Pre-orthographic character string processing and parietal cortex: a role for visual attention in reading?

PubMed

Lobier, Muriel; Peyrin, Carole; Le Bas, Jean-François; Valdois, Sylviane

2012-07-01

The visual front-end of reading is most often associated with orthographic processing. The left ventral occipito-temporal cortex seems to be preferentially tuned for letter string and word processing. In contrast, little is known of the mechanisms responsible for pre-orthographic processing: the processing of character strings regardless of character type. While the superior parietal lobule has been shown to be involved in multiple letter processing, further data is necessary to extend these results to non-letter characters. The purpose of this study is to identify the neural correlates of pre-orthographic character string processing independently of character type. Fourteen skilled adult readers carried out multiple and single element visual categorization tasks with alphanumeric (AN) and non-alphanumeric (nAN) characters under fMRI. The role of parietal cortex in multiple element processing was further probed with a priori defined anatomical regions of interest (ROIs). Participants activated posterior parietal cortex more strongly for multiple than single element processing. ROI analyses showed that bilateral SPL/BA7 was more strongly activated for multiple than single element processing, regardless of character type. In contrast, no multiple element specific activity was found in inferior parietal lobules. These results suggests that parietal mechanisms are involved in pre-orthographic character string processing. We argue that in general, attentional mechanisms are involved in visual word recognition, as an early step of word visual analysis. Copyright © 2012 Elsevier Ltd. All rights reserved.

Inactivation of the infralimbic prefrontal cortex in rats reduces the influence of inappropriate habitual responding in a response-conflict task.

PubMed

Haddon, J E; Killcross, S

2011-12-29

Previous research suggests the infralimbic cortex is important in situations when there is competition between goal-directed and habitual responding. Here we used a response conflict procedure to further explore the involvement of the infralimbic cortex in this relationship. Rats received training on two instrumental biconditional discriminations, one auditory and one visual, in two distinct contexts. One discrimination was "over-trained" relative to the other, "under-trained," discrimination in the ratio 3:1. At test, animals were presented with incongruent audiovisual stimulus compounds of the training stimuli in the under-trained context. The stimulus elements of these test compounds have previously dictated different lever press responses during training. Rats receiving control infusions into the infralimbic cortex showed a significant interference effect, producing more responses to the over-trained (habitual), but context-inappropriate, stimulus element of the incongruent compound. This interference effect was abolished by inactivation of the infralimbic cortex; animals showed a reduced tendency to produce the habitual but inappropriate response compared with animals receiving control infusions. This finding provides evidence that the infralimbic cortex is involved in attenuating the influence of goal-directed behavior, for example context-appropriate responding. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Plasticity in the Rat Prefrontal Cortex: Linking Gene Expression and an Operant Learning with a Computational Theory

PubMed Central

Rapanelli, Maximiliano; Lew, Sergio Eduardo; Frick, Luciana Romina; Zanutto, Bonifacio Silvano

2010-01-01

The plasticity in the medial Prefrontal Cortex (mPFC) of rodents or lateral prefrontal cortex in non human primates (lPFC), plays a key role neural circuits involved in learning and memory. Several genes, like brain-derived neurotrophic factor (BDNF), cAMP response element binding (CREB), Synapsin I, Calcium/calmodulin-dependent protein kinase II (CamKII), activity-regulated cytoskeleton-associated protein (Arc), c-jun and c-fos have been related to plasticity processes. We analysed differential expression of related plasticity genes and immediate early genes in the mPFC of rats during learning an operant conditioning task. Incompletely and completely trained animals were studied because of the distinct events predicted by our computational model at different learning stages. During learning an operant conditioning task, we measured changes in the mRNA levels by Real-Time RT-PCR during learning; expression of these markers associated to plasticity was incremented while learning and such increments began to decline when the task was learned. The plasticity changes in the lPFC during learning predicted by the model matched up with those of the representative gene BDNF. Herein, we showed for the first time that plasticity in the mPFC in rats during learning of an operant conditioning is higher while learning than when the task is learned, using an integrative approach of a computational model and gene expression. PMID:20111591

Effect of Resveratrol Administration on the Element Metabolism in the Blood and Brain Tissues of Rats Subjected to Acute Swimming Exercise.

PubMed

Baltaci, Abdulkerim Kasim; Arslangil, Dilek; Mogulkoc, Rasim; Patlar, Suleyman

2017-02-01

The aim of the present study is to examine how resveratrol administration affects the element metabolism in the blood and brain cortex tissues of rats subjected to an acute swimming exercise. The study was carried out on Wistar-Albino-type adult male rats supplied by the Center. Group 1 is the control group. Group 2 is the swimming control group. Group 3 is the resveratrol (10 mg/kg/day) + swimming group. Group 4 is the resveratrol (10 mg/kg/day) group. Blood and brain cortex tissues were analyzed for some elements. The acute swimming exercise led to increases in the rats' serum iron, selenium, lead, cobalt, and boron levels, while the resveratrol-swimming group has increases in copper, phosphorus, and calcium values. The brain cortex tissue of the resveratrol-swimming group had significantly higher molybdenum levels than others. The results obtained in the study indicate that acute swimming exercise altered the distribution of elements in the serum to a considerable extent; however, resveratrol's affect is limited. Especially, resveratrol supplementation may have a regulatory affect on serum iron and magnesium levels.

Monoaminergic Modulation of Motor Cortex Function

PubMed Central

Vitrac, Clément; Benoit-Marand, Marianne

2017-01-01

Elaboration of appropriate responses to behavioral situations rests on the ability of selecting appropriate motor outcomes in accordance to specific environmental inputs. To this end, the primary motor cortex (M1) is a key structure for the control of voluntary movements and motor skills learning. Subcortical loops regulate the activity of the motor cortex and thus contribute to the selection of appropriate motor plans. Monoamines are key mediators of arousal, attention and motivation. Their firing pattern enables a direct encoding of different states thus promoting or repressing the selection of actions adapted to the behavioral context. Monoaminergic modulation of motor systems has been extensively studied in subcortical circuits. Despite evidence of converging projections of multiple neurotransmitters systems in the motor cortex pointing to a direct modulation of local circuits, their contribution to the execution and learning of motor skills is still poorly understood. Monoaminergic dysregulation leads to impaired plasticity and motor function in several neurological and psychiatric conditions, thus it is critical to better understand how monoamines modulate neural activity in the motor cortex. This review aims to provide an update of our current understanding on the monoaminergic modulation of the motor cortex with an emphasis on motor skill learning and execution under physiological conditions. PMID:29062274

Brain abnormalities in antisocial individuals: implications for the law.

PubMed

Yang, Yaling; Glenn, Andrea L; Raine, Adrian

2008-01-01

With the increasing popularity in the use of brain imaging on antisocial individuals, an increasing number of brain imaging studies have revealed structural and functional impairments in antisocial, psychopathic, and violent individuals. This review summarizes key findings from brain imaging studies on antisocial/aggressive behavior. Key regions commonly found to be impaired in antisocial populations include the prefrontal cortex (particularly orbitofrontal and dorsolateral prefrontal cortex), superior temporal gyrus, amygdala-hippocampal complex, and anterior cingulate cortex. Key functions of these regions are reviewed to provide a better understanding on how deficits in these regions may predispose to antisocial behavior. Objections to the use of imaging findings in a legal context are outlined, and alternative perspectives raised. It is argued that brain dysfunction is a risk factor for antisocial behavior and that it is likely that imaging will play an increasing (albeit limited) role in legal decision-making. (c) 2008 John Wiley & Sons, Ltd.

Spike-train communities: finding groups of similar spike trains.

PubMed

Humphries, Mark D

2011-02-09

Identifying similar spike-train patterns is a key element in understanding neural coding and computation. For single neurons, similar spike patterns evoked by stimuli are evidence of common coding. Across multiple neurons, similar spike trains indicate potential cell assemblies. As recording technology advances, so does the urgent need for grouping methods to make sense of large-scale datasets of spike trains. Existing methods require specifying the number of groups in advance, limiting their use in exploratory analyses. I derive a new method from network theory that solves this key difficulty: it self-determines the maximum number of groups in any set of spike trains, and groups them to maximize intragroup similarity. This method brings us revealing new insights into the encoding of aversive stimuli by dopaminergic neurons, and the organization of spontaneous neural activity in cortex. I show that the characteristic pause response of a rat's dopaminergic neuron depends on the state of the superior colliculus: when it is inactive, aversive stimuli invoke a single pattern of dopaminergic neuron spiking; when active, multiple patterns occur, yet the spike timing in each is reliable. In spontaneous multineuron activity from the cortex of anesthetized cat, I show the existence of neural ensembles that evolve in membership and characteristic timescale of organization during global slow oscillations. I validate these findings by showing that the method both is remarkably reliable at detecting known groups and can detect large-scale organization of dynamics in a model of the striatum.

Cortical Neural Computation by Discrete Results Hypothesis

PubMed Central

Castejon, Carlos; Nuñez, Angel

2016-01-01

One of the most challenging problems we face in neuroscience is to understand how the cortex performs computations. There is increasing evidence that the power of the cortical processing is produced by populations of neurons forming dynamic neuronal ensembles. Theoretical proposals and multineuronal experimental studies have revealed that ensembles of neurons can form emergent functional units. However, how these ensembles are implicated in cortical computations is still a mystery. Although cell ensembles have been associated with brain rhythms, the functional interaction remains largely unclear. It is still unknown how spatially distributed neuronal activity can be temporally integrated to contribute to cortical computations. A theoretical explanation integrating spatial and temporal aspects of cortical processing is still lacking. In this Hypothesis and Theory article, we propose a new functional theoretical framework to explain the computational roles of these ensembles in cortical processing. We suggest that complex neural computations underlying cortical processing could be temporally discrete and that sensory information would need to be quantized to be computed by the cerebral cortex. Accordingly, we propose that cortical processing is produced by the computation of discrete spatio-temporal functional units that we have called “Discrete Results” (Discrete Results Hypothesis). This hypothesis represents a novel functional mechanism by which information processing is computed in the cortex. Furthermore, we propose that precise dynamic sequences of “Discrete Results” is the mechanism used by the cortex to extract, code, memorize and transmit neural information. The novel “Discrete Results” concept has the ability to match the spatial and temporal aspects of cortical processing. We discuss the possible neural underpinnings of these functional computational units and describe the empirical evidence supporting our hypothesis. We propose that fast-spiking (FS) interneuron may be a key element in our hypothesis providing the basis for this computation. PMID:27807408

Cortical Neural Computation by Discrete Results Hypothesis.

PubMed

Castejon, Carlos; Nuñez, Angel

2016-01-01

One of the most challenging problems we face in neuroscience is to understand how the cortex performs computations. There is increasing evidence that the power of the cortical processing is produced by populations of neurons forming dynamic neuronal ensembles. Theoretical proposals and multineuronal experimental studies have revealed that ensembles of neurons can form emergent functional units. However, how these ensembles are implicated in cortical computations is still a mystery. Although cell ensembles have been associated with brain rhythms, the functional interaction remains largely unclear. It is still unknown how spatially distributed neuronal activity can be temporally integrated to contribute to cortical computations. A theoretical explanation integrating spatial and temporal aspects of cortical processing is still lacking. In this Hypothesis and Theory article, we propose a new functional theoretical framework to explain the computational roles of these ensembles in cortical processing. We suggest that complex neural computations underlying cortical processing could be temporally discrete and that sensory information would need to be quantized to be computed by the cerebral cortex. Accordingly, we propose that cortical processing is produced by the computation of discrete spatio-temporal functional units that we have called "Discrete Results" (Discrete Results Hypothesis). This hypothesis represents a novel functional mechanism by which information processing is computed in the cortex. Furthermore, we propose that precise dynamic sequences of "Discrete Results" is the mechanism used by the cortex to extract, code, memorize and transmit neural information. The novel "Discrete Results" concept has the ability to match the spatial and temporal aspects of cortical processing. We discuss the possible neural underpinnings of these functional computational units and describe the empirical evidence supporting our hypothesis. We propose that fast-spiking (FS) interneuron may be a key element in our hypothesis providing the basis for this computation.

Motor cortex stimulation: role of computer modeling.

PubMed

Manola, L; Holsheimer, J

2007-01-01

Motor cortex stimulation (MCS) is a promising clinical technique used to treat chronic, otherwise intractable pain. However, the mechanisms by which the neural elements that are stimulated during MCS induce pain relief are not understood. Neither is it known which of the main neural elements, i.e. cell bodies, dendrites or fibers are immediately excited by the electrical pulses in MCS. Moreover, it is not known what are the effects of MCS on fibers which are parallel or perpendicular to the cortical layers, below or away from the electrode. The therapy and its efficacy are less likely to be improved until it is better understood how it may work. In this chapter, we present our efforts to resolve this issue. Our computer model of MCS is introduced and some of its predictions are discussed. In particular, the influence of stimulus polarity and electrode position on the electrical field and excitation thresholds of different neural elements is addressed. Such predictions, supported with clinical evidence, should help to elucidate the immediate effects of an electrical stimulus applied over the motor cortex and may ultimately lead to optimizations of the therapy.

[Evoked potentials in the human visual cortex when observing whole figures and their elements].

PubMed

Slavutskaia, A V; Mikhaĭlova, E S

2010-01-01

Evoked potentials changes were analyzed in 32 subjects in a task of observing whole and disintegrated images. In the occipital and parietal regions, reactions to a disintegrated image appeared early (within the period of P1 development), and their characteristics were determined by the magnitude of the response to the whole image. In the occipital cortex, a low-amplitude P1 (the 1st group of subjects) increased in response to image disintegration, whereas in cases of a high P1 amplitude (the 2nd group), the tendency to its reduction was observed. In the parietal regions, the effects were distinct only in the 1st group of subjects and different in the right and left hemispheres: in the left hemisphere, the P1 amplitude increased when simpler elements appeared in the image, in the right hemisphere, a change in the spatial disposition of details was more significant. In the inferior temporal cortex, the amplitude of the later wave N1 decreased in response to disintegration, the effect being significant only in the 2nd group of subjects. The appearance of simpler elements in the image resulted in a P3 wave increase in both groups. The results point to topographic and temporal specificity of the reactions of the visual cortex to image disintegration and suggest the existence of various strategies of the visual image analysis at the early stages.

A key role of the prefrontal cortex in the maintenance of chronic tinnitus: An fMRI study using a Stroop task.

PubMed

Araneda, Rodrigo; Renier, Laurent; Dricot, Laurence; Decat, Monique; Ebner-Karestinos, Daniela; Deggouj, Naïma; De Volder, Anne G

2018-01-01

Since we recently showed in behavioural tasks that the top-down cognitive control was specifically altered in tinnitus sufferers, here we wanted to establish the link between this impaired executive function and brain alterations in the frontal cortex in tinnitus patients. Using functional magnetic resonance imaging (fMRI), we monitored the brain activity changes in sixteen tinnitus patients (TP) and their control subjects (CS) while they were performing a spatial Stroop task, both in audition and vision. We observed that TP differed from CS in their functional recruitment of the dorsolateral prefrontal cortex (dlPFC, BA46), the cingulate gyrus and the ventromedial prefrontal cortex (vmPFC, BA10). This recruitment was higher during interference conditions in tinnitus participants than in controls, whatever the sensory modality. Furthermore, the brain activity level in the right dlPFC and vmPFC correlated with the performance in the Stroop task in TP. Due to the direct link between poor executive functions and prefrontal cortex alterations in TP, we postulate that a lack of inhibitory modulation following an impaired top-down cognitive control may maintain tinnitus by hampering habituation mechanisms. This deficit in executive functions caused by prefrontal cortex alterations would be a key-factor in the generation and persistence of tinnitus.

Neurocognitive Elements of Antisocial Behavior: Relevance of an Orbitofrontal Cortex Account

ERIC Educational Resources Information Center

Seguin, Jean R.

2004-01-01

This paper reviews the role of orbitofrontal cortex (OFC) lesions in antisocial behaviors and the adequacy of a strict OFC account of antisocial disorders where there is no evidence of lesion. Neurocognitive accounts of antisocial behaviors are extended beyond the OFC. Several methodological shortcomings specific to this neuroscience approach to…

Distributed and Dynamic Storage of Working Memory Stimulus Information in Extrastriate Cortex

PubMed Central

Sreenivasan, Kartik K.; Vytlacil, Jason; D'Esposito, Mark

2015-01-01

The predominant neurobiological model of working memory (WM) posits that stimulus information is stored via stable elevated activity within highly selective neurons. Based on this model, which we refer to as the canonical model, the storage of stimulus information is largely associated with lateral prefrontal cortex (lPFC). A growing number of studies describe results that cannot be fully explained by the canonical model, suggesting that it is in need of revision. In the present study, we directly test key elements of the canonical model. We analyzed functional MRI data collected as participants performed a task requiring WM for faces and scenes. Multivariate decoding procedures identified patterns of activity containing information about the items maintained in WM (faces, scenes, or both). While information about WM items was identified in extrastriate visual cortex (EC) and lPFC, only EC exhibited a pattern of results consistent with a sensory representation. Information in both regions persisted even in the absence of elevated activity, suggesting that elevated population activity may not represent the storage of information in WM. Additionally, we observed that WM information was distributed across EC neural populations that exhibited a broad range of selectivity for the WM items rather than restricted to highly selective EC populations. Finally, we determined that activity patterns coding for WM information were not stable, but instead varied over the course of a trial, indicating that the neural code for WM information is dynamic rather than static. Together, these findings challenge the canonical model of WM. PMID:24392897

The importance of mammillary body efferents for recency memory: towards a better understanding of diencephalic amnesia.

PubMed

Nelson, Andrew J D; Vann, Seralynne D

2017-07-01

Despite being historically one of the first brain regions linked to memory loss, there remains controversy over the core features of diencephalic amnesia as well as the critical site for amnesia to occur. The mammillary bodies and thalamus appear to be the primary locus of pathology in the cases of diencephalic amnesia, but the picture is complicated by the lack of patients with circumscribed damage. Impaired temporal memory is a consistent neuropsychological finding in Korsakoff syndrome patients, but again, it is unclear whether this deficit is attributable to pathology within the diencephalon or concomitant frontal lobe dysfunction. To address these issues, we used an animal model of diencephalic amnesia and examined the effect of mammillothalamic tract lesions on tests of recency memory. The mammillothalamic tract lesions severely disrupted recency judgements involving multiple items but left intact both recency and familiarity judgements for single items. Subsequently, we used disconnection procedures to assess whether this deficit reflects the indirect involvement of the prefrontal cortex. Crossed-lesion rats, with unilateral lesions of the mammillothalamic tract and medial prefrontal cortex in contralateral hemispheres, were unimpaired on the same recency tests. These results provide the first evidence for the selective importance of mammillary body efferents for recency memory. Moreover, this contribution to recency memory is independent of the prefrontal cortex. More broadly, these findings identify how specific diencephalic structures are vital for key elements of event memory.

Prefrontal-Hippocampal Pathways Underlying Inhibitory Control Over Memory

PubMed Central

Anderson, Michael C.; Bunce, Jamie G.; Barbas, Helen

2016-01-01

A key function of the prefrontal cortex is to support inhibitory control over behavior. It is widely believed that this function extends to stopping cognitive processes as well. Consistent with this, mounting evidence establishes the role of the right lateral prefrontal cortex in a clear case of cognitive control: retrieval suppression. Retrieval suppression refers to the ability to intentionally stop the retrieval process that arises when a reminder to a memory appears. Functional imaging data indicates that retrieval suppression involves top-down modulation of hippocampal activity by the dorsolateral prefrontal cortex, but the anatomical pathways supporting this inhibitory modulation remain unclear. Here we bridge this gap by integrating key findings about retrieval suppression observed through functional imaging with a detailed consideration of relevant anatomical pathways observed in non-human primates. Focusing selectively on the potential role of the anterior cingulate cortex, we develop two hypotheses about the pathways mediating interactions between lateral prefrontal cortex and the medial temporal lobes during suppression, and their cellular targets: the entorhinal gating hypothesis, and thalamo-hippocampal modulation via the nucleus reuniens. We hypothesize that whereas entorhinal gating is well situated to stop retrieval proactively, thalamo-hippocampal modulation may interrupt an ongoing act of retrieval reactively. Isolating the pathways that underlie retrieval suppression holds the potential to advance our understanding of a range of psychiatric disorders characterized by persistent intrusive thoughts. More broadly, an anatomical account of retrieval suppression would provide a key model system for understanding inhibitory control over cognition. PMID:26642918

Neural feedback for instantaneous spatiotemporal modulation of afferent pathways in bi-directional brain-machine interfaces.

PubMed

Liu, Jianbo; Khalil, Hassan K; Oweiss, Karim G

2011-10-01

In bi-directional brain-machine interfaces (BMIs), precisely controlling the delivery of microstimulation, both in space and in time, is critical to continuously modulate the neural activity patterns that carry information about the state of the brain-actuated device to sensory areas in the brain. In this paper, we investigate the use of neural feedback to control the spatiotemporal firing patterns of neural ensembles in a model of the thalamocortical pathway. Control of pyramidal (PY) cells in the primary somatosensory cortex (S1) is achieved based on microstimulation of thalamic relay cells through multiple-input multiple-output (MIMO) feedback controllers. This closed loop feedback control mechanism is achieved by simultaneously varying the stimulation parameters across multiple stimulation electrodes in the thalamic circuit based on continuous monitoring of the difference between reference patterns and the evoked responses of the cortical PY cells. We demonstrate that it is feasible to achieve a desired level of performance by controlling the firing activity pattern of a few "key" neural elements in the network. Our results suggest that neural feedback could be an effective method to facilitate the delivery of information to the cortex to substitute lost sensory inputs in cortically controlled BMIs.

Medial prefrontal cortex neuronal circuits in fear behavior.

PubMed

Courtin, J; Bienvenu, T C M; Einarsson, E Ö; Herry, C

2013-06-14

The medial prefrontal cortex (mPFC) has emerged as a key structure involved in the modulation of fear behavior over the past few decades. Anatomical, functional and electrophysiological studies have begun to shed light on the precise mechanisms by which different prefrontal regions regulate the expression and inhibition of fear behavior. These studies have established a canonical view of mPFC functions during fear behavior with dorsal regions selectively involved in the expression of fear behavior and ventral regions linked to the inhibition of fear behavior. Although numerous reports support this view, recent data have refined this model and suggested that dorsal prefrontal regions might also play an important role in the encoding of fear behavior itself. The recent development of sophisticated approaches such as large scale neuronal recordings, simultaneous multisite recordings of spiking activity and local field potentials (LFPs) along with optogenetic approaches will facilitate the testing of these new hypotheses in the near future. Here we provide an extensive review of the literature on the role of mPFC in fear behavior and propose further directions to dissect the contribution of specific prefrontal neuronal elements and circuits in the regulation of fear behavior. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

A Detailed Data-Driven Network Model of Prefrontal Cortex Reproduces Key Features of In Vivo Activity

PubMed Central

Hass, Joachim; Hertäg, Loreen; Durstewitz, Daniel

2016-01-01

The prefrontal cortex is centrally involved in a wide range of cognitive functions and their impairment in psychiatric disorders. Yet, the computational principles that govern the dynamics of prefrontal neural networks, and link their physiological, biochemical and anatomical properties to cognitive functions, are not well understood. Computational models can help to bridge the gap between these different levels of description, provided they are sufficiently constrained by experimental data and capable of predicting key properties of the intact cortex. Here, we present a detailed network model of the prefrontal cortex, based on a simple computationally efficient single neuron model (simpAdEx), with all parameters derived from in vitro electrophysiological and anatomical data. Without additional tuning, this model could be shown to quantitatively reproduce a wide range of measures from in vivo electrophysiological recordings, to a degree where simulated and experimentally observed activities were statistically indistinguishable. These measures include spike train statistics, membrane potential fluctuations, local field potentials, and the transmission of transient stimulus information across layers. We further demonstrate that model predictions are robust against moderate changes in key parameters, and that synaptic heterogeneity is a crucial ingredient to the quantitative reproduction of in vivo-like electrophysiological behavior. Thus, we have produced a physiologically highly valid, in a quantitative sense, yet computationally efficient PFC network model, which helped to identify key properties underlying spike time dynamics as observed in vivo, and can be harvested for in-depth investigation of the links between physiology and cognition. PMID:27203563

Cognitive impairment related changes in the elemental concentration in the brain of old rat

NASA Astrophysics Data System (ADS)

Serpa, R. F. B.; de Jesus, E. F. O.; Anjos, M. J.; Lopes, R. T.; do Carmo, M. G. T.; Rocha, M. S.; Rodrigues, L. C.; Moreira, S.; Martinez, A. M. B.

2006-11-01

In order to evaluate the elemental concentration as a function of learning and memory deficiency, six different structures of the brain were analyzed by total reflection X-ray fluorescence spectrometry with synchrotron radiation (SR-TXRF). To evaluate the cognitive processes, the animals were tested in an adaptation of the Morris water maze. After the test, the animals were divided into two groups: cognitively healthy (control group) and cognitively impaired. The measurements were carried out at XRF beam line at Light Synchrotron Brazilian laboratory, Campinas, Brazil. The following elements were identified: Al, P, S, Cl, K, Ca, Ti, Cr, Fe, Cu, Zn, Br and Rb. K concentration was higher in all regions of the brain studied for control group than the cognitively impaired group. Moreover, the control group presented higher levels for P and Fe in the entorhinal cortex, in the temporal cortex (only P), in the hypothalamus and in the thalamus, than the cognitively impaired group. Br concentration in the animals which presented cognitive impairment was three times larger in the hypothalamus and thalamus, twice larger in temporal cortex and higher in visual cortex than the cognitively healthy group. Cu was more remarkable in the hippocampus and hypothalamus from the animals with cognitive impairment than the control group. We observed that the cognitively impaired group presented highest concentrations of Br and Cu in certain areas than the control group, on the other hand, this group presented highest levels of K for all brain areas studied.

Disrupted coupling of large-scale networks is associated with relapse behaviour in heroin-dependent men

PubMed Central

Li, Qiang; Liu, Jierong; Wang, Wei; Wang, Yarong; Li, Wei; Chen, Jiajie; Zhu, Jia; Yan, Xuejiao; Li, Yongbin; Li, Zhe; Ye, Jianjun; Wang, Wei

2018-01-01

Background It is unknown whether impaired coupling among 3 core large-scale brain networks (salience [SN], default mode [DMN] and executive control networks [ECN]) is associated with relapse behaviour in treated heroin-dependent patients. Methods We conducted a prospective resting-state functional MRI study comparing the functional connectivity strength among healthy controls and heroin-dependent men who had either relapsed or were in early remission. Men were considered to be either relapsed or in early remission based on urine drug screens during a 3-month follow-up period. We also examined how the coupling of large-scale networks correlated with relapse behaviour among heroin-dependent men. Results We included 20 controls and 50 heroin-dependent men (26 relapsed and 24 early remission) in our analyses. The relapsed men showed greater connectivity than the early remission and control groups between the dorsal anterior cingulate cortex (key node of the SN) and the dorsomedial prefrontal cortex (included in the DMN). The relapsed men and controls showed lower connectivity than the early remission group between the left dorsolateral prefrontal cortex (key node of the left ECN) and the dorsomedial prefrontal cortex. The percentage of positive urine drug screens positively correlated with the coupling between the dorsal anterior cingulate cortex and dorsomedial prefrontal cortex, but negatively correlated with the coupling between the left dorsolateral prefrontal cortex and dorsomedial prefrontal cortex. Limitations We examined deficits in only 3 core networks leading to relapse behaviour. Other networks may also contribute to relapse. Conclusion Greater coupling between the SN and DMN and lower coupling between the left ECN and DMN is associated with relapse behaviour. These findings may shed light on the development of new treatments for heroin addiction. PMID:29252165

Peri-implant stress correlates with bone and cement morphology: Micro-FE modeling of implanted cadaveric glenoids.

PubMed

Wee, Hwabok; Armstrong, April D; Flint, Wesley W; Kunselman, Allen R; Lewis, Gregory S

2015-11-01

Aseptic loosening of cemented joint replacements is a complex biological and mechanical process, and remains a clinical concern especially in patients with poor bone quality. Utilizing high resolution finite element analysis of a series of implanted cadaver glenoids, the objective of this study was to quantify relationships between construct morphology and resulting mechanical stresses in cement and trabeculae. Eight glenoid cadavers were implanted with a cemented central peg implant. Specimens were imaged by micro-CT, and subject-specific finite element models were developed. Bone volume fraction, glenoid width, implant-cortex distance, cement volume, cement-cortex contact, and cement-bone interface area were measured. Axial loading was applied to the implant of each model and stress distributions were characterized. Correlation analysis was completed across all specimens for pairs of morphological and mechanical variables. The amount of trabecular bone with high stress was strongly negatively correlated with both cement volume and contact between the cement and cortex (r = -0.85 and -0.84, p < 0.05). Bone with high stress was also correlated with both glenoid width and implant-cortex distance. Contact between the cement and underlying cortex may dramatically reduce trabecular bone stresses surrounding the cement, and this contact depends on bone shape, cement amount, and implant positioning. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Concentrations of strontium, barium, cadmium, copper, zinc, manganese, chromium, antimony, selenium, and lead in the liver and kidneys of dogs according to age, gender, and the occurrence of chronic kidney disease

PubMed Central

Mainzer, Barbara; Lahrssen-Wiederholt, Monika; Schafft, Helmut; Palavinskas, Richard; Breithaupt, Angele; Zentek, Jürgen

2015-01-01

This study was conducted to measure the concentrations of strontium (Sr), barium (Ba), cadmium (Cd), copper (Cu), zinc (Zn), manganese (Mn), chromium (Cr), antimony (Sb), selenium (Se), and lead (Pb) in canine liver, renal cortex, and renal medulla, and the association of these concentrations with age, gender, and occurrence of chronic kidney disease (CKD). Tissues from 50 dogs were analyzed using inductively coupled plasma mass spectrometry. Cu, Zn, and Mn levels were highest in the liver followed by the renal cortex and renal medulla. The highest Sr, Cd, and Se concentrations were measured in the renal cortex while lower levels were found in the renal medulla and liver. Female dogs had higher tissue concentrations of Sr (liver and renal medulla), Cd (liver), Zn (liver and renal cortex), Cr (liver, renal cortex, and renal medulla), and Pb (liver) than male animals. Except for Mn and Sb, age-dependent variations were observed for all element concentrations in the canine tissues. Hepatic Cd and Cr concentrations were higher in dogs with CKD. In conclusion, the present results provide new knowledge about the storage of specific elements in canine liver and kidneys, and can be considered important reference data for diagnostic methods and further investigations. PMID:25234328

Superior parietal lobule dysfunction in a homogeneous group of dyslexic children with a visual attention span disorder.

PubMed

Peyrin, C; Démonet, J F; N'Guyen-Morel, M A; Le Bas, J F; Valdois, S

2011-09-01

A visual attention (VA) span disorder has been reported in dyslexic children as potentially responsible for their poor reading outcome. The purpose of the current paper was to identify the cerebral correlates of this VA span disorder. For this purpose, 12 French dyslexic children with severe reading and VA span disorders and 12 age-matched control children were engaged in a categorisation task under fMRI. Two flanked and isolated conditions were designed which both involved multiple-element simultaneous visual processing but taxed visual attention differently. For skilled readers, flanked stimuli processing activated a large bilateral cortical network comprising the superior and inferior parietal cortex, the inferior temporal cortex, the striate and extrastriate visual cortex, the middle frontal cortex and the anterior cingulate cortex while the less attention-demanding task of isolated stimuli only activated the inferior occipito-temporal cortex bilaterally. With respect to controls, the dyslexic children showed significantly reduced activation within bilateral parietal and temporal areas during flanked processing, but no difference during the isolated condition. The neural correlates of the processes involved in attention-demanding multi-element processing tasks were more specifically addressed by contrasting the flanked and the isolated conditions. This contrast elicited activation of the left precuneus/superior parietal lobule in the controls, but not in the dyslexic children. These findings provide new insights on the role of parietal regions, in particular the left superior parietal lobule, in the visual attention span and in developmental dyslexia. Copyright © 2010 Elsevier Inc. All rights reserved.

Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala

PubMed Central

Murray, Elisabeth A.; Wise, Steven P.; Drevets, Wayne C.

2010-01-01

Despite considerable effort, the localization of dysfunction in major depressive disorder (MDD) remains poorly understood. We present a hypothesis about its localization that builds on recent findings from primate neuropsychology. The hypothesis has four key components: a deficit in the valuation of ‘self’ underlies the core disorder in MDD; the medial frontal cortex represents ‘self’; interactions between the amygdala and cortical representations update their valuation; and inefficiency in using positive feedback by orbital prefrontal cortex contributes to MDD. PMID:21111403

Portraying the unique contribution of the default mode network to internally driven mnemonic processes

PubMed Central

Shapira-Lichter, Irit; Oren, Noga; Jacob, Yael; Gruberger, Michal; Hendler, Talma

2013-01-01

Numerous neuroimaging studies have implicated default mode network (DMN) involvement in both internally driven processes and memory. Nevertheless, it is unclear whether memory operations reflect a particular case of internally driven processing or alternatively involve the DMN in a distinct manner, possibly depending on memory type. This question is critical for refining neurocognitive memory theorem in the context of other endogenic processes and elucidating the functional significance of this key network. We used functional MRI to examine DMN activity and connectivity patterns while participants overtly generated words according to nonmnemonic (phonemic) or mnemonic (semantic or episodic) cues. Overall, mnemonic word fluency was found to elicit greater DMN activity and stronger within-network functional connectivity compared with nonmnemonic fluency. Furthermore, two levels of functional organization of memory retrieval were shown. First, across both mnemonic tasks, activity was greater mainly in the posterior cingulate cortex, implying selective contribution to generic aspects of memory beyond its general involvement in endogenous processes. Second, parts of the DMN showed distinct selectivity for each of the mnemonic conditions; greater recruitment of the anterior prefrontal cortex, retroesplenial cortex, and hippocampi and elevated connectivity between anterior and posterior medial DMN nodes characterized the semantic condition, whereas increased recruitment of posterior DMN components and elevated connectivity between them characterized the episodic condition. This finding emphasizes the involvement of DMN elements in discrete aspects of memory retrieval. Altogether, our results show a specific contribution of the DMN to memory processes, corresponding to the specific type of memory retrieval. PMID:23479650

Determinants of the electric field during transcranial direct current stimulation.

