The study dates were between March 2013 and May 2015. Two-day fear conditioning and extinction paradigm. Skin conductance responses, blood oxygenation level-dependent responses, trait anxiety scores from the State Trait Anxiety Inventory-Trait Form, and functional connectivity. This study included 21 healthy controls (10 women) and 61 individuals with anxiety disorders (36 women). P values reported for the neuroimaging results are all familywise error corrected. Skin conductance responses during extinction recall did not differ between individuals with anxiety disorders and healthy controls (ηp2 = 0.001, P = .79), where ηp2 is partial eta squared. The anxiety group had lower activation of the ventromedial prefrontal cortex (vmPFC) during extinction recall (ηp2 = 0.178, P = .02). A similar hypoactive pattern was found during early conditioning (ηp2 = 0.106, P = .009). The vmPFC hypoactivation

  18. Neural correlates of explicit and implicit emotion processing in relation to treatment response in pediatric anxiety.

    Science.gov (United States)

    Burkhouse, Katie L; Kujawa, Autumn; Klumpp, Heide; Fitzgerald, Kate D; Monk, Christopher S; Phan, K Luan

    2017-05-01

    Approximately 40%-45% of youth with anxiety disorders do not achieve remission (or a substantial reduction in symptoms) following treatment, highlighting the need to identify predictors of treatment response. Given the well-established link between attentional biases and anxiety disorders in youth and adults, this study examined the neural correlates of directing attention toward and away from emotional faces in relation to pediatric anxiety treatment response. Prior to beginning treatment with the selective serotonin reuptake inhibitor (SSRI) sertraline or cognitive behavior therapy (CBT), 37 youth (age 7-19 years) with generalized and/or social anxiety disorder completed a task with conditions that manipulated whether participants were instructed to match emotional faces (explicit emotion processing) or match shapes in the context of emotional face distractors (implicit emotion processing) during functional magnetic resonance imaging. Results revealed that reduced activation in superior frontal gyrus (SFG), encompassing the dorsal anterior cingulate cortex (ACC) and dorsomedial prefrontal cortex (PFC), during implicit processing of emotional faces predicted a greater reduction in anxiety severity pre-to-post treatment. Post hoc analyses indicated that effects were not significantly moderated by the type of treatment or anxiety type. Findings suggest that less recruitment of SFG, including the dorsal ACC and dorsomedial PFC, during implicit emotion processing predicts a greater reduction in youth anxiety symptoms pre-to-post treatment. Youth who exhibit reduced activation in these areas while matching shapes in the context of emotional face distractors may have more to gain from CBT and SSRI treatment due to preexisting deficits in attentional control. These findings suggest that neuroimaging may be a useful tool for predicting which youth are most likely to benefit from anxiety treatment. © 2016 Association for Child and Adolescent Mental Health.

  19. The N-end rule pathway regulates pathogen responses in plants.

    Science.gov (United States)

    de Marchi, Rémi; Sorel, Maud; Mooney, Brian; Fudal, Isabelle; Goslin, Kevin; Kwaśniewska, Kamila; Ryan, Patrick T; Pfalz, Marina; Kroymann, Juergen; Pollmann, Stephan; Feechan, Angela; Wellmer, Frank; Rivas, Susana; Graciet, Emmanuelle

    2016-05-13

    To efficiently counteract pathogens, plants rely on a complex set of immune responses that are tightly regulated to allow the timely activation, appropriate duration and adequate amplitude of defense programs. The coordination of the plant immune response is known to require the activity of the ubiquitin/proteasome system, which controls the stability of proteins in eukaryotes. Here, we demonstrate that the N-end rule pathway, a subset of the ubiquitin/proteasome system, regulates the defense against a wide range of bacterial and fungal pathogens in the model plant Arabidopsis thaliana. We show that this pathway positively regulates the biosynthesis of plant-defense metabolites such as glucosinolates, as well as the biosynthesis and response to the phytohormone jasmonic acid, which plays a key role in plant immunity. Our results also suggest that the arginylation branch of the N-end rule pathway regulates the timing and amplitude of the defense program against the model pathogen Pseudomonas syringae AvrRpm1.

  20. The broad spectrum of signaling pathways regulated by unfolded protein response in neuronal homeostasis.

    Science.gov (United States)

    Saito, Atsushi; Imaizumi, Kazunori

    2017-06-28

    The protein folding capabilities in the endoplasmic reticulum (ER) are disturbed by alternations in the cellular homeostasis such as the disruption of calcium ion homeostasis, the expression of mutated proteins and oxidative stress. In response to these ER dysfunctions, eukaryotic cells activate canonical branches of signal transduction cascades to restore the protein folding capacity and avoid irreversible damages, collectively termed the unfolded protein response (UPR). Prolonged ER dysfunctions and the downregulation of UPR signaling pathways have been accepted as a crucial trigger for the pathogenesis of various neurodegenerative diseases. Furthermore, recent studies have revealed that the UPR has a wide spectrum of signaling pathways for unique physiological roles in the diverse developmental, differential and lipidomic processes. A developed and intricate ER network exists in the neurites of neurons. Neuronal ER functions and ER-derived signaling mediate efficient communication between cell soma and distal sites through local protein synthesis, sorting and lipogenesis. However, relevant of ER-derived UPR signaling pathways in the elaborate mechanisms regulating neuronal activities, synaptic functions and protective responses against injury is not fully elucidated. In this review, we summarized our current understanding of how the UPR functions provide the appropriate signals for neuronal capabilities. We also reviewed how UPR dysfunctions lead to the pathogenesis of neurodegenerative diseases, and the possibilities ameliorating their toxic effects by targeting UPR components. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  1. Involvement of the ethylene response pathway in dormancy induction in chrysanthemum

    Science.gov (United States)

    Sumitomo, Katsuhiko; Satoh, Shigeru; Hisamatsu, Tamotsu

    2008-01-01

    Temperature plays a significant role in the annual cycling between growth and dormancy of the herbaceous perennial chrysanthemum (Chrysanthemum morifolium Ramat.). After exposure to high summer temperatures, cool temperature triggers dormancy. The cessation of flowering and rosette formation by the cessation of elongation are characteristic of dormant plants, and can be stimulated by exogenous ethylene. Thus, the ethylene response pathway may be involved in temperature-induced dormancy of chrysanthemum. Transgenic chrysanthemums expressing a mutated ethylene receptor gene were used to assess this involvement. The transgenic lines showed reduced ethylene sensitivity: ethylene causes leaf yellowing in wild-type chrysanthemums, but leaves remained green in the transgenic lines. Extension growth and flowering of wild-type and transgenic lines varied between temperatures: at 20 °C, the transgenic lines showed the same stem elongation and flowering as the wild type; at cooler temperatures, the wild type formed rosettes with an inability to flower and entered dormancy, but some transgenic lines continued to elongate and flower. This supports the involvement of the ethylene response pathway in the temperature-induced dormancy of chrysanthemum. At the highest dosage of ethephon, an ethylene-releasing agent, wild-type plants formed rosettes with an inability to flower and became dormant, but one transgenic line did not. This confirms that dormancy is induced via the ethylene response pathway. PMID:18952907

  2. Unique roles of the unfolded protein response pathway in fungal development and differentiation.

    Science.gov (United States)

    Jung, Kwang-Woo; So, Yee-Seul; Bahn, Yong-Sun

    2016-09-15

    Cryptococcus neoformans, a global fungal meningitis pathogen, employs the unfolded protein response pathway. This pathway, which consists of an evolutionarily conserved Ire1 kinase/endoribonuclease and a unique transcription factor (Hxl1), modulates the endoplasmic reticulum stress response and pathogenicity. Here, we report that the unfolded protein response pathway governs sexual and unisexual differentiation of C. neoformans in an Ire1-dependent but Hxl1-independent manner. The ire1∆ mutants showed defects in sexual mating, with reduced cell fusion and pheromone-mediated formation of the conjugation tube. Unexpectedly, these mating defects did not result from defective pheromone production because expression of the mating pheromone gene (MFα1) was strongly induced in the ire1∆ mutant. Ire1 controls sexual differentiation by modulating the function of the molecular chaperone Kar2 and by regulating mating-induced localisation of mating pheromone transporter (Ste6) and receptor (Ste3/Cprα). Deletion of IRE1, but not HXL1, also caused significant defects in unisexual differentiation in a Kar2-independent manner. Moreover, we showed that Rim101 is a novel downstream factor of Ire1 for production of the capsule, which is a unique structural determinant of C. neoformans virulence. Therefore, Ire1 uniquely regulates fungal development and differentiation in an Hxl1-independent manner.

  3. Neural responses in songbird forebrain reflect learning rates, acquired salience, and stimulus novelty after auditory discrimination training

    OpenAIRE

    Bell, Brittany A.; Phan, Mimi L.; Vicario, David S.

    2014-01-01

    How do social interactions form and modulate the neural representations of specific complex signals? This question can be addressed in the songbird auditory system. Like humans, songbirds learn to vocalize by imitating tutors heard during development. These learned vocalizations are important in reproductive and social interactions and in individual recognition. As a model for the social reinforcement of particular songs, male zebra finches were trained to peck for a food reward in response t...

  4. Role of the fission yeast cell integrity MAPK pathway in response to glucose limitation

    Directory of Open Access Journals (Sweden)

    Madrid Marisa

    2013-02-01

    Full Text Available Abstract Background Glucose is a signaling molecule which regulates multiple events in eukaryotic organisms and the most preferred carbon source in the fission yeast Schizosaccharomyces pombe. The ability of this yeast to grow in the absence of glucose becomes strongly limited due to lack of enzymes of the glyoxylate cycle that support diauxic growth. The stress-activated protein kinase (SAPK pathway and its effectors, Sty1 MAPK and transcription factor Atf1, play a critical role in the adaptation of fission yeast to grow on alternative non-fermentable carbon sources by inducing the expression of fbp1+ gene, coding for the gluconeogenic enzyme fructose-1,6-bisphosphatase. The cell integrity Pmk1 pathway is another MAPK cascade that regulates various processes in fission yeast, including cell wall construction, cytokinesis, and ionic homeostasis. Pmk1 pathway also becomes strongly activated in response to glucose deprivation but its role during glucose exhaustion and ensuing adaptation to respiratory metabolism is currently unknown. Results We found that Pmk1 activation in the absence of glucose takes place only after complete depletion of this carbon source and that such activation is not related to an endogenous oxidative stress. Notably, Pmk1 MAPK activation relies on de novo protein synthesis, is independent on known upstream activators of the pathway like Rho2 GTPase, and involves PKC ortholog Pck2. Also, the Glucose/cAMP pathway is required operative for full activation of the Pmk1 signaling cascade. Mutants lacking Pmk1 displayed a partial growth defect in respiratory media which was not observed in the presence of glucose. This phenotype was accompanied by a decreased and delayed expression of transcription factor Atf1 and target genes fbp1+ and pyp2+. Intriguingly, the kinetics of Sty1 activation in Pmk1-less cells was clearly altered during growth adaptation to non-fermentable carbon sources. Conclusions Unknown upstream elements

  5. Differences in neural responses to reward and punishment processing between anorexia nervosa subtypes: An fMRI study.

    Science.gov (United States)

    Murao, Ema; Sugihara, Genichi; Isobe, Masanori; Noda, Tomomi; Kawabata, Michiko; Matsukawa, Noriko; Takahashi, Hidehiko; Murai, Toshiya; Noma, Shun'ichi

    2017-09-01

    Anorexia nervosa (AN) includes the restricting (AN-r) and binge-eating/purging (AN-bp) subtypes, which have been reported to differ regarding their underlying pathophysiologies as well as their behavioral patterns. However, the differences in neural mechanisms of reward systems between AN subtypes remain unclear. The aim of the present study was to explore differences in the neural processing of reward and punishment between AN subtypes. Twenty-three female patients with AN (11 AN-r and 12 AN-bp) and 20 healthy women underwent functional magnetic resonance imaging while performing a monetary incentive delay task. Whole-brain one-way analysis of variance was conducted to test between-group differences. There were significant group differences in brain activation in the rostral anterior cingulate cortex and right posterior insula during loss anticipation, with increased brain activation in the AN-bp group relative to the AN-r and healthy women groups. No significant differences were found during gain anticipation. AN-bp patients showed altered neural responses to punishment in brain regions implicated in emotional arousal. Our findings suggest that individuals with AN-bp are more sensitive to potential punishment than individuals with AN-r and healthy individuals at the neural level. The present study provides preliminary evidence that there are neurobiological differences between AN subtypes with regard to the reward system, especially punishment processing. © 2017 The Authors. Psychiatry and Clinical Neurosciences © 2017 Japanese Society of Psychiatry and Neurology.