PubMed

Opitz, Alexander; Paulus, Walter; Will, Susanne; Antunes, Andre; Thielscher, Axel

2015-04-01

Transcranial direct current stimulation (tDCS) causes a complex spatial distribution of the electric current flow in the head which hampers the accurate localization of the stimulated brain areas. In this study we show how various anatomical features systematically shape the electric field distribution in the brain during tDCS. We constructed anatomically realistic finite element (FEM) models of two individual heads including conductivity anisotropy and different skull layers. We simulated a widely employed electrode montage to induce motor cortex plasticity and moved the stimulating electrode over the motor cortex in small steps to examine the resulting changes of the electric field distribution in the underlying cortex. We examined the effect of skull thickness and composition on the passing currents showing that thinner skull regions lead to higher electric field strengths. This effect is counteracted by a larger proportion of higher conducting spongy bone in thicker regions leading to a more homogenous current over the skull. Using a multiple regression model we could identify key factors that determine the field distribution to a significant extent, namely the thicknesses of the cerebrospinal fluid and the skull, the gyral depth and the distance to the anode and cathode. These factors account for up to 50% of the spatial variation of the electric field strength. Further, we demonstrate that individual anatomical factors can lead to stimulation "hotspots" which are partly resistant to electrode positioning. Our results give valuable novel insights in the biophysical foundation of tDCS and highlight the importance to account for individual anatomical factors when choosing an electrode montage. Copyright © 2015 Elsevier Inc. All rights reserved.

Dissociable Neural Mechanisms Underlying the Modulation of Pain and Anxiety? An fMRI Pilot Study

PubMed Central

Moseley, Graham Lorimer; Berna, Chantal; Ploner, Markus; Tracey, Irene

2014-01-01

The down-regulation of pain through beliefs is commonly discussed as a form of emotion regulation. In line with this interpretation, the analgesic effect has been shown to co-occur with reduced anxiety and increased activity in the ventrolateral prefrontal cortex (VLPFC), which is a key region of emotion regulation. This link between pain and anxiety modulation raises the question whether the two effects are rooted in the same neural mechanism. In this pilot fMRI study, we compared the neural basis of the analgesic and anxiolytic effect of two types of threat modulation: a “behavioral control” paradigm, which involves the ability to terminate a noxious stimulus, and a “safety signaling” paradigm, which involves visual cues that signal the threat (or absence of threat) that a subsequent noxious stimulus might be of unusually high intensity. Analgesia was paralleled by VLPFC activity during behavioral control. Safety signaling engaged elements of the descending pain control system, including the rostral anterior cingulate cortex that showed increased functional connectivity with the periaqueductal gray and VLPFC. Anxiety reduction, in contrast, scaled with dorsolateral prefrontal cortex activation during behavioral control but had no distinct neural signature during safety signaling. Our pilot data therefore suggest that analgesic and anxiolytic effects are instantiated in distinguishable neural mechanisms and differ between distinct stress- and pain-modulatory approaches, supporting the recent notion of multiple pathways subserving top-down modulation of the pain experience. Additional studies in larger cohorts are needed to follow up on these preliminary findings. PMID:25502237

Imbalance in subregional connectivity of the right temporoparietal junction in major depression.

PubMed

Poeppl, Timm B; Müller, Veronika I; Hoffstaedter, Felix; Bzdok, Danilo; Laird, Angela R; Fox, Peter T; Langguth, Berthold; Rupprecht, Rainer; Sorg, Christian; Riedl, Valentin; Goya-Maldonado, Roberto; Gruber, Oliver; Eickhoff, Simon B

2016-08-01

Major depressive disorder (MDD) involves impairment in cognitive and interpersonal functioning. The right temporoparietal junction (RTPJ) is a key brain region subserving cognitive-attentional and social processes. Yet, findings on the involvement of the RTPJ in the pathophysiology of MDD have so far been controversial. Recent connectivity-based parcellation data revealed a topofunctional dualism within the RTPJ, linking its anterior and posterior part (aRTPJ/pRTPJ) to antagonistic brain networks for attentional and social processing, respectively. Comparing functional resting-state connectivity of the aRTPJ and pRTPJ in 72 MDD patients and 76 well-matched healthy controls, we found a seed (aRTPJ/pRTPJ) × diagnosis (MDD/controls) interaction in functional connectivity for eight regions. Employing meta-data from a large-scale neuroimaging database, functional characterization of these regions exhibiting differentially altered connectivity with the aRTPJ/pRTPJ revealed associations with cognitive (dorsolateral prefrontal cortex, parahippocampus) and behavioral (posterior medial frontal cortex) control, visuospatial processing (dorsal visual cortex), reward (subgenual anterior cingulate cortex, medial orbitofrontal cortex, posterior cingulate cortex), as well as memory retrieval and social cognition (precuneus). These findings suggest that an imbalance in connectivity of subregions, rather than disturbed connectivity of the RTPJ as a whole, characterizes the connectional disruption of the RTPJ in MDD. This imbalance may account for key symptoms of MDD in cognitive, emotional, and social domains. Hum Brain Mapp 37:2931-2942, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

The Microcircuit Concept Applied to Cortical Evolution: from Three-Layer to Six-Layer Cortex

PubMed Central

Shepherd, Gordon M.

2011-01-01

Understanding the principles of organization of the cerebral cortex requires insight into its evolutionary history. This has traditionally been the province of anatomists, but evidence regarding the microcircuit organization of different cortical areas is providing new approaches to this problem. Here we use the microcircuit concept to focus first on the principles of microcircuit organization of three-layer cortex in the olfactory cortex, hippocampus, and turtle general cortex, and compare it with six-layer neocortex. From this perspective it is possible to identify basic circuit elements for recurrent excitation and lateral inhibition that are common across all the cortical regions. Special properties of the apical dendrites of pyramidal cells are reviewed that reflect the specific adaptations that characterize the functional operations in the different regions. These principles of microcircuit function provide a new approach to understanding the expanded functional capabilities elaborated by the evolution of the neocortex. PMID:21647397

Addiction as a Stress Surfeit Disorder

PubMed Central

Koob, George F.; Buck, Cara L.; Cohen, Ami; Edwards, Scott; Park, Paula E.; Schlosburg, Joel E.; Schmeichel, Brooke; Vendruscolo, Leandro F.; Wade, Carrie L.; Whitfield, Timothy W.; George, Olivier

2013-01-01

Drug addiction has been conceptualized as a chronically relapsing disorder of compulsive drug seeking and taking that progresses through three stages: binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation. Drug addiction impacts multiple motivational mechanisms and can be conceptualized as a disorder that progresses from positive reinforcement (binge/intoxication stage) to negative reinforcement (withdrawal/negative affect stage). The construct of negative reinforcement is defined as drug taking that alleviates a negative emotional state. Our hypothesis is that the negative emotional state that drives such negative reinforcement is derived from dysregulation of key neurochemical elements involved in the brain stress systems within the frontal cortex, ventral striatum, and extended amygdala. Specific neurochemical elements in these structures include not only recruitment of the classic stress axis mediated by corticotropin-releasing factor (CRF) in the extended amygdala as previously hypothesized but also recruitment of dynorphin-κ opioid aversive systems in the ventral striatum and extended amygdala. Additionally, we hypothesized that these brain stress systems may be engaged in the frontal cortex early in the addiction process. Excessive drug taking engages activation of CRF not only in the extended amygdala, accompanied by anxiety-like states, but also in the medial prefrontal cortex, accompanied by deficits in executive function that may facilitate the transition to compulsive-like responding. Excessive activation of the nucleus accumbens via the release of mesocorticolimbic dopamine or activation of opioid receptors has long been hypothesized to subsequently activate the dynorphin-κ opioid system, which in turn can decrease dopaminergic activity in the mesocorticolimbic dopamine system. Blockade of the κ opioid system can also block anxiety-like and reward deficits associated with withdrawal from drugs of abuse and block the development of compulsive-like responding during extended access to drugs of abuse, suggesting another powerful brain stress/anti-reward system that contributes to compulsive drug seeking. Thus, brain stress response systems are hypothesized to be activated by acute excessive drug intake, to be sensitized during repeated withdrawal, to persist into protracted abstinence, and to contribute to the development and persistence of addiction. The recruitment of anti-reward systems provides a powerful neurochemical basis for the negative emotional states that are responsible for the dark side of addiction. PMID:23747571

The influence of manganese treatment on the distribution of metal elements in rats and the protection by sodium para-amino salicylic acid.

PubMed

Yuan, Zong-Xiang; Chen, Hai-Bin; Li, Shao-Jun; Huang, Xiao-Wei; Mo, Yu-Huan; Luo, Yi-Ni; He, Sheng-Nan; Deng, Xiang-Fa; Lu, Guo-Dong; Jiang, Yue-Ming

2016-07-01

Manganese (Mn) overexposure induced neurological damages, which could be potentially protected by sodium para-aminosalicylic acid (PAS-Na). In this study, we systematically detected the changes of divalent metal elements in most of the organs and analyzed the distribution of the metals in Mn-exposed rats and the protection by PAS-Na. Sprague Dawley (SD) rats received intraperitoneal injections of 15mg/kg MnCl2·4H2O (5d/week for 3 weeks), followed by subcutaneous (back) injections of PAS-Na (100 and 200mg/kg, everyday for 5 weeks). The concentrations of Mn and other metal elements [Iron (Fe), Copper (Cu), Zinc (Zn), Magnesium (Mg), Calcium (Ca)] in major organs (liver, spleen, kidney, thighbone and iliac bone, cerebral cortex, hippocampus and testes) and blood by Inductively Coupled Plasma-Atomic Emission Spectrometry (ICP-AES). The results showed that Mn overexposure significantly increased Mn in most organs, Fe and Zn in liver, Fe and Mg in blood; however decreased Fe, Cu, Zn, Mg and Ca in cortex, Cu and Zn in kidney, Cu and Mg in iliac bone, and Zn in blood. In contrast, PAS-Na treatment restored most changes particularly in cortex. In conclusion, excessive Mn exposure disturbed the balance of other metal elements but PAS-Na post-treatments could restore these alterations. Copyright © 2016 Elsevier GmbH. All rights reserved.

Orofacial Neuropathic Pain Leads to a Hyporesponsive Barrel Cortex with Enhanced Structural Synaptic Plasticity.

PubMed

Thibault, Karine; Rivière, Sébastien; Lenkei, Zsolt; Férézou, Isabelle; Pezet, Sophie

2016-01-01

Chronic pain is a long-lasting debilitating condition that is particularly difficult to treat due to the lack of identified underlying mechanisms. Although several key contributing processes have been described at the level of the spinal cord, very few studies have investigated the supraspinal mechanisms underlying chronic pain. Using a combination of approaches (cortical intrinsic imaging, immunohistochemical and behavioural analysis), our study aimed to decipher the nature of functional and structural changes in a mouse model of orofacial neuropathic pain, focusing on cortical areas involved in various pain components. Our results show that chronic neuropathic orofacial pain is associated with decreased haemodynamic responsiveness to whisker stimulation in the barrel field cortex. This reduced functional activation is likely due to the increased basal neuronal activity (measured indirectly using cFos and phospho-ERK immunoreactivity) observed in several cortical areas, including the contralateral barrel field, motor and cingulate cortices. In the same animals, immunohistochemical analysis of markers for active pre- or postsynaptic elements (Piccolo and phospho-Cofilin, respectively) revealed an increased immunofluorescence in deep cortical layers of the contralateral barrel field, motor and cingulate cortices. These results suggest that long-lasting orofacial neuropathic pain is associated with exacerbated neuronal activity and synaptic plasticity at the cortical level.

The role of long-range connectivity for the characterization of the functional-anatomical organization of the cortex.

PubMed

Knösche, Thomas R; Tittgemeyer, Marc

2011-01-01

This review focuses on the role of long-range connectivity as one element of brain structure that is of key importance for the functional-anatomical organization of the cortex. In this context, we discuss the putative guiding principles for mapping brain function and structure onto the cortical surface. Such mappings reveal a high degree of functional-anatomical segregation. Given that brain regions frequently maintain characteristic connectivity profiles and the functional repertoire of a cortical area is closely related to its anatomical connections, long-range connectivity may be used to define segregated cortical areas. This methodology is called connectivity-based parcellation. Within this framework, we investigate different techniques to estimate connectivity profiles with emphasis given to non-invasive methods based on diffusion magnetic resonance imaging (dMRI) and diffusion tractography. Cortical parcellation is then defined based on similarity between diffusion tractograms, and different clustering approaches are discussed. We conclude that the use of non-invasively acquired connectivity estimates to characterize the functional-anatomical organization of the brain is a valid, relevant, and necessary endeavor. Current and future developments in dMRI technology, tractography algorithms, and models of the similarity structure hold great potential for a substantial improvement and enrichment of the results of the technique.

The orbitofrontal cortex and beyond: from affect to decision-making.

PubMed

Rolls, Edmund T; Grabenhorst, Fabian

2008-11-01

The orbitofrontal cortex represents the reward or affective value of primary reinforcers including taste, touch, texture, and face expression. It learns to associate other stimuli with these to produce representations of the expected reward value for visual, auditory, and abstract stimuli including monetary reward value. The orbitofrontal cortex thus plays a key role in emotion, by representing the goals for action. The learning process is stimulus-reinforcer association learning. Negative reward prediction error neurons are related to this affective learning. Activations in the orbitofrontal cortex correlate with the subjective emotional experience of affective stimuli, and damage to the orbitofrontal cortex impairs emotion-related learning, emotional behaviour, and subjective affective state. With an origin from beyond the orbitofrontal cortex, top-down attention to affect modulates orbitofrontal cortex representations, and attention to intensity modulates representations in earlier cortical areas of the physical properties of stimuli. Top-down word-level cognitive inputs can bias affective representations in the orbitofrontal cortex, providing a mechanism for cognition to influence emotion. Whereas the orbitofrontal cortex provides a representation of reward or affective value on a continuous scale, areas beyond the orbitofrontal cortex such as the medial prefrontal cortex area 10 are involved in binary decision-making when a choice must be made. For this decision-making, the orbitofrontal cortex provides a representation of each specific reward in a common currency.

The neurophysiology of figure-ground segregation in primary visual cortex.

PubMed

Lamme, V A

1995-02-01

The activity of neurons in the primary visual cortex of the awake macaque monkey was recorded while the animals were viewing full screen arrays of either oriented line segments or moving random dots. A square patch of the screen was made to perceptually pop out as a circumscribed figure by virtue of differences between the orientation or the direction of motion of the texture elements within that patch and the surround. The animals were trained to identify the figure patches by making saccadic eye movements towards their positions. Almost every cell gave a significantly larger response to elements belonging to the figure than to similar elements belonging to the background. The figure-ground response enhancement was present along the entire extent of the patch and was absent as soon as the receptive field was outside the patch. The strength of the effect had no relation with classical receptive field properties like orientation or direction selectivity or receptive field size. The response enhancement had a latency of 30-40 msec relative to the onset of the neuronal response itself. The results show that context modulation within primary visual cortex has a highly sophisticated nature, putting the image features the cells are responding to into their fully evaluated perceptual context.

Attention, Emotion, and Deactivation of Default Activity in Inferior Medial Prefrontal Cortex

ERIC Educational Resources Information Center

Geday, Jacob; Gjedde, Albert

2009-01-01

Attention deactivates the inferior medial prefrontal cortex (IMPC), but it is uncertain if emotions can attenuate this deactivation. To test the extent to which common emotions interfere with attention, we measured changes of a blood flow index of brain activity in key areas of the IMPC with positron emission tomography (PET) of labeled water…

Infralimbic Prefrontal Cortex Interacts with Nucleus Accumbens Shell to Unmask Expression of Outcome-Selective Pavlovianto- Instrumental Transfer

ERIC Educational Resources Information Center

Keistler, Colby; Barker, Jacqueline M.; Taylor, Jane R.

2015-01-01

Although several studies have examined the subcortical circuitry underlying Pavlovian-to-instrumental transfer (PIT), the role of medial prefrontal cortex in this behavior is largely unknown. Elucidating the cortical contributions to PIT will be key for understanding how reward-paired cues control behavior in both adaptive and maladaptive context…

Addiction is a Reward Deficit and Stress Surfeit Disorder

PubMed Central

Koob, George F.

2013-01-01

Drug addiction can be defined by a three-stage cycle – binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation – that involves allostatic changes in the brain reward and stress systems. Two primary sources of reinforcement, positive and negative reinforcement, have been hypothesized to play a role in this allostatic process. The negative emotional state that drives negative reinforcement is hypothesized to derive from dysregulation of key neurochemical elements involved in the brain reward and stress systems. Specific neurochemical elements in these structures include not only decreases in reward system function (within-system opponent processes) but also recruitment of the brain stress systems mediated by corticotropin-releasing factor (CRF) and dynorphin-κ opioid systems in the ventral striatum, extended amygdala, and frontal cortex (both between-system opponent processes). CRF antagonists block anxiety-like responses associated with withdrawal, block increases in reward thresholds produced by withdrawal from drugs of abuse, and block compulsive-like drug taking during extended access. Excessive drug taking also engages the activation of CRF in the medial prefrontal cortex, paralleled by deficits in executive function that may facilitate the transition to compulsive-like responding. Neuropeptide Y, a powerful anti-stress neurotransmitter, has a profile of action on compulsive-like responding for ethanol similar to a CRF1 antagonist. Blockade of the κ opioid system can also block dysphoric-like effects associated with withdrawal from drugs of abuse and block the development of compulsive-like responding during extended access to drugs of abuse, suggesting another powerful brain stress system that contributes to compulsive drug seeking. The loss of reward function and recruitment of brain systems provide a powerful neurochemical basis that drives the compulsivity of addiction. PMID:23914176

The Valgus Inclination of the Tibial Component Increases the Risk of Medial Tibial Condylar Fractures in Unicompartmental Knee Arthroplasty.

PubMed

Inoue, Shinji; Akagi, Masao; Asada, Shigeki; Mori, Shigeshi; Zaima, Hironori; Hashida, Masahiko

2016-09-01

Medial tibial condylar fractures (MTCFs) are a rare but serious complication after unicompartmental knee arthroplasty. Although some surgical pitfalls have been reported for MTCFs, it is not clear whether the varus/valgus tibial inclination contributes to the risk of MTCFs. We constructed a 3-dimensional finite elemental method model of the tibia with a medial component and assessed stress concentrations by changing the inclination from 6° varus to 6° valgus. Subsequently, we repeated the same procedure adding extended sagittal bone cuts of 2° and 10° in the posterior tibial cortex. Furthermore, we calculated the bone volume that supported the tibial component, which is considered to affect stress distribution in the medial tibial condyle. Stress concentrations were observed on the medial tibial metaphyseal cortices and on the anterior and posterior tibial cortices in the corner of cut surfaces in all models; moreover, the maximum principal stresses on the posterior cortex were larger than those on the anterior cortex. The extended sagittal bone cuts in the posterior tibial cortex increased the stresses further at these 3 sites. In the models with a 10° extended sagittal bone cut, the maximum principal stress on the posterior cortex increased as the tibial inclination changed from 6° varus to 6° valgus. The bone volume decreased as the inclination changed from varus to valgus. In this finite element method, the risk of MTCFs increases with increasing valgus inclination of the tibial component and with increased extension of the sagittal cut in the posterior tibial cortex. Copyright © 2016 Elsevier Inc. All rights reserved.

A Million-Plus Neuron Model of the Hippocampal Dentate Gyrus: Critical Role for Topography in Determining Spatiotemporal Network Dynamics.

PubMed

Hendrickson, Phillip J; Yu, Gene J; Song, Dong; Berger, Theodore W

2016-01-01

This paper describes a million-plus granule cell compartmental model of the rat hippocampal dentate gyrus, including excitatory, perforant path input from the entorhinal cortex, and feedforward and feedback inhibitory input from dentate interneurons. The model includes experimentally determined morphological and biophysical properties of granule cells, together with glutamatergic AMPA-like EPSP and GABAergic GABAA-like IPSP synaptic excitatory and inhibitory inputs, respectively. Each granule cell was composed of approximately 200 compartments having passive and active conductances distributed throughout the somatic and dendritic regions. Modeling excitatory input from the entorhinal cortex was guided by axonal transport studies documenting the topographical organization of projections from subregions of the medial and lateral entorhinal cortex, plus other important details of the distribution of glutamatergic inputs to the dentate gyrus. Information contained within previously published maps of this major hippocampal afferent were systematically converted to scales that allowed the topographical distribution and relative synaptic densities of perforant path inputs to be quantitatively estimated for inclusion in the current model. Results showed that when medial and lateral entorhinal cortical neurons maintained Poisson random firing, dentate granule cells expressed, throughout the million-cell network, a robust nonrandom pattern of spiking best described as a spatiotemporal "clustering." To identify the network property or properties responsible for generating such firing "clusters," we progressively eliminated from the model key mechanisms, such as feedforward and feedback inhibition, intrinsic membrane properties underlying rhythmic burst firing, and/or topographical organization of entorhinal afferents. Findings conclusively identified topographical organization of inputs as the key element responsible for generating a spatiotemporal distribution of clustered firing. These results uncover a functional organization of perforant path afferents to the dentate gyrus not previously recognized: topography-dependent clusters of granule cell activity as "functional units" or "channels" that organize the processing of entorhinal signals. This modeling study also reveals for the first time how a global signal processing feature of a neural network can evolve from one of its underlying structural characteristics.

A Million-Plus Neuron Model of the Hippocampal Dentate Gyrus: Critical Role for Topography in Determining Spatio-Temporal Network Dynamics

PubMed Central

Hendrickson, Phillip J.; Yu, Gene J.; Song, Dong; Berger, Theodore W.

2016-01-01

Goal This manuscript describes a million-plus granule cell compartmental model of the rat hippocampal dentate gyrus, including excitatory, perforant path input from the entorhinal cortex, and feedforward and feedback inhibitory input from dentate interneurons. Methods The model includes experimentally determined morphological and biophysical properties of granule cells, together with glutamatergic AMPA-like EPSP and GABAergic GABAA-like IPSP synaptic excitatory and inhibitory inputs, respectively. Each granule cell was composed of approximately 200 compartments having passive and active conductances distributed throughout the somatic and dendritic regions. Modeling excitatory input from the entorhinal cortex was guided by axonal transport studies documenting the topographical organization of projections from subregions of the medial and lateral entorhinal cortex, plus other important details of the distribution of glutamatergic inputs to the dentate gyrus. Information contained within previously published maps of this major hippocampal afferent were systematically converted to scales that allowed the topographical distribution and relative synaptic densities of perforant path inputs to be quantitatively estimated for inclusion in the current model. Results Results showed that when medial and lateral entorhinal cortical neurons maintained Poisson random firing, dentate granule cells expressed, throughout the million-cell network, a robust, non-random pattern of spiking best described as spatio-temporal “clustering”. To identify the network property or properties responsible for generating such firing “clusters”, we progressively eliminated from the model key mechanisms such as feedforward and feedback inhibition, intrinsic membrane properties underlying rhythmic burst firing, and/or topographical organization of entorhinal afferents. Conclusion Findings conclusively identified topographical organization of inputs as the key element responsible for generating a spatio-temporal distribution of clustered firing. These results uncover a functional organization of perforant path afferents to the dentate gyrus not previously recognized: topography-dependent clusters of granule cell activity as “functional units” or “channels” that organize the processing of entorhinal signals. This modeling study also reveals for the first time how a global signal processing feature of a neural network can evolve from one of its underlying structural characteristics. PMID:26087482

A theoretical and computational framework for mechanics of the cortex

NASA Astrophysics Data System (ADS)

Torres-SáNchez, Alejandro; Arroyo, Marino

The cell cortex is a thin network of actin filaments lying beneath the cell surface of animal cells. Myosin motors exert contractile forces in this network leading to active stresses, which play a key role in processes such as cytokinesis or cell migration. Thus, understanding the mechanics of the cortex is fundamental to understand the mechanics of animal cells. Due to the dynamic remodeling of the actin network, the cortex behaves as a viscoelastic fluid. Furthermore, due to the difference between its thickness (tens of nanometers) and its dimensions (tens of microns), the cortex can be regarded a surface. Thus, we can model the cortex as a viscoelastic fluid, confined to a surface, that generates active stresses. Interestingly, geometric confinement results in the coupling between shape generation and material flows. In this work we present a theoretical framework to model the mechanics of the cortex that couples elasticity, hydrodynamics and force generation. We complement our theoretical description with a computational setting to simulate the resulting non-linear equations. We use this methodology to understand different processes such as asymmetric cell division or experimental probing of the rheology of the cortex We acknowledge the support of the Europen Research Council through Grant ERC CoG-681434.

Ventromedial prefrontal cortex, adding value to autobiographical memories

PubMed Central

Lin, Wen-Jing; Horner, Aidan J.; Burgess, Neil

2016-01-01

The medial prefrontal cortex (mPFC) has been consistently implicated in autobiographical memory recall and decision making. Its function in decision making tasks is believed to relate to value representation, but its function in autobiographical memory recall is not yet clear. We hypothesised that the mPFC represents the subjective value of elements during autobiographical memory retrieval. Using functional magnetic resonance imaging during an autobiographical memory recall task, we found that the blood oxygen level dependent (BOLD) signal in ventromedial prefrontal cortex (vmPFC) was parametrically modulated by the affective values of items in participants’ memories when they were recalling and evaluating these items. An unrelated modulation by the participant’s familiarity with the items was also observed. During retrieval of the event, the BOLD signal in the same region was modulated by the personal significance and emotional intensity of the memory, which was correlated with the values of the items within them. These results support the idea that vmPFC processes self-relevant information, and suggest that it is involved in representing the personal emotional values of the elements comprising autobiographical memories. PMID:27338616

Ventromedial prefrontal cortex, adding value to autobiographical memories.

PubMed

Lin, Wen-Jing; Horner, Aidan J; Burgess, Neil

2016-06-24

The medial prefrontal cortex (mPFC) has been consistently implicated in autobiographical memory recall and decision making. Its function in decision making tasks is believed to relate to value representation, but its function in autobiographical memory recall is not yet clear. We hypothesised that the mPFC represents the subjective value of elements during autobiographical memory retrieval. Using functional magnetic resonance imaging during an autobiographical memory recall task, we found that the blood oxygen level dependent (BOLD) signal in ventromedial prefrontal cortex (vmPFC) was parametrically modulated by the affective values of items in participants' memories when they were recalling and evaluating these items. An unrelated modulation by the participant's familiarity with the items was also observed. During retrieval of the event, the BOLD signal in the same region was modulated by the personal significance and emotional intensity of the memory, which was correlated with the values of the items within them. These results support the idea that vmPFC processes self-relevant information, and suggest that it is involved in representing the personal emotional values of the elements comprising autobiographical memories.

Effects of oxidative stress-induced changes in the actin cytoskeletal structure on myoblast damage under compressive stress: confocal-based cell-specific finite element analysis.

PubMed

Yao, Yifei; Lacroix, Damien; Mak, Arthur F T

2016-12-01

Muscle cells are frequently subjected to both mechanical and oxidative stresses in various physiological and pathological situations. To explore the mechanical mechanism of muscle cell damage under loading and oxidative stresses, we experimentally studied the effects of extrinsic hydrogen peroxides on the actin cytoskeletal structure in C2C12 myoblasts and presented a finite element (FE) analysis of how such changes in the actin cytoskeletal structure affected a myoblast's capability to resist damage under compression. A confocal-based cell-specific FE model was built to parametrically study the effects of stress fiber density, fiber cross-sectional area, fiber tensile prestrain, as well as the elastic moduli of the stress fibers, actin cortex, nucleus and cytoplasm. The results showed that a decrease in the elastic moduli of both the stress fibers and actin cortex could increase the average tensile strain on the actin cortex-membrane structure and reduce the apparent cell elastic modulus. Assuming the cell would die when a certain percentage of membrane elements were strained beyond a threshold, a lower elastic modulus of actin cytoskeleton would compromise the compressive resistance of a myoblast and lead to cell death more readily. This model was used with a Weibull distribution function to successfully describe the extent of myoblasts damaged in a monolayer under compression.

Timing, timing, timing: Fast decoding of object information from intracranial field potentials in human visual cortex

PubMed Central

Liu, Hesheng; Agam, Yigal; Madsen, Joseph R.; Kreiman, Gabriel

2010-01-01

Summary The difficulty of visual recognition stems from the need to achieve high selectivity while maintaining robustness to object transformations within hundreds of milliseconds. Theories of visual recognition differ in whether the neuronal circuits invoke recurrent feedback connections or not. The timing of neurophysiological responses in visual cortex plays a key role in distinguishing between bottom-up and top-down theories. Here we quantified at millisecond resolution the amount of visual information conveyed by intracranial field potentials from 912 electrodes in 11 human subjects. We could decode object category information from human visual cortex in single trials as early as 100 ms post-stimulus. Decoding performance was robust to depth rotation and scale changes. The results suggest that physiological activity in the temporal lobe can account for key properties of visual recognition. The fast decoding in single trials is compatible with feed-forward theories and provides strong constraints for computational models of human vision. PMID:19409272

A Corticothalamic Circuit Model for Sound Identification in Complex Scenes

PubMed Central

Otazu, Gonzalo H.; Leibold, Christian

2011-01-01

The identification of the sound sources present in the environment is essential for the survival of many animals. However, these sounds are not presented in isolation, as natural scenes consist of a superposition of sounds originating from multiple sources. The identification of a source under these circumstances is a complex computational problem that is readily solved by most animals. We present a model of the thalamocortical circuit that performs level-invariant recognition of auditory objects in complex auditory scenes. The circuit identifies the objects present from a large dictionary of possible elements and operates reliably for real sound signals with multiple concurrently active sources. The key model assumption is that the activities of some cortical neurons encode the difference between the observed signal and an internal estimate. Reanalysis of awake auditory cortex recordings revealed neurons with patterns of activity corresponding to such an error signal. PMID:21931668

The prefrontal cortex: categories, concepts and cognition.

PubMed Central

Miller, Earl K; Freedman, David J; Wallis, Jonathan D

2002-01-01

The ability to generalize behaviour-guiding principles and concepts from experience is key to intelligent, goal-directed behaviour. It allows us to deal efficiently with a complex world and to adapt readily to novel situations. We review evidence that the prefrontal cortex-the cortical area that reaches its greatest elaboration in primates-plays a central part in acquiring and representing this information. The prefrontal cortex receives highly processed information from all major forebrain systems, and neurophysiological studies suggest that it synthesizes this into representations of learned task contingencies, concepts and task rules. In short, the prefrontal cortex seems to underlie our internal representations of the 'rules of the game'. This may provide the necessary foundation for the complex behaviour of primates, in whom this structure is most elaborate. PMID:12217179

Cognitive processing in the primary visual cortex: from perception to memory.

PubMed

Supèr, Hans

2002-01-01

The primary visual cortex is the first cortical area of the visual system that receives information from the external visual world. Based on the receptive field characteristics of the neurons in this area, it has been assumed that the primary visual cortex is a pure sensory area extracting basic elements of the visual scene. This information is then subsequently further processed upstream in the higher-order visual areas and provides us with perception and storage of the visual environment. However, recent findings show that such neural implementations are observed in the primary visual cortex. These neural correlates are expressed by the modulated activity of the late response of a neuron to a stimulus, and most likely depend on recurrent interactions between several areas of the visual system. This favors the concept of a distributed nature of visual processing in perceptual organization.

Structural and functional neural correlates of music perception.

PubMed

Limb, Charles J

2006-04-01

This review article highlights state-of-the-art functional neuroimaging studies and demonstrates the novel use of music as a tool for the study of human auditory brain structure and function. Music is a unique auditory stimulus with properties that make it a compelling tool with which to study both human behavior and, more specifically, the neural elements involved in the processing of sound. Functional neuroimaging techniques represent a modern and powerful method of investigation into neural structure and functional correlates in the living organism. These methods have demonstrated a close relationship between the neural processing of music and language, both syntactically and semantically. Greater neural activity and increased volume of gray matter in Heschl's gyrus has been associated with musical aptitude. Activation of Broca's area, a region traditionally considered to subserve language, is important in interpreting whether a note is on or off key. The planum temporale shows asymmetries that are associated with the phenomenon of perfect pitch. Functional imaging studies have also demonstrated activation of primitive emotional centers such as ventral striatum, midbrain, amygdala, orbitofrontal cortex, and ventral medial prefrontal cortex in listeners of moving musical passages. In addition, studies of melody and rhythm perception have elucidated mechanisms of hemispheric specialization. These studies show the power of music and functional neuroimaging to provide singularly useful tools for the study of brain structure and function.

Characterization of postsynaptic calcium signals in the pyramidal neurons of anterior cingulate cortex

PubMed Central

Li, Xu-Hui; Song, Qian; Chen, Tao; Zhuo, Min

2017-01-01

Calcium signaling is critical for synaptic transmission and plasticity. N-methyl-D-aspartic acid (NMDA) receptors play a key role in synaptic potentiation in the anterior cingulate cortex. Most previous studies of calcium signaling focus on hippocampal neurons, little is known about the activity-induced calcium signals in the anterior cingulate cortex. In the present study, we show that NMDA receptor-mediated postsynaptic calcium signals induced by different synaptic stimulation in anterior cingulate cortex pyramidal neurons. Single and multi-action potentials evoked significant suprathreshold Ca2+ increases in somas and spines. Both NMDA receptors and voltage-gated calcium channels contributed to this increase. Postsynaptic Ca2+signals were induced by puff-application of glutamate, and a NMDA receptor antagonist AP5 blocked these signals in both somas and spines. Finally, long-term potentiation inducing protocols triggered postsynaptic Ca2+ influx, and these influx were NMDA receptor dependent. Our results provide the first study of calcium signals in the anterior cingulate cortex and demonstrate that NMDA receptors play important roles in postsynaptic calcium signals in anterior cingulate cortex pyramidal neurons. PMID:28726541

Structural brain correlates of unconstrained motor activity in people with schizophrenia.

PubMed

Farrow, Tom F D; Hunter, Michael D; Wilkinson, Iain D; Green, Russell D J; Spence, Sean A

2005-11-01

Avolition affects quality of life in chronic schizophrenia. We investigated the relationship between unconstrained motor activity and the volume of key executive brain regions in 16 male patients with schizophrenia. Wristworn actigraphy monitors were used to record motor activity over a 20 h period. Structural magnetic resonance imaging brain scans were parcellated and individual volumes for anterior cingulate cortex and dorsolateral prefrontal cortex extracted. Patients'total activity was positively correlated with volume of left anterior cingulate cortex. These data suggest that the volume of specific executive structures may affect (quantifiable) motor behaviours, having further implications for models of the 'will' and avolition.

Mapping perception to action in piano practice: a longitudinal DC-EEG study

PubMed Central

Bangert, Marc; Altenmüller, Eckart O

2003-01-01

Background Performing music requires fast auditory and motor processing. Regarding professional musicians, recent brain imaging studies have demonstrated that auditory stimulation produces a co-activation of motor areas, whereas silent tapping of musical phrases evokes a co-activation in auditory regions. Whether this is obtained via a specific cerebral relay station is unclear. Furthermore, the time course of plasticity has not yet been addressed. Results Changes in cortical activation patterns (DC-EEG potentials) induced by short (20 minute) and long term (5 week) piano learning were investigated during auditory and motoric tasks. Two beginner groups were trained. The 'map' group was allowed to learn the standard piano key-to-pitch map. For the 'no-map' group, random assignment of keys to tones prevented such a map. Auditory-sensorimotor EEG co-activity occurred within only 20 minutes. The effect was enhanced after 5-week training, contributing elements of both perception and action to the mental representation of the instrument. The 'map' group demonstrated significant additional activity of right anterior regions. Conclusion We conclude that musical training triggers instant plasticity in the cortex, and that right-hemispheric anterior areas provide an audio-motor interface for the mental representation of the keyboard. PMID:14575529

A network of networks model to study phase synchronization using structural connection matrix of human brain

NASA Astrophysics Data System (ADS)

Ferrari, F. A. S.; Viana, R. L.; Reis, A. S.; Iarosz, K. C.; Caldas, I. L.; Batista, A. M.

2018-04-01

The cerebral cortex plays a key role in complex cortical functions. It can be divided into areas according to their function (motor, sensory and association areas). In this paper, the cerebral cortex is described as a network of networks (cortex network), we consider that each cortical area is composed of a network with small-world property (cortical network). The neurons are assumed to have bursting properties with the dynamics described by the Rulkov model. We study the phase synchronization of the cortex network and the cortical networks. In our simulations, we verify that synchronization in cortex network is not homogeneous. Besides, we focus on the suppression of neural phase synchronization. Synchronization can be related to undesired and pathological abnormal rhythms in the brain. For this reason, we consider the delayed feedback control to suppress the synchronization. We show that delayed feedback control is efficient to suppress synchronous behavior in our network model when an appropriate signal intensity and time delay are defined.

Brain Mechanisms Supporting Discrimination of Sensory Features of Pain: A New Model

PubMed Central

Oshiro, Yoshitetsu; Quevedo, Alexandre S.; McHaffie, John G.; Kraft, Robert A.; Coghill, Robert C.

2010-01-01

Pain can be very intense or only mild, and can be well localized or diffuse. To date, little is known as to how such distinct sensory aspects of noxious stimuli are processed by the human brain. Using functional magnetic resonance imaging and a delayed match-to-sample task, we show that discrimination of pain intensity, a non-spatial aspect of pain, activates a ventrally directed pathway extending bilaterally from the insular cortex to the prefrontal cortex. This activation is distinct from the dorsally-directed activation of the posterior parietal cortex and right dorsolateral prefrontal cortex that occurs during spatial discrimination of pain. Both intensity and spatial discrimination tasks activate highly similar aspects of the anterior cingulate cortex, suggesting that this structure contributes to common elements of the discrimination task such as the monitoring of sensory comparisons and response selection. Taken together, these results provide the foundation for a new model of pain in which bidirectional dorsal and ventral streams preferentially amplify and process distinct sensory features of noxious stimuli according to top-down task demands. PMID:19940188

Switching modes in corticogenesis: mechanisms of neuronal subtype transitions and integration in the cerebral cortex

PubMed Central

Toma, Kenichi; Hanashima, Carina

2015-01-01

Information processing in the cerebral cortex requires the activation of diverse neurons across layers and columns, which are established through the coordinated production of distinct neuronal subtypes and their placement along the three-dimensional axis. Over recent years, our knowledge of the regulatory mechanisms of the specification and integration of neuronal subtypes in the cerebral cortex has progressed rapidly. In this review, we address how the unique cytoarchitecture of the neocortex is established from a limited number of progenitors featuring neuronal identity transitions during development. We further illuminate the molecular mechanisms of the subtype-specific integration of these neurons into the cerebral cortex along the radial and tangential axis, and we discuss these key features to exemplify how neocortical circuit formation accomplishes economical connectivity while maintaining plasticity and evolvability to adapt to environmental changes. PMID:26321900

Serial and Parallel Processing in the Primate Auditory Cortex Revisited

PubMed Central

Recanzone, Gregg H.; Cohen, Yale E.

2009-01-01

Over a decade ago it was proposed that the primate auditory cortex is organized in a serial and parallel manner in which there is a dorsal stream processing spatial information and a ventral stream processing non-spatial information. This organization is similar to the “what”/“where” processing of the primate visual cortex. This review will examine several key studies, primarily electrophysiological, that have tested this hypothesis. We also review several human imaging studies that have attempted to define these processing streams in the human auditory cortex. While there is good evidence that spatial information is processed along a particular series of cortical areas, the support for a non-spatial processing stream is not as strong. Why this should be the case and how to better test this hypothesis is also discussed. PMID:19686779

Chapter 4. Cytomechanics of hair basics of the mechanical stability.

PubMed

Popescu, Crisan; Höcker, Hartwig

2009-01-01

Hair is a complex "cornified" multicellular tissue composed of cuticle and cortex cells mechanically acting as a whole. The cuticle cells overlap and cortex cells interdigitate, all cells being composed of different morphological elements and separated by the cell membrane complex (CMC). The CMC and the morphological elements of the cortex cells, the macrofibrils, composed of microfibrils or intermediate filaments (IFs), and the intermacrofibrillar and intermicrofibrillar cement or the amorphous matrix material determine the mechanical properties of hair. The IFs consist of alpha-keratin molecules being arranged in a sophisticated way of two parallel monomers and antiparallel and shifted dimers rationalized by the amino acid composition and sequence. The mechanical properties of hair result from mechanical interlocking effects, hydrophobic effects, hydrogen bridges, Coulombic interactions, and (covalent) isodipeptide and, in particular, disulfide bridges on a molecular level. The mechanical models applied to hair are based on a simple two-component system, the microfibril/matrix structure. An important regime of the stress-strain curve is the transition of the molecules of the microfibrils from the alpha-helical to the beta-sheet structure. Due to the longitudinal orientation of the IF molecules the longitudinal swelling of the fibers in water is negligible, the radial swelling, however, is substantial.

Alkali metals levels in the human brain tissue: Anatomical region differences and age-related changes.

PubMed

Ramos, Patrícia; Santos, Agostinho; Pinto, Edgar; Pinto, Nair Rosas; Mendes, Ricardo; Magalhães, Teresa; Almeida, Agostinho

2016-12-01

The link between trace elements imbalances (both "toxic" and "essential") in the human brain and neurodegenerative disease has been subject of extensive research. More recently, some studies have highlighted the potential role of the homeostasis deregulation of alkali metals in specific brain regions as key factor in the pathogenesis of neurodegenerative diseases such as multiple sclerosis and Alzheimer's disease. Using flame atomic emission spectrometry and inductively coupled plasma-mass spectrometry after microwave-assisted acid digestion of the samples, alkali metals (Na, K, Li, Rb and Cs) were determined in 14 different areas of the human brain (frontal cortex, superior and middle temporal gyri, caudate nucleus, putamen, globus pallidus, cingulated gyrus, hippocampus, inferior parietal lobule, visual cortex of the occipital lobe, midbrain, pons, medulla and cerebellum) of adult individuals (n=42; 71±12, range: 50-101 years old) with no known history and evidence of neurodegenerative, neurological or psychiatric disorder. Potassium was found as the most abundant alkali metal, followed by Na, Rb, Cs and Li. Lithium, K and Cs distribution showed to be quite heterogeneous. On the contrary, Rb and Na appeared quite homogeneously distributed within the human brain tissue. The lowest levels of Na, K, Rb and Li were found in the brainstem (midbrain, medulla and pons) and cerebellum, while the lowest levels of Cs were found in the frontal cortex. The highest levels of K (mean±sd; range 15.5±2.5; 8.9-21.8mg/g) Rb (17.2±6.1; 3.9-32.4μg/g and Cs (83.4±48.6; 17.3-220.5ng/g) were found in putamen. The highest levels of Na and Li were found in the frontal cortex (11.6±2.4; 6.6-17.1mg/g) and caudate nucleus (7.6±4.6 2.2-21.3ng/g), respectively. Although K, Cs and Li levels appear to remain largely unchanged with age, some age-related changes were observed for Na and Rb levels in particular brain regions (namely in the hippocampus). Copyright © 2016 Elsevier GmbH. All rights reserved.

Increased Expression of Brain-Derived Neurotrophic Factor Transcripts I and VI, cAMP Response Element Binding, and Glucocorticoid Receptor in the Cortex of Patients with Temporal Lobe Epilepsy.

PubMed

Martínez-Levy, G A; Rocha, L; Rodríguez-Pineda, F; Alonso-Vanegas, M A; Nani, A; Buentello-García, R M; Briones-Velasco, M; San-Juan, D; Cienfuegos, J; Cruz-Fuentes, C S

2018-05-01

A body of evidence supports a relevant role of brain-derived neurotrophic factor (BDNF) in temporal lobe epilepsy (TLE). Magnetic resonance data reveal that the cerebral atrophy extends to regions that are functionally and anatomically connected with the hippocampus, especially the temporal cortex. We previously reported an increased expression of BDNF messenger for the exon VI in the hippocampus of temporal lobe epilepsy patients compared to an autopsy control group. Altered levels of this particular transcript were also associated with pre-surgical use of certain psychotropic. We extended here our analysis of transcripts I, II, IV, and VI to the temporal cortex since this cerebral region holds intrinsic communication with the hippocampus and is structurally affected in patients with TLE. We also assayed the cyclic adenosine monophosphate response element-binding (CREB) and glucocorticoid receptor (GR) genes as there is experimental evidence of changes in their expression associated with BDNF and epilepsy. TLE and pre-surgical pharmacological treatment were considered as the primary clinical independent variables. Transcripts BDNF I and BDNF VI increased in the temporal cortex of patients with pharmacoresistant TLE. The expression of CREB and GR expression follow the same direction. Pre-surgical use of selective serotonin reuptake inhibitors, carbamazepine (CBZ) and valproate (VPA), was associated with the differential expression of specific BDNF transcripts and CREB and GR genes. These changes could have functional implication in the plasticity mechanisms related to temporal lobe epilepsy.

Does ventrolateral prefrontal cortex help in searching for the lost key? Evidence from an fNIRS study.

PubMed

Carrieri, Marika; Lancia, Stefania; Bocchi, Alessia; Ferrari, Marco; Piccardi, Laura; Quaresima, Valentina

2018-06-01

The Key Search Task (KST) is a neuropsychological test that requires strategies for searching a lost key in an imaginary field. This request may involve different cognitive processes as mental imagery and navigation planning. This study was aimed at investigating, by a twenty-channel functional near-infrared spectroscopy (fNIRS) system, the hemodynamic response (i.e., oxygenated-hemoglobin (O 2 Hb) and deoxygenated-hemoglobin (HHb) changes) of the prefrontal cortex in navigation planning. A right ventrolateral prefrontal cortex (rVLPFC) activation during the KST was hypothesized. Thirty-eight volunteers performed the KST and a Control Task (CT), the latter requiring the volunteers to mark the X letter. An activation (i.e., increase/decrease in O 2 Hb/HHb) of: 1) rVLPFC during the KST execution, and 2) bilateral dorsolateral prefrontal cortex (DLPFC) during the CT execution was found. The present study provides a contribution in localizing the rVLPFC as the critically active region, within the frontal lobes, that was found maximally activated during mental navigation in the mind's eye of healthy participants while performing the KST. Considering the contribution of rVLPFC in spatial navigation, its activation suggests that the KST could be adopted in the clinical routine for investigating navigation planning. Compared to other neuroimaging techniques, fNIRS (with its relatively low physical constraints) contributes to better clarifying the role of rVLPFC in some aspects of human navigation. Therefore, the combined use of the fNIRS and the KST could be considered as an innovative and valid tool to evaluate fundamental functions for everyday life, such as spatial navigation planning.

Spatial embedding of structural similarity in the cerebral cortex

PubMed Central

Song, H. Francis; Kennedy, Henry; Wang, Xiao-Jing

2014-01-01

Recent anatomical tracing studies have yielded substantial amounts of data on the areal connectivity underlying distributed processing in cortex, yet the fundamental principles that govern the large-scale organization of cortex remain unknown. Here we show that functional similarity between areas as defined by the pattern of shared inputs or outputs is a key to understanding the areal network of cortex. In particular, we report a systematic relation in the monkey, human, and mouse cortex between the occurrence of connections from one area to another and their similarity distance. This characteristic relation is rooted in the wiring distance dependence of connections in the brain. We introduce a weighted, spatially embedded random network model that robustly gives rise to this structure, as well as many other spatial and topological properties observed in cortex. These include features that were not accounted for in any previous model, such as the wide range of interareal connection weights. Connections in the model emerge from an underlying distribution of spatially embedded axons, thereby integrating the two scales of cortical connectivity—individual axons and interareal pathways—into a common geometric framework. These results provide insights into the origin of large-scale connectivity in cortex and have important implications for theories of cortical organization. PMID:25368200

Ventromedial prefrontal and anterior cingulate cortex adopt choice and default reference frames during sequential multialternative choice

PubMed Central

Boorman, Erie D; Rushworth, Matthew F; Behrens, Tim E

2013-01-01

Although damage to medial frontal cortex causes profound decision-making impairments, it has been difficult to pinpoint the relative contributions of key anatomical subdivisions. Here we use fMRI to examine the contributions of human ventromedial prefrontal cortex (vmPFC) and dorsal anterior cingulate cortex (dACC) during sequential choices between multiple alternatives – two key features of choices made in ecological settings. By carefully constructing options whose current value at any given decision was dissociable from their longer-term value, we were able to examine choices in current and long-term frames of reference. We present evidence showing that activity at choice and feedback in vmPFC and dACC was tied to the current choice and the best long-term option, respectively. vmPFC, mid-cingulate, and PCC encoded the relative value between the chosen and next-best option at each sequential decision, whereas dACC encoded the relative value of adapting choices from the option with the highest value in the longer-term. Furthermore, at feedback we identify temporally dissociable effects that predict repetition of the current choice and adaptation away from the long-term best option in vmPFC and dACC, respectively. These functional dissociations at choice and feedback suggest that sequential choices are subject to competing cortical mechanisms. PMID:23392656

Brain activity in the right-frontal pole and lateral occipital cortex predicts successful post-operatory outcome after surgery for anterior glenoumeral instability.

PubMed

Zanchi, Davide; Cunningham, Gregory; Lädermann, Alexandre; Ozturk, Mehmet; Hoffmeyer, Pierre; Haller, Sven

2017-03-29

Shoulder apprehension is more complex than a pure mechanical problem of the shoulder, creating a scar at the brain level that prevents the performance of specific movements. Surgery corrects for shoulder instability at the physical level, but a re-dislocation within the first year is rather common. Predicting which patient will be likely to have re-dislocation is therefore crucial. We hypothesized that the assessment of neural activity at baseline and follow-up is the key factor to predict the post-operatory outcome. 13 patients with shoulder apprehension (30.03 ± 7.64 years) underwent clinical and fMRI examination before and one year after surgery for shoulder dislocation contrasting apprehension cue videos and control videos. Data analyses included task-related general linear model (GLM) and correlations imaging results with clinical scores. Clinical examination showed decreased pain and increased shoulder functions for post-op vs. pre-op. Coherently, GLM results show decreased activation of the left pre-motor cortex for post-surgery vs. pre-surgery. Right-frontal pole and right-occipital cortex activity predicts good recovery of shoulder function measured by STT. Our findings demonstrate that beside physical changes, changes at the brain level also occur one year after surgery. In particular, decreased activity in pre-motor and orbito-frontal cortex is key factor for a successful post-operatory outcome.

The Responsive Amygdala: Treatment-induced Alterations in Functional Connectivity in Pediatric Complex Regional Pain Syndrome

PubMed Central

Simons, LE; Pielech, M; Erpelding, N; Linnman, C; Moulton, E; Sava, S; Lebel, A; Serrano, P; Sethna, N; Berde, C; Becerra, L; Borsook, D

2014-01-01

The amygdala is a key brain region with efferent and afferent neural connections that involve complex behaviors such as pain, reward, fear and anxiety. This study evaluated resting state functional connectivity of the amygdala with cortical and subcortical regions in a group of chronic pain patients (pediatric complex regional pain syndrome) with age-gender matched controls before and after intensive physical-biobehavioral pain treatment. Our main findings include (1) enhanced functional connectivity from the amygdala to multiple cortical, subcortical, and cerebellar regions in patients compared to controls, with differences predominantly in the left amygdala in the pre-treated condition (disease state); (2) dampened hyperconnectivity from the left amygdala to the motor cortex, parietal lobe, and cingulate cortex after intensive pain rehabilitation treatment within patients with nominal differences observed among healthy controls from Time 1 to Time 2 (treatment effects); (3) functional connectivity to several regions key to fear circuitry (prefrontal cortex, bilateral middle temporal lobe, bilateral cingulate, hippocampus) correlated with higher pain-related fear scores and (4) decreases in pain-related fear associated with decreased connectivity between the amygdala and the motor and somatosensory cortex, cingulate, and frontal areas. Our data suggest that there are rapid changes in amygdala connectivity following an aggressive treatment program in children with chronic pain and intrinsic amygdala functional connectivity activity serving as a potential indicator of treatment response. PMID:24861582

Copper localization, elemental content, and thallus colour in the copper hyperaccumulator lichen Lecanora sierrae from California

USGS Publications Warehouse

Purvis, O.W.; Bennett, J.P.; Spratt, J.

2011-01-01

An unusual dark blue-green lichen, Lecanora sierrae, was discovered over 30 years ago by Czehura near copper mines in the Lights Creek District, Plumas County, Northern California. Using atomic absorption spectroscopy, Czehura found that dark green lichen samples from Warren Canyon contained 4% Cu in ash and suggested that its colour was due to copper accumulation in the cortex. The present study addressed the hypothesis that the green colour in similar material we sampled from Warren Canyon in 2008, is caused by copper localization in the thallus. Optical microscopy and electron microprobe analysis of specimens of L. sierrae confirmed that copper localization took place in the cortex. Elemental analyses of L. sierrae and three other species from the same localities showed high enrichments of copper and selenium, suggesting that copper selenates or selenites might occur in these lichens and be responsible for the unusual colour. Copyright ?? 2011 British Lichen Society.

Copper localization, elemental content, and thallus colour in the copper hyperaccumulator lichen Lecanora sierra from California

USGS Publications Warehouse

Purvis, O.W.; Bennett, J.P.; Spratt, J.

2011-01-01

An unusual dark blue-green lichen, Lecanora sierrae, was discovered over 30 years ago by Czehura near copper mines in the Lights Creek District, Plumas County, Northern California. Using atomic absorption spectroscopy, Czehura found that dark green lichen samples from Warren Canyon contained 4% Cu in ash and suggested that its colour was due to copper accumulation in the cortex. The present study addressed the hypothesis that the green colour in similar material we sampled from Warren Canyon in 2008, is caused by copper localization in the thallus. Optical microscopy and electron microprobe analysis of specimens of L. sierrae confirmed that copper localization took place in the cortex. Elemental analyses of L. sierrae and three other species from the same localities showed high enrichments of copper and selenium, suggesting that copper selenates or selenites might occur in these lichens and be responsible for the unusual colour.

Mineral element correlation with adenohypophyseal-adrenal cortex function and stress.

PubMed

Flynn, A; Pories, W J; Strain, W H; Hill, O A

1971-09-10

A statistical correlationl was made between adrenocorticotropin (ACTH) and four elements in rats under control, stress, and stress-recovery conditions. Blood serum zinc showed a strong positive correlation with the rise in ACTH during stress and its decline in stress recovery. Serum calcium, copper, and magnesium demonstrated little correlation with ACTH changes. The strong ACTH-zinc correlation points to an as yet undefined interaction between ACTH and zinc

Mechanical strength assessment of a drilled hole in the contralateral cortex at the end of the open wedge for high tibial osteotomy.

PubMed

Diffo Kaze, Arnaud; Maas, Stefan; Hoffmann, Alexander; Pape, Dietrich

2017-12-01

This study aimed to investigate, by means of finite element analysis, the effect of a drill hole at the end of a horizontal osteotomy to reduce the risk of lateral cortex fracture while performing an opening wedge high tibial osteotomy (OWHTO). The question was whether drilling a hole relieves stress and increases the maximum correction angle without fracture of the lateral cortex depending on the ductility of the cortical bone. Two different types of osteotomy cuts were considered; one with a drill hole (diameter 5 mm) and the other without the hole. The drill holes were located about 20 mm distally to the tibial plateau and 6 mm medially to the lateral cortex, such that the minimal thickness of the contralateral cortical bone was 5 mm. Based on finite element calculations, two approaches were used to compare the two types of osteotomy cuts considered: (1) Assessing the static strength using local stresses following the idea of the FKM-guideline, subsequently referred to as the "FKM approach" and (2) limiting the total strain during the opening of the osteotomy wedge, subsequently referred to as "strain approach". A critical opening angle leading to crack initiation in the opposite lateral cortex was determined for each approach and was defined as comparative parameter. The relation to bone aging was investigated by considering the material parameters of cortical bones from young and old subjects. The maximum equivalent (von-Mises) stress was smaller for the cases with a drill hole at the end of the osteotomy cut. The critical angle was approximately 1.5 times higher for the specimens with a drill hole compared to those without. This corresponds to an average increase of 50%. The calculated critical angle for all approaches is below 5°. The critical angle depends on the used approach, on patient's age and assumed ductility of the cortical bone. Drilling a hole at the end of the osteotomy reduces the stresses in the lateral cortex and increases the critical opening angle prior to cracking of the opposite cortex in specimen with small correction angles. But the difference from having a drill hole or not is not so significant, especially for older patients. The ductility of the cortical bone is the decisive parameter for the critical opening angle.

Further evidence for the impact of a genome-wide-supported psychosis risk variant in ZNF804A on the Theory of Mind Network.

PubMed

Mohnke, Sebastian; Erk, Susanne; Schnell, Knut; Schütz, Claudia; Romanczuk-Seiferth, Nina; Grimm, Oliver; Haddad, Leila; Pöhland, Lydia; Garbusow, Maria; Schmitgen, Mike M; Kirsch, Peter; Esslinger, Christine; Rietschel, Marcella; Witt, Stephanie H; Nöthen, Markus M; Cichon, Sven; Mattheisen, Manuel; Mühleisen, Thomas; Jensen, Jimmy; Schott, Björn H; Maier, Wolfgang; Heinz, Andreas; Meyer-Lindenberg, Andreas; Walter, Henrik

2014-04-01

The single-nucleotide polymorphism (SNP) rs1344706 in ZNF804A is one of the best-supported risk variants for psychosis. We hypothesized that this SNP contributes to the development of schizophrenia by affecting the ability to understand other people's mental states. This skill, commonly referred to as Theory of Mind (ToM), has consistently been found to be impaired in schizophrenia. Using functional magnetic resonance imaging, we previously showed that in healthy individuals rs1344706 impacted on activity and connectivity of key areas of the ToM network, including the dorsomedial prefrontal cortex, temporo-parietal junction, and the posterior cingulate cortex, which show aberrant activity in schizophrenia patients, too. We aimed to replicate these results in an independent sample of 188 healthy German volunteers. In order to assess the reliability of brain activity elicited by the ToM task, 25 participants performed the task twice with an interval of 14 days showing excellent accordance in recruitment of key ToM areas. Confirming our previous results, we observed decreasing activity of the left temporo-parietal junction, dorsomedial prefrontal cortex, and the posterior cingulate cortex with increasing number of risk alleles during ToM. Complementing our replication sample with the discovery sample, analyzed in a previous report (total N=297), further revealed negative genotype effects in the left dorsomedial prefrontal cortex as well as in the temporal and parietal regions. In addition, as shown previously, rs1344706 risk allele dose positively predicted increased frontal-temporo-parietal connectivity. These findings confirm the effects of the psychosis risk variant in ZNF804A on the dysfunction of the ToM network.

Further Evidence for the Impact of a Genome-Wide-Supported Psychosis Risk Variant in ZNF804A on the Theory of Mind Network

PubMed Central

Mohnke, Sebastian; Erk, Susanne; Schnell, Knut; Schütz, Claudia; Romanczuk-Seiferth, Nina; Grimm, Oliver; Haddad, Leila; Pöhland, Lydia; Garbusow, Maria; Schmitgen, Mike M; Kirsch, Peter; Esslinger, Christine; Rietschel, Marcella; Witt, Stephanie H; Nöthen, Markus M; Cichon, Sven; Mattheisen, Manuel; Mühleisen, Thomas; Jensen, Jimmy; Schott, Björn H; Maier, Wolfgang; Heinz, Andreas; Meyer-Lindenberg, Andreas; Walter, Henrik

2014-01-01

The single-nucleotide polymorphism (SNP) rs1344706 in ZNF804A is one of the best-supported risk variants for psychosis. We hypothesized that this SNP contributes to the development of schizophrenia by affecting the ability to understand other people's mental states. This skill, commonly referred to as Theory of Mind (ToM), has consistently been found to be impaired in schizophrenia. Using functional magnetic resonance imaging, we previously showed that in healthy individuals rs1344706 impacted on activity and connectivity of key areas of the ToM network, including the dorsomedial prefrontal cortex, temporo-parietal junction, and the posterior cingulate cortex, which show aberrant activity in schizophrenia patients, too. We aimed to replicate these results in an independent sample of 188 healthy German volunteers. In order to assess the reliability of brain activity elicited by the ToM task, 25 participants performed the task twice with an interval of 14 days showing excellent accordance in recruitment of key ToM areas. Confirming our previous results, we observed decreasing activity of the left temporo-parietal junction, dorsomedial prefrontal cortex, and the posterior cingulate cortex with increasing number of risk alleles during ToM. Complementing our replication sample with the discovery sample, analyzed in a previous report (total N=297), further revealed negative genotype effects in the left dorsomedial prefrontal cortex as well as in the temporal and parietal regions. In addition, as shown previously, rs1344706 risk allele dose positively predicted increased frontal–temporo-parietal connectivity. These findings confirm the effects of the psychosis risk variant in ZNF804A on the dysfunction of the ToM network. PMID:24247043

Decreased GABA receptor in the cerebral cortex of epileptic rats: effect of Bacopa monnieri and Bacoside-A.

PubMed

Mathew, Jobin; Balakrishnan, Savitha; Antony, Sherin; Abraham, Pretty Mary; Paulose, C S

2012-02-24

Gamma amino butyric acid (GABA), the principal inhibitory neurotransmitter in the cerebral cortex, maintains the inhibitory tones that counter balances neuronal excitation. When this balance is perturbed, seizures may ensue. In the present study, alterations of the general GABA, GABAA and GABAB receptors in the cerebral cortex of the epileptic rat and the therapeutic application of Bacopa monnieri were investigated. Scatchard analysis of [3H]GABA, [3H]bicuculline and [3H]baclofen in the cerebral cortex of the epileptic rat showed significant decrease in Bmax (P < 0.001) compared to control. Real Time PCR amplification of GABA receptor subunits such as GABAAά1, GABAAγ, GABAAδ, GABAB and GAD where down regulated (P < 0.001) in epileptic rats. GABAAά5 subunit and Cyclic AMP responsible element binding protein were up regulated. Confocal imaging study confirmed the decreased GABA receptors in epileptic rats. Epileptic rats have deficit in radial arm and Y maze performance. Bacopa monnieri and Bacoside-A treatment reverses epilepsy associated changes to near control suggesting that decreased GABA receptors in the cerebral cortex have an important role in epileptic occurrence; Bacopa monnieri and Bacoside-A have therapeutic application in epilepsy management.

Neural basis for generalized quantifier comprehension.

PubMed

McMillan, Corey T; Clark, Robin; Moore, Peachie; Devita, Christian; Grossman, Murray

2005-01-01

Generalized quantifiers like "all cars" are semantically well understood, yet we know little about their neural representation. Our model of quantifier processing includes a numerosity device, operations that combine number elements and working memory. Semantic theory posits two types of quantifiers: first-order quantifiers identify a number state (e.g. "at least 3") and higher-order quantifiers additionally require maintaining a number state actively in working memory for comparison with another state (e.g. "less than half"). We used BOLD fMRI to test the hypothesis that all quantifiers recruit inferior parietal cortex associated with numerosity, while only higher-order quantifiers recruit prefrontal cortex associated with executive resources like working memory. Our findings showed that first-order and higher-order quantifiers both recruit right inferior parietal cortex, suggesting that a numerosity component contributes to quantifier comprehension. Moreover, only probes of higher-order quantifiers recruited right dorsolateral prefrontal cortex, suggesting involvement of executive resources like working memory. We also observed activation of thalamus and anterior cingulate that may be associated with selective attention. Our findings are consistent with a large-scale neural network centered in frontal and parietal cortex that supports comprehension of generalized quantifiers.

Self-development: integrating cognitive, socioemotional, and neuroimaging perspectives.

PubMed

Pfeifer, Jennifer H; Peake, Shannon J

2012-01-01

This review integrates cognitive, socioemotional, and neuroimaging perspectives on self-development. Neural correlates of key processes implicated in personal and social identity are reported from studies of children, adolescents, and adults, including autobiographical memory, direct and reflected self-appraisals, and social exclusion. While cortical midline structures of medial prefrontal cortex and medial posterior parietal cortex are consistently identified in neuroimaging studies considering personal identity from a primarily cognitive perspective ("who am I?"), additional regions are implicated by studies considering personal and social identity from a more socioemotional perspective ("what do others think about me, where do I fit in?"), especially in child or adolescent samples. The involvement of these additional regions (including tempo-parietal junction and posterior superior temporal sulcus, temporal poles, anterior insula, ventral striatum, anterior cingulate cortex, middle cingulate cortex, and ventrolateral prefrontal cortex) suggests mentalizing, emotion, and emotion regulation are central to self-development. In addition, these regions appear to function atypically during personal and social identity tasks in autism and depression, exhibiting a broad pattern of hypoactivation and hyperactivation, respectively. Copyright © 2011 Elsevier Ltd. All rights reserved.

Neurons in the Frontal Lobe Encode the Value of Multiple Decision Variables

PubMed Central

Kennerley, Steven W.; Dahmubed, Aspandiar F.; Lara, Antonio H.; Wallis, Jonathan D.

2009-01-01

A central question in behavioral science is how we select among choice alternatives to obtain consistently the most beneficial outcomes. Three variables are particularly important when making a decision: the potential payoff, the probability of success, and the cost in terms of time and effort. A key brain region in decision making is the frontal cortex as damage here impairs the ability to make optimal choices across a range of decision types. We simultaneously recorded the activity of multiple single neurons in the frontal cortex while subjects made choices involving the three aforementioned decision variables. This enabled us to contrast the relative contribution of the anterior cingulate cortex (ACC), the orbito-frontal cortex, and the lateral prefrontal cortex to the decision-making process. Neurons in all three areas encoded value relating to choices involving probability, payoff, or cost manipulations. However, the most significant signals were in the ACC, where neurons encoded multiplexed representations of the three different decision variables. This supports the notion that the ACC is an important component of the neural circuitry underlying optimal decision making. PMID:18752411

Connexin31.1 deficiency in the mouse impairs object memory and modulates open-field exploration, acetylcholine esterase levels in the striatum, and cAMP response element-binding protein levels in the striatum and piriform cortex.

PubMed

Dere, E; Zheng-Fischhöfer, Q; Viggiano, D; Gironi Carnevale, U A; Ruocco, L A; Zlomuzica, A; Schnichels, M; Willecke, K; Huston, J P; Sadile, A G

2008-05-02

Neuronal gap junctions in the brain, providing intercellular electrotonic signal transfer, have been implicated in physiological and behavioral correlates of learning and memory. In connexin31.1 (Cx31.1) knockout (KO) mice the coding region of the Cx31.1 gene was replaced by a LacZ reporter gene. We investigated the impact of Cx31.1 deficiency on open-field exploration, the behavioral response to an odor, non-selective attention, learning and memory performance, and the levels of memory-related proteins in the hippocampus, striatum and the piriform cortex. In terms of behavior, the deletion of the Cx31.1 coding DNA in the mouse led to increased exploratory behaviors in a novel environment, and impaired one-trial object recognition at all delays tested. Despite strong Cx31.1 expression in the peripheral and central olfactory system, Cx31.1 KO mice exhibited normal behavioral responses to an odor. We found increased levels of acetylcholine esterase (AChE) and cAMP response element-binding protein (CREB) in the striatum of Cx31.1 KO mice. In the piriform cortex the Cx31.1 KO mice had an increased heterogeneity of CREB expression among neurons. In conclusion, gap-junctions featuring the Cx31.1 protein might be involved in open-field exploration as well as object memory and modulate levels of AChE and CREB in the striatum and piriform cortex.

An analysis of nonlinear dynamics underlying neural activity related to auditory induction in the rat auditory cortex.