  6. Beauty is in the belief of the beholder: cognitive influences on the neural response to facial attractiveness.

    Science.gov (United States)

    Thiruchselvam, Ravi; Harper, Jessica; Homer, Abigail L

    2016-12-01

    Judgments of facial attractiveness are central to decision-making in various domains, but little is known about the extent to which they are malleable. In this study, we used EEG/ERP methods to examine two novel influences on neural and subjective responses to facial attractiveness: an observer's expectation and repetition. In each trial of our task, participants viewed either an ordinary or attractive face. To alter expectations, the faces were preceded by a peer-rating that ostensibly reflected the overall attractiveness value assigned to that face by other individuals. To examine the impact of repetition, trials were presented twice throughout the experimental session. Results showed that participants' expectations about a person's attractiveness level powerfully altered both the neural response (i.e. the late positive potential; LPP) and self-reported attractiveness ratings. Intriguingly, repetition enhanced both the LPP and self-reported attractiveness as well. Exploratory analyses further suggested that both observer expectation and repetition modulated early neural responses (i.e. the early posterior negativity; EPN) elicited by facial attractiveness. Collectively, these results highlight novel influences on a core social judgment that underlies individuals' affective lives. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  7. Serotonin 2A Receptor Signaling Underlies LSD-induced Alteration of the Neural Response to Dynamic Changes in Music.

    Science.gov (United States)

    Barrett, Frederick S; Preller, Katrin H; Herdener, Marcus; Janata, Petr; Vollenweider, Franz X

    2017-09-28

    Classic psychedelic drugs (serotonin 2A, or 5HT2A, receptor agonists) have notable effects on music listening. In the current report, blood oxygen level-dependent (BOLD) signal was collected during music listening in 25 healthy adults after administration of placebo, lysergic acid diethylamide (LSD), and LSD pretreated with the 5HT2A antagonist ketanserin, to investigate the role of 5HT2A receptor signaling in the neural response to the time-varying tonal structure of music. Tonality-tracking analysis of BOLD data revealed that 5HT2A receptor signaling alters the neural response to music in brain regions supporting basic and higher-level musical and auditory processing, and areas involved in memory, emotion, and self-referential processing. This suggests a critical role of 5HT2A receptor signaling in supporting the neural tracking of dynamic tonal structure in music, as well as in supporting the associated increases in emotionality, connectedness, and meaningfulness in response to music that are commonly observed after the administration of LSD and other psychedelics. Together, these findings inform the neuropsychopharmacology of music perception and cognition, meaningful music listening experiences, and altered perception of music during psychedelic experiences. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  8. Neural responses in songbird forebrain reflect learning rates, acquired salience, and stimulus novelty after auditory discrimination training.

    Science.gov (United States)

    Bell, Brittany A; Phan, Mimi L; Vicario, David S

    2015-03-01

    How do social interactions form and modulate the neural representations of specific complex signals? This question can be addressed in the songbird auditory system. Like humans, songbirds learn to vocalize by imitating tutors heard during development. These learned vocalizations are important in reproductive and social interactions and in individual recognition. As a model for the social reinforcement of particular songs, male zebra finches were trained to peck for a food reward in response to one song stimulus (GO) and to withhold responding for another (NoGO). After performance reached criterion, single and multiunit neural responses to both trained and novel stimuli were obtained from multiple electrodes inserted bilaterally into two songbird auditory processing areas [caudomedial mesopallium (CMM) and caudomedial nidopallium (NCM)] of awake, restrained birds. Neurons in these areas undergo stimulus-specific adaptation to repeated song stimuli, and responses to familiar stimuli adapt more slowly than to novel stimuli. The results show that auditory responses differed in NCM and CMM for trained (GO and NoGO) stimuli vs. novel song stimuli. When subjects were grouped by the number of training days required to reach criterion, fast learners showed larger neural responses and faster stimulus-specific adaptation to all stimuli than slow learners in both areas. Furthermore, responses in NCM of fast learners were more strongly left-lateralized than in slow learners. Thus auditory responses in these sensory areas not only encode stimulus familiarity, but also reflect behavioral reinforcement in our paradigm, and can potentially be modulated by social interactions. Copyright © 2015 the American Physiological Society.

  9. Timescale of silver nanoparticle transformation in neural cell cultures impacts measured cell response

    Science.gov (United States)

    Hume, Stephanie L.; Chiaramonti, Ann N.; Rice, Katherine P.; Schwindt, Rani K.; MacCuspie, Robert I.; Jeerage, Kavita M.

    2015-07-01

    Both serum protein concentration and ionic strength are important factors in nanoparticle transformation within cell culture environments. However, silver nanoparticles are not routinely tracked at their working concentration in the specific medium used for in vitro toxicology studies. Here we evaluated the transformation of electrostatically stabilized citrate nanoparticles (C-AgNPs) and sterically stabilized polyvinylpyrrolidone nanoparticles (PVP-AgNPs) in a low-serum ( 0.2 mg/mL bovine serum albumin) culture medium, while measuring the response of rat cortex neural progenitor cells, which differentiate in this culture environment. After 24 h, silver nanoparticles at concentrations up to 10 µg/mL did not affect adenosine triphosphate levels, whereas silver ions decreased adenosine triphosphate levels at concentrations of 1.1 µg/mL or higher. After 240 h, both silver nanoparticles, as well as silver ion, unambiguously decreased adenosine triphosphate levels at concentrations of 1 and 1.1 µg/mL, respectively, suggesting particle dissolution. Particle transformation was investigated in 1:10 diluted, 1:2 diluted, or undiluted differentiation medium, all having an identical protein concentration, to separate the effect of serum protein stabilization from ionic strength destabilization. Transmission electron microscopy images indicated that particles in 1:10 medium were not surrounded by proteins, whereas particles became clustered within a non-crystalline protein matrix after 24 h in 1:2 medium and at 0 h in undiluted medium. Despite evidence for a protein corona, particles were rapidly destabilized by high ionic strength media. Polyvinylpyrrolidone increased the stability of singly dispersed particles compared to citrate ligands; however, differences were negligible after 4 h in 1:2 medium or after 1 h in undiluted medium. Thus low-serum culture environments do not provide sufficient colloidal stability for long-term toxicology studies with citrate- or

  10. Enhanced Neural Responses to Imagined Primary Rewards Predict Reduced Monetary Temporal Discounting.

    Science.gov (United States)

    Hakimi, Shabnam; Hare, Todd A

    2015-09-23

    The pervasive tendency to discount the value of future rewards varies considerably across individuals and has important implications for health and well-being. Here, we used fMRI with human participants to examine whether an individual's neural representation of an imagined primary reward predicts the degree to which the value of delayed monetary payments is discounted. Because future rewards can never be experienced at the time of choice, imagining or simulating the benefits of a future reward may play a critical role in decisions between alternatives with either immediate or delayed benefits. We found that enhanced ventromedial prefrontal cortex response during imagined primary reward receipt was correlated with reduced discounting in a separate monetary intertemporal choice task. Furthermore, activity in enhanced ventromedial prefrontal cortex during reward imagination predicted temporal discounting behavior both between- and within-individual decision makers with 62% and 73% mean balanced accuracy, respectively. These results suggest that the quality of reward imagination may impact the degree to which future outcomes are discounted. Significance statement: We report a novel test of the hypothesis that an important factor influencing the discount rate for future rewards is the quality with which they are imagined or estimated in the present. Previous work has shown that temporal discounting is linked to individual characteristics ranging from general intelligence to the propensity for addiction. We demonstrate that individual differences in a neurobiological measure of primary reward imagination are significantly correlated with discounting rates for future monetary payments. Moreover, our neurobiological measure of imagination can be used to accurately predict choice behavior both between and within individuals. These results suggest that improving reward imagination may be a useful therapeutic target for individuals whose high discount rates promote

  11. Modeling and optimization of ethanol fermentation using Saccharomyces cerevisiae: Response surface methodology and artificial neural network

    Directory of Open Access Journals (Sweden)

    Esfahanian Mehri

    2013-01-01

    Full Text Available In this study, the capabilities of response surface methodology (RSM and artificial neural networks (ANN for modeling and optimization of ethanol production from glucoseusing Saccharomyces cerevisiae in batch fermentation process were investigated. Effect of three independent variables in a defined range of pH (4.2-5.8, temperature (20-40ºC and glucose concentration (20-60 g/l on the cell growth and ethanol production was evaluated. Results showed that prediction accuracy of ANN was apparently similar to RSM. At optimum condition of temperature (32°C, pH (5.2 and glucose concentration (50 g/l suggested by the statistical methods, the maximum cell dry weight and ethanol concentration obtained from RSM were 12.06 and 16.2 g/l whereas experimental values were 12.09 and 16.53 g/l, respectively. The present study showed that using ANN as fitness function, the maximum cell dry weight and ethanol concentration were 12.05 and 16.16 g/l, respectively. Also, the coefficients of determination for biomass and ethanol concentration obtained from RSM were 0.9965 and 0.9853 and from ANN were 0.9975 and 0.9936, respectively. The process parameters optimization was successfully conducted using RSM and ANN; however prediction by ANN was slightly more precise than RSM. Based on experimental data maximum yield of ethanol production of 0.5 g ethanol/g substrate (97 % of theoretical yield was obtained.

  12. Timescale of silver nanoparticle transformation in neural cell cultures impacts measured cell response

    Energy Technology Data Exchange (ETDEWEB)

    Hume, Stephanie L.; Chiaramonti, Ann N.; Rice, Katherine P.; Schwindt, Rani K. [National Institute of Standards and Technology (NIST), Applied Chemicals and Materials Division (United States); MacCuspie, Robert I. [National Institute of Standards and Technology (NIST), Materials Measurement Science Division (United States); Jeerage, Kavita M., E-mail: jeerage@boulder.nist.gov [National Institute of Standards and Technology (NIST), Applied Chemicals and Materials Division (United States)

    2015-07-15

    Both serum protein concentration and ionic strength are important factors in nanoparticle transformation within cell culture environments. However, silver nanoparticles are not routinely tracked at their working concentration in the specific medium used for in vitro toxicology studies. Here we evaluated the transformation of electrostatically stabilized citrate nanoparticles (C-AgNPs) and sterically stabilized polyvinylpyrrolidone nanoparticles (PVP-AgNPs) in a low-serum (∼ 0.2 mg/mL bovine serum albumin) culture medium, while measuring the response of rat cortex neural progenitor cells, which differentiate in this culture environment. After 24 h, silver nanoparticles at concentrations up to 10 µg/mL did not affect adenosine triphosphate levels, whereas silver ions decreased adenosine triphosphate levels at concentrations of 1.1 µg/mL or higher. After 240 h, both silver nanoparticles, as well as silver ion, unambiguously decreased adenosine triphosphate levels at concentrations of 1 and 1.1 µg/mL, respectively, suggesting particle dissolution. Particle transformation was investigated in 1:10 diluted, 1:2 diluted, or undiluted differentiation medium, all having an identical protein concentration, to separate the effect of serum protein stabilization from ionic strength destabilization. Transmission electron microscopy images indicated that particles in 1:10 medium were not surrounded by proteins, whereas particles became clustered within a non-crystalline protein matrix after 24 h in 1:2 medium and at 0 h in undiluted medium. Despite evidence for a protein corona, particles were rapidly destabilized by high ionic strength media. Polyvinylpyrrolidone increased the stability of singly dispersed particles compared to citrate ligands; however, differences were negligible after 4 h in 1:2 medium or after 1 h in undiluted medium. Thus low-serum culture environments do not provide sufficient colloidal stability for long-term toxicology studies with citrate

  13. Enhanced neural responsiveness to reward associated with obesity in the absence of food-related stimuli.

    Science.gov (United States)

    Opel, Nils; Redlich, Ronny; Grotegerd, Dominik; Dohm, Katharina; Haupenthal, Cordula; Heindel, Walter; Kugel, Harald; Arolt, Volker; Dannlowski, Udo

    2015-06-01

    Obesity has been characterized by alterations in brain structure and function associated with emotion processing and regulation. Particularly, aberrations in food-related reward processing have been frequently demonstrated in obese subjects. However, it remains unclear whether reward-associated functional aberrations in obesity are specific for food-related stimuli or represent a general deficit in reward processing, extending to other stimulus domains. Given the crucial role of rewarding effects in the development of obesity and the ongoing discussion on overlapping neurobiological traits of obesity and psychiatric disorders such as depression and substance-related disorders, this study aimed to investigate the possibility of altered reward processing in obese subjects to occur in the absence of food-related stimuli during a monetary reward condition. Twenty-nine healthy obese subjects (body mass index >30) and 29 healthy, age-, and sex-matched control subjects of normal weight underwent functional MRI during a frequently used card guessing paradigm. A Group × Condition (win vs. loss) ANOVA was conducted to investigate differences between obese and normal-weight subjects. We found significant Group × Condition interaction effects in brain areas involved in emotion regulation and reward processing including the insula, the striatum, and the orbitofrontal cortex (OFC). This interaction was predominantly driven by a significant increase in blood oxygenation level dependent (BOLD) response in obese individuals while experiencing reward. Enhanced neural activation in obesity during reward processing seems to be apparent even in the absence of food-related stimuli and, thus, might point to generalized dysfunctions in reward-related brain circuits in obese individuals. © 2015 Wiley Periodicals, Inc.

  14. Endocrine responses and acute mTOR pathway phosphorylation to resistance exercise with leucine and whey

    Directory of Open Access Journals (Sweden)

    MT Lane

    2017-02-01

    Full Text Available Leucine ingestion reportedly activates the mTOR pathway in skeletal muscle, contributing to a hypertrophy response. The purpose of the study was to compare the post-resistance exercise effects of leucine and whey protein supplementation on endocrine responses and muscle mTOR pathway phosphorylation. On visit 1, subjects (X±SD; n=20; age=27.8±2.8yrs provided baseline blood samples for analysis of cortisol, glucose and insulin; a muscle biopsy of the vastus lateralis muscle to assess mTOR signaling pathway phosphorylation; and were tested for maximum strength on the leg press and leg extension exercises. For visits 2 and 3, subjects were randomized in a double-blind crossover design to ingest either leucine and whey protein (10g+10g; supplement or a non-caloric placebo. During these visits, 5 sets of 10 repetitions were performed on both exercises, immediately followed by ingestion of the supplement or placebo. Blood was sampled 30 min post-, and a muscle biopsy 45 min post-exercise. Western blots quantified total and phosphorylated proteins. Insulin increased (α<.05 with supplementation with no change in glucose compared to placebo. Relative phosphorylation of AKT and rpS6 were greater with leucine and whey supplementation compared to placebo. Supplementation of leucine and whey protein immediately after heavy resistance exercise increases anabolic signaling in human skeletal muscle.

  15. Disturbances in Response Inhibition and Emotional Processing as Potential Pathways to Violence in Schizophrenia: A High-Density Event-Related Potential Study.

    Science.gov (United States)

    Krakowski, Menahem I; De Sanctis, Pierfilippo; Foxe, John J; Hoptman, Matthew J; Nolan, Karen; Kamiel, Stephanie; Czobor, Pal

    2016-07-01

    Increased susceptibility to emotional triggers and poor response inhibition are important in the etiology of violence in schizophrenia. Our goal was to evaluate abnormalities in neurophysiological mechanisms underlying response inhibition and emotional processing in violent patients with schizophrenia (VS) and 3 different comparison groups: nonviolent patients (NV), healthy controls (HC) and nonpsychotic violent subjects (NPV). We recorded high-density Event-Related Potentials (ERPs) and behavioral responses during an Emotional Go/NoGo Task in 35 VS, 24 NV, 28 HC and 31 NPV subjects. We also evaluated psychiatric symptoms and impulsivity. The neural and behavioral deficits in violent patients were most pronounced when they were presented with negative emotional stimuli: They responded more quickly than NV when they made commission errors (ie, failure of inhibition), and evidenced N2 increases and P3 decreases. In contrast, NVs showed little change in reaction time or ERP amplitude with emotional stimuli. These N2 and P3 amplitude changes in VSs showed a strong association with greater impulsivity. Besides these group specific changes, VSs shared deficits with NV, mostly N2 reduction, and with violent nonpsychotic subjects, particularly P3 reduction. Negative affective triggers have a strong impact on violent patients with schizophrenia which may have both behavioral and neural manifestations. The resulting activation could interfere with response inhibition. The affective disruption of response inhibition, identified in this study, may index an important pathway to violence in schizophrenia and suggest new modes of treatment. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  16. Sensory neural pathways revisited to unravel the temporal dynamics of the Simon effect: A model-based cognitive neuroscience approach.

    Science.gov (United States)

    Salzer, Yael; de Hollander, Gilles; Forstmann, Birte U

    2017-06-01

    The Simon task is one of the most prominent interference tasks and has been extensively studied in experimental psychology and cognitive neuroscience. Despite years of research, the underlying mechanism driving the phenomenon and its temporal dynamics are still disputed. Within the framework of the review, we adopt a model-based cognitive neuroscience approach. We first go over key findings in the literature of the Simon task, discuss competing qualitative cognitive theories and the difficulty of testing them empirically. We then introduce sequential sampling models, a particular class of mathematical cognitive process models. Finally, we argue that the brain architecture accountable for the processing of spatial ('where') and non-spatial ('what') information, could constrain these models. We conclude that there is a clear need to bridge neural and behavioral measures, and that mathematical cognitive models may facilitate the construction of this bridge and work towards revealing the underlying mechanisms of the Simon effect. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Buffering social influence: neural correlates of response inhibition predict driving safety in the presence of a peer.

    Science.gov (United States)

    Cascio, Christopher N; Carp, Joshua; O'Donnell, Matthew Brook; Tinney, Francis J; Bingham, C Raymond; Shope, Jean T; Ouimet, Marie Claude; Pradhan, Anuj K; Simons-Morton, Bruce G; Falk, Emily B

    2015-01-01

    Adolescence is a period characterized by increased sensitivity to social cues, as well as increased risk-taking in the presence of peers. For example, automobile crashes are the leading cause of death for adolescents, and driving with peers increases the risk of a fatal crash. Growing evidence points to an interaction between neural systems implicated in cognitive control and social and emotional context in predicting adolescent risk. We tested such a relationship in recently licensed teen drivers. Participants completed an fMRI session in which neural activity was measured during a response inhibition task, followed by a separate driving simulator session 1 week later. Participants drove alone and with a peer who was randomly assigned to express risk-promoting or risk-averse social norms. The experimentally manipulated social context during the simulated drive moderated the relationship between individual differences in neural activity in the hypothesized cognitive control network (right inferior frontal gyrus, BG) and risk-taking in the driving context a week later. Increased activity in the response inhibition network was not associated with risk-taking in the presence of a risky peer but was significantly predictive of safer driving in the presence of a cautious peer, above and beyond self-reported susceptibility to peer pressure. Individual differences in recruitment of the response inhibition network may allow those with stronger inhibitory control to override risky tendencies when in the presence of cautious peers. This relationship between social context and individual differences in brain function expands our understanding of neural systems involved in top-down cognitive control during adolescent development.

  18. Selective responses of enzymes in the two parallel pathways of rosmarinic acid biosynthetic pathway to elicitors in Salvia miltiorrhiza hairy root cultures.

    Science.gov (United States)

    Zhang, Shuncang; Yan, Yan; Wang, Bangqing; Liang, Zongsuo; Liu, Yan; Liu, Fenghua; Qi, Zhihong

    2014-05-01

    Rosmarinic acid and salvianolic acid B are two important phenolic compounds with therapeutic properties in Salvia miltiorrhiza Bunge. The biosynthesis of rosmarinic acid is initiated by two parallel pathways, namely the phenylpropanoid pathway and the tyrosine-derived pathway. Salvianolic acid B is a structural dimer of rosmarinic acid and is believed to be derived from rosmarinic acid. In the current study, methyl jasmonate (MeJA) and hyphal extracts from fungi were used as elicitors to examine the relationship between enzymes in the two parallel pathways and accumulation of phenolic compounds in S. miltiorrhiza hairy root cultures. The results showed that accumulations of rosmarinic acid, salvianolic acid B and total phenolics were enhanced by MeJA while suppressed by fugal extracts. Responses of enzymes in the tyrosine-derived pathway, at both the gene transcript and enzyme activity levels, showed a better consistency with alterations of phenolic compounds content after the two elicitors treated. Our study implied that compared with enzymes in the phenylpropanoid pathway, enzymes in the tyrosine-derived pathway are more correlated to rosmarinic acid and salvianolic acid B biosynthesis in S. miltiorrhiza hairy roots. Copyright © 2013 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  19. Gestational naltrexone ameliorates fetal ethanol exposures enhancing effect on the postnatal behavioral and neural response to ethanol.

    Science.gov (United States)

    Youngentob, Steven L; Kent, Paul F; Youngentob, Lisa M

    2012-10-01

    The association between gestational exposure to ethanol and adolescent ethanol abuse is well established. Recent animal studies support the role of fetal ethanol experience-induced chemosensory plasticity as contributing to this observation. Previously, we established that fetal ethanol exposure, delivered through a dam's diet throughout gestation, tuned the neural response of the peripheral olfactory system of early postnatal rats to the odor of ethanol. This occurred in conjunction with a loss of responsiveness to other odorants. The instinctive behavioral response to the odor of ethanol was also enhanced. Importantly, there was a significant contributory link between the altered response to the odor of ethanol and increased ethanol avidity when assessed in the same animals. Here, we tested whether the neural and behavioral olfactory plasticity, and their relationship to enhanced ethanol intake, is a result of the mere exposure to ethanol or whether it requires the animal to associate ethanol's reinforcing properties with its odor attributes. In this later respect, the opioid system is important in the mediation (or modulation) of the reinforcing aspects of ethanol. To block endogenous opiates during prenatal life, pregnant rats received daily intraperitoneal administration of the opiate antagonist naltrexone from gestational day 6-21 jointly with ethanol delivered via diet. Relative to control progeny, we found that gestational exposure to naltrexone ameliorated the enhanced postnatal behavioral response to the odor of ethanol and postnatal drug avidity. Our findings support the proposition that in utero ethanol-induced olfactory plasticity (and its relationship to postnatal intake) requires, at least in part, the associative pairing between ethanol's odor quality and its reinforcing aspects. We also found suggestive evidence that fetal naltrexone ameliorated the untoward effects of gestational ethanol exposure on the neural response to non

  20. Retinoblastoma pathway defects show differential ability to activate the constitutive DNA damage response in human tumorigenesis

    DEFF Research Database (Denmark)

    Tort, F.; Bartkova, J.; Sehested, M.