PubMed

Noto, M; Nishikawa, J; Tateno, T

2016-03-24

A sound interrupted by silence is perceived as discontinuous. However, when high-intensity noise is inserted during the silence, the missing sound may be perceptually restored and be heard as uninterrupted. This illusory phenomenon is called auditory induction. Recent electrophysiological studies have revealed that auditory induction is associated with the primary auditory cortex (A1). Although experimental evidence has been accumulating, the neural mechanisms underlying auditory induction in A1 neurons are poorly understood. To elucidate this, we used both experimental and computational approaches. First, using an optical imaging method, we characterized population responses across auditory cortical fields to sound and identified five subfields in rats. Next, we examined neural population activity related to auditory induction with high temporal and spatial resolution in the rat auditory cortex (AC), including the A1 and several other AC subfields. Our imaging results showed that tone-burst stimuli interrupted by a silent gap elicited early phasic responses to the first tone and similar or smaller responses to the second tone following the gap. In contrast, tone stimuli interrupted by broadband noise (BN), considered to cause auditory induction, considerably suppressed or eliminated responses to the tone following the noise. Additionally, tone-burst stimuli that were interrupted by notched noise centered at the tone frequency, which is considered to decrease the strength of auditory induction, partially restored the second responses from the suppression caused by BN. To phenomenologically mimic the neural population activity in the A1 and thus investigate the mechanisms underlying auditory induction, we constructed a computational model from the periphery through the AC, including a nonlinear dynamical system. The computational model successively reproduced some of the above-mentioned experimental results. Therefore, our results suggest that a nonlinear, self-exciting system is a key element for qualitatively reproducing A1 population activity and to understand the underlying mechanisms. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Sensorimotor Integration by Corticospinal System

PubMed Central

Moreno-López, Yunuen; Olivares-Moreno, Rafael; Cordero-Erausquin, Matilde; Rojas-Piloni, Gerardo

2016-01-01

The corticospinal (CS) tract is a complex system which targets several areas of the spinal cord. In particular, the CS descending projection plays a major role in motor command, which results from direct and indirect control of spinal cord pre-motor interneurons as well as motoneurons. But in addition, this system is also involved in a selective and complex modulation of sensory feedback. Despite recent evidence confirms that CS projections drive distinct segmental neural circuits that are part of the sensory and pre-motor pathways, little is known about the spinal networks engaged by the corticospinal tract (CST), the organization of CS projections, the intracortical microcircuitry, and the synaptic interactions in the sensorimotor cortex (SMC) that may encode different cortical outputs to the spinal cord. Here is stressed the importance of integrated approaches for the study of sensorimotor function of CS system, in order to understand the functional compartmentalization and hierarchical organization of layer 5 output neurons, who are key elements for motor control and hence, of behavior. PMID:27013985

Sensorimotor Integration by Corticospinal System.

PubMed

Moreno-López, Yunuen; Olivares-Moreno, Rafael; Cordero-Erausquin, Matilde; Rojas-Piloni, Gerardo

2016-01-01

The corticospinal (CS) tract is a complex system which targets several areas of the spinal cord. In particular, the CS descending projection plays a major role in motor command, which results from direct and indirect control of spinal cord pre-motor interneurons as well as motoneurons. But in addition, this system is also involved in a selective and complex modulation of sensory feedback. Despite recent evidence confirms that CS projections drive distinct segmental neural circuits that are part of the sensory and pre-motor pathways, little is known about the spinal networks engaged by the corticospinal tract (CST), the organization of CS projections, the intracortical microcircuitry, and the synaptic interactions in the sensorimotor cortex (SMC) that may encode different cortical outputs to the spinal cord. Here is stressed the importance of integrated approaches for the study of sensorimotor function of CS system, in order to understand the functional compartmentalization and hierarchical organization of layer 5 output neurons, who are key elements for motor control and hence, of behavior.

Imitation, mirror neurons and autism.

PubMed

Williams, J H; Whiten, A; Suddendorf, T; Perrett, D I

2001-06-01

Various deficits in the cognitive functioning of people with autism have been documented in recent years but these provide only partial explanations for the condition. We focus instead on an imitative disturbance involving difficulties both in copying actions and in inhibiting more stereotyped mimicking, such as echolalia. A candidate for the neural basis of this disturbance may be found in a recently discovered class of neurons in frontal cortex, 'mirror neurons' (MNs). These neurons show activity in relation both to specific actions performed by self and matching actions performed by others, providing a potential bridge between minds. MN systems exist in primates without imitative and 'theory of mind' abilities and we suggest that in order for them to have become utilized to perform social cognitive functions, sophisticated cortical neuronal systems have evolved in which MNs function as key elements. Early developmental failures of MN systems are likely to result in a consequent cascade of developmental impairments characterised by the clinical syndrome of autism.

Altered figure-ground perception in monkeys with an extra-striate lesion.

PubMed

Supèr, Hans; Lamme, Victor A F

2007-11-05

The visual system binds and segments the elements of an image into coherent objects and their surroundings. Recent findings demonstrate that primary visual cortex is involved in this process of figure-ground organization. In the primary visual cortex the late part of a neural response to a stimulus correlates with figure-ground segregation and perception. Such a late onset indicates an involvement of feedback projections from higher visual areas. To investigate the possible role of feedback in figure-ground perception we removed dorsal extra-striate areas of the monkey visual cortex. The findings show that figure-ground perception is reduced when the figure is presented in the lesioned hemifield and perception is normal when the figure appeared in the intact hemifield. In conclusion, our observations show the importance for recurrent processing in visual perception.

A decade of decoding reward-related fMRI signals and where we go from here.

PubMed

Kahnt, Thorsten

2017-06-04

Information about potential rewards in the environment is essential for guiding adaptive behavior, and understanding neural reward processes may provide insights into neuropsychiatric dysfunctions. Over the past 10 years, multivoxel pattern analysis (MVPA) techniques have been used to study brain areas encoding information about expected and experienced outcomes. These studies have identified reward signals throughout the brain, including the striatum, medial prefrontal cortex, orbitofrontal cortex, dorsolateral prefrontal cortex, and parietal cortex. This review article discusses some of the assumptions and models that are used to interpret results from these studies, and how they relate to findings from animal electrophysiology. The article reviews and summarizes some of the key findings from MVPA studies on reward. In particular, it first focuses on studies that, in addition to mapping out the brain areas that process rewards, have provided novel insights into the coding mechanisms of value and reward. Then, it discusses examples of how multivariate imaging approaches are being used more recently to decode features of expected rewards that go beyond value, such as the identity of an expected outcome or the action required to obtain it. The study of such complex and multifaceted reward representations highlights the key advantage of using representational methods, which are uniquely able to reveal these signals and may narrow the gap between animal and human research. Applied in a clinical context, MVPA may advance our understanding of neuropsychiatric disorders and the development of novel treatment strategies. Copyright © 2017 Elsevier Inc. All rights reserved.

Reinforcement Learning of Linking and Tracing Contours in Recurrent Neural Networks

PubMed Central

Brosch, Tobias; Neumann, Heiko; Roelfsema, Pieter R.

2015-01-01

The processing of a visual stimulus can be subdivided into a number of stages. Upon stimulus presentation there is an early phase of feedforward processing where the visual information is propagated from lower to higher visual areas for the extraction of basic and complex stimulus features. This is followed by a later phase where horizontal connections within areas and feedback connections from higher areas back to lower areas come into play. In this later phase, image elements that are behaviorally relevant are grouped by Gestalt grouping rules and are labeled in the cortex with enhanced neuronal activity (object-based attention in psychology). Recent neurophysiological studies revealed that reward-based learning influences these recurrent grouping processes, but it is not well understood how rewards train recurrent circuits for perceptual organization. This paper examines the mechanisms for reward-based learning of new grouping rules. We derive a learning rule that can explain how rewards influence the information flow through feedforward, horizontal and feedback connections. We illustrate the efficiency with two tasks that have been used to study the neuronal correlates of perceptual organization in early visual cortex. The first task is called contour-integration and demands the integration of collinear contour elements into an elongated curve. We show how reward-based learning causes an enhancement of the representation of the to-be-grouped elements at early levels of a recurrent neural network, just as is observed in the visual cortex of monkeys. The second task is curve-tracing where the aim is to determine the endpoint of an elongated curve composed of connected image elements. If trained with the new learning rule, neural networks learn to propagate enhanced activity over the curve, in accordance with neurophysiological data. We close the paper with a number of model predictions that can be tested in future neurophysiological and computational studies. PMID:26496502

Memory-guided attention in the anterior thalamus.

PubMed

Leszczyński, Marcin; Staudigl, Tobias

2016-07-01

The anterior thalamus is densely connected with both the hippocampus and the prefrontal cortex. It is known to play a role in learning and episodic memory. Given its connectivity profile with the prefrontal cortex, it may also be expected to contribute to executive functions. Recent studies in both rodents and humans add to our understanding of anterior thalamic function, suggesting that it is a key region for allocating attention. We discuss the convergence between studies in rodents and humans, both of which imply that the anterior thalamus may play a key role in memory-guided attention. We suggest that efficient allocation of attention to memory representations requires interaction between the memory-related hippocampal and the attention related fronto-parietal networks. We further propose that the anterior thalamus is a hub that connects and modulates both systems. Copyright © 2016 Elsevier Ltd. All rights reserved.

A Spiking Working Memory Model Based on Hebbian Short-Term Potentiation.

PubMed

Fiebig, Florian; Lansner, Anders

2017-01-04

A dominant theory of working memory (WM), referred to as the persistent activity hypothesis, holds that recurrently connected neural networks, presumably located in the prefrontal cortex, encode and maintain WM memory items through sustained elevated activity. Reexamination of experimental data has shown that prefrontal cortex activity in single units during delay periods is much more variable than predicted by such a theory and associated computational models. Alternative models of WM maintenance based on synaptic plasticity, such as short-term nonassociative (non-Hebbian) synaptic facilitation, have been suggested but cannot account for encoding of novel associations. Here we test the hypothesis that a recently identified fast-expressing form of Hebbian synaptic plasticity (associative short-term potentiation) is a possible mechanism for WM encoding and maintenance. Our simulations using a spiking neural network model of cortex reproduce a range of cognitive memory effects in the classical multi-item WM task of encoding and immediate free recall of word lists. Memory reactivation in the model occurs in discrete oscillatory bursts rather than as sustained activity. We relate dynamic network activity as well as key synaptic characteristics to electrophysiological measurements. Our findings support the hypothesis that fast Hebbian short-term potentiation is a key WM mechanism. Working memory (WM) is a key component of cognition. Hypotheses about the neural mechanism behind WM are currently under revision. Reflecting recent findings of fast Hebbian synaptic plasticity in cortex, we test whether a cortical spiking neural network model with such a mechanism can learn a multi-item WM task (word list learning). We show that our model can reproduce human cognitive phenomena and achieve comparable memory performance in both free and cued recall while being simultaneously compatible with experimental data on structure, connectivity, and neurophysiology of the underlying cortical tissue. These findings are directly relevant to the ongoing paradigm shift in the WM field. Copyright © 2017 Fiebig and Lansner.

A Spiking Working Memory Model Based on Hebbian Short-Term Potentiation

PubMed Central

Fiebig, Florian

2017-01-01

A dominant theory of working memory (WM), referred to as the persistent activity hypothesis, holds that recurrently connected neural networks, presumably located in the prefrontal cortex, encode and maintain WM memory items through sustained elevated activity. Reexamination of experimental data has shown that prefrontal cortex activity in single units during delay periods is much more variable than predicted by such a theory and associated computational models. Alternative models of WM maintenance based on synaptic plasticity, such as short-term nonassociative (non-Hebbian) synaptic facilitation, have been suggested but cannot account for encoding of novel associations. Here we test the hypothesis that a recently identified fast-expressing form of Hebbian synaptic plasticity (associative short-term potentiation) is a possible mechanism for WM encoding and maintenance. Our simulations using a spiking neural network model of cortex reproduce a range of cognitive memory effects in the classical multi-item WM task of encoding and immediate free recall of word lists. Memory reactivation in the model occurs in discrete oscillatory bursts rather than as sustained activity. We relate dynamic network activity as well as key synaptic characteristics to electrophysiological measurements. Our findings support the hypothesis that fast Hebbian short-term potentiation is a key WM mechanism. SIGNIFICANCE STATEMENT Working memory (WM) is a key component of cognition. Hypotheses about the neural mechanism behind WM are currently under revision. Reflecting recent findings of fast Hebbian synaptic plasticity in cortex, we test whether a cortical spiking neural network model with such a mechanism can learn a multi-item WM task (word list learning). We show that our model can reproduce human cognitive phenomena and achieve comparable memory performance in both free and cued recall while being simultaneously compatible with experimental data on structure, connectivity, and neurophysiology of the underlying cortical tissue. These findings are directly relevant to the ongoing paradigm shift in the WM field. PMID:28053032

Neural Network Cloud Classification Research

DTIC Science & Technology

1993-03-01

analysis of the database made this study possible. We would also like to thank Don Chisolm and Rosemary Dyer for their enlightening discussions and...elements of the model correspond closely to neurophysiological data about the visual cortex. Efficient versions of the BCS and FCS have been

Investigating virtual reality navigation in amnestic mild cognitive impairment using fMRI.

PubMed

Migo, E M; O'Daly, O; Mitterschiffthaler, M; Antonova, E; Dawson, G R; Dourish, C T; Craig, K J; Simmons, A; Wilcock, G K; McCulloch, E; Jackson, S H D; Kopelman, M D; Williams, S C R; Morris, R G

2016-01-01

Spatial navigation requires a well-established network of brain regions, including the hippocampus, caudate nucleus, and retrosplenial cortex. Amnestic Mild Cognitive Impairment (aMCI) is a condition with predominantly memory impairment, conferring a high predictive risk factor for dementia. aMCI is associated with hippocampal atrophy and subtle deficits in spatial navigation. We present the first use of a functional Magnetic Resonance Imaging (fMRI) navigation task in aMCI, using a virtual reality analog of the Radial Arm Maze. Compared with controls, aMCI patients showed reduced activity in the hippocampus bilaterally, retrosplenial cortex, and left dorsolateral prefrontal cortex. Reduced activation in key areas for successful navigation, as well as additional regions, was found alongside relatively normal task performance. Results also revealed increased activity in the right dorsolateral prefrontal cortex in aMCI patients, which may reflect compensation for reduced activations elsewhere. These data support suggestions that fMRI spatial navigation tasks may be useful for staging of progression in MCI.

Local structure of human hair spatially resolved by sub-micron X-ray beam.

PubMed

Stanić, Vesna; Bettini, Jefferson; Montoro, Fabiano Emmanuel; Stein, Aaron; Evans-Lutterodt, Kenneth

2015-11-30

Human hair has three main regions, the medulla, the cortex, and the cuticle. An existing model for the cortex suggests that the α-keratin- based intermediate filaments (IFs) align with the hair's axis, but are orientationally disordered in-plane. We found that there is a new region in the cortex near the cuticle's boundary in which the IFs are aligned with the hair's axis, but additionally, they are orientationally ordered in-plane due to the presence of the cuticle/hair boundary. Further into the cortex, the IF arrangement becomes disordered, eventually losing all in-plane orientation. We also find that in the cuticle, a key diffraction feature is absent, indicating the presence of the β-keratin rather than that of the α-keratin phase. This is direct structural evidence that the cuticle contains β-keratin sheets. This work highlights the importance of using a sub-micron x-ray beam to unravel the structures of poorly ordered, multi-phase systems.

Elaboration of the Visual Pathways from the Study of War-Related Cranial Injuries: The Period from the Russo-Japanese War to World War I.

PubMed

Lanska, Douglas J

2016-01-01

As a result of the wars in the early 20th century, elaboration of the visual pathways was greatly facilitated by the meticulous study of visual defects in soldiers who had suffered focal injuries to the visual cortex. Using relatively crude techniques, often under difficult wartime circumstances, investigators successfully mapped key features of the visual pathways. Studies during the Russo- Japanese War (1904-1905) by Tatsuji Inouye (1881-1976) and during World War I by Gordon Holmes (1876-1965), William Lister (1868-1944), and others produced increasingly refined retinotopic maps of the primary visual cortex, which were later supported and refined by studies during and after World War II. Studies by George Riddoch (1888-1947) during World War I also demonstrated that some patients could still perceive motion despite blindness caused by damage to their visual cortex and helped to establish the concept of functional partitioning of visual processes in the occipital cortex. © 2016 S. Karger AG, Basel.

The gene cortex controls mimicry and crypsis in butterflies and moths.

PubMed

Nadeau, Nicola J; Pardo-Diaz, Carolina; Whibley, Annabel; Supple, Megan A; Saenko, Suzanne V; Wallbank, Richard W R; Wu, Grace C; Maroja, Luana; Ferguson, Laura; Hanly, Joseph J; Hines, Heather; Salazar, Camilo; Merrill, Richard M; Dowling, Andrea J; ffrench-Constant, Richard H; Llaurens, Violaine; Joron, Mathieu; McMillan, W Owen; Jiggins, Chris D

2016-06-02

The wing patterns of butterflies and moths (Lepidoptera) are diverse and striking examples of evolutionary diversification by natural selection. Lepidopteran wing colour patterns are a key innovation, consisting of arrays of coloured scales. We still lack a general understanding of how these patterns are controlled and whether this control shows any commonality across the 160,000 moth and 17,000 butterfly species. Here, we use fine-scale mapping with population genomics and gene expression analyses to identify a gene, cortex, that regulates pattern switches in multiple species across the mimetic radiation in Heliconius butterflies. cortex belongs to a fast-evolving subfamily of the otherwise highly conserved fizzy family of cell-cycle regulators, suggesting that it probably regulates pigmentation patterning by regulating scale cell development. In parallel with findings in the peppered moth (Biston betularia), our results suggest that this mechanism is common within Lepidoptera and that cortex has become a major target for natural selection acting on colour and pattern variation in this group of insects.

You and your kin: Neural signatures of family-based group perception in the subgenual cortex.

PubMed

Rüsch, Nicolas; Bado, Patricia; Zahn, Roland; Bramati, Ivanei E; de Oliveira-Souza, Ricardo; Moll, Jorge

2014-01-01

Attachment to one's kin as an in-group emerges from a fundamental human motivation and is vital for human survival. Despite important recent advances in the field of social neuroscience, the neural mechanisms underlying family-related in-group perception remain obscure. To examine the neural basis of perceiving family-related in-group boundaries in response to written kinship scenarios, we used functional magnetic resonance imaging in 27 healthy adults and obtained self-report ratings of family-related entitativity, which measures to what degree participants perceive their family as a coherent and distinct group in society. We expected that activity in the subgenual cingulate cortex and septo-hypothalamic region would track individual differences in entitativity. Perceiving one's family as a distinct and cohesive group (high entitativity) was associated with increased subgenual cortex response to kinship scenarios. The subgenual cingulate cortex may represent a key link between kin-related emotional attachment and group perception, providing a neurobiological basis for group belongingness.

Volition and conflict in human medial frontal cortex.

PubMed

Nachev, Parashkev; Rees, Geraint; Parton, Andrew; Kennard, Christopher; Husain, Masud

2005-01-26

Controversy surrounds the role of human medial frontal cortex in controlling actions. Although damage to this area leads to severe difficulties in spontaneously initiating actions, the precise mechanisms underlying such "volitional" deficits remain to be established. Previous studies have implicated the medial frontal cortex in conflict monitoring and the control of voluntary action, suggesting that these key processes are functionally related or share neural substrates. Here, we combine a novel behavioral paradigm with functional imaging of the oculomotor system to reveal, for the first time, a functional subdivision of the pre-supplementary motor area (pre-SMA) into anatomically distinct areas that respond exclusively to either volition or conflict. We also demonstrate that activity in the supplementary eye field (SEF) distinguishes between success and failure in changing voluntary action plans during conflict, suggesting a role for the SEF in implementing the resolution of conflicting actions. We propose a functional architecture of human medial frontal cortex that incorporates the generation of action plans and the resolution of conflict.

An Algorithm for Simple and Complex Feature Detection: From Retina to Primary Visual Cortex

DTIC Science & Technology

1993-02-01

the thalamic lateral geniculate nucleus is available in Jones (1985) from which the following relevant details were extracted. The LGN receives...J.C.Horton. (1984). "Receptive field properties in the cat’s area 17 in the advance of on-center geniculate input." Journal of Neuroscience, 4, pp...center element LGN lateral geniculate nucleus of the thalamus 7XO thalamic sustained principal off-center element TXi thalamic sustained principal on

Regional brain responses associated with drinking water during thirst and after its satiation

PubMed Central

Saker, Pascal; Farrell, Michael J.; Adib, Faiz R. M.; Egan, Gary F.; McKinley, Michael J.; Denton, Derek A.

2014-01-01

The instinct of thirst was a cardinal element in the successful colonization by vertebrates of the dry land of the planet, which began in the Ordovician period about 400 million y ago. It is a commonplace experience in humans that drinking water in response to thirst following fluid loss is a pleasant experience. However, continuing to drink water once thirst has been satiated becomes unpleasant and, eventually, quite aversive. Functional MRI experiments reported here show pleasantness of drinking is associated with activation in the anterior cingulate cortex (Brodmann area 32) and the orbitofrontal cortex. The unpleasantness and aversion of overdrinking is associated with activation in the midcingulate cortex, insula, amygdala, and periaqueductal gray. Drinking activations in the putamen and cerebellum also correlated with the unpleasantness of water, and the motor cortex showed increased activation during overdrinking compared with drinking during thirst. These activations in motor regions may possibly reflect volitional effort to conduct compliant drinking in the face of regulatory mechanisms inhibiting intake. The results suggestive of a specific inhibitory system in the control of drinking are unique. PMID:24706817

Regional brain responses associated with drinking water during thirst and after its satiation.

PubMed

Saker, Pascal; Farrell, Michael J; Adib, Faiz R M; Egan, Gary F; McKinley, Michael J; Denton, Derek A

2014-04-08

The instinct of thirst was a cardinal element in the successful colonization by vertebrates of the dry land of the planet, which began in the Ordovician period about 400 million y ago. It is a commonplace experience in humans that drinking water in response to thirst following fluid loss is a pleasant experience. However, continuing to drink water once thirst has been satiated becomes unpleasant and, eventually, quite aversive. Functional MRI experiments reported here show pleasantness of drinking is associated with activation in the anterior cingulate cortex (Brodmann area 32) and the orbitofrontal cortex. The unpleasantness and aversion of overdrinking is associated with activation in the midcingulate cortex, insula, amygdala, and periaqueductal gray. Drinking activations in the putamen and cerebellum also correlated with the unpleasantness of water, and the motor cortex showed increased activation during overdrinking compared with drinking during thirst. These activations in motor regions may possibly reflect volitional effort to conduct compliant drinking in the face of regulatory mechanisms inhibiting intake. The results suggestive of a specific inhibitory system in the control of drinking are unique.

Harmonic template neurons in primate auditory cortex underlying complex sound processing

PubMed Central

Feng, Lei

2017-01-01

Harmonicity is a fundamental element of music, speech, and animal vocalizations. How the auditory system extracts harmonic structures embedded in complex sounds and uses them to form a coherent unitary entity is not fully understood. Despite the prevalence of sounds rich in harmonic structures in our everyday hearing environment, it has remained largely unknown what neural mechanisms are used by the primate auditory cortex to extract these biologically important acoustic structures. In this study, we discovered a unique class of harmonic template neurons in the core region of auditory cortex of a highly vocal New World primate, the common marmoset (Callithrix jacchus), across the entire hearing frequency range. Marmosets have a rich vocal repertoire and a similar hearing range to that of humans. Responses of these neurons show nonlinear facilitation to harmonic complex sounds over inharmonic sounds, selectivity for particular harmonic structures beyond two-tone combinations, and sensitivity to harmonic number and spectral regularity. Our findings suggest that the harmonic template neurons in auditory cortex may play an important role in processing sounds with harmonic structures, such as animal vocalizations, human speech, and music. PMID:28096341

Infralimbic prefrontal cortex interacts with nucleus accumbens shell to unmask expression of outcome-selective Pavlovian-to-instrumental transfer

PubMed Central

Keistler, Colby; Barker, Jacqueline M.

2015-01-01

Although several studies have examined the subcortical circuitry underlying Pavlovian-to-instrumental transfer (PIT), the role of medial prefrontal cortex in this behavior is largely unknown. Elucidating the cortical contributions to PIT will be key for understanding how reward-paired cues control behavior in both adaptive and maladaptive context (i.e., addiction). Here we use bilateral lesions in a rat model to show that infralimbic prefrontal cortex (ilPFC) is necessary for appropriate expression of PIT. Further, we show that ilPFC mediates this effect via functional connectivity with nucleus accumbens shell (NAcS). Together, these data provide the first demonstration that a specific cortico-striatal circuit is necessary for cue-invigorated reward seeking during specific PIT. PMID:26373829

Intelligence moderates reinforcement learning: a mini-review of the neural evidence

PubMed Central

2014-01-01

Our understanding of the neural basis of reinforcement learning and intelligence, two key factors contributing to human strivings, has progressed significantly recently. However, the overlap of these two lines of research, namely, how intelligence affects neural responses during reinforcement learning, remains uninvestigated. A mini-review of three existing studies suggests that higher IQ (especially fluid IQ) may enhance the neural signal of positive prediction error in dorsolateral prefrontal cortex, dorsal anterior cingulate cortex, and striatum, several brain substrates of reinforcement learning or intelligence. PMID:25185818

Intelligence moderates reinforcement learning: a mini-review of the neural evidence.

PubMed

Chen, Chong

2015-06-01

Our understanding of the neural basis of reinforcement learning and intelligence, two key factors contributing to human strivings, has progressed significantly recently. However, the overlap of these two lines of research, namely, how intelligence affects neural responses during reinforcement learning, remains uninvestigated. A mini-review of three existing studies suggests that higher IQ (especially fluid IQ) may enhance the neural signal of positive prediction error in dorsolateral prefrontal cortex, dorsal anterior cingulate cortex, and striatum, several brain substrates of reinforcement learning or intelligence. Copyright © 2015 the American Physiological Society.

Decreased GABA receptor in the cerebral cortex of epileptic rats: effect of Bacopa monnieri and Bacoside-A

PubMed Central

2012-01-01

Abstact Background Gamma amino butyric acid (GABA), the principal inhibitory neurotransmitter in the cerebral cortex, maintains the inhibitory tones that counter balances neuronal excitation. When this balance is perturbed, seizures may ensue. Methods In the present study, alterations of the general GABA, GABAA and GABAB receptors in the cerebral cortex of the epileptic rat and the therapeutic application of Bacopa monnieri were investigated. Results Scatchard analysis of [3H]GABA, [3H]bicuculline and [3H]baclofen in the cerebral cortex of the epileptic rat showed significant decrease in Bmax (P < 0.001) compared to control. Real Time PCR amplification of GABA receptor subunits such as GABAAά1, GABAAγ, GABAAδ, GABAB and GAD where down regulated (P < 0.001) in epileptic rats. GABAAά5 subunit and Cyclic AMP responsible element binding protein were up regulated. Confocal imaging study confirmed the decreased GABA receptors in epileptic rats. Epileptic rats have deficit in radial arm and Y maze performance. Conclusions Bacopa monnieri and Bacoside-A treatment reverses epilepsy associated changes to near control suggesting that decreased GABA receptors in the cerebral cortex have an important role in epileptic occurrence; Bacopa monnieri and Bacoside-A have therapeutic application in epilepsy management. PMID:22364254

Assessment of Traumatic Brain Injury by Increased 64Cu Uptake on 64CuCl2 PET/CT

PubMed Central

Peng, Fangyu; Muzik, Otto; Gatson, Joshua; Kernie, Steven G.; Diaz-Arrastia, Ramon

2015-01-01

Copper is a nutritional trace element required for cell proliferation and wound repair. Methods To explore increased copper uptake as a biomarker for noninvasive assessment of traumatic brain injury (TBI), experimental TBI in C57BL/6 mice was induced by controlled cortical impact, and 64Cu uptake in the injured cortex was assessed with 64CuCl2 PET/CT. Results At 24 h after intravenous injection of the tracer, uptake was significantly higher in the injured cortex of TBI mice (1.15 ± 0.53 percentage injected dose per gram of tissue [%ID/g]) than in the uninjured cortex of mice without TBI (0.53 ± 0.07 %ID/g, P = 0.027) or the cortex of mice that received an intracortical injection of zymosan A (0.62 ± 0.22 %ID/g, P = 0.025). Furthermore, uptake in the traumatized cortex of untreated TBI mice (1.15 ± 0.53 %ID/g) did not significantly differ from that in minocycline-treated TBI mice (0.93 ± 0.30 %ID/g, P = 0.33). Conclusion Overall, the data suggest that increased 64Cu uptake in traumatized brain tissues holds potential as a new biomarker for noninvasive assessment of TBI with 64CuCl2 PET/CT. PMID:26112025

Motor cortex guides selection of predictable movement targets

PubMed Central

Woodgate, Philip J.W.; Strauss, Soeren; Sami, Saber A.; Heinke, Dietmar

2016-01-01

The present paper asks whether the motor cortex contributes to prediction-based guidance of target selection. This question was inspired by recent evidence that suggests (i) recurrent connections from the motor system into the attentional system may extract movement-relevant perceptual information and (ii) that the motor cortex cannot only generate predictions of the sensory consequences of movements but may also operate as predictor of perceptual events in general. To test this idea we employed a choice reaching task requiring participants to rapidly reach and touch a predictable or unpredictable colour target. Motor cortex activity was modulated via transcranial direct current stimulation (tDCS). In Experiment 1 target colour repetitions were predictable. Under such conditions anodal tDCS facilitated selection versus sham and cathodal tDCS. This improvement was apparent for trajectory curvature but not movement initiation. Conversely, where no predictability of colour was embedded reach performance was unaffected by tDCS. Finally, the results of a key-press experiment suggested that motor cortex involvement is restricted to tasks where the predictable target colour is movement-relevant. The outcomes are interpreted as evidence that the motor system contributes to the top-down guidance of selective attention to movement targets. PMID:25835319

Impairment in judgement of the moral emotion guilt following orbitofrontal cortex damage.

PubMed

Funayama, Michitaka; Koreki, Akihiro; Muramatsu, Taro; Mimura, Masaru; Kato, Motoichiro; Abe, Takayuki

2018-04-19

Although neuroimaging studies have provided evidence for an association between moral emotions and the orbitofrontal cortex, studies on patients with focal lesions using experimental probes of moral emotions are scarce. Here, we addressed this topic by presenting a moral emotion judgement task to patients with focal brain damage. Four judgement tasks in a simple pairwise choice paradigm were given to 72 patients with cerebrovascular disease. These tasks consisted of a perceptual line judgement task as a control task; the objects' preference task as a basic preference judgement task; and two types of moral emotion judgement task, an anger task and a guilt task. A multiple linear regression analysis was performed on each set of task performance scores to take into account potential confounders. Performance on the guilt emotion judgement task negatively correlated with the orbitofrontal cortex damage, but not with the other variables. Results for the other judgement tasks did not reach statistical significance. The close association between orbitofrontal cortex damage and a decrease in guilt emotion judgement consistency might suggest that the orbitofrontal cortex plays a key role in the sense of guilt, a hallmark of morality. © 2018 The British Psychological Society.

Oxidative stress and cell death in the cerebral cortex as a long-term consequence of neonatal hypoglycemia.

PubMed

Anju, T R; Akhilraj, P R; Paulose, C S

2016-09-01

Neonatal hypoglycemia limits glucose supply to cells leading to long-term consequences in brain function. The present study evaluated antioxidant and cell death factors' alterations in cerebral cortex of 1-month-old rats exposed to neonatal hypoglycemia. Gene expression studies by real-time PCR were carried out using gene-specific TaqMan probes. Fluorescent dyes were used for immunohistochemistry and nuclear staining and imaged by confocal microscope. Total antioxidant level and expression of antioxidant enzymes - superoxide dismutase (SOD) and gluthathione peroxide (GPx) - mRNA was significantly reduced along with high peroxide level in the cerebral cortex of 1-month-old rats exposed to neonatal hypoglycemia. Real-time PCR analysis showed an upregulation of Bax, caspase 3, and caspase 8 gene expression. Confocal imaging with TOPRO-3 staining and immunohistochemistry with caspase 3 antibody indicated cell death activation. The reduced free radical scavenging capability coupled with the expression of key factors involved in cell death pathway points to the possibility of oxidative stress in the cortex of 1-month-old rats exposed to neonatal hypoglycemia. The observed results indicate the effects of neonatal hypoglycemia in determining the antioxidant capability of cerebral cortex in a later stage of life.

Thirst-Dependent Activity of the Insular Cortex Reflects its Emotion-Related Subdivision: A Cerebral Blood Flow Study.

PubMed

Meier, Lea; Federspiel, Andrea; Jann, Kay; Wiest, Roland; Strik, Werner; Dierks, Thomas

2018-04-26

Recent studies investigating neural correlates of human thirst have identified various subcortical and telencephalic brain areas. The experience of thirst represents a homeostatic emotion and a state that slowly evolves over time. Therefore, the present study aims at systematically examining cerebral perfusion during the parametric progression of thirst. We measured subjective thirst ratings, serum parameters and cerebral blood flow in 20 healthy subjects across four different thirst stages: intense thirst, moderate thirst, subjective satiation and physiological satiation. Imaging data revealed dehydration-related perfusion differences in previously identified brain areas, such as the anterior cingulate cortex, the middle temporal gyrus and the insular cortex. However, significant differences across all four thirst stages (including the moderate thirst level), were exclusively found in the posterior insular cortex. The subjective thirst ratings over the different thirst stages, however, were associated with perfusion differences in the right anterior insula. These findings add to our understanding of the insular cortex as a key player in human thirst - both on the level of physiological dehydration and the level of the subjective thirst experience. Copyright © 2018. Published by Elsevier Ltd.

Two Alzheimer’s disease risk genes increase entorhinal cortex volume in young adults

PubMed Central

DiBattista, Amanda Marie; Stevens, Benson W.; Rebeck, G. William; Green, Adam E.