    2006-01-01

    activation. Here, we show that, in a series of human colorectal adenomas, those with deregulation of cyclin D1 and/or p16(Ink4a) showed little evidence of constitutive DNA damage response (DDR), contrary to cyclin E-overexpressing higher-grade cases. These observations were consistent with diverse cell...... culture models with differential defects of retinoblastoma pathway components, as overexpression of cyclin D1 or lack of p16(Ink4a), either alone or combined, did not elicit detectable DDR. In contrast, inactivation of pRb, the key component of the pathway, activated the DDR in cultured human or mouse...... cells, analogous to elevated cyclin E. These results highlight differential effect of diverse oncogenic events on driving the 'cancer cell cycles' and their ability to deregulate the replication-driving CDK2 kinase and to alarm the DDR as a potential anticancer barrier in accordance...

  1. Prolonged sleep restriction induces changes in pathways involved in cholesterol metabolism and inflammatory responses

    Science.gov (United States)

    Aho, Vilma; Ollila, Hanna M.; Kronholm, Erkki; Bondia-Pons, Isabel; Soininen, Pasi; Kangas, Antti J.; Hilvo, Mika; Seppälä, Ilkka; Kettunen, Johannes; Oikonen, Mervi; Raitoharju, Emma; Hyötyläinen, Tuulia; Kähönen, Mika; Viikari, Jorma S.A.; Härmä, Mikko; Sallinen, Mikael; Olkkonen, Vesa M.; Alenius, Harri; Jauhiainen, Matti; Paunio, Tiina; Lehtimäki, Terho; Salomaa, Veikko; Orešič, Matej; Raitakari, Olli T.; Ala-Korpela, Mika; Porkka-Heiskanen, Tarja

    2016-01-01

    Sleep loss and insufficient sleep are risk factors for cardiometabolic diseases, but data on how insufficient sleep contributes to these diseases are scarce. These questions were addressed using two approaches: an experimental, partial sleep restriction study (14 cases and 7 control subjects) with objective verification of sleep amount, and two independent epidemiological cohorts (altogether 2739 individuals) with questions of sleep insufficiency. In both approaches, blood transcriptome and serum metabolome were analysed. Sleep loss decreased the expression of genes encoding cholesterol transporters and increased expression in pathways involved in inflammatory responses in both paradigms. Metabolomic analyses revealed lower circulating large HDL in the population cohorts among subjects reporting insufficient sleep, while circulating LDL decreased in the experimental sleep restriction study. These findings suggest that prolonged sleep deprivation modifies inflammatory and cholesterol pathways at the level of gene expression and serum lipoproteins, inducing changes toward potentially higher risk for cardiometabolic diseases. PMID:27102866

  2. Cellular Pathways in Response to Ionizing Radiation and Their Targetability for Tumor Radiosensitization

    Directory of Open Access Journals (Sweden)

    Patrick Maier

    2016-01-01

    Full Text Available During the last few decades, improvements in the planning and application of radiotherapy in combination with surgery and chemotherapy resulted in increased survival rates of tumor patients. However, the success of radiotherapy is impaired by two reasons: firstly, the radioresistance of tumor cells and, secondly, the radiation-induced damage of normal tissue cells located in the field of ionizing radiation. These limitations demand the development of drugs for either radiosensitization of tumor cells or radioprotection of normal tissue cells. In order to identify potential targets, a detailed understanding of the cellular pathways involved in radiation response is an absolute requirement. This review describes the most important pathways of radioresponse and several key target proteins for radiosensitization.

  3. Regional neural response differences in the determination of faces or houses positioned in a wide visual field.

    Science.gov (United States)

    Wang, Bin; Yan, Tianyi; Wu, Jinglong; Chen, Kewei; Imajyo, Satoshi; Ohno, Seiichiro; Kanazawa, Susumu

    2013-01-01

    In human visual cortex, the primary visual cortex (V1) is considered to be essential for visual information processing; the fusiform face area (FFA) and parahippocampal place area (PPA) are considered as face-selective region and places-selective region, respectively. Recently, a functional magnetic resonance imaging (fMRI) study showed that the neural activity ratios between V1 and FFA were constant as eccentricities increasing in central visual field. However, in wide visual field, the neural activity relationships between V1 and FFA or V1 and PPA are still unclear. In this work, using fMRI and wide-view present system, we tried to address this issue by measuring neural activities in V1, FFA and PPA for the images of faces and houses aligning in 4 eccentricities and 4 meridians. Then, we further calculated ratio relative to V1 (RRV1) as comparing the neural responses amplitudes in FFA or PPA with those in V1. We found V1, FFA, and PPA showed significant different neural activities to faces and houses in 3 dimensions of eccentricity, meridian, and region. Most importantly, the RRV1s in FFA and PPA also exhibited significant differences in 3 dimensions. In the dimension of eccentricity, both FFA and PPA showed smaller RRV1s at central position than those at peripheral positions. In meridian dimension, both FFA and PPA showed larger RRV1s at upper vertical positions than those at lower vertical positions. In the dimension of region, FFA had larger RRV1s than PPA. We proposed that these differential RRV1s indicated FFA and PPA might have different processing strategies for encoding the wide field visual information from V1. These different processing strategies might depend on the retinal position at which faces or houses are typically observed in daily life. We posited a role of experience in shaping the information processing strategies in the ventral visual cortex.

  4. Analysis of the Human Mucosal Response to Cholera Reveals Sustained Activation of Innate Immune Signaling Pathways.

    Science.gov (United States)

    Bourque, Daniel L; Bhuiyan, Taufiqur Rahman; Genereux, Diane P; Rashu, Rasheduzzaman; Ellis, Crystal N; Chowdhury, Fahima; Khan, Ashraful I; Haq Alam, Nur; Lazina Hossain, Anik Paul; Mayo-Smith, Leslie M; Charles, Richelle C; Weil, Ana A; LaRocque, Regina C; Calderwood, Stephen B; Ryan, Edward T; Karlsson, Elinor K; Qadri, Firdausi; Harris, Jason B

    2017-11-13

    To better understand the innate immune response to Vibrio cholerae infection, we tracked gene expression in the duodenal mucosa of eleven Bangladeshi adults with cholera, using biopsies obtained immediately after rehydration and at 30 and 180 days later. We identified differentially expressed genes and performed an analysis to predict differentially regulated pathways and upstream regulators. During acute cholera, there was a broad increase in the expression of genes associated with innate immunity, including activation of the NF-κB, MAPK, and TLR-mediated signaling pathways, which unexpectedly persisted even 30 days after infection. Focusing on early differences in gene expression, we identified 37 genes that were differentially expressed on days 2 and 30 across eleven participants. These genes included the endosomal toll like receptor, TLR8, which was expressed in lamina propria cells. Underscoring a potential role for endosomal TLR-mediated signaling in vivo, our pathway analysis found that IRF7 and interferons β1 and α2 were among the top upstream regulators activated during cholera. Among innate immune effectors, we found that DUOX2, an NADPH-oxidase involved in the maintenance of intestinal homeostasis, was upregulated in intestinal epithelial cells during cholera. Notably, the observed increases in DUOX2 and TLR8 expression were also modeled in vitro when stimulating Caco-2 or THP-1 cells, respectively, with live V. cholerae but not with heat killed organisms or cholera toxin alone. These previously unidentified features of the innate immune response to V. cholerae extend our understanding mucosal immune signaling pathways and effectors activated in vivo following cholera. Copyright © 2017 American Society for Microbiology.

  5. Inhibition of ER stress and unfolding protein response pathways causes skeletal muscle wasting during cancer cachexia

    Science.gov (United States)

    Bohnert, Kyle R.; Gallot, Yann S.; Sato, Shuichi; Xiong, Guangyan; Hindi, Sajedah M.; Kumar, Ashok

    2016-01-01

    Cachexia is a devastating syndrome that causes morbidity and mortality in a large number of patients with cancer. However, the mechanisms of cancer cachexia remain poorly understood. Accumulation of misfolded proteins in the endoplasmic reticulum (ER) causes stress. The ER responds to this stress through activating certain pathways commonly known as the unfolding protein response (UPR). The main function of UPR is to restore homeostasis, but excessive or prolonged activation of UPR can lead to pathologic conditions. In this study, we examined the role of ER stress and UPR in regulation of skeletal muscle mass in naïve conditions and during cancer cachexia. Our results demonstrate that multiple markers of ER stress are highly activated in skeletal muscle of Lewis lung carcinoma (LLC) and ApcMin/+ mouse models of cancer cachexia. Treatment of mice with 4-phenylbutyrate (4-PBA), a chemical chaperon and a potent inhibitor of ER stress, significantly reduced skeletal muscle strength and mass in both control and LLC-bearing mice. Blocking the UPR also increased the proportion of fast-type fibers in soleus muscle of both control and LLC-bearing mice. Inhibition of UPR reduced the activity of Akt/mTOR pathway and increased the expression of the components of the ubiquitin–proteasome system and autophagy in LLC-bearing mice. Moreover, we found that the inhibition of UPR causes severe atrophy in cultured myotubes. Our study provides initial evidence that ER stress and UPR pathways are essential for maintaining skeletal muscle mass and strength and for protection against cancer cachexia.—Bohnert, K. R., Gallot, Y. S., Sato, S., Xiong, G., Hindi, S. M., Kumar, A. Inhibition of ER stress and unfolding protein response pathways causes skeletal muscle wasting during cancer cachexia. PMID:27206451

  6. A glutamatergic network mediates lithium response in bipolar disorder as defined by epigenome pathway analysis.

    Science.gov (United States)

    Higgins, Gerald A; Allyn-Feuer, Ari; Barbour, Edward; Athey, Brian D

    2015-01-01

    A regulatory network in the human brain mediating lithium response in bipolar patients was revealed by analysis of functional SNPs from genome-wide association studies (GWAS) and published gene association studies, followed by epigenome mapping. An initial set of 23,312 SNPs in linkage disequilibrium with lead SNPs, and sub-threshold GWAS SNPs rescued by pathway analysis, were studied in the same populations. These were assessed using our workflow and annotation by the epigenome roadmap consortium. Twenty-seven percent of 802 SNPs that were associated with lithium response (13 published studies gene association studies and two GWAS) were shared in common with 1281 SNPs from 18 GWAS examining psychiatric disorders and adverse events associated with lithium treatment. Nineteen SNPs were annotated as active regulatory elements such as enhancers and promoters in a tissue-specific manner. They were located within noncoding regions of ten genes: ANK3, ARNTL, CACNA1C, CACNG2, CDKN1A, CREB1, GRIA2, GSK3B, NR1D1 and SLC1A2. Following gene set enrichment and pathway analysis, these genes were found to be significantly associated (p = 10(-27); Fisher exact test) with an AMPA2 glutamate receptor network in human brain. Our workflow results showed concordance with annotation of regulatory elements from the epigenome roadmap. Analysis of cognate mRNA and enhancer RNA exhibited patterns consistent with an integrated pathway in human brain. This pharmacoepigenomic regulatory pathway is located in the same brain regions that exhibit tissue volume loss in bipolar disorder. Although in silico analysis requires biological validation, the approach provides value for identification of candidate variants that may be used in pharmacogenomic testing to identify bipolar patients likely to respond to lithium.

  7. Simulation of a Classically Conditioned Response: Components of the Input Trace and a Cerebellar Neural Network Implementation of the Sutton-Barto-Desmond Model.