2014-01-01

Alzheimer’s disease (AD) risk genes alter brain structure and function decades before disease onset. Apolipoprotein E (APOE) is the strongest known genetic risk factor for AD, and a related gene, apolipoprotein J (APOJ), also affects disease risk. However, the extent to which these genes affect brain structure in young adults remains unclear. Here, we report that AD risk alleles of these two genes, APOE-ε4 and APOJ-C, cumulatively alter brain volume in young adults. Using voxel-based morphometry (VBM) in 57 individuals, we examined the entorhinal cortex, one of the earliest brain regions affected in AD pathogenesis. Apolipoprotein E-ε4 carriers exhibited higher right entorhinal cortex volume compared to non-carriers. Interestingly, APOJ-C risk genotype was associated with higher bilateral entorhinal cortex volume in non-APOE-ε4 carriers. To determine the combined disease risk of APOE and APOJ status per subject, we used cumulative odds ratios as regressors for volumetric measurements. Higher disease risk corresponded to greater right entorhinal cortex volume. These results suggest that, years before disease onset, two key AD genetic risk factors may exert influence on the structure of a brain region where AD pathogenesis takes root. PMID:25339884

Lynx1 Limits Dendritic Spine Turnover in the Adult Visual Cortex

PubMed Central

Sajo, Mari

2016-01-01

Dendritic spine turnover becomes limited in the adult cerebral cortex. Identification of specific aspects of spine dynamics that can be unmasked in adulthood and its regulatory molecular mechanisms could provide novel therapeutic targets for inducing plasticity at both the functional and structural levels for robust recovery from brain disorders and injuries in adults. Lynx1, an endogenous inhibitor of nicotinic acetylcholine receptors, was previously shown to increase its expression in adulthood and thus to limit functional ocular dominance plasticity in adult primary visual cortex (V1). However, the role of this “brake” on spine dynamics is not known. We examined the contribution of Lynx1 on dendritic spine turnover before and after monocular deprivation (MD) in adult V1 with chronic in vivo imaging using two-photon microscopy and determined the spine turnover rate of apical dendrites of layer 5 (L5) and L2/3 pyramidal neurons in adult V1 of Lynx1 knock-out (KO) mice. We found that the deletion of Lynx1 doubled the baseline spine turnover rate, suggesting that the spine dynamics in the adult cortex is actively limited by the presence of Lynx1. After MD, adult Lynx1-KO mice selectively exhibit higher rate of spine loss with no difference in gain rate in L5 neurons compared with control wild-type counterparts, revealing a key signature of spine dynamics associated with robust functional plasticity in adult V1. Overall, Lynx1 could be a promising therapeutic target to induce not only functional, but also structural plasticity at the level of spine dynamics in the adult brain. SIGNIFICANCE STATEMENT Dendritic spine turnover becomes limited in the adult cortex. In mouse visual cortex, a premier model of experience-dependent plasticity, we found that the deletion of Lynx1, a nicotinic “brake” for functional plasticity, doubled the baseline spine turnover in adulthood, suggesting that the spine dynamics in the adult cortex is actively limited by Lynx1. After visual deprivation, spine loss, but not gain rate, remains higher in adult Lynx1 knock-out mice than in control wild-type mice, revealing a key signature of spine dynamics associated with robust functional plasticity. Lynx1 would be a promising target to induce not only functional, but also structural plasticity at the level of spine dynamics in adulthood. PMID:27605620

Electron microscope study of the vitelline body of some spider oocytes.

PubMed

SOTELO, J R; TRUJILLO-CENOZ, O

1957-03-25

THE STRUCTURE OF THE VITELLINE NUCLEI OF LYCOSIDAE AND THOMISIDAE WAS DESCRIBED AS FOLLOWS: Vitelline nuclei are constituted of two parts: (a) a peripheral layer (vitelline body cortex), and (b) a central core. The vitelline body cortex is demonstrated to be formed by many cisternae of the endoplasmic reticulum among which mitochondria and Golgi elements are intermingled. The central core is made up mainly of a special type of body described under the name of "capsulated body." Capsulated bodies comprise a capsular layer, limited by a membrane, and two central masses called "geminated masses," each one limited by a double membrane. Irregular masses of closely packed vesicles are found in some cases among the capsulated bodies and free vesicles are present in large numbers. The optical properties of the vitelline body cortex compared with the electron microscope findings lead us to the concept that this layer is a "composite body" according to Weiner's theory.

A morphological basis for orientation tuning in primary visual cortex.

PubMed

Mooser, François; Bosking, William H; Fitzpatrick, David

2004-08-01

Feedforward connections are thought to be important in the generation of orientation-selective responses in visual cortex by establishing a bias in the sampling of information from regions of visual space that lie along a neuron's axis of preferred orientation. It remains unclear, however, which structural elements-dendrites or axons-are ultimately responsible for conveying this sampling bias. To explore this question, we have examined the spatial arrangement of feedforward axonal connections that link non-oriented neurons in layer 4 and orientation-selective neurons in layer 2/3 of visual cortex in the tree shrew. Target sites of labeled boutons in layer 2/3 resulting from focal injections of biocytin in layer 4 show an orientation-specific axial bias that is sufficient to confer orientation tuning to layer 2/3 neurons. We conclude that the anisotropic arrangement of axon terminals is the principal source of the orientation bias contributed by feedforward connections.

TRPV1 channels are critical brain inflammation detectors and neuropathic pain biomarkers in mice

PubMed Central

Marrone, Maria Cristina; Morabito, Annunziato; Giustizieri, Michela; Chiurchiù, Valerio; Leuti, Alessandro; Mattioli, Marzia; Marinelli, Sara; Riganti, Loredana; Lombardi, Marta; Murana, Emanuele; Totaro, Antonio; Piomelli, Daniele; Ragozzino, Davide; Oddi, Sergio; Maccarrone, Mauro; Verderio, Claudia; Marinelli, Silvia

2017-01-01

The capsaicin receptor TRPV1 has been widely characterized in the sensory system as a key component of pain and inflammation. A large amount of evidence shows that TRPV1 is also functional in the brain although its role is still debated. Here we report that TRPV1 is highly expressed in microglial cells rather than neurons of the anterior cingulate cortex and other brain areas. We found that stimulation of microglial TRPV1 controls cortical microglia activation per se and indirectly enhances glutamatergic transmission in neurons by promoting extracellular microglial microvesicles shedding. Conversely, in the cortex of mice suffering from neuropathic pain, TRPV1 is also present in neurons affecting their intrinsic electrical properties and synaptic strength. Altogether, these findings identify brain TRPV1 as potential detector of harmful stimuli and a key player of microglia to neuron communication. PMID:28489079

The dopamine beta-hydroxylase inhibitor nepicastat increases dopamine release and potentiates psychostimulant-induced dopamine release in the prefrontal cortex.

PubMed

Devoto, Paola; Flore, Giovanna; Saba, Pierluigi; Bini, Valentina; Gessa, Gian Luigi

2014-07-01

The dopamine-beta-hydroxylase inhibitor nepicastat has been shown to reproduce disulfiram ability to suppress the reinstatement of cocaine seeking after extinction in rats. To clarify its mechanism of action, we examined the effect of nepicastat, given alone or in association with cocaine or amphetamine, on catecholamine release in the medial prefrontal cortex and the nucleus accumbens, two key regions involved in the reinforcing and motivational effects of cocaine and in the reinstatement of cocaine seeking. Nepicastat effect on catecholamines was evaluated by microdialysis in freely moving rats. Nepicastat reduced noradrenaline release both in the medial prefrontal cortex and in the nucleus accumbens, and increased dopamine release in the medial prefrontal cortex but not in the nucleus accumbens. Moreover, nepicastat markedly potentiated cocaine- and amphetamine-induced extracellular dopamine accumulation in the medial prefrontal cortex but not in the nucleus accumbens. Extracellular dopamine accumulation produced by nepicastat alone or by its combination with cocaine or amphetamine was suppressed by the α2 -adrenoceptor agonist clonidine. It is suggested that nepicastat, by suppressing noradrenaline synthesis and release, eliminated the α2 -adrenoceptor mediated inhibitory mechanism that constrains dopamine release and cocaine- and amphetamine-induced dopamine release from noradrenaline or dopamine terminals in the medial prefrontal cortex. © 2012 The Authors, Addiction Biology © 2012 Society for the Study of Addiction.

A Computational Model of Spatial Visualization Capacity

DTIC Science & Technology

2008-03-07

GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 61102F 6. AUTHOR(S) Don Lyon; Glenn Gunzelmann; Kevin Gluck 5d. PROJECT NUMBER 2313 5e. TASK NUMBER AS...specialization in prefrontal cortex: Effects of verbalizability, imageability and meaning. Journal of Neurolinguistics , 16, 361–382. Diwadkar, V. A

Reduced Global Functional Connectivity of the Medial Prefrontal Cortex in Major Depressive Disorder

PubMed Central

Murrough, James W.; Abdallah, Chadi G.; Anticevic, Alan; Collins, Katherine A.; Geha, Paul; Averill, Lynnette A.; Schwartz, Jaclyn; DeWilde, Kaitlin E.; Averill, Christopher; Yang, Genevieve Jia-wei; Wong, Edmund; Tang, Cheuk Y.; Krystal, John H.; Iosifescu, Dan V.; Charney, Dennis S.

2016-01-01

Background Major depressive disorder is a disabling neuropsychiatric condition that is associated with disrupted functional connectivity across brain networks. The precise nature of altered connectivity, however, remains incompletely understood. The current study was designed to examine the coherence of large-scale connectivity in depression using a recently developed technique termed global brain connectivity. Methods A total of 82 subjects, including medication-free patients with major depression (n=57) and healthy volunteers (n=25) underwent functional magnetic resonance imaging with resting data acquisition for functional connectivity analysis. Global brain connectivity was computed as the mean of each voxel’s time series correlation with every other voxel and compared between study groups. Relationships between global connectivity and depressive symptom severity measured using the Montgomery-Åsberg Depression Rating Scale were examined by means of linear correlation. Results Relative to the healthy group, patients with depression evidenced reduced global connectivity bilaterally within multiple regions of medial and lateral prefrontal cortex. The largest between-group difference was observed within the right subgenual anterior cingulate cortex, extending into ventromedial prefrontal cortex bilaterally (Hedges’ g = −1.48, p<0.000001). Within the depressed group, patients with the lowest connectivity evidenced the highest symptom severity within ventromedial prefrontal cortex (r = −0.47, p=0.0005). Conclusions Patients with major depressive evidenced abnormal large-scale functional coherence in the brain that was centered within the subgenual cingulate cortex, and medial prefrontal cortex more broadly. These data extend prior studies of connectivity in depression and demonstrate that functional disconnection of the medial prefrontal cortex is a key pathological feature of the disorder. PMID:27144347

Reducing prefrontal gamma-aminobutyric acid activity induces cognitive, behavioral, and dopaminergic abnormalities that resemble schizophrenia.

PubMed

Enomoto, Takeshi; Tse, Maric T; Floresco, Stan B

2011-03-01

Perturbations in gamma-aminobutyric acid (GABA)-related markers have been reported in the prefrontal cortex of schizophrenic patients. However, a preclinical assessment of how suppression of prefrontal cortex GABA activity may reflect behavioral and cognitive pathologies observed in schizophrenia is forthcoming. We assessed the effects of pharmacologic blockade of prefrontal cortex GABA(A) receptors in rats on executive functions and other behaviors related to schizophrenia, as well as neural activity of midbrain dopamine neurons. Blockade of prefrontal cortex GABA(A) receptors with bicuculline (12.5-50 ng) did not affect working memory accuracy but did increase response latencies, resembling speed of processing deficits observed in schizophrenia. Prefrontal cortex GABA(A) blockade did not impede simple discrimination or reversal learning but did impair set-shifting in a manner dependent on when these treatments were given. Reducing GABA activity before the set-shift impaired the ability to acquire a novel strategy, whereas treatment before the initial discrimination increased perseveration during the shift. Latent inhibition was unaffected by bicuculline infusions before the preexposure/conditioning phases, suggesting that reduced prefrontal cortex GABA activity does not impair "learned irrelevance." GABA(A) blockade increased locomotor activity and showed synergic effects with a subthreshold dose of amphetamine. Furthermore, reducing medial prefrontal cortex GABA activity selectively increased phasic burst firing of ventral tegmental area dopamine neurons, without altering the their overall population activity. These results suggest that prefrontal cortex GABA hypofunction may be a key contributing factor to deficits in speed of processing, cognitive flexibility, and enhanced phasic dopamine activity observed in schizophrenia. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

DREAM mediates cAMP-dependent, Ca2+-induced stimulation of GFAP gene expression and regulates cortical astrogliogenesis.

PubMed

Cebolla, Beatriz; Fernández-Pérez, Antonio; Perea, Gertrudis; Araque, Alfonso; Vallejo, Mario

2008-06-25

In the developing mouse brain, once the generation of neurons is mostly completed during the prenatal period, precisely coordinated signals act on competent neural precursors to direct their differentiation into astrocytes, which occurs mostly after birth. Among these signals, those provided by neurotrophic cytokines and bone morphogenetic proteins appear to have a key role in triggering the neurogenic to gliogenic switch and in regulating astrocyte numbers. In addition, we have reported previously that the neurotrophic peptide pituitary adenylate cyclase-activating polypeptide (PACAP) is able to promote astrocyte differentiation of cortical precursors via activation of a cAMP-dependent pathway. Signals acting on progenitor cells of the developing cortex to generate astrocytes activate glial fibrillary acidic protein (GFAP) gene expression, but the transcriptional mechanisms that regulate this activation are unclear. Here, we identify the previously known transcriptional repressor downstream regulatory element antagonist modulator (DREAM) as an activator of GFAP gene expression. We found that DREAM occupies specific sites on the GFAP promoter before and after differentiation is initiated by exposure of cortical progenitor cells to PACAP. PACAP raises intracellular calcium concentration via a mechanism that requires cAMP, and DREAM-mediated transactivation of the GFAP gene requires the integrity of calcium-binding domains. Cortical progenitor cells from dream(-/-) mice fail to express GFAP in response to PACAP. Moreover, the neonatal cortex of dream(-/-) mice exhibits a reduced number of astrocytes and increased number of neurons. These results identify the PACAP-cAMP-Ca(2+)-DREAM cascade as a new pathway to activate GFAP gene expression during astrocyte differentiation.

LSD modulates music-induced imagery via changes in parahippocampal connectivity.

PubMed

Kaelen, Mendel; Roseman, Leor; Kahan, Joshua; Santos-Ribeiro, Andre; Orban, Csaba; Lorenz, Romy; Barrett, Frederick S; Bolstridge, Mark; Williams, Tim; Williams, Luke; Wall, Matthew B; Feilding, Amanda; Muthukumaraswamy, Suresh; Nutt, David J; Carhart-Harris, Robin

2016-07-01

Psychedelic drugs such as lysergic acid diethylamide (LSD) were used extensively in psychiatry in the past and their therapeutic potential is beginning to be re-examined today. Psychedelic psychotherapy typically involves a patient lying with their eyes-closed during peak drug effects, while listening to music and being supervised by trained psychotherapists. In this context, music is considered to be a key element in the therapeutic model; working in synergy with the drug to evoke therapeutically meaningful thoughts, emotions and imagery. The underlying mechanisms involved in this process have, however, never been formally investigated. Here we studied the interaction between LSD and music-listening on eyes-closed imagery by means of a placebo-controlled, functional magnetic resonance imaging (fMRI) study. Twelve healthy volunteers received intravenously administered LSD (75µg) and, on a separate occasion, placebo, before being scanned under eyes-closed resting conditions with and without music-listening. The parahippocampal cortex (PHC) has previously been linked with (1) music-evoked emotion, (2) the action of psychedelics, and (3) mental imagery. Imaging analyses therefore focused on changes in the connectivity profile of this particular structure. Results revealed increased PHC-visual cortex (VC) functional connectivity and PHC to VC information flow in the interaction between music and LSD. This latter result correlated positively with ratings of enhanced eyes-closed visual imagery, including imagery of an autobiographical nature. These findings suggest a plausible mechanism by which LSD works in combination with music listening to enhance certain subjective experiences that may be useful in a therapeutic context. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

MicroRNA-132 dysregulation in schizophrenia has implications for both neurodevelopment and adult brain function

PubMed Central

Miller, Brooke H.; Zeier, Zane; Xi, Li; Lanz, Thomas A.; Deng, Shibing; Strathmann, Julia; Willoughby, David; Kenny, Paul J.; Elsworth, John D.; Lawrence, Matthew S.; Roth, Robert H.; Edbauer, Dieter; Kleiman, Robin J.; Wahlestedt, Claes

2012-01-01

Schizophrenia is characterized by affective, cognitive, neuromorphological, and molecular abnormalities that may have a neurodevelopmental origin. MicroRNAs (miRNAs) are small noncoding RNA sequences critical to neurodevelopment and adult neuronal processes by coordinating the activity of multiple genes within biological networks. We examined the expression of 854 miRNAs in prefrontal cortical tissue from 100 control, schizophrenic, and bipolar subjects. The cyclic AMP-responsive element binding- and NMDA-regulated microRNA miR-132 was significantly down-regulated in both the schizophrenic discovery cohort and a second, independent set of schizophrenic subjects. Analysis of miR-132 target gene expression in schizophrenia gene-expression microarrays identified 26 genes up-regulated in schizophrenia subjects. Consistent with NMDA-mediated hypofunction observed in schizophrenic subjects, administration of an NMDA antagonist to adult mice results in miR-132 down-regulation in the prefrontal cortex. Furthermore, miR-132 expression in the murine prefrontal cortex exhibits significant developmental regulation and overlaps with critical neurodevelopmental processes during adolescence. Adult prefrontal expression of miR-132 can be down-regulated by pharmacologic inhibition of NMDA receptor signaling during a brief postnatal period. Several key genes, including DNMT3A, GATA2, and DPYSL3, are regulated by miR-132 and exhibited altered expression either during normal neurodevelopment or in tissue from adult schizophrenic subjects. Our data suggest miR-132 dysregulation and subsequent abnormal expression of miR-132 target genes contribute to the neurodevelopmental and neuromorphological pathologies present in schizophrenia. PMID:22315408

Responses of medial and ventrolateral prefrontal cortex to interpersonal conflict for resources.

PubMed

Koban, Leonie; Pichon, Swann; Vuilleumier, Patrik

2014-05-01

Little is known about brain mechanisms recruited during the monitoring and appraisal of social conflicts--for instance, when individuals compete with each other for the same resources. We designed a novel experimental task inducing resource conflicts between two individuals. In an event-related functional magnetic resonance imaging (fMRI) design, participants played with another human participant or against a computer, who across trials chose either different (no-conflict) or the same tokens (conflict trials) in order to obtain monetary gains. In conflict trials, the participants could decide whether they would share the token, and the resulting gain, with the other person or instead keep all points for themselves. Behaviorally, participants shared much more often when playing with a human partner than with a computer. fMRI results demonstrated that the dorsal mediofrontal cortex was selectively activated during human conflicts. This region might play a key role in detecting situations in which self- and social interest are incompatible and require behavioral adjustment. In addition, we found a conflict-related response in the right ventrolateral prefrontal cortex that correlated with measures of social relationship and individual sharing behavior. Taken together, these findings reveal a key role of these prefrontal areas for the appraisal and resolution of interpersonal resource conflicts.

The evolution of cortical development: the synapsid-diapsid divergence.

PubMed

Goffinet, Andre M

2017-11-15

The cerebral cortex covers the rostral part of the brain and, in higher mammals and particularly humans, plays a key role in cognition and consciousness. It is populated with neuronal cell bodies distributed in radially organized layers. Understanding the common and lineage-specific molecular mechanisms that orchestrate cortical development and evolution are key issues in neurobiology. During evolution, the cortex appeared in stem amniotes and evolved divergently in two main branches of the phylogenetic tree: the synapsids (which led to present day mammals) and the diapsids (reptiles and birds). Comparative studies in organisms that belong to those two branches have identified some common principles of cortical development and organization that are possibly inherited from stem amniotes and regulated by similar molecular mechanisms. These comparisons have also highlighted certain essential features of mammalian cortices that are absent or different in diapsids and that probably evolved after the synapsid-diapsid divergence. Chief among these is the size and multi-laminar organization of the mammalian cortex, and the propensity to increase its area by folding. Here, I review recent data on cortical neurogenesis, neuronal migration and cortical layer formation and folding in this evolutionary perspective, and highlight important unanswered questions for future investigation. © 2017. Published by The Company of Biologists Ltd.

Responses of medial and ventrolateral prefrontal cortex to interpersonal conflict for resources

PubMed Central

Koban, Leonie; Pichon, Swann; Vuilleumier, Patrik

2014-01-01

Little is known about brain mechanisms recruited during the monitoring and appraisal of social conflicts—for instance, when individuals compete with each other for the same resources. We designed a novel experimental task inducing resource conflicts between two individuals. In an event-related functional magnetic resonance imaging (fMRI) design, participants played with another human participant or against a computer, who across trials chose either different (no-conflict) or the same tokens (conflict trials) in order to obtain monetary gains. In conflict trials, the participants could decide whether they would share the token, and the resulting gain, with the other person or instead keep all points for themselves. Behaviorally, participants shared much more often when playing with a human partner than with a computer. fMRI results demonstrated that the dorsal mediofrontal cortex was selectively activated during human conflicts. This region might play a key role in detecting situations in which self- and social interest are incompatible and require behavioral adjustment. In addition, we found a conflict-related response in the right ventrolateral prefrontal cortex that correlated with measures of social relationship and individual sharing behavior. Taken together, these findings reveal a key role of these prefrontal areas for the appraisal and resolution of interpersonal resource conflicts. PMID:23460073

Bupropion Administration Increases Resting-State Functional Connectivity in Dorso-Medial Prefrontal Cortex.

PubMed

Rzepa, Ewelina; Dean, Zola; McCabe, Ciara

2017-06-01

Patients on the selective serotonergic reuptake inhibitors like citalopram report emotional blunting. We showed previously that citalopram reduces resting-state functional connectivity in healthy volunteers in a number of brain regions, including the dorso-medial prefrontal cortex, which may be related to its clinical effects. Bupropion is a dopaminergic and noradrenergic reuptake inhibitor and is not reported to cause emotional blunting. However, how bupropion affects resting-state functional connectivity in healthy controls remains unknown. Using a within-subjects, repeated-measures, double-blind, crossover design, we examined 17 healthy volunteers (9 female, 8 male). Volunteers received 7 days of bupropion (150 mg/d) and 7 days of placebo treatment and underwent resting-state functional Magnetic Resonance Imaging. We selected seed regions in the salience network (amygdala and pregenual anterior cingulate cortex) and the central executive network (dorsal medial prefrontal cortex). Mood and anhedonia measures were also recorded and examined in relation to resting-state functional connectivity. Relative to placebo, bupropion increased resting-state functional connectivity in healthy volunteers between the dorsal medial prefrontal cortex seed region and the posterior cingulate cortex and the precuneus cortex, key parts of the default mode network. These results are opposite to that which we found with 7 days treatment of citalopram in healthy volunteers. These results reflect a different mechanism of action of bupropion compared with selective serotonergic reuptake inhibitors. These results help explain the apparent lack of emotional blunting caused by bupropion in depressed patients. © The Author 2017. Published by Oxford University Press on behalf of CINP.

Key Elements of a Good Mathematics Lesson as Seen by Japanese Junior High School Teachers

ERIC Educational Resources Information Center

Ebaeguin, Marlon; Stephens, Max

2016-01-01

This study makes a comparison between what literature on Japanese Lesson Study suggests are key elements of a good mathematics lesson and what junior high school mathematics teachers in Japan value in planning their lessons. The teachers' strong consensus in their endorsements of these key elements explains why Japanese teachers strongly support…

Posterior Cingulate Cortex: Adapting Behavior to a Changing World

PubMed Central

Pearson, John M.; Heilbronner, Sarah R.; Barack, David L.; Hayden, Benjamin Y.; Platt, Michael L.

2011-01-01

When has the world changed enough to warrant a new approach? The answer depends upon current needs, behavioral flexibility, and prior knowledge about the environment. Formal approaches solve the problem by integrating the recent history of rewards, errors, uncertainty, and context via Bayesian inference to detect changes in the world and alter behavioral policy. Neuronal activity in posterior cingulate cortex (CGp)—a key node in the default network—is known to vary with learning, memory, reward, and task engagement. We propose that these modulations reflect the underlying process of change detection and motivate subsequent shifts in behavior. PMID:21420893

Memory: Organization and Control

PubMed Central

Eichenbaum, Howard

2017-01-01

A major goal of memory research is to understand how cognitive processes in memory are supported at the level of brain systems and network representations. Especially promising in this direction are new findings in humans and animals that converge in indicating a key role for the hippocampus in the systematic organization of memories. New findings also indicate that the prefrontal cortex may play an equally important role in the active control of memory organization during both encoding and retrieval. Observations about the dialog between the hippocampus and prefrontal cortex provide new insights into the operation of the larger brain system that serves memory. PMID:27687117

Method and apparatus for staking optical elements

DOEpatents

Woods, Robert O.

1988-01-01

A method and apparatus for staking two optical elements together in order to retain their alignment is disclosed. The apparatus includes a removable adaptor made up of first and second adaptor bodies each having a lateral slot in their front and side faces. The adaptor also includes a system for releasably attaching each adaptor body to a respective optical element such that when the two optical elements are positioned relative to one another the adaptor bodies are adjacent and the lateral slots therein are aligned to form key slots. The adaptor includes keys which are adapted to fit into the key slots. A curable filler material is employed to retain the keys in the key slots and thereby join the first and second adaptor bodies to form the adaptor. Also disclosed is a method for staking together two optical elements employing the adaptor of the present invention.

Method and apparatus for staking optical elements

DOEpatents

Woods, Robert O.

1988-10-04

A method and apparatus for staking two optical elements together in order to retain their alignment is disclosed. The apparatus includes a removable adaptor made up of first and second adaptor bodies each having a lateral slot in their front and side faces. The adaptor also includes a system for releasably attaching each adaptor body to a respective optical element such that when the two optical elements are positioned relative to one another the adaptor bodies are adjacent and the lateral slots therein are aligned to form key slots. The adaptor includes keys which are adapted to fit into the key slots. A curable filler material is employed to retain the keys in the key slots and thereby join the first and second adaptor bodies to form the adaptor. Also disclosed is a method for staking together two optical elements employing the adaptor of the present invention.

Volition and conflict in human medial frontal cortex

PubMed Central

Nachev, Parashkev; Rees, Geraint; Parton, Andrew; Kennard, Christopher; Husain, Masud

2009-01-01

Summary Controversy surrounds the role of human medial frontal cortex in controlling actions[1-5]. Although damage to this area leads to severe difficulties in spontaneously initiating actions[6], the precise mechanisms underlying such ‘volitional’ deficits remain to be established. Previous studies have implicated the medial frontal cortex in conflict monitoring[7-10] and the control of voluntary action[11, 12], suggesting that these key processes are functionally related or share neural substrates. Here we combine a novel behavioural paradigm with functional imaging of the oculomotor system to reveal for the first time a functional subdivision of the pre-supplementary motor area (pre-SMA) into anatomically distinct areas responding exclusively to volition or to conflict. We also demonstrate that activity in the supplementary eye field (SEF) distinguishes between success and failure in changing voluntary action plans during conflict, suggesting a role for the SEF in implementing the resolution of conflicting actions. We propose a functional architecture of human medial frontal cortex that incorporates the generation of action plans and the resolution of conflict. PMID:15668167

Integrating Information from Different Senses in the Auditory Cortex

PubMed Central

King, Andrew J.; Walker, Kerry M.M.

2015-01-01

Multisensory integration was once thought to be the domain of brain areas high in the cortical hierarchy, with early sensory cortical fields devoted to unisensory processing of inputs from their given set of sensory receptors. More recently, a wealth of evidence documenting visual and somatosensory responses in auditory cortex, even as early as the primary fields, has changed this view of cortical processing. These multisensory inputs may serve to enhance responses to sounds that are accompanied by other sensory cues, effectively making them easier to hear, but may also act more selectively to shape the receptive field properties of auditory cortical neurons to the location or identity of these events. We discuss the new, converging evidence that multiplexing of neural signals may play a key role in informatively encoding and integrating signals in auditory cortex across multiple sensory modalities. We highlight some of the many open research questions that exist about the neural mechanisms that give rise to multisensory integration in auditory cortex, which should be addressed in future experimental and theoretical studies. PMID:22798035

Ventromedial prefrontal cortex stimulation enhances memory and hippocampal neurogenesis in the middle-aged rats

PubMed Central

Liu, Albert; Jain, Neeraj; Vyas, Ajai; Lim, Lee Wei

2015-01-01

Memory dysfunction is a key symptom of age-related dementia. Although recent studies have suggested positive effects of electrical stimulation for memory enhancement, its potential targets remain largely unknown. In this study, we hypothesized that spatially targeted deep brain stimulation of ventromedial prefrontal cortex enhanced memory functions in a middle-aged rat model. Our results show that acute stimulation enhanced the short-, but not the long-term memory in the novel-object recognition task. Interestingly, after chronic high-frequency stimulation, both the short- and long-term memories were robustly improved in the novel-object recognition test and Morris water-maze spatial task compared to sham. Our results also demonstrated that chronic ventromedial prefrontal cortex high-frequency stimulation upregulated neurogenesis-associated genes along with enhanced hippocampal cell proliferation. Importantly, these memory behaviors were strongly correlated with the hippocampal neurogenesis. Overall, these findings suggest that chronic ventromedial prefrontal cortex high-frequency stimulation may serve as a novel effective therapeutic target for dementia-related disorders. DOI: http://dx.doi.org/10.7554/eLife.04803.001 PMID:25768425

Brain-heart coupling at the P300 latency is linked to anterior cingulate cortex and insula--a cardio-electroencephalographic covariance tracing study.

PubMed

Panitz, Christian; Wacker, Jan; Stemmler, Gerhard; Mueller, Erik M

2013-09-01

Prior work on the coupling of cortical and cardiac responses to feedback demonstrated that feedback-evoked single-trial EEG magnitudes 300 ms post-stimulus predict the degree of subsequent cardiac acceleration. The main goal of the current study was to explore the neural sources of this phenomenon using (a) independent component analysis in conjunction with dipole fitting and (b) low resolution electromagnetic tomography (LORETA) in N=14 participants who performed a gambling task with feedback presented after each trial. It was shown that independent components localized near anterior cingulate cortex produced robust within-subjects correlations with feedback-evoked heart-period, suggesting that anterior cingulate cortex activity 300ms after feedback presentation predicts the strength of subsequent cardiac acceleration. Moreover, interindividual differences in evoked left insular cortex LORETA-estimated activity at around 300ms moderated within-subjects EEG-heart period correlations. These results suggest that key regions of central autonomic control are involved in cortico-cardiac coupling evoked by feedback stimuli. Copyright © 2013 Elsevier B.V. All rights reserved.

Coevolution of radial glial cells and the cerebral cortex

PubMed Central

De Juan Romero, Camino

2015-01-01

Abstract Radial glia cells play fundamental roles in the development of the cerebral cortex, acting both as the primary stem and progenitor cells, as well as the guides for neuronal migration and lamination. These critical functions of radial glia cells in cortical development have been discovered mostly during the last 15 years and, more recently, seminal studies have demonstrated the existence of a remarkable diversity of additional cortical progenitor cell types, including a variety of basal radial glia cells with key roles in cortical expansion and folding, both in ontogeny and phylogeny. In this review, we summarize the main cellular and molecular mechanisms known to be involved in cerebral cortex development in mouse, as the currently preferred animal model, and then compare these with known mechanisms in other vertebrates, both mammal and nonmammal, including human. This allows us to present a global picture of how radial glia cells and the cerebral cortex seem to have coevolved, from reptiles to primates, leading to the remarkable diversity of vertebrate cortical phenotypes. GLIA 2015;63:1303–1319 PMID:25808466

Prefrontal Cortex Corticotropin-Releasing Factor Receptor 1 Conveys Acute Stress-Induced Executive Dysfunction.

PubMed

Uribe-Mariño, Andrés; Gassen, Nils C; Wiesbeck, Maximilian F; Balsevich, Georgia; Santarelli, Sara; Solfrank, Beate; Dournes, Carine; Fries, Gabriel R; Masana, Merce; Labermeier, Christiana; Wang, Xiao-Dong; Hafner, Kathrin; Schmid, Bianca; Rein, Theo; Chen, Alon; Deussing, Jan M; Schmidt, Mathias V

2016-11-15

The medial prefrontal cortex (mPFC) subserves complex cognition and is impaired by stress. Corticotropin-releasing factor (CRF), through CRF receptor 1 (CRFR1), constitutes a key element of the stress response. However, its contribution to the effects of stress in the mPFC remains unclear. Mice were exposed to acute social defeat stress and subsequently to either the temporal order memory (n = 11-12) or reversal learning (n = 9-11) behavioral test. Changes in mPFC Crhr1 messenger RNA levels were measured in acutely stressed mice (n = 12). Crhr1 loxP/loxP mice received either intra-mPFC adeno-associated virus-Cre or empty microinjections (n = 17-20) and then were submitted to acute stress and later to the behavioral tests. Co-immunoprecipitation was used to detect activation of the protein kinase A (PKA) signaling pathway in the mPFC of acutely stressed mice (n = 8) or intra-mPFC CRF injected mice (n = 7). Finally, mice received intra-mPFC CRF (n = 11) and/or Rp-isomer cyclic adenosine 3',5' monophosphorothioate (Rp-cAMPS) (n = 12) microinjections and underwent behavioral testing. We report acute stress-induced effects on mPFC-mediated cognition, identify CRF-CRFR1-containing microcircuits within the mPFC, and demonstrate stress-induced changes in Crhr1 messenger RNA expression. Importantly, intra-mPFC CRFR1 deletion abolishes acute stress-induced executive dysfunction, whereas intra-mPFC CRF mimics acute stress-induced mPFC dysfunction. Acute stress and intra-mPFC CRF activate the PKA signaling pathway in the mPFC, leading to cyclic AMP response element binding protein phosphorylation in intra-mPFC CRFR1-expressing neurons. Finally, PKA blockade reverses the intra-mPFC CRF-induced executive dysfunction. Taken together, these results unravel a molecular mechanism linking acute stress to executive dysfunction via CRFR1. This will aid in the development of novel therapeutic targets for stress-induced cognitive dysfunction. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Assessment of Traumatic Brain Injury by Increased 64Cu Uptake on 64CuCl2 PET/CT.

PubMed

Peng, Fangyu; Muzik, Otto; Gatson, Joshua; Kernie, Steven G; Diaz-Arrastia, Ramon

2015-08-01

Copper is a nutritional trace element required for cell proliferation and wound repair. To explore increased copper uptake as a biomarker for noninvasive assessment of traumatic brain injury (TBI), experimental TBI in C57BL/6 mice was induced by controlled cortical impact, and (64)Cu uptake in the injured cortex was assessed with (64)CuCl2 PET/CT. At 24 h after intravenous injection of the tracer, uptake was significantly higher in the injured cortex of TBI mice (1.15 ± 0.53 percentage injected dose per gram of tissue [%ID/g]) than in the uninjured cortex of mice without TBI (0.53 ± 0.07 %ID/g, P = 0.027) or the cortex of mice that received an intracortical injection of zymosan A (0.62 ± 0.22 %ID/g, P = 0.025). Furthermore, uptake in the traumatized cortex of untreated TBI mice (1.15 ± 0.53 %ID/g) did not significantly differ from that in minocycline-treated TBI mice (0.93 ± 0.30 %ID/g, P = 0.33). Overall, the data suggest that increased (64)Cu uptake in traumatized brain tissues holds potential as a new biomarker for noninvasive assessment of TBI with (64)CuCl2 PET/CT. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Effects of medial prefrontal cortex lesions in rats on the what-where-when memory of a fear conditioning event.

PubMed

Li, Jay-Shake; Hsiao, Kun-Yuan; Chen, Wei-Min

2011-03-17

Previous animal studies have defined the ability to remember the details of what, where, and when of an event as an episodic-like memory to be used to model episodic memory in humans. Numerous findings indicate that the hippocampal-frontal cortical circuitry plays a major part in its neural mechanism. Researchers have intensively studied roles of diverse hippocampus sub-regions using animal models. By contrast, the impact of prefrontal cortex lesions on episodic-like memory in animals is still unknown. Here we show that Wistar rats with bilateral medial prefrontal cortex lesions failed to use the temporal-contextual information to retrieve memory of a fear-conditioning event, indicating impairments in their episodic-like memory. Subsequent experiments excluded alternative interpretations that the manipulation impaired the fear-conditioning per se, or interfered with the sensory preconditioning process. We concluded that damages in this area might impair temporal information processing, or interfere with integrating temporal and contextual elements of fear-conditioning events to form a conjunctive entity. These findings can help understand how the medial prefrontal cortex contributes to episodic-like memory. Copyright © 2010 Elsevier B.V. All rights reserved.

Dissecting the actin cortex density and membrane-cortex distance in living cells by super-resolution microscopy

NASA Astrophysics Data System (ADS)

Clausen, M. P.; Colin-York, H.; Schneider, F.; Eggeling, C.; Fritzsche, M.

2017-02-01

Nanoscale spacing between the plasma membrane and the underlying cortical actin cytoskeleton profoundly modulates cellular morphology, mechanics, and function. Measuring this distance has been a key challenge in cell biology. Current methods for dissecting the nanoscale spacing either limit themselves to complex survey design using fixed samples or rely on diffraction-limited fluorescence imaging whose spatial resolution is insufficient to quantify distances on the nanoscale. Using dual-color super-resolution STED (stimulated-emission-depletion) microscopy, we here overcome this challenge and accurately measure the density distribution of the cortical actin cytoskeleton and the distance between the actin cortex and the membrane in live Jurkat T-cells. We found an asymmetric cortical actin density distribution with a mean width of 230 (+105/-125) nm. The spatial distances measured between the maximum density peaks of the cortex and the membrane were bi-modally distributed with mean values of 50  ±  15 nm and 120  ±  40 nm, respectively. Taken together with the finite width of the cortex, our results suggest that in some regions the cortical actin is closer than 10 nm to the membrane and a maximum of 20 nm in others.

A role for intermediate radial glia in the tangential expansion of the mammalian cerebral cortex.

PubMed

Reillo, Isabel; de Juan Romero, Camino; García-Cabezas, Miguel Ángel; Borrell, Víctor

2011-07-01

The cerebral cortex of large mammals undergoes massive surface area expansion and folding during development. Specific mechanisms to orchestrate the growth of the cortex in surface area rather than in thickness are likely to exist, but they have not been identified. Analyzing multiple species, we have identified a specialized type of progenitor cell that is exclusive to mammals with a folded cerebral cortex, which we named intermediate radial glia cell (IRGC). IRGCs express Pax6 but not Tbr2, have a radial fiber contacting the pial surface but not the ventricular surface, and are found in both the inner subventricular zone and outer subventricular zone (OSVZ). We find that IRGCs are massively generated in the OSVZ, thus augmenting the numbers of radial fibers. Fanning out of this expanding radial fiber scaffold promotes the tangential dispersion of radially migrating neurons, allowing for the growth in surface area of the cortical sheet. Accordingly, the tangential expansion of particular cortical regions was preceded by high proliferation in the underlying OSVZ, whereas the experimental reduction of IRGCs impaired the tangential dispersion of neurons and resulted in a smaller cortical surface. Thus, the generation of IRGCs plays a key role in the tangential expansion of the mammalian cerebral cortex.

Facilitated beam-walking recovery during acute phase by kynurenic acid treatment in a rat model of photochemically induced thrombosis causing focal cerebral ischemia.

PubMed

Abo, Masahiro; Yamauchi, Hideki; Suzuki, Masahiko; Sakuma, Mio; Urashima, Mitsuyoshi

We previously demonstrated the presence of activated areas in the non-injured contralateral sensorimotor cortex in addition to the ipsilateral sensorimotor cortex of the area surrounding a brain infarction, using a rat model of focal photochemically induced thrombosis (PIT) and functional magnetic resonance imaging. Using this model, we next applied gene expression profiling to screen key molecules upregulated in the activated area. RNA was extracted from the ipsilateral and contralateral sensorimotor cortex to the focal brain infarction and from the sham controlled cortex, and hybridized to gene-expression profiling arrays containing 1,322 neurology-related genes. Results showed that glycine receptors were upregulated in both the ipsilateral and contralateral cortex to the focal ischemic lesion. To prove the preclinical significance of upregulated glycine receptors, kynurenic acid, an endogenous antagonist to glycine receptors on neuronal cells, was administered intrathecally. As a result, the kynurenic acid significantly improved behavioral recovery within 10 days from paralysis induced by the focal PIT (p < 0.0001), as evaluated with beam walking. These results suggest that intrathecal administration of a glycine receptor antagonist may facilitate behavioral recovery during the acute phase after brain infarction. Copyright (c) 2006 S. Karger AG, Basel.

Thalamocortical Connections Drive Intracortical Activation of Functional Columns in the Mislaminated Reeler Somatosensory Cortex

PubMed Central

Wagener, Robin J.; Witte, Mirko; Guy, Julien; Mingo-Moreno, Nieves; Kügler, Sebastian; Staiger, Jochen F.

2016-01-01

Neuronal wiring is key to proper neural information processing. Tactile information from the rodent's whiskers reaches the cortex via distinct anatomical pathways. The lemniscal pathway relays whisking and touch information from the ventral posteromedial thalamic nucleus to layer IV of the primary somatosensory “barrel” cortex. The disorganized neocortex of the reeler mouse is a model system that should severely compromise the ingrowth of thalamocortical axons (TCAs) into the cortex. Moreover, it could disrupt intracortical wiring. We found that neuronal intermingling within the reeler barrel cortex substantially exceeded previous descriptions, leading to the loss of layers. However, viral tracing revealed that TCAs still specifically targeted transgenically labeled spiny layer IV neurons. Slice electrophysiology and optogenetics proved that these connections represent functional synapses. In addition, we assessed intracortical activation via immediate-early-gene expression resulting from a behavioral exploration task. The cellular composition of activated neuronal ensembles suggests extensive similarities in intracolumnar information processing in the wild-type and reeler brains. We conclude that extensive ectopic positioning of neuronal partners can be compensated for by cell-autonomous mechanisms that allow for the establishment of proper connectivity. Thus, genetic neuronal fate seems to be of greater importance for correct cortical wiring than radial neuronal position. PMID:26564256

Motor programming when sequencing multiple elements of the same duration.

PubMed

Magnuson, Curt E; Robin, Donald A; Wright, David L

2008-11-01

Motor programming at the self-select paradigm was adopted in 2 experiments to examine the processing demands of independent processes. One process (INT) is responsible for organizing the internal features of the individual elements in a movement (e.g., response duration). The 2nd process (SEQ) is responsible for placing the elements into the proper serial order before execution. Participants in Experiment 1 performed tasks involving 1 key press or sequences of 4 key presses of the same duration. Implementing INT and SEQ was more time consuming for key-pressing sequences than for single key-press tasks. Experiment 2 examined whether the INT costs resulting from the increase in sequence length observed in Experiment 1 resulted from independent planning of each sequence element or via a separate "multiplier" process that handled repetitions of elements of the same duration. Findings from Experiment 2, in which participants performed single key presses or double or triple key sequences of the same duration, suggested that INT is involved with the independent organization of each element contained in the sequence. Researchers offer an elaboration of the 2-process account of motor programming to incorporate the present findings and the findings from other recent sequence-learning research.

The toxic influence of dibromoacetic acid on the hippocampus and pre-frontal cortex of rat: involvement of neuroinflammation response and oxidative stress.

PubMed

Jiang, Wenbo; Li, Bai; Chen, Yingying; Gao, Shuying

2017-12-01

Dibromoacetic acid (DBA) exsits in drinking water as a by-product of disinfection as a result of chlorination or ozonation processes. Hippocampus and pre-frontal cortex are the key structures in memory formation and weanling babies are more sensitive to environmental toxicant than adults, so this study was conducted to evaluate the potential neurotoxicity effects of DBA exposure when administered intragastrically for 4 weeks to weanling Sprague-Dawley rats, at concentration of 0, 20, 50, 125 mg/kg via the neurobehavioral and neurochemical effects. Results indicated that animals weight gain and food consumption were not significantly affected by DBA. However, morris water maze test showed varying degrees of changes between control and high-dose group. Additionally, the level of malondialdehyde (MDA) and generation of reactive oxygen species (ROS) in the hippocampus and pre-frontal cortex of rats increased significantly. The activities of total superoxide dismutase (SOD) and the glutathione (GSH) content in the hippocampus and pre-frontal cortex of rats decreased significantly after treatment with DBA. Treatment with DBA increased the protein and mRNA expression of Iba-1, NF-κB, TNF-α, IL-6, IL-1β and HO-1 in the hippocampus and pre-frontal cortex of rats. These data suggested that DBA had a toxic influence on the hippocampus and pre-frontal cortex of rats, and that the mechanism of toxicity might be associated with the neuroinflammation response and oxidative stress.

Dichoptic training enables the adult amblyopic brain to learn.

PubMed

Li, Jinrong; Thompson, Benjamin; Deng, Daming; Chan, Lily Y L; Yu, Minbin; Hess, Robert F

2013-04-22

Adults with amblyopia, a common visual cortex disorder caused primarily by binocular disruption during an early critical period, do not respond to conventional therapy involving occlusion of one eye. But it is now clear that the adult human visual cortex has a significant degree of plasticity, suggesting that something must be actively preventing the adult brain from learning to see through the amblyopic eye. One possibility is an inhibitory signal from the contralateral eye that suppresses cortical inputs from the amblyopic eye. Such a gating mechanism could explain the apparent lack of plasticity within the adult amblyopic visual cortex. Here we provide direct evidence that alleviating suppression of the amblyopic eye through dichoptic stimulus presentation induces greater levels of plasticity than forced use of the amblyopic eye alone. This indicates that suppression is a key gating mechanism that prevents the amblyopic brain from learning to see. Copyright © 2013 Elsevier Ltd. All rights reserved.

Modulation of value representation by social context in the primate orbitofrontal cortex.

PubMed

Azzi, João C B; Sirigu, Angela; Duhamel, Jean-René

2012-02-07

Primates depend for their survival on their ability to understand their social environment, and their behavior is often shaped by social circumstances. We report that the orbitofrontal cortex, a brain region involved in motivation and reward, is tuned to social information. Macaque monkeys worked to collect rewards for themselves and two monkey partners. Behaviorally, monkeys discriminated between cues signaling large and small [corrected] rewards, and between cues signaling rewards to self only and reward to both self and another monkey, with a preference for the former over the latter in both instances. Single neurons recorded during this task encoded the meaning of visual cues that predicted the magnitude of future rewards, as well as the motivational value of rewards obtained in a social context. Furthermore, neuronal activity was found to track momentary social preferences and partner's identity and social rank. The orbitofrontal cortex thus contains key neuronal mechanisms for the evaluation of social information.

Persistent neuronal activity in human prefrontal cortex links perception and action

PubMed Central

Haller, Matar; Case, John; Crone, Nathan E.; Chang, Edward F.; King-Stephens, David; Laxer, Kenneth D.; Weber, Peter B.; Parvizi, Josef; Knight, Robert T.; Shestyuk, Avgusta Y.

2017-01-01

How do humans flexibly respond to changing environmental demands on a sub-second temporal scale? Extensive research has highlighted the key role of the prefrontal cortex in flexible decision-making and adaptive behavior, yet the core mechanisms that translate sensory information into behavior remain undefined. Utilizing direct human cortical recordings, we investigated the temporal and spatial evolution of neuronal activity, indexed by the broadband gamma signal, while sixteen participants performed a broad range of self-paced cognitive tasks. Here we describe a robust domain- and modality-independent pattern of persistent stimulus-to-response neural activation that encodes stimulus features and predicts motor output on a trial-by-trial basis with near-perfect accuracy. Observed across a distributed network of brain areas, this persistent neural activation is centered in the prefrontal cortex and is required for successful response implementation, providing a functional substrate for domain-general transformation of perception into action, critical for flexible behavior.

Cortical visual prostheses: from microstimulation to functional percept

NASA Astrophysics Data System (ADS)

Najarpour Foroushani, Armin; Pack, Christopher C.; Sawan, Mohamad

2018-04-01

Cortical visual prostheses are intended to restore vision by targeted electrical stimulation of the visual cortex. The perception of spots of light, called phosphenes, resulting from microstimulation of the visual pathway, suggests the possibility of creating meaningful percept made of phosphenes. However, to date electrical stimulation of V1 has still not resulted in perception of phosphenated images that goes beyond punctate spots of light. In this review, we summarize the clinical and experimental progress that has been made in generating phosphenes and modulating their associated perceptual characteristics in human and macaque primary visual cortex (V1). We focus specifically on the effects of different microstimulation parameters on perception and we analyse key challenges facing the generation of meaningful artificial percepts. Finally, we propose solutions to these challenges based on the application of supervised learning of population codes for spatial stimulation of visual cortex.

Cortical activity in the null space: permitting preparation without movement

PubMed Central

Kaufman, Matthew T.; Churchland, Mark M.; Ryu, Stephen I.; Shenoy, Krishna V.

2014-01-01

Neural circuits must perform computations and then selectively output the results to other circuits. Yet synapses do not change radically at millisecond timescales. A key question then is: how is communication between neural circuits controlled? In motor control, brain areas directly involved in driving movement are active well before movement begins. Muscle activity is some readout of neural activity, yet remains largely unchanged during preparation. Here we find that during preparation, while the monkey holds still, changes in motor cortical activity cancel out at the level of these population readouts. Motor cortex can thereby prepare the movement without prematurely causing it. Further, we found evidence that this mechanism also operates in dorsal premotor cortex (PMd), largely accounting for how preparatory activity is attenuated in primary motor cortex (M1). Selective use of “output-null” vs. “output-potent” patterns of activity may thus help control communication to the muscles and between these brain areas. PMID:24487233

Emotional facilitation of sensory processing in the visual cortex.

PubMed

Schupp, Harald T; Junghöfer, Markus; Weike, Almut I; Hamm, Alfons O

2003-01-01

A key function of emotion is the preparation for action. However, organization of successful behavioral strategies depends on efficient stimulus encoding. The present study tested the hypothesis that perceptual encoding in the visual cortex is modulated by the emotional significance of visual stimuli. Event-related brain potentials were measured while subjects viewed pleasant, neutral, and unpleasant pictures. Early selective encoding of pleasant and unpleasant images was associated with a posterior negativity, indicating primary sources of activation in the visual cortex. The study also replicated previous findings in that affective cues also elicited enlarged late positive potentials, indexing increased stimulus relevance at higher-order stages of stimulus processing. These results support the hypothesis that sensory encoding of affective stimuli is facilitated implicitly by natural selective attention. Thus, the affect system not only modulates motor output (i.e., favoring approach or avoidance dispositions), but already operates at an early level of sensory encoding.

Nested Interrupt Analysis of Low Cost and High Performance Embedded Systems Using GSPN Framework

NASA Astrophysics Data System (ADS)

Lin, Cheng-Min

Interrupt service routines are a key technology for embedded systems. In this paper, we introduce the standard approach for using Generalized Stochastic Petri Nets (GSPNs) as a high-level model for generating CTMC Continuous-Time Markov Chains (CTMCs) and then use Markov Reward Models (MRMs) to compute the performance for embedded systems. This framework is employed to analyze two embedded controllers with low cost and high performance, ARM7 and Cortex-M3. Cortex-M3 is designed with a tail-chaining mechanism to improve the performance of ARM7 when a nested interrupt occurs on an embedded controller. The Platform Independent Petri net Editor 2 (PIPE2) tool is used to model and evaluate the controllers in terms of power consumption and interrupt overhead performance. Using numerical results, in spite of the power consumption or interrupt overhead, Cortex-M3 performs better than ARM7.

MicroRNA-132 regulates recognition memory and synaptic plasticity in the perirhinal cortex

PubMed Central

Scott, Helen L; Tamagnini, Francesco; Narduzzo, Katherine E; Howarth, Joanna L; Lee, Youn-Bok; Wong, Liang-Fong; Brown, Malcolm W; Warburton, Elizabeth C; Bashir, Zafar I; Uney, James B

2012-01-01

Evidence suggests that the acquisition of recognition memory depends upon CREB-dependent long-lasting changes in synaptic plasticity in the perirhinal cortex. The CREB-responsive microRNA miR-132 has been shown to regulate synaptic transmission and we set out to investigate a role for this microRNA in recognition memory and its underlying plasticity mechanisms. To this end we mediated the specific overexpression of miR-132 selectively in the rat perirhinal cortex and demonstrated impairment in short-term recognition memory. This functional deficit was associated with a reduction in both long-term depression and long-term potentiation. These results confirm that microRNAs are key coordinators of the intracellular pathways that mediate experience-dependent changes in the brain. In addition, these results demonstrate a role for miR-132 in the neuronal mechanisms underlying the formation of short-term recognition memory. PMID:22845676

Theory of mind and frontal lobe pathology in schizophrenia: a voxel-based morphometry study.

PubMed

Hirao, Kazuyuki; Miyata, Jun; Fujiwara, Hironobu; Yamada, Makiko; Namiki, Chihiro; Shimizu, Mitsuaki; Sawamoto, Nobukatsu; Fukuyama, Hidenao; Hayashi, Takuji; Murai, Toshiya

2008-10-01

Impaired ability to infer the mental states of others (theory of mind; ToM) is considered to be a key contributor to the poor social functioning of patients with schizophrenia. Although neuroimaging and lesion studies have provided empirical evidence for the neural basis of ToM ability, including the involvement of several prefrontal and temporal structures, the association between pathology of these structures and ToM impairment in schizophrenia patients is less well understood. To address this issue, we investigated structural brain abnormalities and ToM impairment in patients with schizophrenia, and examined the relationship between them. Twenty schizophrenia patients and 20 age-, sex- and education-matched healthy participants underwent magnetic resonance imaging (MRI) and were examined for ToM ability based on the revised version of the "Reading the Mind in the Eyes" (or Eyes) test [Baron-Cohen, S., Wheelwright, S., Hill, J., Raste, Y., Plumb, I., 2001. The 'Reading the Mind in the Eyes' test revised version: A study with normal adults, and adults with Asperger syndrome or high-functioning autism. J. Child Psychol. Psychiatry 42, 241-251]. Voxel-based morphometry (VBM) was performed to investigate regional brain alterations. Relative to normal controls, schizophrenia patients exhibited gray matter reductions in the dorsomedial prefrontal cortex (DMPFC), left ventrolateral prefrontal cortex (VLPFC), ventromedial prefrontal cortex (VMPFC), anterior cingulate cortex (ACC), right superior temporal gyrus (STG) and right insula. The patients performed poorly on the Eyes test. Importantly, poor performance on the Eyes test was found to be associated with gray matter reduction in the left VLPFC in the patient group. These results suggest that prefrontal cortical reduction, especially in the left VLPFC, is a key pathology underlying the difficulties faced by schizophrenia patients in inferring the mental states of others.

Distinction of Neurons, Glia and Endothelial Cells in the Cerebral Cortex: An Algorithm Based on Cytological Features

PubMed Central

García-Cabezas, Miguel Á.; John, Yohan J.; Barbas, Helen; Zikopoulos, Basilis

2016-01-01

The estimation of the number or density of neurons and types of glial cells and their relative proportions in different brain areas are at the core of rigorous quantitative neuroanatomical studies. Unfortunately, the lack of detailed, updated, systematic and well-illustrated descriptions of the cytology of neurons and glial cell types, especially in the primate brain, makes such studies especially demanding, often limiting their scope and broad use. Here, following an extensive analysis of histological materials and the review of current and classical literature, we compile a list of precise morphological criteria that can facilitate and standardize identification of cells in stained sections examined under the microscope. We describe systematically and in detail the cytological features of neurons and glial cell types in the cerebral cortex of the macaque monkey and the human using semithin and thick sections stained for Nissl. We used this classical staining technique because it labels all cells in the brain in distinct ways. In addition, we corroborate key distinguishing characteristics of different cell types in sections immunolabeled for specific markers counterstained for Nissl and in ultrathin sections processed for electron microscopy. Finally, we summarize the core features that distinguish each cell type in easy-to-use tables and sketches, and structure these key features in an algorithm that can be used to systematically distinguish cellular types in the cerebral cortex. Moreover, we report high inter-observer algorithm reliability, which is a crucial test for obtaining consistent and reproducible cell counts in unbiased stereological studies. This protocol establishes a consistent framework that can be used to reliably identify and quantify cells in the cerebral cortex of primates as well as other mammalian species in health and disease. PMID:27847469

How do emotion and motivation direct executive control?

PubMed

Pessoa, Luiz

2009-04-01

Emotion and motivation have crucial roles in determining human behavior. Yet, how they interact with cognitive control functions is less understood. Here, the basic elements of a conceptual framework for understanding how they interact are introduced. More broadly, the 'dual competition' framework proposes that emotion and motivation affect both perceptual and executive competition. In particular, the anterior cingulate cortex is hypothesized to be engaged in attentional/effortful control mechanisms and to interact with several other brain structures, including the amygdala and nucleus accumbens, in integrating affectively significant signals with control signals in prefrontal cortex. An implication of the proposal is that emotion and motivation can either enhance or impair behavioral performance depending on how they interact with control functions.

Using OCT-based microangiography for in vivo longitudinal study of arteriogenesis (Conference Presentation)

NASA Astrophysics Data System (ADS)

Li, Yuandong; Choi, Woo June; Wang, Ruikang K.

2017-03-01

The adaptive growth of collateral vessels, termed "arteriogenesis", is crucial for maintaining regional blood supply during arterial obstruction and offsetting the adverse effect of tissue ischemia. Stimulation of arteriogenesis has been applied for the treatment of occlusive vascular diseases, and in vivo imaging of the progressive development of collateral vessel will facilitate a better understanding of the mechanism. We present using high-resolution OCT-based microangiography (OMAG) to image arteriogenesis process longitudinally in mouse cerebral cortex after middle cerebral artery occlusion (MCAO). We imaged the collateral arterioles at the arteriolo-arteriolar anastomosis (AAA) within 7-day period after MCAO to reveal key elements of collateral vessel remodeling, including alteration in vessel morphology, velocity and directionality of blood flow. The magnitudes of changes in these parameters matched the time course of the active building of collateral vessels stated in previous studies using histology. Hence, OMAG is a promising imaging tool for non-invasive longitudinal study of functional collateral vessel growth in small animal models and can be potentially applied in the experimental study of arteriogenesis stimulation.

Morphological and functional aspects of progenitors perturbed in cortical malformations

PubMed Central

Bizzotto, Sara; Francis, Fiona

2015-01-01

In this review, we discuss molecular and cellular mechanisms important for the function of neuronal progenitors during development, revealed by their perturbation in different cortical malformations. We focus on a class of neuronal progenitors, radial glial cells (RGCs), which are renowned for their unique morphological and behavioral characteristics, constituting a key element during the development of the mammalian cerebral cortex. We describe how the particular morphology of these cells is related to their roles in the orchestration of cortical development and their influence on other progenitor types and post-mitotic neurons. Important for disease mechanisms, we overview what is currently known about RGC cellular components, cytoskeletal mechanisms, signaling pathways and cell cycle characteristics, focusing on how defects lead to abnormal development and cortical malformation phenotypes. The multiple recent entry points from human genetics and animal models are contributing to our understanding of this important cell type. Combining data from phenotypes in the mouse reveals molecules which potentially act in common pathways. Going beyond this, we discuss future directions that may provide new data in this expanding area. PMID:25729350

Decimetre Waves and Cerebellar Cortex Key Element - Purkinje Cells

NASA Astrophysics Data System (ADS)

Maharramov, Akif A.

2007-04-01

Acute experiments have been carried out on both decerebrated and anaesthetized adult cats exposed to Decimetre Range Microwaves (DRM) (λ=65 cm, duration of exposition -10 min., at least) by the help of a 2 cm radius contact applicator located on the temple part of the head with cerebellum in the centre of projection of irradiation conducted from portable physiotherapeutic apparatus ``Romashka''. Extracelullar registration of Purkinje Cells (PC) impulse activities have been led by glass microelectrodes. Statistical and computational analyses of PC activities have been realized by the help of histograms - the characteristic distribution of the number of interimpulse intervals (II) between electrical discharges of a neuron on the II durations, drawn up by the help of a computer. The results obtained revealed the reaction of PC to DRM as a succession of starting to react of PC electrophysiological parameters, beginning from decreasing of known ``Inhibitory Pause'' duration, and further, at first, ``Simple Spikes'' then ``Complex Spikes'' frequencies' increase, and furthermore, durations' increase in ``Big Interimpulse Intervals'', parameter, introduced for the first time by us, in this way, showing the ``evolutionary'' nature of Electromagnetic Fields and Living object interactions.

Richness in Functional Connectivity Depends on the Neuronal Integrity within the Posterior Cingulate Cortex

PubMed Central

Lord, Anton R.; Li, Meng; Demenescu, Liliana R.; van den Meer, Johan; Borchardt, Viola; Krause, Anna Linda; Heinze, Hans-Jochen; Breakspear, Michael; Walter, Martin

2017-01-01

The brain's connectivity skeleton—a rich club of strongly interconnected members—was initially shown to exist in human structural networks, but recent evidence suggests a functional counterpart. This rich club typically includes key regions (or hubs) from multiple canonical networks, reducing the cost of inter-network communication. The posterior cingulate cortex (PCC), a hub node embedded within the default mode network, is known to facilitate communication between brain networks and is a key member of the “rich club.” Here, we assessed how metabolic signatures of neuronal integrity and cortical thickness influence the global extent of a functional rich club as measured using the functional rich club coefficient (fRCC). Rich club estimation was performed on functional connectivity of resting state brain signals acquired at 3T in 48 healthy adult subjects. Magnetic resonance spectroscopy was measured in the same session using a point resolved spectroscopy sequence. We confirmed convergence of functional rich club with a previously established structural rich club. N-acetyl aspartate (NAA) in the PCC is significantly correlated with age (p = 0.001), while the rich club coefficient showed no effect of age (p = 0.106). In addition, we found a significant quadratic relationship between fRCC and NAA concentration in PCC (p = 0.009). Furthermore, cortical thinning in the PCC was correlated with a reduced rich club coefficient after accounting for age and NAA. In conclusion, we found that the fRCC is related to a marker of neuronal integrity in a key region of the cingulate cortex. Furthermore, cortical thinning in the same area was observed, suggesting that both cortical thinning and neuronal integrity in the hub regions influence functional integration of at a whole brain level. PMID:28439224

Richness in Functional Connectivity Depends on the Neuronal Integrity within the Posterior Cingulate Cortex.

PubMed

Lord, Anton R; Li, Meng; Demenescu, Liliana R; van den Meer, Johan; Borchardt, Viola; Krause, Anna Linda; Heinze, Hans-Jochen; Breakspear, Michael; Walter, Martin

2017-01-01

The brain's connectivity skeleton-a rich club of strongly interconnected members-was initially shown to exist in human structural networks, but recent evidence suggests a functional counterpart. This rich club typically includes key regions (or hubs) from multiple canonical networks, reducing the cost of inter-network communication. The posterior cingulate cortex (PCC), a hub node embedded within the default mode network, is known to facilitate communication between brain networks and is a key member of the "rich club." Here, we assessed how metabolic signatures of neuronal integrity and cortical thickness influence the global extent of a functional rich club as measured using the functional rich club coefficient (fRCC). Rich club estimation was performed on functional connectivity of resting state brain signals acquired at 3T in 48 healthy adult subjects. Magnetic resonance spectroscopy was measured in the same session using a point resolved spectroscopy sequence. We confirmed convergence of functional rich club with a previously established structural rich club. N-acetyl aspartate (NAA) in the PCC is significantly correlated with age ( p = 0.001), while the rich club coefficient showed no effect of age (p = 0.106). In addition, we found a significant quadratic relationship between fRCC and NAA concentration in PCC ( p = 0.009). Furthermore, cortical thinning in the PCC was correlated with a reduced rich club coefficient after accounting for age and NAA. In conclusion, we found that the fRCC is related to a marker of neuronal integrity in a key region of the cingulate cortex. Furthermore, cortical thinning in the same area was observed, suggesting that both cortical thinning and neuronal integrity in the hub regions influence functional integration of at a whole brain level.

Selection, integration, and conflict monitoring; assessing the nature and generality of prefrontal cognitive control mechanisms.

PubMed

Badre, David; Wagner, Anthony D

2004-02-05

Prefrontal cortex (PFC) supports flexible behavior by mediating cognitive control, though the elemental forms of control supported by PFC remain a central debate. Dorsolateral PFC (DLPFC) is thought to guide response selection under conditions of response conflict or, alternatively, may refresh recently active representations within working memory. Lateral frontopolar cortex (FPC) may also adjudicate response conflict, though others propose that FPC supports higher order control processes such as subgoaling and integration. Anterior cingulate cortex (ACC) is hypothesized to upregulate response selection by detecting response conflict; it remains unclear whether ACC functions generalize beyond monitoring response conflict. The present fMRI experiment directly tested these competing theories regarding the functional roles of DLPFC, FPC, and ACC. Results reveal dissociable control processes in PFC, with mid-DLPFC selectively mediating resolution of response conflict and FPC further mediating subgoaling/integration. ACC demonstrated a broad sensitivity to control demands, suggesting a generalized role in modulating cognitive control.

Unseen fearful faces promote amygdala guidance of attention.

PubMed

Troiani, Vanessa; Price, Elinora T; Schultz, Robert T

2014-02-01

Little is known about the network of brain regions activated prior to explicit awareness of emotionally salient social stimuli. We investigated this in a functional magnetic resonance imaging study using a technique that combined elements of binocular rivalry and motion flash suppression in order to prevent awareness of fearful faces and houses. We found increased left amygdala and fusiform gyrus activation for fearful faces compared to houses, despite suppression from awareness. Psychophysiological interaction analyses showed that amygdala activation was associated with task-specific (fearful faces greater than houses) modulation of an attention network, including bilateral pulvinar, bilateral insula, left frontal eye fields, left intraparietal sulcus and early visual cortex. Furthermore, we report an unexpected main effect of increased left parietal cortex activation associated with suppressed fearful faces compared to suppressed houses. This parietal finding is the first report of increased dorsal stream activation for a social object despite suppression, which suggests that information can reach parietal cortex for a class of emotionally salient social objects, even in the absence of awareness.

Adult Visual Cortical Plasticity

PubMed Central

Gilbert, Charles D.; Li, Wu

2012-01-01

The visual cortex has the capacity for experience dependent change, or cortical plasticity, that is retained throughout life. Plasticity is invoked for encoding information during perceptual learning, by internally representing the regularities of the visual environment, which is useful for facilitating intermediate level vision - contour integration and surface segmentation. The same mechanisms have adaptive value for functional recovery after CNS damage, such as that associated with stroke or neurodegenerative disease. A common feature to plasticity in primary visual cortex (V1) is an association field that links contour elements across the visual field. The circuitry underlying the association field includes a plexus of long range horizontal connections formed by cortical pyramidal cells. These connections undergo rapid and exuberant sprouting and pruning in response to removal of sensory input, which can account for the topographic reorganization following retinal lesions. Similar alterations in cortical circuitry may be involved in perceptual learning, and the changes observed in V1 may be representative of how learned information is encoded throughout the cerebral cortex. PMID:22841310

Relationship between individual neuron and network spontaneous activity in developing mouse cortex.

PubMed

Barnett, Heather M; Gjorgjieva, Julijana; Weir, Keiko; Comfort, Cara; Fairhall, Adrienne L; Moody, William J

2014-12-15

Spontaneous synchronous activity (SSA) that propagates as electrical waves is found in numerous central nervous system structures and is critical for normal development, but the mechanisms of generation of such activity are not clear. In previous work, we showed that the ventrolateral piriform cortex is uniquely able to initiate SSA in contrast to the dorsal neocortex, which participates in, but does not initiate, SSA (Lischalk JW, Easton CR, Moody WJ. Dev Neurobiol 69: 407-414, 2009). In this study, we used Ca(2+) imaging of cultured embryonic day 18 to postnatal day 2 coronal slices (embryonic day 17 + 1-4 days in culture) of the mouse cortex to investigate the different activity patterns of individual neurons in these regions. In the piriform cortex where SSA is initiated, a higher proportion of neurons was active asynchronously between waves, and a larger number of groups of coactive cells was present compared with the dorsal cortex. When we applied GABA and glutamate synaptic antagonists, asynchronous activity and cellular clusters remained, while synchronous activity was eliminated, indicating that asynchronous activity is a result of cell-intrinsic properties that differ between these regions. To test the hypothesis that higher levels of cell-autonomous activity in the piriform cortex underlie its ability to initiate waves, we constructed a conductance-based network model in which three layers differed only in the proportion of neurons able to intrinsically generate bursting behavior. Simulations using this model demonstrated that a gradient of intrinsic excitability was sufficient to produce directionally propagating waves that replicated key experimental features, indicating that the higher level of cell-intrinsic activity in the piriform cortex may provide a substrate for SSA generation. Copyright © 2014 the American Physiological Society.