    Science.gov (United States)

    1987-09-14

    the Input Trace and a Cerebellar Neural Network Implementation of the Sutton-Barto-Desmond Model Diana E. J. Blazis and John W. Moore COINS Technical...efferent pathway of the CR. li order for (ClHs to lie generated by on- ){(s inst ead of off-I)(,Cs, there would h ave o le ;i <,gral inversion .orniewher

  8. Functioning of peripheral Ia pathways in infants with typical development: responses in antagonist muscle pairs.

    Science.gov (United States)

    Teulier, Caroline; Ulrich, Beverly D; Martin, Bernard

    2011-02-01

    In muscle responses of proprioceptive origin, including the stretch/tendon reflex (T-reflex), the corresponding reciprocal excitation and irradiation to distant muscles have been described from newborn infants to older adults. However, the functioning of other responses mediated primarily by Ia-afferents has not been investigated in infants. Understanding the typical development of these multiple pathways is critical to determining potential problems in their development in populations affected by neurological disease, such as spina bifida or cerebral palsy. Hence, the goal of the present study was to quantify the excitability of Ia-mediated responses in lower limb muscles of infants with typical development. These responses were elicited by mechanical stimulation applied to the distal tendons of the gastrocnemius-soleus (GS), tibialis anterior (TA) and quadriceps (QAD) muscles of both legs in twelve 2- to 10-month-old infants and recorded simultaneously in antagonist muscle pairs by surface EMG. Tendon taps alone elicited responses in either, both or neither muscle. The homonymous response (T-reflex) was less frequent in the TA than the GS or QAD muscle. An 80 Hz vibration superimposed on tendon taps induced primarily an inhibition of monosynaptic responses; however, facilitation also occurred in either muscle of the recorded pair. These responses were not influenced significantly by age or gender. Vibration alone produced a tonic reflex response in the vibrated muscle (TVR) and/or the antagonist muscle (AVR). However, for the TA muscle the TVR was more frequently elicited in older than younger infants. High variability was common to all responses. Overall, the random distribution and inconsistency of muscle responses suggests that the gain of Ia-mediated feedback is unstable. We propose that during infancy the central nervous system needs to learn to set stable feedback gain, or destination of proprioceptive assistance, based on their use during functional

  9. Haptic fMRI: accurately estimating neural responses in motor, pre-motor, and somatosensory cortex during complex motor tasks.

    Science.gov (United States)

    Menon, Samir; Yu, Michelle; Kay, Kendrick; Khatib, Oussama

    2014-01-01

    Haptics combined with functional magnetic resonance imaging (Haptic fMRI) can non-invasively study how the human brain coordinates movement during complex manipulation tasks, yet avoiding associated fMRI artifacts remains a challenge. Here, we demonstrate confound-free neural activation measurements using Haptic fMRI for an unconstrained three degree-of-freedom motor task that involves planning, reaching, and visually guided trajectory tracking. Our haptic interface tracked subjects' hand motions, velocities, and accelerations (sample-rate, 350Hz), and provided continuous realtime visual feedback. During fMRI acquisition, we achieved uniform response latencies (reaching, 0.7-1.1s; tracking, 0.4-0.65s); minimized hand jitter (neural activation across cortex; unreliable motions and response latencies, which reduce statistical power; and task-correlated head motion, which causes spurious fMRI activation. Haptic fMRI can thus reliably elicit and localize heterogeneous neural activation for different tasks in motor (movement), pre-motor (planning), and somatosensory (limb displacement) cortex, demonstrating that it is feasible to use the technique to study how the brain achieves three dimensional motor control.

  10. Where does brain neural activation in aesthetic responses to visual art occur? Meta-analytic evidence from neuroimaging studies.

    Science.gov (United States)

    Boccia, M; Barbetti, S; Piccardi, L; Guariglia, C; Ferlazzo, F; Giannini, A M; Zaidel, D W

    2016-01-01

    Here we aimed at finding the neural correlates of the general aspect of visual aesthetic experience (VAE) and those more strictly correlated with the content of the artworks. We applied a general activation likelihood estimation (ALE) meta-analysis to 47 fMRI experiments described in 14 published studies. We also performed four separate ALE analyses in order to identify the neural substrates of reactions to specific categories of artworks, namely portraits, representation of real-world-visual-scenes, abstract paintings, and body sculptures. The general ALE revealed that VAE relies on a bilateral network of areas, and the individual ALE analyses revealed different maximal activation for the artworks' categories as function of their content. Specifically, different content-dependent areas of the ventral visual stream are involved in VAE, but a few additional brain areas are involved as well. Thus, aesthetic-related neural responses to art recruit widely distributed networks in both hemispheres including content-dependent brain areas of the ventral visual stream. Together, the results suggest that aesthetic responses are not independent of sensory, perceptual, and cognitive processes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Transcriptome changes in the phenylpropanoid pathway of Glycine max in response to Pseudomonas syringae infection

    Directory of Open Access Journals (Sweden)

    Gonzalez Delkin O

    2006-11-01

    Full Text Available Abstract Background Reports of plant molecular responses to pathogenic infections have pinpointed increases in activity of several genes of the phenylpropanoid pathway leading to the synthesis of lignin and flavonoids. The majority of those findings were derived from single gene studies and more recently from several global gene expression analyses. We undertook a global transcriptional analysis focused on the response of genes of the multiple branches of the phenylpropanoid pathway to infection by the Pseudomonas syringae pv. glycinea with or without the avirulence gene avrB to characterize more broadly the contribution of the multiple branches of the pathway to the resistance response in soybean. Transcript abundance in leaves was determined from analysis of soybean cDNA microarray data and hybridizations to RNA blots with specific gene probes. Results The majority of the genes surveyed presented patterns of increased transcript accumulation. Some increased rapidly, 2 and 4 hours after inoculation, while others started to accumulate slowly by 8 – 12 hours. In contrast, transcripts of a few genes decreased in abundance 2 hours post inoculation. Most interestingly was the opposite temporal fluctuation in transcript abundance between early responsive genes in defense (CHS and IFS1 and F3H, the gene encoding a pivotal enzyme in the synthesis of anthocyanins, proanthocyanidins and flavonols. F3H transcripts decreased rapidly 2 hours post inoculation and increased during periods when CHS and IFS transcripts decreased. It was also determined that all but one (CHS4 family member genes (CHS1, CHS2, CHS3, CHS5, CHS6 and CHS7/8 accumulated higher transcript levels during the defense response provoked by the avirulent pathogen challenge. Conclusion Based on the mRNA profiles, these results show the strong bias that soybean has towards increasing the synthesis of isoflavonoid phytoalexins concomitant with the down regulation of genes required for the

  12. Determination of breast cancer response to bevacizumab therapy using contrast-enhanced ultrasound and artificial neural networks.

    Science.gov (United States)

    Hoyt, Kenneth; Warram, Jason M; Umphrey, Heidi; Belt, Lin; Lockhart, Mark E; Robbin, Michelle L; Zinn, Kurt R

    2010-04-01

    The purpose of this study was to evaluate contrast-enhanced ultrasound and neural network data classification for determining the breast cancer response to bevacizumab therapy in a murine model. An ultrasound scanner operating in the harmonic mode was used to measure ultrasound contrast agent (UCA) time-intensity curves in vivo. Twenty-five nude athymic mice with orthotopic breast cancers received a 30-microL tail vein bolus of a perflutren microsphere UCA, and baseline tumor imaging was performed using microbubble destruction-replenishment techniques. Subsequently, 15 animals received a 0.2-mg injection of bevacizumab, whereas 10 control animals received an equivalent dose of saline. Animals were reimaged on days 1, 2, 3, and 6 before euthanasia. Histologic assessment of excised tumor sections was performed. Time-intensity curve analysis for a given region of interest was conducted using customized software. Tumor perfusion metrics on days 1, 2, 3, and 6 were modeled using neural network data classification schemes (60% learning and 40% testing) to predict the breast cancer response to therapy. The breast cancer response to a single dose of bevacizumab in a murine model was immediate and transient. Permutations of input to the neural network data classification scheme revealed that tumor perfusion data within 3 days of bevacizumab dosing was sufficient to minimize the prediction error to 10%, whereas measurements of physical tumor size alone did not appear adequate to assess the therapeutic response. Contrast-enhanced ultrasound may be a useful tool for determining the response to bevacizumab therapy and monitoring the subsequent restoration of blood flow to breast cancer.

  13. Neural responses to visual food cues according to weight status: a systematic review of functional magnetic resonance imaging studies.

    Science.gov (United States)

    Pursey, Kirrilly M; Stanwell, Peter; Callister, Robert J; Brain, Katherine; Collins, Clare E; Burrows, Tracy L

    2014-01-01

    Emerging evidence from recent neuroimaging studies suggests that specific food-related behaviors contribute to the development of obesity. The aim of this review was to report the neural responses to visual food cues, as assessed by functional magnetic resonance imaging (fMRI), in humans of differing weight status. Published studies to 2014 were retrieved and included if they used visual food cues, studied humans >18 years old, reported weight status, and included fMRI outcomes. Sixty studies were identified that investigated the neural responses of healthy weight participants (n = 26), healthy weight compared to obese participants (n = 17), and weight-loss interventions (n = 12). High-calorie food images were used in the majority of studies (n = 36), however, image selection justification was only provided in 19 studies. Obese individuals had increased activation of reward-related brain areas including the insula and orbitofrontal cortex in response to visual food cues compared to healthy weight individuals, and this was particularly evident in response to energy dense cues. Additionally, obese individuals were more responsive to food images when satiated. Meta-analysis of changes in neural activation post-weight loss revealed small areas of convergence across studies in brain areas related to emotion, memory, and learning, including the cingulate gyrus, lentiform nucleus, and precuneus. Differential activation patterns to visual food cues were observed between obese, healthy weight, and weight-loss populations. Future studies require standardization of nutrition variables and fMRI outcomes to enable more direct comparisons between studies.

  14. Optimization of extraction of linarin from Flos chrysanthemi indici by response surface methodology and artificial neural network.

    Science.gov (United States)

    Pan, Hongye; Zhang, Qing; Cui, Keke; Chen, Guoquan; Liu, Xuesong; Wang, Longhu

    2017-05-01

    The extraction of linarin from Flos chrysanthemi indici by ethanol was investigated. Two modeling techniques, response surface methodology and artificial neural network, were adopted to optimize the process parameters, such as, ethanol concentration, extraction period, extraction frequency, and solvent to material ratio. We showed that both methods provided good predictions, but artificial neural network provided a better and more accurate result. The optimum process parameters include, ethanol concentration of 74%, extraction period of 2 h, extraction three times, solvent to material ratio of 12 mL/g. The experiment yield of linarin was 90.5% that deviated less than 1.6% from that obtained by predicted result. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Existential neuroscience: a functional magnetic resonance imaging investigation of neural responses to reminders of one’s mortality

    Science.gov (United States)

    Loktyushin, Alexander; Arndt, Jamie; Küstermann, Ekkehard; Lo, Yin-Yueh; Kuhl, Julius; Eggert, Lucas

    2012-01-01

    A considerable body of evidence derived from terror management theory indicates that the awareness of mortality represents a potent psychological threat engendering various forms of psychological defense. However, extant research has yet to examine the neurological correlates of cognitions about one’s inevitable death. The present study thus investigated in 17 male participants patterns of neural activation elicited by mortality threat. To induce mortality threat, participants answered questions arranged in trial blocks that referred to fear of death and dying. In the control condition participants answered questions about fear of dental pain. Neural responses to mortality threat were greater than to pain threat in right amygdala, left rostral anterior cingulate cortex, and right caudate nucleus. We discuss implications of these findings for stimulating further research into the neurological correlates of managing existential fear. PMID:21266462

  16. 3D culture broadly regulates tumor cell hypoxia response and angiogenesis via pro-inflammatory pathways.

    Science.gov (United States)

    DelNero, Peter; Lane, Maureen; Verbridge, Scott S; Kwee, Brian; Kermani, Pouneh; Hempstead, Barbara; Stroock, Abraham; Fischbach, Claudia

    2015-07-01

    Oxygen status and tissue dimensionality are critical determinants of tumor angiogenesis, a hallmark of cancer and an enduring target for therapeutic intervention. However, it is unclear how these microenvironmental conditions interact to promote neovascularization, due in part to a lack of comprehensive, unbiased data sets describing tumor cell gene expression as a function of oxygen levels within three-dimensional (3D) culture. Here, we utilized alginate-based, oxygen-controlled 3D tumor models to study the interdependence of culture context and the hypoxia response. Microarray gene expression analysis of tumor cells cultured in 2D versus 3D under ambient or hypoxic conditions revealed striking interdependence between culture dimensionality and hypoxia response, which was mediated in part by pro-inflammatory signaling pathways. In particular, interleukin-8 (IL-8) emerged as a major player in the microenvironmental regulation of the hypoxia program. Notably, this interaction between dimensionality and oxygen status via IL-8 increased angiogenic sprouting in a 3D endothelial invasion assay. Taken together, our data suggest that pro-inflammatory pathways are critical regulators of tumor hypoxia response within 3D environments that ultimately impact tumor angiogenesis, potentially providing important therapeutic targets. Furthermore, these results highlight the importance of pathologically relevant tissue culture models to study the complex physical and chemical processes by which the cancer microenvironment mediates new vessel formation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Relaxation response induces temporal transcriptome changes in energy metabolism, insulin secretion and inflammatory pathways.

    Directory of Open Access Journals (Sweden)

    Manoj K Bhasin

    Full Text Available The relaxation response (RR is the counterpart of the stress response. Millennia-old practices evoking the RR include meditation, yoga and repetitive prayer. Although RR elicitation is an effective therapeutic intervention that counteracts the adverse clinical effects of stress in disorders including hypertension, anxiety, insomnia and aging, the underlying molecular mechanisms that explain these clinical benefits remain undetermined. To assess rapid time-dependent (temporal genomic changes during one session of RR practice among healthy practitioners with years of RR practice and also in novices before and after 8 weeks of RR training, we measured the transcriptome in peripheral blood prior to, immediately after, and 15 minutes after listening to an RR-eliciting or a health education CD. Both short-term and long-term practitioners evoked significant temporal gene expression changes with greater significance in the latter as compared to novices. RR practice enhanced expression of genes associated with energy metabolism, mitochondrial function, insulin secretion and telomere maintenance, and reduced expression of genes linked to inflammatory response and stress-related pathways. Interactive network analyses of RR-affected pathways identified mitochondrial ATP synthase and insulin (INS as top upregulated critical molecules (focus hubs and NF-κB pathway genes as top downregulated focus hubs. Our results for the first time indicate that RR elicitation, particularly after long-term practice, may evoke its downstream health benefits by improving mitochondrial energy production and utilization and thus promoting mitochondrial resiliency through upregulation of ATPase and insulin function. Mitochondrial resiliency might also be promoted by RR-induced downregulation of NF-κB-associated upstream and downstream targets that mitigates stress.

  18. VARIABILITY OF NEURONAL RESPONSES: TYPES AND FUNCTIONAL SIGNIFICANCE IN NEUROPLASTICITY AND NEURAL DARWINISM

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    Alexander Chervyakov

    2016-11-01

    Full Text Available In many cases, neural signals detected under the same external experimental conditions significantly change from trial to trial. The variability phenomenon, which complicates extraction of reproducible results and is ignored in many studies by averaging, has attracted attention of researchers in recent years. In this paper, we classify possible types of variability based on its functional significance and describe features of each type. We describe the key adaptive significance of variability at the neural network level and the degeneracy phenomenon that may be important for learning processes in connection with the principle of neuronal group selection.

  19. Prospero-related homeobox 1 (Prox1 at the crossroads of diverse pathways during adult neural fate specification

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    Athanasios eStergiopoulos

    2015-01-01

    Full Text Available Over the last decades, adult neurogenesis in the central nervous system (CNS has emerged as a fundamental process underlying physiology and disease. Recent evidence indicates that the homeobox transcription factor Prox1 is a critical intrinsic regulator of neurogenesis in the embryonic CNS and adult dentate gyrus (DG of the hippocampus, acting in multiple ways and instructed by extrinsic cues and intrinsic factors. In the embryonic CNS, Prox1 is mechanistically involved in the regulation of proliferation versus differentiation decisions of NSCs, promoting cell cycle exit and neuronal differentiation, while inhibits astrogliogenesis. During the complex differentiation events in adult hippocampal neurogenesis, Prox1 is required for maintenance of intermediate progenitors (IPs, differentiation and maturation of glutamatergic interneurons, as well as specification of DG cell identity over CA3 pyramidal fate. The mechanism by which Prox1 exerts multiple functions involves distinct signaling pathways currently not fully highlighted. In this mini-review, we thoroughly discuss the Prox1-dependent phenotypes and molecular pathways in adult neurogenesis in relation to different upstream signaling cues and cell fate determinants. In addition, we discuss the possibility that Prox1 may act as a cross-talk point between diverse signaling cascades to achieve specific outcomes during adult neurogenesis.

  20. Implications of stemness-related signaling pathways in breast cancer response to therapy.

    Science.gov (United States)

    Angeloni, Valentina; Tiberio, Paola; Appierto, Valentina; Daidone, Maria Grazia

    2015-04-01

    There is accumulating evidence that breast cancer may arise from a small subpopulation of transformed mammary stem/progenitor cells, termed breast cancer-initiating cells (BCICs), responsible for initiation and maintenance of cancer. BCICs have been identified in clinical specimens based on CD44(+)/CD24(-/low) membrane expression and/or enzymatic activity of aldehyde dehydrogenase 1 (ALDH1+), or isolated and in vitro propagated as non-adherent spheres. This cell population has been demonstrated to be able to recreate, when injected in mice even at very low concentrations, the same histopathological features of the tumor they were derived from and to escape from current therapeutic strategies. Alterations in genes involved in stemness-related pathways, such as Wnt, Notch, and Sonic Hedgehog, have been proven to play a role in breast cancer progression. Targeting these key elements represents an attractive option, with a solid rationale, although possible concerns may derive from the poor knowledge of tolerance and efficacy of inhibiting these mechanisms without inducing severe side effects. In addition, efforts to develop alternative BCIC-targeted therapies against stemness markers (CD44 and ALDH1) and molecules involved in regulating EMT- and HER2-related pathways, or able to reverse the multi-drug resistance phenotype, or to induce differentiation and to control cell survival pathways are currently ongoing and encouraging results from pre-clinical studies have already been obtained using in vitro and in vivo models. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Amygdala-prefrontal pathways and the dopamine system affect nociceptive responses in the prefrontal cortex

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    Onozawa Kitaro

    2011-11-01

    Full Text Available Abstract Background We previously demonstrated nociceptive discharges to be evoked by mechanical noxious stimulation in the prefrontal cortex (PFC. The nociceptive responses recorded in the PFC are conceivably involved in the affective rather than the sensory-discriminative dimension of pain. The PFC receives dense projection from the limbic system. Monosynaptic projections from the basolateral nucleus of the amygdala (BLA to the PFC are known to produce long-lasting synaptic plasticity. We examined effects of high frequency stimulation (HFS delivered to the BLA on nociceptive responses in the rat PFC. Results HFS induced long lasting suppression (LLS of the specific high threshold responses of nociceptive neurons in the PFC. Microinjection of N-methyl-D-aspartic acid (NMDA receptor antagonists (2-amino-5-phosphonovaleric acid (APV, dizocilpine (MK-801 and also metabotropic glutamate receptor (mGluR group antagonists (α-methyl-4-carboxyphenylglycine (MCPG, and 2-[(1S,2S-2-carboxycyclopropyl]-3-(9H-xanthen-9-yl-D-alanine (LY341495, prevented the induction of LLS of nociceptive responses. We also examined modulatory effects of dopamine (DA on the LLS of nociceptive responses. With depletion of DA in response to 6-hydroxydopamine (6-OHDA injection into the ipsilateral forebrain bundle, LLS of nociceptive responses was decreased, while nociceptive responses were normally evoked. Antagonists of DA receptor subtypes D2 (sulpiride and D4 (3-{[4-(4-chlorophenyl piperazin-1-yl] methyl}-1H-pyrrolo [2, 3-b] pyridine (L-745,870, microinjected into the PFC, inhibited LLS of nociceptive responses. Conclusions Our results indicate that BLA-PFC pathways inhibited PFC nociceptive cell activities and that the DA system modifies the BLA-PFC regulatory function.

  2. Amygdala-prefrontal pathways and the dopamine system affect nociceptive responses in the prefrontal cortex

    Science.gov (United States)

    2011-01-01

    Background We previously demonstrated nociceptive discharges to be evoked by mechanical noxious stimulation in the prefrontal cortex (PFC). The nociceptive responses recorded in the PFC are conceivably involved in the affective rather than the sensory-discriminative dimension of pain. The PFC receives dense projection from the limbic system. Monosynaptic projections from the basolateral nucleus of the amygdala (BLA) to the PFC are known to produce long-lasting synaptic plasticity. We examined effects of high frequency stimulation (HFS) delivered to the BLA on nociceptive responses in the rat PFC. Results HFS induced long lasting suppression (LLS) of the specific high threshold responses of nociceptive neurons in the PFC. Microinjection of N-methyl-D-aspartic acid (NMDA) receptor antagonists (2-amino-5-phosphonovaleric acid (APV), dizocilpine (MK-801)) and also metabotropic glutamate receptor (mGluR) group antagonists (α-methyl-4-carboxyphenylglycine (MCPG), and 2-[(1S,2S)-2-carboxycyclopropyl]-3-(9H-xanthen-9-yl)-D-alanine (LY341495)), prevented the induction of LLS of nociceptive responses. We also examined modulatory effects of dopamine (DA) on the LLS of nociceptive responses. With depletion of DA in response to 6-hydroxydopamine (6-OHDA) injection into the ipsilateral forebrain bundle, LLS of nociceptive responses was decreased, while nociceptive responses were normally evoked. Antagonists of DA receptor subtypes D2 (sulpiride) and D4 (3-{[4-(4-chlorophenyl) piperazin-1-yl] methyl}-1H-pyrrolo [2, 3-b] pyridine (L-745,870)), microinjected into the PFC, inhibited LLS of nociceptive responses. Conclusions Our results indicate that BLA-PFC pathways inhibited PFC nociceptive cell activities and that the DA system modifies the BLA-PFC regulatory function. PMID:22085449

  3. Preparation of agar nanospheres: comparison of response surface and artificial neural network modeling by a genetic algorithm approach.

    Science.gov (United States)

    Zaki, Mohammad Reza; Varshosaz, Jaleh; Fathi, Milad

    2015-05-20

    Multivariate nature of drug loaded nanospheres manufacturing in term of multiplicity of involved factors makes it a time consuming and expensive process. In this study genetic algorithm (GA) and artificial neural network (ANN), two tools inspired by natural process, were employed to optimize and simulate the manufacturing process of agar nanospheres. The efficiency of GA was evaluated against the response surface methodology (RSM). The studied responses included particle size, poly dispersity index, zeta potential, drug loading and release efficiency. GA predicted greater extremum values for response factors compared to RSM. However, real values showed some deviations from predicted data. Appropriate agreement was found between ANN model predicted and real values for all five response factors with high correlation coefficients. GA was more successful than RSM in optimization and along with ANN were efficient tools in optimizing and modeling the fabrication process of drug loaded in agar nanospheres. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Goal-independent mechanisms for free response generation: creative and pseudo-random performance share neural substrates.

    Science.gov (United States)

    de Manzano, Örjan; Ullén, Fredrik

    2012-01-02

    To what extent free response generation in different tasks uses common and task-specific neurocognitive processes has remained unclear. Here, we investigated overlap and differences in neural activity during musical improvisation and pseudo-random response generation. Brain activity was measured using fMRI in a group of professional classical pianists, who performed musical improvisation of melodies, pseudo-random key-presses and a baseline condition (sight-reading), on either two, six or twelve keys on a piano keyboard. The results revealed an extensive overlap in neural activity between the two generative conditions. Active regions included the dorsolateral and dorsomedial prefrontal cortices, inferior frontal gyrus, anterior cingulate cortex and pre-SMA. No regions showed higher activity in improvisation than in pseudo-random generation. These findings suggest that the activated regions fulfill generic functions that are utilized in different types of free generation tasks, independent of overall goal. In contrast, pseudo-random generation was accompanied by higher activity than improvisation in several regions. This presumably reflects the participants' musical expertise as well as the pseudo-random generation task's high load on attention, working memory, and executive control. The results highlight the significance of using naturalistic tasks to study human behavior and cognition. No brain activity was related to the size of the response set. We discuss that this may reflect that the musicians were able to use specific strategies for improvisation, by which there was no simple relationship between response set size and neural activity. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. Hybrid response surface methodology-artificial neural network optimization of drying process of banana slices in a forced convective dryer.