Community engagement as conflict prevention: Understanding the social license to operate

NASA Astrophysics Data System (ADS)

Knih, Dejana

This thesis examines community engagement as a form of conflict prevention in order to obtain the social license to operate (SLO) in Alberta's oil and gas industry. It does this by answering the question: what are the key elements of the Social License to Operate and how can these elements be applied to community engagement/consultation in a way that prevents conflicts in Alberta's oil and gas industry? The underlying assumption of this thesis is that building good relationships and working collaboratively functions as a form of conflict prevention and that this in turn leads to the SLO. This thesis outlines the key features of both successful community engagement and of the SLO, to provide a guideline for what is needed to obtain the SLO. Data was collected from semi-structured interviews and through a literature review. The data analysis concluded that there are direct parallels between the key elements of effective community engagement and the key elements of the SLO as identified in the interviews. These parallels are: knowing the community, addressing community needs, corporate social responsibility, relationship building, follow through and evidence for what has been done, executive buy-in, excellent communication, and open dialogue, all within a process which is principled (there is trust, understanding, transparency and respect), inclusive, dynamic, flexible, ongoing, and long-term. Moreover, the key elements of effective community engagement and of the SLO identified in the interviews also overlapped with those found in the literature review, with only one exception. The literature review explicitly named early involvement as a key element of both effective community engagement and the SLO, whereas the interview participants only explicitly indicated it as a key factor of community engagement and implied it to be a key element of the SLO.

The role of the posterior cingulate cortex in cognition and disease

PubMed Central

Sharp, David J.

2014-01-01

The posterior cingulate cortex is a highly connected and metabolically active brain region. Recent studies suggest it has an important cognitive role, although there is no consensus about what this is. The region is typically discussed as having a unitary function because of a common pattern of relative deactivation observed during attentionally demanding tasks. One influential hypothesis is that the posterior cingulate cortex has a central role in supporting internally-directed cognition. It is a key node in the default mode network and shows increased activity when individuals retrieve autobiographical memories or plan for the future, as well as during unconstrained ‘rest’ when activity in the brain is ‘free-wheeling’. However, other evidence suggests that the region is highly heterogeneous and may play a direct role in regulating the focus of attention. In addition, its activity varies with arousal state and its interactions with other brain networks may be important for conscious awareness. Understanding posterior cingulate cortex function is likely to be of clinical importance. It is well protected against ischaemic stroke, and so there is relatively little neuropsychological data about the consequences of focal lesions. However, in other conditions abnormalities in the region are clearly linked to disease. For example, amyloid deposition and reduced metabolism is seen early in Alzheimer’s disease. Functional neuroimaging studies show abnormalities in a range of neurological and psychiatric disorders including Alzheimer’s disease, schizophrenia, autism, depression and attention deficit hyperactivity disorder, as well as ageing. Our own work has consistently shown abnormal posterior cingulate cortex function following traumatic brain injury, which predicts attentional impairments. Here we review the anatomy and physiology of the region and how it is affected in a range of clinical conditions, before discussing its proposed functions. We synthesize key findings into a novel model of the region’s function (the ‘Arousal, Balance and Breadth of Attention’ model). Dorsal and ventral subcomponents are functionally separated and differences in regional activity are explained by considering: (i) arousal state; (ii) whether attention is focused internally or externally; and (iii) the breadth of attentional focus. The predictions of the model can be tested within the framework of complex dynamic systems theory, and we propose that the dorsal posterior cingulate cortex influences attentional focus by ‘tuning’ whole-brain metastability and so adjusts how stable brain network activity is over time. PMID:23869106

Prefrontal Cortex and Social Cognition in Mouse and Man

PubMed Central

Bicks, Lucy K.; Koike, Hiroyuki; Akbarian, Schahram; Morishita, Hirofumi

2015-01-01

Social cognition is a complex process that requires the integration of a wide variety of behaviors, including salience, reward-seeking, motivation, knowledge of self and others, and flexibly adjusting behavior in social groups. Not surprisingly, social cognition represents a sensitive domain commonly disrupted in the pathology of a variety of psychiatric disorders including Autism Spectrum Disorder (ASD) and Schizophrenia (SCZ). Here, we discuss convergent research from animal models to human disease that implicates the prefrontal cortex (PFC) as a key regulator in social cognition, suggesting that disruptions in prefrontal microcircuitry play an essential role in the pathophysiology of psychiatric disorders with shared social deficits. We take a translational perspective of social cognition, and review three key behaviors that are essential to normal social processing in rodents and humans, including social motivation, social recognition, and dominance hierarchy. A shared prefrontal circuitry may underlie these behaviors. Social cognition deficits in animal models of neurodevelopmental disorders like ASD and SCZ have been linked to an altered balance of excitation and inhibition (E/I ratio) within the cortex generally, and PFC specifically. A clear picture of the mechanisms by which altered E/I ratio in the PFC might lead to disruptions of social cognition across a variety of behaviors is not well understood. Future studies should explore how disrupted developmental trajectory of prefrontal microcircuitry could lead to altered E/I balance and subsequent deficits in the social domain. PMID:26635701

A Synaptic Basis for Memory Storage in the Cerebral Cortex

NASA Astrophysics Data System (ADS)

Bear, Mark F.

1996-11-01

A cardinal feature of neurons in the cerebral cortex is stimulus selectivity, and experience-dependent shifts in selectivity are a common correlate of memory formation. We have used a theoretical ``learning rule,'' devised to account for experience-dependent shifts in neuronal selectivity, to guide experiments on the elementary mechanisms of synaptic plasticity in hippocampus and neocortex. These experiments reveal that many synapses in hippocampus and neocortex are bidirectionally modifiable, that the modifications persist long enough to contribute to long-term memory storage, and that key variables governing the sign of synaptic plasticity are the amount of NMDA receptor activation and the recent history of cortical activity.

Identification of alpha-enolase as a nuclear DNA-binding protein in the zona fasciculata but not the zona reticularis of the human adrenal cortex.

PubMed

Wang, Weiye; Wang, Lishan; Endoh, Akira; Hummelke, Geoffrey; Hawks, Christina L; Hornsby, Peter J

2005-01-01

In order to establish whether there are differences in DNA-binding proteins between zona fasciculata (ZF) and zona reticularis (ZR) cells of the human adrenal cortex, we prepared nuclear extracts from separated ZF and ZR cells. The formation of DNA-protein complexes was studied using an element in the first intron of the type I and type II 3beta-hydroxysteroid dehydrogenase genes (HSD3B1 and HSD3B2). Using the element in the HSD3B2 gene as a probe, a complex (C1) was formed with extracts from ZF cells but was formed only at a low level with ZR cell extracts. Another pair of complexes (C2/C3) was formed with both ZF and ZR cell extracts. The ZF-specific protein forming C1 was enriched by column chromatography on DEAE-Sepharose and carboxymethyl-Sepharose. Oligonucleotide competition analysis on the enriched fraction gave results consistent with those obtained on the unfractionated material. A further enrichment was brought about by passing the protein over an oligonucleotide affinity column based on the HSD3B2 element. The protein bound to the column was identified as alpha-enolase by mass spectrometry. Although alpha-enolase is a glycolytic enzyme, it binds to specific DNA sequences and has been found to be present in nuclei of various cell types. We performed immunohistochemistry on sections of adult human adrenal cortex and found alpha-enolase to be located in nuclei of ZF cells but to be predominantly cytoplasmic in ZR cells. Transfection of an alpha-enolase expression vector into NCI-H295R human adrenocortical cells increased HSD3B2 promoter activity, suggesting a possible functional role for this protein in regulation of HSD3B2 expression.

Assessing the Psychedelic "After-Glow" in Ayahuasca Users: Post-Acute Neurometabolic and Functional Connectivity Changes Are Associated with Enhanced Mindfulness Capacities.

PubMed

Sampedro, Frederic; de la Fuente Revenga, Mario; Valle, Marta; Roberto, Natalia; Domínguez-Clavé, Elisabet; Elices, Matilde; Luna, Luís Eduardo; Crippa, José Alexandre S; Hallak, Jaime E C; de Araujo, Draulio B; Friedlander, Pablo; Barker, Steven A; Álvarez, Enrique; Soler, Joaquim; Pascual, Juan C; Feilding, Amanda; Riba, Jordi

2017-09-01

Ayahuasca is a plant tea containing the psychedelic 5-HT2A agonist N,N-dimethyltryptamine and harmala monoamine-oxidase inhibitors. Acute administration leads to neurophysiological modifications in brain regions of the default mode network, purportedly through a glutamatergic mechanism. Post-acutely, ayahuasca potentiates mindfulness capacities in volunteers and induces rapid and sustained antidepressant effects in treatment-resistant patients. However, the mechanisms underlying these fast and maintained effects are poorly understood. Here, we investigated in an open-label uncontrolled study in 16 healthy volunteers ayahuasca-induced post-acute neurometabolic and connectivity modifications and their association with mindfulness measures. Using 1H-magnetic resonance spectroscopy and functional connectivity, we compared baseline and post-acute neurometabolites and seed-to-voxel connectivity in the posterior and anterior cingulate cortex after a single ayahuasca dose. Magnetic resonance spectroscopy showed post-acute reductions in glutamate+glutamine, creatine, and N-acetylaspartate+N-acetylaspartylglutamate in the posterior cingulate cortex. Connectivity was increased between the posterior cingulate cortex and the anterior cingulate cortex, and between the anterior cingulate cortex and limbic structures in the right medial temporal lobe. Glutamate+glutamine reductions correlated with increases in the "nonjudging" subscale of the Five Facets Mindfulness Questionnaire. Increased anterior cingulate cortex-medial temporal lobe connectivity correlated with increased scores on the self-compassion questionnaire. Post-acute neural changes predicted sustained elevations in nonjudging 2 months later. These results support the involvement of glutamate neurotransmission in the effects of psychedelics in humans. They further suggest that neurometabolic changes in the posterior cingulate cortex, a key region within the default mode network, and increased connectivity between the anterior cingulate cortex and medial temporal lobe structures involved in emotion and memory potentially underlie the post-acute psychological effects of ayahuasca. © The Author 2017. Published by Oxford University Press on behalf of CINP.

Assessing the Psychedelic “After-Glow” in Ayahuasca Users: Post-Acute Neurometabolic and Functional Connectivity Changes Are Associated with Enhanced Mindfulness Capacities

PubMed Central

Sampedro, Frederic; de la Fuente Revenga, Mario; Valle, Marta; Roberto, Natalia; Domínguez-Clavé, Elisabet; Elices, Matilde; Luna, Luís Eduardo; Crippa, José Alexandre S; Hallak, Jaime E C; de Araujo, Draulio B; Friedlander, Pablo; Barker, Steven A; Álvarez, Enrique; Soler, Joaquim; Pascual, Juan C; Feilding, Amanda

2017-01-01

Abstract Background Ayahuasca is a plant tea containing the psychedelic 5-HT2A agonist N,N-dimethyltryptamine and harmala monoamine-oxidase inhibitors. Acute administration leads to neurophysiological modifications in brain regions of the default mode network, purportedly through a glutamatergic mechanism. Post-acutely, ayahuasca potentiates mindfulness capacities in volunteers and induces rapid and sustained antidepressant effects in treatment-resistant patients. However, the mechanisms underlying these fast and maintained effects are poorly understood. Here, we investigated in an open-label uncontrolled study in 16 healthy volunteers ayahuasca-induced post-acute neurometabolic and connectivity modifications and their association with mindfulness measures. Methods Using 1H-magnetic resonance spectroscopy and functional connectivity, we compared baseline and post-acute neurometabolites and seed-to-voxel connectivity in the posterior and anterior cingulate cortex after a single ayahuasca dose. Results Magnetic resonance spectroscopy showed post-acute reductions in glutamate+glutamine, creatine, and N-acetylaspartate+N-acetylaspartylglutamate in the posterior cingulate cortex. Connectivity was increased between the posterior cingulate cortex and the anterior cingulate cortex, and between the anterior cingulate cortex and limbic structures in the right medial temporal lobe. Glutamate+glutamine reductions correlated with increases in the “nonjudging” subscale of the Five Facets Mindfulness Questionnaire. Increased anterior cingulate cortex-medial temporal lobe connectivity correlated with increased scores on the self-compassion questionnaire. Post-acute neural changes predicted sustained elevations in nonjudging 2 months later. Conclusions These results support the involvement of glutamate neurotransmission in the effects of psychedelics in humans. They further suggest that neurometabolic changes in the posterior cingulate cortex, a key region within the default mode network, and increased connectivity between the anterior cingulate cortex and medial temporal lobe structures involved in emotion and memory potentially underlie the post-acute psychological effects of ayahuasca. PMID:28525587

Diffusive shunting of gases and other molecules in the renal vasculature: physiological and evolutionary significance.

PubMed

Ngo, Jennifer P; Ow, Connie P C; Gardiner, Bruce S; Kar, Saptarshi; Pearson, James T; Smith, David W; Evans, Roger G

2016-11-01

Countercurrent systems have evolved in a variety of biological systems that allow transfer of heat, gases, and solutes. For example, in the renal medulla, the countercurrent arrangement of vascular and tubular elements facilitates the trapping of urea and other solutes in the inner medulla, which in turn enables the formation of concentrated urine. Arteries and veins in the cortex are also arranged in a countercurrent fashion, as are descending and ascending vasa recta in the medulla. For countercurrent diffusion to occur, barriers to diffusion must be small. This appears to be characteristic of larger vessels in the renal cortex. There must also be gradients in the concentration of molecules between afferent and efferent vessels, with the transport of molecules possible in either direction. Such gradients exist for oxygen in both the cortex and medulla, but there is little evidence that large gradients exist for other molecules such as carbon dioxide, nitric oxide, superoxide, hydrogen sulfide, and ammonia. There is some experimental evidence for arterial-to-venous (AV) oxygen shunting. Mathematical models also provide evidence for oxygen shunting in both the cortex and medulla. However, the quantitative significance of AV oxygen shunting remains a matter of controversy. Thus, whereas the countercurrent arrangement of vasa recta in the medulla appears to have evolved as a consequence of the evolution of Henle's loop, the evolutionary significance of the intimate countercurrent arrangement of blood vessels in the renal cortex remains an enigma. Copyright © 2016 the American Physiological Society.

The industrial melanism mutation in British peppered moths is a transposable element.

PubMed

Van't Hof, Arjen E; Campagne, Pascal; Rigden, Daniel J; Yung, Carl J; Lingley, Jessica; Quail, Michael A; Hall, Neil; Darby, Alistair C; Saccheri, Ilik J

2016-06-02

Discovering the mutational events that fuel adaptation to environmental change remains an important challenge for evolutionary biology. The classroom example of a visible evolutionary response is industrial melanism in the peppered moth (Biston betularia): the replacement, during the Industrial Revolution, of the common pale typica form by a previously unknown black (carbonaria) form, driven by the interaction between bird predation and coal pollution. The carbonaria locus has been coarsely localized to a 200-kilobase region, but the specific identity and nature of the sequence difference controlling the carbonaria-typica polymorphism, and the gene it influences, are unknown. Here we show that the mutation event giving rise to industrial melanism in Britain was the insertion of a large, tandemly repeated, transposable element into the first intron of the gene cortex. Statistical inference based on the distribution of recombined carbonaria haplotypes indicates that this transposition event occurred around 1819, consistent with the historical record. We have begun to dissect the mode of action of the carbonaria transposable element by showing that it increases the abundance of a cortex transcript, the protein product of which plays an important role in cell-cycle regulation, during early wing disc development. Our findings fill a substantial knowledge gap in the iconic example of microevolutionary change, adding a further layer of insight into the mechanism of adaptation in response to natural selection. The discovery that the mutation itself is a transposable element will stimulate further debate about the importance of 'jumping genes' as a source of major phenotypic novelty.

Cardiorespiratory concerns shape brain responses during automatic panic-related scene processing in patients with panic disorder

PubMed Central

Feldker, Katharina; Heitmann, Carina Yvonne; Neumeister, Paula; Brinkmann, Leonie; Bruchmann, Maximillan; Zwitserlood, Pienie; Straube, Thomas

2018-01-01

Background Increased automatic processing of threat-related stimuli has been proposed as a key element in panic disorder. Little is known about the neural basis of automatic processing, in particular to task-irrelevant, panic-related, ecologically valid stimuli, or about the association between brain activation and symptomatology in patients with panic disorder. Methods The present event-related functional MRI (fMRI) study compared brain responses to task-irrelevant, panic-related and neutral visual stimuli in medication-free patients with panic disorder and healthy controls. Panic-related and neutral scenes were presented while participants performed a spatially non-overlapping bar orientation task. Correlation analyses investigated the association between brain responses and panic-related aspects of symptomatology, measured using the Anxiety Sensitivity Index (ASI). Results We included 26 patients with panic disorder and 26 heatlhy controls in our analysis. Compared with controls, patients with panic disorder showed elevated activation in the amygdala, brainstem, thalamus, insula, anterior cingulate cortex and midcingulate cortex in response to panic-related versus neutral task-irrelevant stimuli. Furthermore, fear of cardiovascular symptoms (a subcomponent of the ASI) was associated with insula activation, whereas fear of respiratory symptoms was associated with brainstem hyperactivation in patients with panic disorder. Limitations The additional implementation of measures of autonomic activation, such as pupil diameter, heart rate, or electrodermal activity, would have been informative during the fMRI scan as well as during the rating procedure. Conclusion Results reveal a neural network involved in the processing of panic-related distractor stimuli in patients with panic disorder and suggest an automatic weighting of panic-related information depending on the magnitude of cardiovascular and respiratory symptoms. Insula and brainstem activations show function-related associations with specific components of panic symptomatology. PMID:29252163

Cardiorespiratory concerns shape brain responses during automatic panic-related scene processing in patients with panic disorder.

PubMed

Feldker, Katharina; Heitmann, Carina Yvonne; Neumeister, Paula; Brinkmann, Leonie; Bruchmann, Maximillan; Zwitserlood, Pienie; Straube, Thomas

2018-01-01

Increased automatic processing of threat-related stimuli has been proposed as a key element in panic disorder. Little is known about the neural basis of automatic processing, in particular to task-irrelevant, panic-related, ecologically valid stimuli, or about the association between brain activation and symptomatology in patients with panic disorder. The present event-related functional MRI (fMRI) study compared brain responses to task-irrelevant, panic-related and neutral visual stimuli in medication-free patients with panic disorder and healthy controls. Panic-related and neutral scenes were presented while participants performed a spatially nonoverlapping bar orientation task. Correlation analyses investigated the association between brain responses and panic-related aspects of symptomatology, measured using the Anxiety Sensitivity Index (ASI). We included 26 patients with panic disorder and 26 heatlhy controls in our analysis. Compared with controls, patients with panic disorder showed elevated activation in the amygdala, brainstem, thalamus, insula, anterior cingulate cortex and midcingulate cortex in response to panic-related versus neutral task-irrelevant stimuli. Furthermore, fear of cardiovascular symptoms (a subcomponent of the ASI) was associated with insula activation, whereas fear of respiratory symptoms was associated with brainstem hyperactivation in patients with panic disorder. The additional implementation of measures of autonomic activation, such as pupil diameter, heart rate, or electrodermal activity, would have been informative during the fMRI scan as well as during the rating procedure. Results reveal a neural network involved in the processing of panic-related distractor stimuli in patients with panic disorder and suggest an automatic weighting of panic-related information depending on the magnitude of cardiovascular and respiratory symptoms. Insula and brainstem activations show function-related associations with specific components of panic symptomatology.

Cardiorespiratory concerns shape brain responses during automatic panic-related scene processing in patients with panic disorder.

PubMed

Feldker, Katharina; Heitmann, Carina Yvonne; Neumeister, Paula; Brinkmann, Leonie; Bruchmann, Maximillan; Zwitserlood, Pienie; Straube, Thomas

2017-09-26

Increased automatic processing of threat-related stimuli has been proposed as a key element in panic disorder. Little is known about the neural basis of automatic processing, in particular to task-irrelevant, panic-related, ecologically valid stimuli, or about the association between brain activation and symptomatology in patients with panic disorder. The present event-related fMRI study compared brain responses to task-irrelevant, panic-related and neutral visual stimuli in medication-free patients with panic disorder and healthy controls. Panic-related and neutral scenes were presented while participants performed a spatially nonoverlapping bar orientation task. Correlation analyses investigated the association between brain responses and panic-related aspects of symptomatology, measured using the Anxiety Sensitivity Index (ASI). We included 26 patients with panic disorder and 26 heatlhy controls in our analysis. Compared with controls, patients with panic disorder showed elevated activation in the amygdala, brainstem, thalamus, insula, anterior cingulate cortex and midcingulate cortex in response to panic-related versus neutral task-irrelevant stimuli. Furthermore, fear of cardiovascular symptoms (a subcomponent of the ASI) was associated with insula activation, whereas fear of respiratory symptoms was associated with brainstem hyperactivation in patients with panic disorder. The additional implementation of measures of autonomic activation, such as pupil diameter, heart rate, or electrodermal activity, would have been informative during the fMRI scan as well as during the rating procedure. Results reveal a neural network involved in the processing of panic-related distractor stimuli in patients with panic disorder and suggest an automatic weighting of panic-related information depending on the magnitude of cardiovascular and respiratory symptoms. Insula and brainstem activations show function-related associations with specific components of panic symptomatology.

An Embedded 4-Channel Receive-Only RF Coil Array for fMRI Experiments of the Somatosensory Pathway in Conscious Awake Marmosets at 7T

PubMed Central

Papoti, Daniel; Yen, Cecil Chern-Chyi; Mackel, Julie B.; Merkle, Hellmut; Silva, Afonso C.

2014-01-01

Functional Magnetic Resonance Imaging (fMRI) has established itself as the main research tool in neuroscience and brain cognitive research. The common marmoset (Callithrix jacchus) is a non-human primate model of increasing interest in biomedical research. However, commercial MRI coils for marmosets are not generally available. The present work describes the design and construction of a 4-channel receive-only surface RF coil array with excellent signal-to-noise ratio (SNR) specifically optimized for fMRI experiments in awake marmosets in response to somatosensory stimulation. The array was designed as part of a helmet-based head restraint system used to prevent motion during the scans. High SNR was obtained by building the coil array using a thin and flexible substrate glued to the inner surface of the restraint helmet, so as to minimize the distance between the array elements and the somatosensory cortex. Decoupling between coil elements was achieved by partial geometrical overlapping and by connecting them to home-built low input impedance preamplifiers. In vivo images show excellent coverage of the brain cortical surface with high sensitivity near the somatosensory cortex. Embedding the coil elements within the restraint helmet allowed fMRI data in response to somatosensory stimulation to be collected with high sensitivity and reproducibility in conscious, awake marmosets. PMID:23696219

Different Cortical Dynamics in Face and Body Perception: An MEG study

PubMed Central

Meeren, Hanneke K. M.; de Gelder, Beatrice; Ahlfors, Seppo P.; Hämäläinen, Matti S.; Hadjikhani, Nouchine

2013-01-01

Evidence from functional neuroimaging indicates that visual perception of human faces and bodies is carried out by distributed networks of face and body-sensitive areas in the occipito-temporal cortex. However, the dynamics of activity in these areas, needed to understand their respective functional roles, are still largely unknown. We monitored brain activity with millisecond time resolution by recording magnetoencephalographic (MEG) responses while participants viewed photographs of faces, bodies, and control stimuli. The cortical activity underlying the evoked responses was estimated with anatomically-constrained noise-normalised minimum-norm estimate and statistically analysed with spatiotemporal cluster analysis. Our findings point to distinct spatiotemporal organization of the neural systems for face and body perception. Face-selective cortical currents were found at early latencies (120–200 ms) in a widespread occipito-temporal network including the ventral temporal cortex (VTC). In contrast, early body-related responses were confined to the lateral occipito-temporal cortex (LOTC). These were followed by strong sustained body-selective responses in the orbitofrontal cortex from 200–700 ms, and in the lateral temporal cortex and VTC after 500 ms latency. Our data suggest that the VTC region has a key role in the early processing of faces, but not of bodies. Instead, the LOTC, which includes the extra-striate body area (EBA), appears the dominant area for early body perception, whereas the VTC contributes to late and post-perceptual processing. PMID:24039712

The shared neural basis of empathy and facial imitation accuracy.

PubMed

Braadbaart, L; de Grauw, H; Perrett, D I; Waiter, G D; Williams, J H G

2014-01-01

Empathy involves experiencing emotion vicariously, and understanding the reasons for those emotions. It may be served partly by a motor simulation function, and therefore share a neural basis with imitation (as opposed to mimicry), as both involve sensorimotor representations of intentions based on perceptions of others' actions. We recently showed a correlation between imitation accuracy and Empathy Quotient (EQ) using a facial imitation task and hypothesised that this relationship would be mediated by the human mirror neuron system. During functional Magnetic Resonance Imaging (fMRI), 20 adults observed novel 'blends' of facial emotional expressions. According to instruction, they either imitated (i.e. matched) the expressions or executed alternative, pre-prescribed mismatched actions as control. Outside the scanner we replicated the association between imitation accuracy and EQ. During fMRI, activity was greater during mismatch compared to imitation, particularly in the bilateral insula. Activity during imitation correlated with EQ in somatosensory cortex, intraparietal sulcus and premotor cortex. Imitation accuracy correlated with activity in insula and areas serving motor control. Overlapping voxels for the accuracy and EQ correlations occurred in premotor cortex. We suggest that both empathy and facial imitation rely on formation of action plans (or a simulation of others' intentions) in the premotor cortex, in connection with representations of emotional expressions based in the somatosensory cortex. In addition, the insula may play a key role in the social regulation of facial expression. © 2013.

Cholinergic enhancement of visual attention and neural oscillations in the human brain.

PubMed

Bauer, Markus; Kluge, Christian; Bach, Dominik; Bradbury, David; Heinze, Hans Jochen; Dolan, Raymond J; Driver, Jon

2012-03-06

Cognitive processes such as visual perception and selective attention induce specific patterns of brain oscillations. The neurochemical bases of these spectral changes in neural activity are largely unknown, but neuromodulators are thought to regulate processing. The cholinergic system is linked to attentional function in vivo, whereas separate in vitro studies show that cholinergic agonists induce high-frequency oscillations in slice preparations. This has led to theoretical proposals that cholinergic enhancement of visual attention might operate via gamma oscillations in visual cortex, although low-frequency alpha/beta modulation may also play a key role. Here we used MEG to record cortical oscillations in the context of administration of a cholinergic agonist (physostigmine) during a spatial visual attention task in humans. This cholinergic agonist enhanced spatial attention effects on low-frequency alpha/beta oscillations in visual cortex, an effect correlating with a drug-induced speeding of performance. By contrast, the cholinergic agonist did not alter high-frequency gamma oscillations in visual cortex. Thus, our findings show that cholinergic neuromodulation enhances attentional selection via an impact on oscillatory synchrony in visual cortex, for low rather than high frequencies. We discuss this dissociation between high- and low-frequency oscillations in relation to proposals that lower-frequency oscillations are generated by feedback pathways within visual cortex. Copyright © 2012 Elsevier Ltd. All rights reserved.

Exposure to Inorganic Mercury Causes Oxidative Stress, Cell Death, and Functional Deficits in the Motor Cortex.

PubMed

Teixeira, Francisco B; de Oliveira, Ana C A; Leão, Luana K R; Fagundes, Nathália C F; Fernandes, Rafael M; Fernandes, Luanna M P; da Silva, Márcia C F; Amado, Lilian L; Sagica, Fernanda E S; de Oliveira, Edivaldo H C; Crespo-Lopez, Maria E; Maia, Cristiane S F; Lima, Rafael R

2018-01-01

Mercury is a toxic metal that can be found in the environment in three different forms - elemental, organic and inorganic. Inorganic mercury has a lower liposolubility, which results in a lower organism absorption and reduced passage through the blood-brain barrier. For this reason, exposure models that use inorganic mercury in rats in order to evaluate its effects on the central nervous system are rare, especially in adult subjects. This study investigated if a chronic exposure to low doses of mercury chloride (HgCl2), an inorganic form of mercury, is capable of promoting motor alterations and neurodegenerative in the motor cortex of adult rats. Forty animals were exposed to a dose of 0.375 mg/kg/day, for 45 days. They were then submitted to motor evaluation and euthanized to collect the motor cortex. Measurement of mercury deposited in the brain parenchyma, evaluation of oxidative balance, quantification of cellular cytotoxicity and apoptosis and density of mature neurons and astrocytes of the motor cortex were performed. It was observed that chronic exposure to inorganic mercury caused a decrease in balance and fine motor coordination, formation of mercury deposits and oxidative stress verified by the increase of lipoperoxidation and nitrite concentration and a decrease of the total antioxidant capacity. In addition, we found that this model of exposure to inorganic mercury caused cell death by cytotoxicity and induction of apoptosis with a decreased number of neurons and astrocytes in the motor cortex. Our results provide evidence that exposure to inorganic mercury in low doses, even in spite of its poor ability to cross biological barriers, is still capable of inducing motor deficits, cell death by cytotoxicity and apoptosis, and oxidative stress in the motor cortex of adult rats.

Computational modeling of direct neuronal recruitment during intracortical microstimulation in somatosensory cortex.

PubMed

Overstreet, C K; Klein, J D; Helms Tillery, S I

2013-12-01

Electrical stimulation of cortical tissue could be used to deliver sensory information as part of a neuroprosthetic device, but current control of the location, resolution, quality, and intensity of sensations elicited by intracortical microstimulation (ICMS) remains inadequate for this purpose. One major obstacle to resolving this problem is the poor understanding of the neural activity induced by ICMS. Even with new imaging methods, quantifying the activity of many individual neurons within cortex is difficult. We used computational modeling to examine the response of somatosensory cortex to ICMS. We modeled the axonal arbors of eight distinct morphologies of interneurons and seven types of pyramidal neurons found in somatosensory cortex and identified their responses to extracellular stimulation. We then combined these axonal elements to form a multi-layered slab of simulated cortex and investigated the patterns of neural activity directly induced by ICMS. Specifically we estimated the number, location, and variety of neurons directly recruited by stimulation on a single penetrating microelectrode. The population of neurons activated by ICMS was dependent on both stimulation strength and the depth of the electrode within cortex. Strikingly, stimulation recruited interneurons and pyramidal neurons in very different patterns. Interneurons are primarily recruited within a dense, continuous region around the electrode, while pyramidal neurons were recruited in a sparse fashion both near the electrode and up to several millimeters away. Thus ICMS can lead to an unexpectedly complex spatial distribution of firing neurons. These results lend new insights to the complexity and range of neural activity that can be induced by ICMS. This work also suggests mechanisms potentially responsible for the inconsistency and unnatural quality of sensations initiated by ICMS. Understanding these mechanisms will aid in the design of stimulation that can be used to generate effective sensory feedback for neuroprosthetic devices.

Exposure to Inorganic Mercury Causes Oxidative Stress, Cell Death, and Functional Deficits in the Motor Cortex

PubMed Central

Teixeira, Francisco B.; de Oliveira, Ana C. A.; Leão, Luana K. R.; Fagundes, Nathália C. F.; Fernandes, Rafael M.; Fernandes, Luanna M. P.; da Silva, Márcia C. F.; Amado, Lilian L.; Sagica, Fernanda E. S.; de Oliveira, Edivaldo H. C.; Crespo-Lopez, Maria E.; Maia, Cristiane S. F.; Lima, Rafael R.

2018-01-01

Mercury is a toxic metal that can be found in the environment in three different forms – elemental, organic and inorganic. Inorganic mercury has a lower liposolubility, which results in a lower organism absorption and reduced passage through the blood–brain barrier. For this reason, exposure models that use inorganic mercury in rats in order to evaluate its effects on the central nervous system are rare, especially in adult subjects. This study investigated if a chronic exposure to low doses of mercury chloride (HgCl2), an inorganic form of mercury, is capable of promoting motor alterations and neurodegenerative in the motor cortex of adult rats. Forty animals were exposed to a dose of 0.375 mg/kg/day, for 45 days. They were then submitted to motor evaluation and euthanized to collect the motor cortex. Measurement of mercury deposited in the brain parenchyma, evaluation of oxidative balance, quantification of cellular cytotoxicity and apoptosis and density of mature neurons and astrocytes of the motor cortex were performed. It was observed that chronic exposure to inorganic mercury caused a decrease in balance and fine motor coordination, formation of mercury deposits and oxidative stress verified by the increase of lipoperoxidation and nitrite concentration and a decrease of the total antioxidant capacity. In addition, we found that this model of exposure to inorganic mercury caused cell death by cytotoxicity and induction of apoptosis with a decreased number of neurons and astrocytes in the motor cortex. Our results provide evidence that exposure to inorganic mercury in low doses, even in spite of its poor ability to cross biological barriers, is still capable of inducing motor deficits, cell death by cytotoxicity and apoptosis, and oxidative stress in the motor cortex of adult rats. PMID:29867340

Erk regulation of actin capping and bundling by Eps8 promotes cortex tension and leader bleb-based migration

PubMed Central

Logue, Jeremy S; Cartagena-Rivera, Alexander X; Baird, Michelle A; Davidson, Michael W; Chadwick, Richard S; Waterman, Clare M

2015-01-01

Within the confines of tissues, cancer cells can use blebs to migrate. Eps8 is an actin bundling and capping protein whose capping activity is inhibited by Erk, a key MAP kinase that is activated by oncogenic signaling. We tested the hypothesis that Eps8 acts as an Erk effector to modulate actin cortex mechanics and thereby mediate bleb-based migration of cancer cells. Cells confined in a non-adhesive environment migrate in the direction of a very large ‘leader bleb.’ Eps8 bundling activity promotes cortex tension and intracellular pressure to drive leader bleb formation. Eps8 capping and bundling activities act antagonistically to organize actin within leader blebs, and Erk mediates this effect. An Erk biosensor reveals concentrated kinase activity within leader blebs. Bleb contents are trapped by the narrow neck that separates the leader bleb from the cell body. Thus, Erk activity promotes actin bundling by Eps8 to enhance cortex tension and drive the bleb-based migration of cancer cells under non-adhesive confinement. DOI: http://dx.doi.org/10.7554/eLife.08314.001 PMID:26163656

Evolution and development of the mammalian cerebral cortex.