    Science.gov (United States)

    Taheri-Garavand, Amin; Karimi, Fatemeh; Karimi, Mahmoud; Lotfi, Valiullah; Khoobbakht, Golmohammad

    2017-01-01

    The aim of the study is to fit models for predicting surfaces using the response surface methodology and the artificial neural network to optimize for obtaining the maximum acceptability using desirability functions methodology in a hot air drying process of banana slices. The drying air temperature, air velocity, and drying time were chosen as independent factors and moisture content, drying rate, energy efficiency, and exergy efficiency were dependent variables or responses in the mentioned drying process. A rotatable central composite design as an adequate method was used to develop models for the responses in the response surface methodology. Moreover, isoresponse contour plots were useful to predict the results by performing only a limited set of experiments. The optimum operating conditions obtained from the artificial neural network models were moisture content 0.14 g/g, drying rate 1.03 g water/g h, energy efficiency 0.61, and exergy efficiency 0.91, when the air temperature, air velocity, and drying time values were equal to -0.42 (74.2 ℃), 1.00 (1.50 m/s), and -0.17 (2.50 h) in the coded units, respectively.

  6. Effect of maternal rumination and disengagement during childhood on offspring neural response to reward in late adolescence.

    Science.gov (United States)

    Morgan, Judith K; Shaw, Daniel S; Jacobs, Rachel H; Romens, Sarah E; Sitnick, Stephanie L; Forbes, Erika E

    2017-04-30

    Maternal rumination is a cognitive-affective trait that could influence offspring's ability to respond flexibly to positive and negative events, depending on the quality of maternal problem-solving behaviors with which rumination co-occurs. As reward circuitry is sensitive to stressors and related to risk for depression, reward circuitry is an appropriate candidate mechanism for how maternal characteristics influence offspring. We evaluated the independent and combined effect of maternal rumination and disengagement on adolescent neural response to reward win and loss. Participants were 122 boys and their mothers from low-income, urban backgrounds followed prospectively in a longitudinal study. The combination of high maternal rumination at child age 6 and high maternal disengagement during problem-solving at child age 10-12 was associated with lower anterior cingulate response to winning reward at age 20, but unrelated to neural response to losing reward. Lower anterior cingulate response to winning reward was associated with fewer anxiety symptoms during late adulthood. Findings suggest that maternal rumination occurring within the context of maternal disengagement during challenging experiences may be related to offspring blunted engagement during positive events. Helping highly ruminative mothers to restructure repetitive negative thoughts and to develop context-appropriate problem-solving behaviors may be important for promoting offspring affective development. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  7. Acute D3 Antagonist GSK598809 Selectively Enhances Neural Response During Monetary Reward Anticipation in Drug and Alcohol Dependence.

    Science.gov (United States)

    Murphy, Anna; Nestor, Liam J; McGonigle, John; Paterson, Louise; Boyapati, Venkataramana; Ersche, Karen D; Flechais, Remy; Kuchibatla, Shankar; Metastasio, Antonio; Orban, Csaba; Passetti, Filippo; Reed, Laurence; Smith, Dana; Suckling, John; Taylor, Eleanor; Robbins, Trevor W; Lingford-Hughes, Anne; Nutt, David J; Deakin, John Fw; Elliott, Rebecca

    2017-04-01

    Evidence suggests that disturbances in neurobiological mechanisms of reward and inhibitory control maintain addiction and provoke relapse during abstinence. Abnormalities within the dopamine system may contribute to these disturbances and pharmacologically targeting the D3 dopamine receptor (DRD3) is therefore of significant clinical interest. We used functional magnetic resonance imaging to investigate the acute effects of the DRD3 antagonist GSK598809 on anticipatory reward processing, using the monetary incentive delay task (MIDT), and response inhibition using the Go/No-Go task (GNGT). A double-blind, placebo-controlled, crossover design approach was used in abstinent alcohol dependent, abstinent poly-drug dependent and healthy control volunteers. For the MIDT, there was evidence of blunted ventral striatal response to reward in the poly-drug-dependent group under placebo. GSK598809 normalized ventral striatal reward response and enhanced response in the DRD3-rich regions of the ventral pallidum and substantia nigra. Exploratory investigations suggested that the effects of GSK598809 were mainly driven by those with primary dependence on alcohol but not on opiates. Taken together, these findings suggest that GSK598809 may remediate reward deficits in substance dependence. For the GNGT, enhanced response in the inferior frontal cortex of the poly-drug group was found. However, there were no effects of GSK598809 on the neural network underlying response inhibition nor were there any behavioral drug effects on response inhibition. GSK598809 modulated the neural network underlying reward anticipation but not response inhibition, suggesting that DRD3 antagonists may restore reward deficits in addiction.

  8. Healthy Adolescents' Neural Response to Reward: Associations with Puberty, Positive Affect, and Depressive Symptoms

    Science.gov (United States)

    Forbes, Erika E.; Ryan, Neal D.; Phillips, Mary L.; Manuck, Stephen B.; Worthman, Carol M.; Moyles, Donna L.; Tarr, Jill A.; Sciarrillo, Samantha R.; Dahl, Ronald E.

    2010-01-01

    Objective: Changes in reward-related behavior are an important component of normal adolescent affective development. Understanding the neural underpinnings of these normative changes creates a foundation for investigating adolescence as a period of vulnerability to affective disorders, substance use disorders, and health problems. Studies of…

  9. Dissociable Patterns of Neural Activity during Response Inhibition in Depressed Adolescents with and without Suicidal Behavior

    Science.gov (United States)

    Pan, Lisa A.; Batezati-Alves, Silvia C.; Almeida, Jorge R. C.; Segreti, AnnaMaria; Akkal, Dalila; Hassel, Stefanie; Lakdawala, Sara; Brent, David A.; Phillips, Mary L.

    2011-01-01

    Objectives: Impaired attentional control and behavioral control are implicated in adult suicidal behavior. Little is known about the functional integrity of neural circuitry supporting these processes in suicidal behavior in adolescence. Method: Functional magnetic resonance imaging was used in 15 adolescent suicide attempters with a history of…

  10. Exogenous testosterone enhances responsiveness to social threat in the neural circuitry of social aggression in humans.

    NARCIS (Netherlands)

    Hermans, E.J.; Ramsey, N.F.; Honk, J van

    2008-01-01

    BACKGROUND: In a range of species, the androgen steroid testosterone is known to potentiate neural circuits involved in intraspecific aggression. Disorders of impulsive aggression in humans have likewise been associated with high testosterone levels, but human evidence for the link between

  11. Neural response to alcohol taste cues in youth : Effects of the OPRM1 gene

    NARCIS (Netherlands)

    Korucuoglu, Ozlem; Gladwin, Thomas E.; Baas, Frank; Mocking, Roel J. T.; Ruhé, Henricus G.; Groot, Paul F. C.; Wiers, Reinout W.

    2017-01-01

    Genetic variations in the mu-opioid receptor (OPRM1) gene have been related to high sensitivity to rewarding effects of alcohol. The current study focuses on the neural circuitry underlying this phenomenon using an alcohol versus water taste-cue reactivity paradigm in a young sample at relatively

  12. Psychological and neural responses to art embody viewer and artwork histories.

    Science.gov (United States)

    Vartanian, Oshin; Kaufman, James C

    2013-04-01

    The research programs of empirical aesthetics and neuroaesthetics have reflected deep concerns about viewers' sensitivities to artworks' historical contexts by investigating the impact of two factors on art perception: viewers' developmental (and educational) histories and the contextual histories of artworks. These considerations are consistent with data demonstrating that art perception is underwritten by dynamically reconfigured and evolutionarily adapted neural and psychological mechanisms.

  13. PPAR signaling pathway may be an important predictor of breast cancer response to neoadjuvant chemotherapy.

    Science.gov (United States)

    Chen, Y Z; Xue, J Y; Chen, C M; Yang, B L; Xu, Q H; Wu, F; Liu, F; Ye, X; Meng, X; Liu, G Y; Shen, Z Z; Shao, Z M; Wu, J

    2012-11-01

    Neoadjuvant chemotherapy for advanced breast cancer may improve the radicality for a subset of patients, but others may suffer from severe adverse drug reactions without any benefit. To predict the responses to chemotherapy, we performed a phase II trial of neoadjuvant chemotherapy using a weekly PCb [paclitaxel (Taxol) plus carboplatin] regimen for stage II/III breast cancer and assessed the correlation between baseline gene expression and the tumor response to treatment. A total of 61 patients with stage II-III breast cancer were included and administered four cycles of preoperative PCb. We performed a gene expression analysis using Affymetrix HG-U133 Plus 2.0 GeneChip arrays in 31 breast cancer tissues. Differentially expressed genes (DEGs) were identified by the significance analysis of microarrays (SAM) program using a false discovery rate of 0.05. The Functional Annotation Tool in the DAVID Bioinformatics Resources was used to perform the gene functional enrichment analysis. The other 30 patients (15 pCR and 15 non-pCR patients) were available as an independent validation set to test the selected DEGs by quantitative real-time PCR analysis (qRT-PCR). By analyzing six pathological complete response (pCR) patients and 25 patients with non-pCR, 300 probes (231 genes) were identified as differentially expressed between pCR and residual disease by the SAM program when the fold change was >2. The gene functional enrichment analysis revealed 15 prominent gene categories that were different between pCR and non-pCR patients, most notably the genes involved in the peroxisome proliferator-activated receptor (PPAR), DNA repair and ER signal pathways and in the immune-related gene cluster. The qRT-PCR analysis results for the genes in the PPAR pathway (LPL, SORBS1, PLTP, SCD5, MMP1 and CSTA) in independent validation set were consistent with the results from the microarray data analysis. In the present study, we identified a number of gene categories pertinent to the

  14. Irrepressible, truncated auxin response factors: natural roles and applications in dissecting auxin gene regulation pathways.

    Science.gov (United States)

    Ckurshumova, Wenzislava; Krogan, Naden T; Marcos, Danielle; Caragea, Adriana E; Berleth, Thomas

    2012-08-01

    The molecularly well-characterized auxin signal transduction pathway involves two evolutionarily conserved families interacting through their C-terminal domains III and IV: the Auxin Response Factors (ARFs) and their repressors the Aux/IAAs, to control auxin-responsive genes, among them genes involved in auxin transport. ( 1) (,) ( 2) We have developed a new genetic tool to study ARF function. Using MONOPTEROS (MP)/ARF5, we have generated a truncated version of MP (MPΔ), ( 3) which has lost the target domains for repression by Aux/IAA proteins. Besides exploring genetic interactions between MP and Aux/IAAs, we used this construct to trace MP's role in vascular patterning, a previously characterized auxin dependent process. ( 4) (,) ( 5) Here we summarize examples of naturally occurring truncated ARFs and summarize potential applications of truncated ARFs as analytical tools.

  15. Heat-Responsive Photosynthetic and Signaling Pathways in Plants: Insight from Proteomics

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    Xiaoli Wang

    2017-10-01

    Full Text Available Heat stress is a major abiotic stress posing a serious threat to plants. Heat-responsive mechanisms in plants are complicated and fine-tuned. Heat signaling transduction and photosynthesis are highly sensitive. Therefore, a thorough understanding of the molecular mechanism in heat stressed-signaling transduction and photosynthesis is necessary to protect crop yield. Current high-throughput proteomics investigations provide more useful information for underlying heat-responsive signaling pathways and photosynthesis modulation in plants. Several signaling components, such as guanosine triphosphate (GTP-binding protein, nucleoside diphosphate kinase, annexin, and brassinosteroid-insensitive I-kinase domain interacting protein 114, were proposed to be important in heat signaling transduction. Moreover, diverse protein patterns of photosynthetic proteins imply that the modulations of stomatal CO2 exchange, photosystem II, Calvin cycle, ATP synthesis, and chlorophyll biosynthesis are crucial for plant heat tolerance.

  16. Metformin inhibits inflammatory response via AMPK-PTEN pathway in vascular smooth muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sun Ae [Department of Pharmacology, Aging-Associated Vascular Disease Research Center, College of Medicine, Yeungnam University, Daegu 705-717 (Korea, Republic of); Choi, Hyoung Chul, E-mail: hcchoi@med.yu.ac.kr [Department of Pharmacology, Aging-Associated Vascular Disease Research Center, College of Medicine, Yeungnam University, Daegu 705-717 (Korea, Republic of)

    2012-09-07

    Highlights: Black-Right-Pointing-Pointer PTEN was induced by metformin and inhibited by compound C and AMPK siRNA. Black-Right-Pointing-Pointer Metformin suppressed TNF-{alpha}-induced COX-2 and iNOS mRNA expression. Black-Right-Pointing-Pointer Compound C and bpv (pic) increased iNOS and COX-2 protein expression. Black-Right-Pointing-Pointer NF-{kappa}B activation was restored by inhibiting AMPK and PTEN. Black-Right-Pointing-Pointer AMPK and PTEN regulated TNF-{alpha}-induced ROS production in VSMCs. -- Abstract: Atherosclerosis is a chronic inflammation of the coronary arteries. Vascular smooth muscle cells (VSMCs) stimulated by cytokines and chemokines accelerate the inflammatory response and migrate to the injured endothelium during the progression of atherosclerosis. Activation of AMP activated protein kinase (AMPK), a key sensor maintaining metabolic homeostasis, suppresses the inflammatory response. However, how AMPK regulates the inflammatory response is poorly understood. To identify the mechanism of this response, we focused on phosphatase and tensin homolog (PTEN), which is a negative regulator of inflammation. We investigated that activation of AMPK-induced PTEN expression and suppression of the inflammatory response through the AMPK-PTEN pathway in VSMCs. We treated with the well-known AMPK activator metformin to induce PTEN expression. PTEN was induced by metformin (2 mM) and inhibited by compound C (10 {mu}M) and AMPK siRNA. Tumor necrosis factor-alpha (TNF-{alpha}) was used to induce inflammation. The inflammatory response was confirmed by cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS) expression, and activation of nuclear factor (NF)-{kappa}B. Metformin suppressed COX-2 and iNOS mRNA and protein expression dose dependently. Treatment with compound C and bpv (pic) in the presence of metformin, iNOS and COX-2 protein expression increased. NF-{kappa}B activation decreased in response to metformin and was restored by inhibiting AMPK

  17. A model for integrating elementary neural functions into delayed-response behavior.

    Directory of Open Access Journals (Sweden)

    Thomas Gisiger

    2006-04-01

    Full Text Available It is well established that various cortical regions can implement a wide array of neural processes, yet the mechanisms which integrate these processes into behavior-producing, brain-scale activity remain elusive. We propose that an important role in this respect might be played by executive structures controlling the traffic of information between the cortical regions involved. To illustrate this hypothesis, we present a neural network model comprising a set of interconnected structures harboring stimulus-related activity (visual representation, working memory, and planning, and a group of executive units with task-related activity patterns that manage the information flowing between them. The resulting dynamics allows the network to perform the dual task of either retaining an image during a delay (delayed-matching to sample task, or recalling from this image another one that has been associated with it during training (delayed-pair association task. The model reproduces behavioral and electrophysiological data gathered on the inferior temporal and prefrontal cortices of primates performing these same tasks. It also makes predictions on how neural activity coding for the recall of the image associated with the sample emerges and becomes prospective during the training phase. The network dynamics proves to be very stable against perturbations, and it exhibits signs of scale-invariant organization and cooperativity. The present network represents a possible neural implementation for active, top-down, prospective memory retrieval in primates. The model suggests that brain activity leading to performance of cognitive tasks might be organized in modular fashion, simple neural functions becoming integrated into more complex behavior by executive structures harbored in prefrontal cortex and/or basal ganglia.

  18. Upregulation of Interferon-inducible and damage response pathways in chronic graft-versus-host disease

    Science.gov (United States)

    Hakim, Frances T.; Memon, Sarfraz; Jin, Ping; Imanguli, Matin M.; Wang, Huan; Rehman, Najibah; Yan, Xiao-Yi; Rose, Jeremy; Mays, Jacqueline W.; Dhamala, Susan; Kapoor, Veena; Telford, William; Dickinson, John; Davis, Sean; Halverson, David; Naik, Haley B.; Baird, Kristin; Fowler, Daniel; Stroncek, David; Cowen, Edward W.; Pavletic, Steven Z.; Gress, Ronald E.

    2016-01-01

    Although Chronic Graft-versus-Host Disease (CGVHD) is the primary non-relapse complication of allogeneic transplantation, understanding of its pathogenesis is limited. To identify the main operant pathways across the spectrum of CGVHD, we analyzed gene expression in circulating monocytes, chosen as in situ systemic reporter cells. Microarrays identified two interrelated pathways: (1) Interferon-inducible genes and (2) innate receptors for cellular damage. Corroborating these with multiplex RNA quantitation, we found that multiple IFN-inducible genes (affecting lymphocyte trafficking, differentiation and antigen presentation) were concurrently upregulated in CGVHD monocytes compared to normal and nonCGVHD controls. IFN-inducible chemokines were elevated in both lichenoid and sclerotic CGHVD plasma and linked to CXCR3+ lymphocyte trafficking. Furthermore, the IFN-inducible genes CXCL10 and TNFSF13B (BAFF) levels were correlated at both the gene and plasma levels, implicating IFN-induction as a factor in elevated BAFF levels in CGVHD. In the second pathway, DAMP/PAMP receptor genes capable of inducing Type I IFN were upregulated. Type I IFN-inducible MxA was expressed in proportion to CGVHD activity in skin, mucosa and glands, and expression of TLR and RIG-1 receptor genes correlated with upregulation of Type I IFN-inducible genes in monocytes. Finally, in serial analyses following transplant, IFN-inducible and damage-response genes were upregulated in monocytes at CGVHD onset and declined upon therapy and resolution in both lichenoid and sclerotic CGVHD patients. This interlocking analysis of IFN-inducible genes, plasma analytes and tissue immunohistochemistry strongly supports a unifying hypothesis of induction of IFN by innate response to cellular damage as a mechanism for initiation and persistence of CGVHD. PMID:27694491

  19. Late Phase of the Endoplasmic Reticulum Stress Response Pathway Is Regulated by Hog1 MAP Kinase*

    Science.gov (United States)

    Bicknell, Alicia A.; Tourtellotte, Joel; Niwa, Maho

    2010-01-01

    When unfolded proteins accumulate in the endoplasmic reticulum (ER) causing ER stress, the unfolded protein response (UPR) responds rapidly to induce a transcriptional program that functions to alleviate the stress. However, under extreme conditions, when UPR activation is not sufficient to alleviate ER stress, the stress may persist long term. Very little is known about how the cell responds to persistent ER stress that is not resolved by the immediate activation of the UPR. We show that Hog1 MAP kinase becomes phosphorylated during the late stage of ER stress and helps the ER regain homeostasis. Although Hog1 is well known to function in osmotic stress and cell wall integrity pathways, we show that the activation mechanism for Hog1 during ER stress is distinct from both of these pathways. During late stage ER stress, upon phosphorylation, Hog1 translocates into the nucleus and regulates gene expression. Subsequently, Hog1 returns to the cytoplasm, where its phosphorylation levels remain high. From its cytoplasmic location, Hog1 contributes to the activation of autophagy by enhancing the stability of Atg8, a critical autophagy protein. Thus, Hog1 coordinates a multifaceted response to persistent ER stress. PMID:20382742

  20. Dysregulation of complement system and CD4+ T cell activation pathways implicated in allergic response.

    Directory of Open Access Journals (Sweden)

    Alexessander Couto Alves

    Full Text Available Allergy is a complex disease that is likely to involve dysregulated CD4+ T cell activation. Here we propose a novel methodology to gain insight into how coordinated behaviour emerges between disease-dysregulated pathways in response to pathophysiological stimuli. Using peripheral blood mononuclear cells of allergic rhinitis patients and controls cultured with and without pollen allergens, we integrate CD4+ T cell gene expression from microarray data and genetic markers of allergic sensitisation from GWAS data at the pathway level using enrichment analysis; implicating the complement system in both cellular and systemic response to pollen allergens. We delineate a novel disease network linking T cell activation to the complement system that is significantly enriched for genes exhibiting correlated gene expression and protein-protein interactions, suggesting a tight biological coordination that is dysregulated in the disease state in response to pollen allergen but not to diluent. This novel disease network has high predictive power for the gene and protein expression of the Th2 cytokine profile (IL-4, IL-5, IL-10, IL-13 and of the Th2 master regulator (GATA3, suggesting its involvement in the early stages of CD4+ T cell differentiation. Dissection of the complement system gene expression identifies 7 genes specifically associated with atopic response to pollen, including C1QR1, CFD, CFP, ITGB2, ITGAX and confirms the role of C3AR1 and C5AR1. Two of these genes (ITGB2 and C3AR1 are also implicated in the network linking complement system to T cell activation, which comprises 6 differentially expressed genes. C3AR1 is also significantly associated with allergic sensitisation in GWAS data.

  1. Disparity in neural and subjective responses to food images in women with obesity and normal-weight women.

    Science.gov (United States)

    Carbine, Kaylie A; Larson, Michael J; Romney, Lora; Bailey, Bruce W; Tucker, Larry A; Christensen, William F; LeCheminant, James D

    2017-02-01

    Self-reports tend to differ from objective measurements of food intake, particularly in adults with obesity; however, no studies have examined how neural responses to food (an objective measure) and subjective ratings of food differ by BMI status. This study tested normal-weight women (NWW) and women with obesity (OBW) for group differences in neural indices of attention towards food pictures, subjective ratings of these pictures, and the disparity between objective and subjective measurements. Twenty-two NWW (21.8 ± 1.7 kg/m 2 ) and 22 OBW (37.0 ± 5.7 kg/m 2 ) viewed food and flower pictures while late positive potential amplitude, an event-related potential, was recorded. Participants rated pictures for arousal and valence. Late positive potential amplitude was larger toward food than flower pictures. OBW self-reported flower pictures as more pleasant than food; NWW showed no difference for pleasantness. There were no significant main effects or interactions for arousal. Standardized scores showed that only on subjective, but not objective, measures did OBW compared with NWW disproportionately indicate food pictures as less pleasant than flowers. Compared with NWW, OBW showed larger discrepancies between neural and subjective reports of attention towards food. Inaccurate self-reports of attention towards food may reduce the efficiency of health interventions. © 2016 The Obesity Society.

  2. A Robust Intelligent Framework for Multiple Response Statistical Optimization Problems Based on Artificial Neural Network and Taguchi Method

    Directory of Open Access Journals (Sweden)

    Ali Salmasnia

    2012-01-01

    Full Text Available An important problem encountered in product or process design is the setting of process variables to meet a required specification of quality characteristics (response variables, called a multiple response optimization (MRO problem. Common optimization approaches often begin with estimating the relationship between the response variable with the process variables. Among these methods, response surface methodology (RSM, due to simplicity, has attracted most attention in recent years. However, in many manufacturing cases, on one hand, the relationship between the response