PubMed

Molnár, Zoltán; Kaas, Jon H; de Carlos, Juan A; Hevner, Robert F; Lein, Ed; Němec, Pavel

2014-01-01

Comparative developmental studies of the mammalian brain can identify key changes that can generate the diverse structures and functions of the brain. We have studied how the neocortex of early mammals became organized into functionally distinct areas, and how the current level of cortical cellular and laminar specialization arose from the simpler premammalian cortex. We demonstrate the neocortical organization in early mammals, which helps to elucidate how the large, complex human brain evolved from a long line of ancestors. The radial and tangential enlargement of the cortex was driven by changes in the patterns of cortical neurogenesis, including alterations in the proportions of distinct progenitor types. Some cortical cell populations travel to the cortex through tangential migration whereas others migrate radially. A number of recent studies have begun to characterize the chick, mouse and human and nonhuman primate cortical transcriptome to help us understand how gene expression relates to the development and anatomical and functional organization of the adult neocortex. Although all mammalian forms share the basic layout of cortical areas, the areal proportions and distributions are driven by distinct evolutionary pressures acting on sensory and motor experiences during the individual ontogenies. © 2014 S. Karger AG, Basel.

Dopamine Promotes Motor Cortex Plasticity and Motor Skill Learning via PLC Activation

PubMed Central

Rioult-Pedotti, Mengia-Seraina; Pekanovic, Ana; Atiemo, Clement Osei; Marshall, John; Luft, Andreas Rüdiger

2015-01-01

Dopaminergic neurons in the ventral tegmental area, the major midbrain nucleus projecting to the motor cortex, play a key role in motor skill learning and motor cortex synaptic plasticity. Dopamine D1 and D2 receptor antagonists exert parallel effects in the motor system: they impair motor skill learning and reduce long-term potentiation. Traditionally, D1 and D2 receptor modulate adenylyl cyclase activity and cyclic adenosine monophosphate accumulation in opposite directions via different G-proteins and bidirectionally modulate protein kinase A (PKA), leading to distinct physiological and behavioral effects. Here we show that D1 and D2 receptor activity influences motor skill acquisition and long term synaptic potentiation via phospholipase C (PLC) activation in rat primary motor cortex. Learning a new forelimb reaching task is severely impaired in the presence of PLC, but not PKA-inhibitor. Similarly, long term potentiation in motor cortex, a mechanism involved in motor skill learning, is reduced when PLC is inhibited but remains unaffected by the PKA inhibitor. Skill learning deficits and reduced synaptic plasticity caused by dopamine antagonists are prevented by co-administration of a PLC agonist. These results provide evidence for a role of intracellular PLC signaling in motor skill learning and associated cortical synaptic plasticity, challenging the traditional view of bidirectional modulation of PKA by D1 and D2 receptors. These findings reveal a novel and important action of dopamine in motor cortex that might be a future target for selective therapeutic interventions to support learning and recovery of movement resulting from injury and disease. PMID:25938462

Underconnectivity between voice-selective cortex and reward circuitry in children with autism.

PubMed

Abrams, Daniel A; Lynch, Charles J; Cheng, Katherine M; Phillips, Jennifer; Supekar, Kaustubh; Ryali, Srikanth; Uddin, Lucina Q; Menon, Vinod

2013-07-16

Individuals with autism spectrum disorders (ASDs) often show insensitivity to the human voice, a deficit that is thought to play a key role in communication deficits in this population. The social motivation theory of ASD predicts that impaired function of reward and emotional systems impedes children with ASD from actively engaging with speech. Here we explore this theory by investigating distributed brain systems underlying human voice perception in children with ASD. Using resting-state functional MRI data acquired from 20 children with ASD and 19 age- and intelligence quotient-matched typically developing children, we examined intrinsic functional connectivity of voice-selective bilateral posterior superior temporal sulcus (pSTS). Children with ASD showed a striking pattern of underconnectivity between left-hemisphere pSTS and distributed nodes of the dopaminergic reward pathway, including bilateral ventral tegmental areas and nucleus accumbens, left-hemisphere insula, orbitofrontal cortex, and ventromedial prefrontal cortex. Children with ASD also showed underconnectivity between right-hemisphere pSTS, a region known for processing speech prosody, and the orbitofrontal cortex and amygdala, brain regions critical for emotion-related associative learning. The degree of underconnectivity between voice-selective cortex and reward pathways predicted symptom severity for communication deficits in children with ASD. Our results suggest that weak connectivity of voice-selective cortex and brain structures involved in reward and emotion may impair the ability of children with ASD to experience speech as a pleasurable stimulus, thereby impacting language and social skill development in this population. Our study provides support for the social motivation theory of ASD.

Orbito-frontal cortex and thalamus volumes in the patients with obsessive-compulsive disorder before and after cognitive behavioral therapy.

PubMed

Atmaca, Murad; Yildirim, Hanefi; Yilmaz, Seda; Caglar, Neslihan; Mermi, Osman; Korkmaz, Sevda; Akaslan, Unsal; Gurok, M Gurkan; Kekilli, Yasemin; Turkcapar, Hakan

2018-07-01

Background The effect of a variety of treatment modalities including psychopharmacological and cognitive behavioral therapy on the brain volumes and neurochemicals have not been investigated enough in the patients with obsessive-compulsive disorder. Therefore, in the present study, we aimed to investigate the effect of cognitive behavioral therapy on the volumes of the orbito-frontal cortex and thalamus regions which seem to be abnormal in the patients with obsessive-compulsive disorder. We hypothesized that there would be change in the volumes of the orbito-frontal cortex and thalamus. Methods Twelve patients with obsessive-compulsive disorder and same number of healthy controls were included into the study. At the beginning of the study, the volumes of the orbito-frontal cortex and thalamus were compared by using magnetic resonance imaging. In addition, volumes of these regions were measured before and after the cognitive behavioral therapy treatment in the patient group. Results The patients with obsessive-compulsive disorder had greater left and right thalamus volumes and smaller left and right orbito-frontal cortex volumes compared to those of healthy control subjects at the beginning of the study. When we compared baseline volumes of the patients with posttreatment ones, we detected that thalamus volumes significantly decreased throughout the period for both sides and that the orbito-frontal cortex volumes significantly increased throughout the period for only left side. Conclusions In summary, we found that cognitive behavioral therapy might volumetrically affect the key brain regions involved in the neuroanatomy of obsessive-compulsive disorder. However, future studies with larger sample are required.

A Visual Cortical Network for Deriving Phonological Information from Intelligible Lip Movements.

PubMed

Hauswald, Anne; Lithari, Chrysa; Collignon, Olivier; Leonardelli, Elisa; Weisz, Nathan

2018-05-07

Successful lip-reading requires a mapping from visual to phonological information [1]. Recently, visual and motor cortices have been implicated in tracking lip movements (e.g., [2]). It remains unclear, however, whether visuo-phonological mapping occurs already at the level of the visual cortex-that is, whether this structure tracks the acoustic signal in a functionally relevant manner. To elucidate this, we investigated how the cortex tracks (i.e., entrains to) absent acoustic speech signals carried by silent lip movements. Crucially, we contrasted the entrainment to unheard forward (intelligible) and backward (unintelligible) acoustic speech. We observed that the visual cortex exhibited stronger entrainment to the unheard forward acoustic speech envelope compared to the unheard backward acoustic speech envelope. Supporting the notion of a visuo-phonological mapping process, this forward-backward difference of occipital entrainment was not present for actually observed lip movements. Importantly, the respective occipital region received more top-down input, especially from left premotor, primary motor, and somatosensory regions and, to a lesser extent, also from posterior temporal cortex. Strikingly, across participants, the extent of top-down modulation of the visual cortex stemming from these regions partially correlated with the strength of entrainment to absent acoustic forward speech envelope, but not to present forward lip movements. Our findings demonstrate that a distributed cortical network, including key dorsal stream auditory regions [3-5], influences how the visual cortex shows sensitivity to the intelligibility of speech while tracking silent lip movements. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Cooperative interactions between hippocampal and striatal systems support flexible navigation

PubMed Central

Brown, Thackery I; Ross, Robert S; Tobyne, Sean M; Stern, Chantal E

2012-01-01

Research in animals and humans has demonstrated that the hippocampus is critical for retrieving distinct representations of overlapping sequences of information. There is recent evidence that the caudate nucleus and orbitofrontal cortex are also involved in disambiguation of overlapping spatial representations. The hippocampus and caudate are functionally distinct regions, but both have anatomical links with the orbitofrontal cortex. The present study used an fMRI-based functional connectivity analysis in humans to examine the functional relationship between the hippocampus, caudate, and orbitofrontal cortex when participants use contextual information to navigate well-learned spatial routes which share common elements. Participants were trained outside the scanner to navigate virtual mazes from a first-person perspective. Overlapping condition mazes began and ended at distinct locations, but converged in the middle to share some hallways with another maze. Non-overlapping condition mazes did not share any hallways with any other maze. Successful navigation through the overlapping hallways required contextual information identifying the current navigational route to guide the appropriate response for a given trial. Results revealed greater functional connectivity between the hippocampus, caudate, and orbitofrontal cortex for overlapping mazes compared to non-overlapping mazes. The current findings suggest that the hippocampus and caudate interact with prefrontal structures cooperatively for successful contextually-dependent navigation. PMID:22266411

Learning a New Selection Rule in Visual and Frontal Cortex.

PubMed

van der Togt, Chris; Stănişor, Liviu; Pooresmaeili, Arezoo; Albantakis, Larissa; Deco, Gustavo; Roelfsema, Pieter R

2016-08-01

How do you make a decision if you do not know the rules of the game? Models of sensory decision-making suggest that choices are slow if evidence is weak, but they may only apply if the subject knows the task rules. Here, we asked how the learning of a new rule influences neuronal activity in the visual (area V1) and frontal cortex (area FEF) of monkeys. We devised a new icon-selection task. On each day, the monkeys saw 2 new icons (small pictures) and learned which one was relevant. We rewarded eye movements to a saccade target connected to the relevant icon with a curve. Neurons in visual and frontal cortex coded the monkey's choice, because the representation of the selected curve was enhanced. Learning delayed the neuronal selection signals and we uncovered the cause of this delay in V1, where learning to select the relevant icon caused an early suppression of surrounding image elements. These results demonstrate that the learning of a new rule causes a transition from fast and random decisions to a more considerate strategy that takes additional time and they reveal the contribution of visual and frontal cortex to the learning process. © The Author 2016. Published by Oxford University Press.

How do emotion and motivation direct executive control?

PubMed Central

Pessoa, Luiz

2009-01-01

Emotion and motivation have crucial roles in determining human behavior. Yet, how they interact with cognitive control functions is less understood. Here, the basic elements of a conceptual framework for understanding how they interact are introduced. More broadly, the `dual competition' framework proposes that emotion and motivation affect both perceptual and executive competition. In particular, the anterior cingulate cortex is hypothesized to be engaged in attentional/effortful control mechanisms and to interact with several other brain structures, including the amygdala and nucleus accumbens, in integrating affectively significant signals with control signals in prefrontal cortex. An implication of the proposal is that emotion and motivation can either enhance or impair behavioral performance depending on how they interact with control functions. PMID:19285913

The role of the parahippocampal cortex in cognition

PubMed Central

Aminoff, Elissa M.; Kveraga, Kestutis; Bar, Moshe

2013-01-01

The parahippocampal cortex (PHC) has been associated with many cognitive processes, including visuospatial processing and episodic memory. To characterize the role of PHC in cognition a framework is required that unifies these disparate processes. An overarching account was proposed, whereby the PHC is part of a network of brain regions that processes contextual associations. Contextual associations are the principal element underlying many higher-level cognitive processes, and thus are suitable for unifying the PHC literature. Recent findings are reviewed that provide support for the contextual associations account of PHC function. In addition to reconciling a vast breadth of literature, the synthesis presented expands the implications of the proposed account and gives rise to new and general questions about context and cognition. PMID:23850264

Perceptual grouping in the human brain: common processing of different cues.

PubMed

Seymour, Kiley; Karnath, Hans-Otto; Himmelbach, Marc

2008-12-03

The perception of global scenes and objects consisting of multiple constituents is based on the integration of local elements or features. Gestalt grouping cues, such as proximity or similarity, can aid this process. Using functional MRI we investigated whether grouping guided by different gestalt cues rely on distinct networks in the brain or share a common network. Our study revealed that gestalt grouping involved the inferior parietal cortex, middle temporal gyrus and prefrontal cortex irrespective of the specific cue used. These findings agree with observations in neurological patients, which suggest that inferior parietal regions may aid the integration of local features into a global gestalt. Damage to this region results in simultanagnosia, a deficit in perceiving multiple objects and global scenes.

SDMS: A scientific data management system

NASA Technical Reports Server (NTRS)

Massena, W. A.

1978-01-01

SDMS is a data base management system developed specifically to support scientific programming applications. It consists of a data definition program to define the forms of data bases, and FORTRAN-compatible subroutine calls to create and access data within them. Each SDMS data base contains one or more data sets. A data set has the form of a relation. Each column of a data set is defined to be either a key or data element. Key elements must be scalar. Data elements may also be vectors or matrices. The data elements in each row of the relation form an element set. SDMS permits direct storage and retrieval of an element set by specifying the corresponding key element values. To support the scientific environment, SDMS allows the dynamic creation of data bases via subroutine calls. It also allows intermediate or scratch data to be stored in temporary data bases which vanish at job end.

Ordered versus Unordered Map for Primitive Data Types

DTIC Science & Technology

2015-09-01

mapped to some element. C++ provides two types of map containers within the standard template library, the std ::map and the std ::unordered_map...classes. As the name implies, the containers main functional difference is that the elements in the std ::map are ordered by the key, and the std ...unordered_map are not ordered based on their key. The std ::unordered_map elements are placed into “buckets” based on a hash value computed for their key

Neuronal activity in primate auditory cortex during the performance of audiovisual tasks.

PubMed

Brosch, Michael; Selezneva, Elena; Scheich, Henning

2015-03-01

This study aimed at a deeper understanding of which cognitive and motivational aspects of tasks affect auditory cortical activity. To this end we trained two macaque monkeys to perform two different tasks on the same audiovisual stimulus and to do this with two different sizes of water rewards. The monkeys had to touch a bar after a tone had been turned on together with an LED, and to hold the bar until either the tone (auditory task) or the LED (visual task) was turned off. In 399 multiunits recorded from core fields of auditory cortex we confirmed that during task engagement neurons responded to auditory and non-auditory stimuli that were task-relevant, such as light and water. We also confirmed that firing rates slowly increased or decreased for several seconds during various phases of the tasks. Responses to non-auditory stimuli and slow firing changes were observed during both the auditory and the visual task, with some differences between them. There was also a weak task-dependent modulation of the responses to auditory stimuli. In contrast to these cognitive aspects, motivational aspects of the tasks were not reflected in the firing, except during delivery of the water reward. In conclusion, the present study supports our previous proposal that there are two response types in the auditory cortex that represent the timing and the type of auditory and non-auditory elements of a auditory tasks as well the association between elements. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

The possible mechanism of Parkinson's disease progressive damage and the preventive effect of GM1 in the rat model induced by 6-hydroxydopamine.

PubMed

Xu, Renshi; Zhou, Yiyi; Fang, Xin; Lu, Yi; Li, Jiao; Zhang, Jie; Deng, Xia; Li, Shujuan

2014-12-10

The progressive pathogenesis and prevention of Parkinson's disease (PD) remains unknown at present. Therefore, the present study aimed to investigate the possible progressive pathogenesis and prevention of PD. Our study investigated the content of glutamate, mitochondria calcium, calmodulin, malonaldehyde and trace elements in striatum, cerebral cortex and hippocampus tissues; and the expression of bcl-2, bax and neuronal nitric oxide synthase (nNOS) in substantia nigra and striatum; and the change of apomorphine induced rotation behavior; and the treatmental effect of monosialotetrahexosylganglioside (GM1) intraperitoneal administration for 14 days in a PD rat model induced by 6-hydroxydopamine. The results revealed that the content of glutamate significantly decreased, and that of mitochondria calcium, calmodulin, malonaldehyde and ferrum significantly increased in striatum, cerebral cortex and hippocampus tissues; the content of magnesium significantly decreased, and that of cuprum and zinc significantly increased in cerebral cortex; the expression of bcl-2 significantly decreased, and that of bax and nNOS significantly increased in substantia nigra and striatum in PD rat. GM1 can partially improve the apomorphine induced rotation behavior and changes of glutamate, mitochondria calcium, calmodulin content in striatum of PD rat. Data suggested that dysfunction of excitatory amino acids neurotransmitter, calcium homeostasis disorder, abnormal metabolism of oxygen free radicals, abnormal trace elements distribution and/or deposition and excessive apoptosis participated in the progressive process of PD, and that GM1 could partially prevent the progressive damage. Copyright © 2014 Elsevier B.V. All rights reserved.

Plasticity and stability of visual field maps in adult primary visual cortex

PubMed Central

Wandell, Brian A.; Smirnakis, Stelios M.

2010-01-01

Preface It is important to understand the balance between cortical plasticity and stability in various systems and spatial scales in the adult brain. We review measurements of adult plasticity in primary visual cortex (V1), a structure that has a key role in distributing visual information. There are claims of plasticity at multiple spatial scales in adult V1, but many inconsistencies in the data raise questions about the extent and nature of such plasticity. Understanding is further limited by a lack of quantitative models to guide the interpretation of the data. These problems limit efforts to translate research findings about adult cortical plasticity into significant clinical, educational and policy applications. PMID:19904279

Task-dependent recurrent dynamics in visual cortex

PubMed Central

Tajima, Satohiro; Koida, Kowa; Tajima, Chihiro I; Suzuki, Hideyuki; Aihara, Kazuyuki; Komatsu, Hidehiko

2017-01-01

The capacity for flexible sensory-action association in animals has been related to context-dependent attractor dynamics outside the sensory cortices. Here, we report a line of evidence that flexibly modulated attractor dynamics during task switching are already present in the higher visual cortex in macaque monkeys. With a nonlinear decoding approach, we can extract the particular aspect of the neural population response that reflects the task-induced emergence of bistable attractor dynamics in a neural population, which could be obscured by standard unsupervised dimensionality reductions such as PCA. The dynamical modulation selectively increases the information relevant to task demands, indicating that such modulation is beneficial for perceptual decisions. A computational model that features nonlinear recurrent interaction among neurons with a task-dependent background input replicates the key properties observed in the experimental data. These results suggest that the context-dependent attractor dynamics involving the sensory cortex can underlie flexible perceptual abilities. DOI: http://dx.doi.org/10.7554/eLife.26868.001 PMID:28737487

Similarities and differences between parietal and frontal patients in autobiographical and constructed experience tasks

PubMed Central

Berryhill, Marian E.; Picasso, Lauren; Arnold, Robert; Drowos, David; Olson, Ingrid R.

2010-01-01

Recent findings suggest that constructed experience, the ability to envision future events, activates the same cortical network as recollection of past events. For example, damage to one key area, the hippocampus, impairs patients' ability to remember the past and to imagine novel experiences (Hassabis, Kumaran, Vann & Maguire, 2007). Here, we investigated whether damage to two other areas, posterior parietal cortex and prefrontal cortex, also impairs this ability. Patients with bilateral posterior parietal lesions or unilateral prefrontal lesions were tested in their ability to describe imaginary future events. Only parietal patients were impaired at freely describing autobiographical memories, but both patient groups were impaired when elaborating constructed experiences. This dissociation suggests that parietal and prefrontal structures are differentially involved in constructed experience. Current tasks may impose overly broad cognitive demands making it impossible to specify the deficient cognitive component in any patient group. These findings provide additional constraints regarding the mechanistic role of the parietal cortex in memory. PMID:20096710

A major gene controls mimicry and crypsis in butterflies and moths

PubMed Central

Nadeau, Nicola J.; Pardo-Diaz, Carolina; Whibley, Annabel; Supple, Megan; Saenko, Suzanne V.; Wallbank, Richard W. R.; Wu, Grace C.; Maroja, Luana; Ferguson, Laura; Hanly, Joseph J.; Hines, Heather; Salazar, Camilo; Merrill, Richard; Dowling, Andrea; ffrench-Constant, Richard; Llaurens, Violaine; Joron, Mathieu; McMillan, W. Owen; Jiggins, Chris D.

2016-01-01

The wing patterns of butterflies and moths (Lepidoptera) are diverse and striking examples of evolutionary diversification by natural selection1,2. Lepidopteran wing colour patterns are a key innovation, consisting of arrays of coloured scales. We still lack a general understanding of how these patterns are controlled and if there is any commonality across the 160,000 moth and 17,000 butterfly species. Here, we identify a gene, cortex, through fine-scale mapping using population genomics and gene expression analyses, which regulates pattern switches in multiple species across the mimetic radiation in Heliconius butterflies. cortex belongs to a fast evolving subfamily of the otherwise highly conserved fizzy family of cell cycle regulators3, suggesting that it most likely regulates pigmentation patterning through regulation of scale cell development. In parallel with findings in the peppered moth (Biston betularia)4, our results suggest that this mechanism is common within Lepidoptera and that cortex has become a major target for natural selection acting on colour and pattern variation in this group of insects. PMID:27251285

Hyperconnectivity of prefrontal cortex to amygdala projections in a mouse model of macrocephaly/autism syndrome.

PubMed

Huang, Wen-Chin; Chen, Youjun; Page, Damon T

2016-11-15

Multiple autism risk genes converge on the regulation of mTOR signalling, which is a key effector of neuronal growth and connectivity. We show that mTOR signalling is dysregulated during early postnatal development in the cerebral cortex of germ-line heterozygous Pten mutant mice (Pten +/- ), which model macrocephaly/autism syndrome. The basolateral amygdala (BLA) receives input from subcortical-projecting neurons in the medial prefrontal cortex (mPFC). Analysis of mPFC to BLA axonal projections reveals that Pten +/- mice exhibit increased axonal branching and connectivity, which is accompanied by increased activity in the BLA in response to social stimuli and social behavioural deficits. The latter two phenotypes can be suppressed by pharmacological inhibition of S6K1 during early postnatal life or by reducing the activity of mPFC-BLA circuitry in adulthood. These findings identify a mechanism of altered connectivity that has potential relevance to the pathophysiology of macrocephaly/autism syndrome and autism spectrum disorders featuring dysregulated mTOR signalling.

The Functional Architecture of the Brain Underlies Strategic Deception in Impression Management

PubMed Central

Luo, Qiang; Ma, Yina; Bhatt, Meghana A.; Montague, P. Read; Feng, Jianfeng

2017-01-01

Impression management, as one of the most essential skills of social function, impacts one's survival and success in human societies. However, the neural architecture underpinning this social skill remains poorly understood. By employing a two-person bargaining game, we exposed three strategies involving distinct cognitive processes for social impression management with different levels of strategic deception. We utilized a novel adaptation of Granger causality accounting for signal-dependent noise (SDN), which captured the directional connectivity underlying the impression management during the bargaining game. We found that the sophisticated strategists engaged stronger directional connectivity from both dorsal anterior cingulate cortex and retrosplenial cortex to rostral prefrontal cortex, and the strengths of these directional influences were associated with higher level of deception during the game. Using the directional connectivity as a neural signature, we identified the strategic deception with 80% accuracy by a machine-learning classifier. These results suggest that different social strategies are supported by distinct patterns of directional connectivity among key brain regions for social cognition. PMID:29163095

Hyperconnectivity of prefrontal cortex to amygdala projections in a mouse model of macrocephaly/autism syndrome

PubMed Central

Huang, Wen-Chin; Chen, Youjun; Page, Damon T.

2016-01-01

Multiple autism risk genes converge on the regulation of mTOR signalling, which is a key effector of neuronal growth and connectivity. We show that mTOR signalling is dysregulated during early postnatal development in the cerebral cortex of germ-line heterozygous Pten mutant mice (Pten+/−), which model macrocephaly/autism syndrome. The basolateral amygdala (BLA) receives input from subcortical-projecting neurons in the medial prefrontal cortex (mPFC). Analysis of mPFC to BLA axonal projections reveals that Pten+/− mice exhibit increased axonal branching and connectivity, which is accompanied by increased activity in the BLA in response to social stimuli and social behavioural deficits. The latter two phenotypes can be suppressed by pharmacological inhibition of S6K1 during early postnatal life or by reducing the activity of mPFC–BLA circuitry in adulthood. These findings identify a mechanism of altered connectivity that has potential relevance to the pathophysiology of macrocephaly/autism syndrome and autism spectrum disorders featuring dysregulated mTOR signalling. PMID:27845329

Re-thinking the role of motor cortex: Context-sensitive motor outputs?

PubMed Central

Gandolla, Marta; Ferrante, Simona; Molteni, Franco; Guanziroli, Eleonora; Frattini, Tiziano; Martegani, Alberto; Ferrigno, Giancarlo; Friston, Karl; Pedrocchi, Alessandra; Ward, Nick S.

2014-01-01

The standard account of motor control considers descending outputs from primary motor cortex (M1) as motor commands and efference copy. This account has been challenged recently by an alternative formulation in terms of active inference: M1 is considered as part of a sensorimotor hierarchy providing top–down proprioceptive predictions. The key difference between these accounts is that predictions are sensitive to the current proprioceptive context, whereas efference copy is not. Using functional electric stimulation to experimentally manipulate proprioception during voluntary movement in healthy human subjects, we assessed the evidence for context sensitive output from M1. Dynamic causal modeling of functional magnetic resonance imaging responses showed that FES altered proprioception increased the influence of M1 on primary somatosensory cortex (S1). These results disambiguate competing accounts of motor control, provide some insight into the synaptic mechanisms of sensory attenuation and may speak to potential mechanisms of action of FES in promoting motor learning in neurorehabilitation. PMID:24440530

Re-thinking the role of motor cortex: context-sensitive motor outputs?

PubMed

Gandolla, Marta; Ferrante, Simona; Molteni, Franco; Guanziroli, Eleonora; Frattini, Tiziano; Martegani, Alberto; Ferrigno, Giancarlo; Friston, Karl; Pedrocchi, Alessandra; Ward, Nick S

2014-05-01

The standard account of motor control considers descending outputs from primary motor cortex (M1) as motor commands and efference copy. This account has been challenged recently by an alternative formulation in terms of active inference: M1 is considered as part of a sensorimotor hierarchy providing top-down proprioceptive predictions. The key difference between these accounts is that predictions are sensitive to the current proprioceptive context, whereas efference copy is not. Using functional electric stimulation to experimentally manipulate proprioception during voluntary movement in healthy human subjects, we assessed the evidence for context sensitive output from M1. Dynamic causal modeling of functional magnetic resonance imaging responses showed that FES altered proprioception increased the influence of M1 on primary somatosensory cortex (S1). These results disambiguate competing accounts of motor control, provide some insight into the synaptic mechanisms of sensory attenuation and may speak to potential mechanisms of action of FES in promoting motor learning in neurorehabilitation. Copyright © 2014 unknown. Published by Elsevier Inc. All rights reserved.

Pedophilia is linked to reduced activation in hypothalamus and lateral prefrontal cortex during visual erotic stimulation.

PubMed

Walter, Martin; Witzel, Joachim; Wiebking, Christine; Gubka, Udo; Rotte, Michael; Schiltz, Kolja; Bermpohl, Felix; Tempelmann, Claus; Bogerts, Bernhard; Heinze, Hans Jochen; Northoff, Georg

2007-09-15

Although pedophilia is of high public concern, little is known about underlying neural mechanisms. Although pedophilic patients are sexually attracted to prepubescent children, they show no sexual interest toward adults. This study aimed to investigate the neural correlates of deficits of sexual and emotional arousal in pedophiles. Thirteen pedophilic patients and 14 healthy control subjects were tested for differential neural activity during visual stimulation with emotional and erotic pictures with functional magnetic resonance imaging. Regions showing differential activations during the erotic condition comprised the hypothalamus, the periaqueductal gray, and dorsolateral prefrontal cortex, the latter correlating with a clinical measure. Alterations of emotional processing concerned the amygdala-hippocampus and dorsomedial prefrontal cortex. Hypothesized regions relevant for processing of erotic stimuli in healthy individuals showed reduced activations during visual erotic stimulation in pedophilic patients. This suggests an impaired recruitment of key structures that might contribute to an altered sexual interest of these patients toward adults.

Effect of electroacupuncture on the expression of interlukin-1beta mRNA after transient focal cerebral ischemia.

PubMed

Xu, Zhen-Feng; Wu, Gen-Cheng; Cao, Xiao-Ding

2002-01-01

It has been reported that interleukin-1beta (IL-1beta ) play a key role in the pathogenesis of cerebral ischemia. Acupuncture is an effective traditional medical therapy in China. The aim of present study was to evaluate the effect of electroacupuncture (EA) on IL-1beta mRNA expression after middle cerebral artery occlusion (MCAO) in rats. Using in situ hybridization technique, it was found that in the MCAO group the expression of IL-1beta mRNA was significantly increased at 2h, 6h, 12h after reperfusion in cerebral ischemic cortex compared with normal group. In EA+ MCAO group the expression of IL-1beta mRNA was significantly decreased at 2h, 6h and 12h in ischemic cortex compared with MCAO group. The results indicated that EA might decrease the IL-1beta protein expression by reducing the IL-beta mRNA expression in ischemic cortex.

The Functional Architecture of the Brain Underlies Strategic Deception in Impression Management.

PubMed

Luo, Qiang; Ma, Yina; Bhatt, Meghana A; Montague, P Read; Feng, Jianfeng

2017-01-01

Impression management, as one of the most essential skills of social function, impacts one's survival and success in human societies. However, the neural architecture underpinning this social skill remains poorly understood. By employing a two-person bargaining game, we exposed three strategies involving distinct cognitive processes for social impression management with different levels of strategic deception. We utilized a novel adaptation of Granger causality accounting for signal-dependent noise (SDN), which captured the directional connectivity underlying the impression management during the bargaining game. We found that the sophisticated strategists engaged stronger directional connectivity from both dorsal anterior cingulate cortex and retrosplenial cortex to rostral prefrontal cortex, and the strengths of these directional influences were associated with higher level of deception during the game. Using the directional connectivity as a neural signature, we identified the strategic deception with 80% accuracy by a machine-learning classifier. These results suggest that different social strategies are supported by distinct patterns of directional connectivity among key brain regions for social cognition.

Adaptation to conflict via context-driven anticipatory signals in the dorsomedial prefrontal cortex.

PubMed

Horga, Guillermo; Maia, Tiago V; Wang, Pengwei; Wang, Zhishun; Marsh, Rachel; Peterson, Bradley S

2011-11-09

Behavioral interference elicited by competing response tendencies adapts to contextual changes. Recent nonhuman primate research suggests a key mnemonic role of distinct prefrontal cells in supporting such context-driven behavioral adjustments by maintaining conflict information across trials, but corresponding prefrontal functions have yet to be probed in humans. Using event-related functional magnetic resonance imaging, we investigated the human neural substrates of contextual adaptations to conflict. We found that a neural system comprising the rostral dorsomedial prefrontal cortex and portions of the dorsolateral prefrontal cortex specifically encodes the history of previously experienced conflict and influences subsequent adaptation to conflict on a trial-by-trial basis. This neural system became active in anticipation of stimulus onsets during preparatory periods and interacted with a second neural system engaged during the processing of conflict. Our findings suggest that a dynamic interaction between a system that represents conflict history and a system that resolves conflict underlies the contextual adaptation to conflict.

Adaptation to Conflict via Context-Driven Anticipatory Signals in the Dorsomedial Prefrontal Cortex

PubMed Central

Horga, Guillermo; Maia, Tiago V.; Wang, Pengwei; Wang, Zhishun; Marsh, Rachel; Peterson, Bradley S.

2011-01-01

Behavioral interference elicited by competing response tendencies adapts to contextual changes. Recent nonhuman primate research suggests a key mnemonic role of distinct prefrontal cells in supporting such context-driven behavioral adjustments by maintaining conflict information across trials, but corresponding prefrontal functions have yet to be probed in humans. Using event-related functional magnetic resonance imaging (fMRI), we investigated the human neural substrates of contextual adaptations to conflict. We found that a neural system comprising the rostral dorsomedial prefrontal cortex and portions of the dorsolateral prefrontal cortex specifically encodes the history of previously experienced conflict and influences subsequent adaptation to conflict on a trial-by-trial basis. This neural system became active in anticipation of stimulus onsets during preparatory periods and interacted with a second neural system engaged during the processing of conflict. Our findings suggest that a dynamic interaction between a system that represents conflict history and a system that resolves conflict underlies the contextual adaptation to conflict. PMID:22072672

Parcellation in Left Lateral Parietal Cortex Is Similar in Adults and Children

PubMed Central

Nelson, Steven M.; Cohen, Alexander L.; Power, Jonathan D.; Coalson, Rebecca S.; Miezin, Francis M.; Vogel, Alecia C.; Dubis, Joseph W.; Church, Jessica A.; Petersen, Steven E.; Schlaggar, Bradley L.

2012-01-01

A key question in developmental neuroscience involves understanding how and when the cerebral cortex is partitioned into distinct functional areas. The present study used functional connectivity MRI mapping and graph theory to identify putative cortical areas and generate a parcellation scheme of left lateral parietal cortex (LLPC) in 7 to 10-year-old children and adults. Results indicated that a majority of putative LLPC areas could be matched across groups (mean distance between matched areas across age: 3.15 mm). Furthermore, the boundaries of children's putative LLPC areas respected the boundaries generated from the adults' parcellation scheme for a majority of children's areas (13/15). Consistent with prior research, matched LLPC areas showed age-related differences in functional connectivity strength with other brain regions. These results suggest that LLPC cortical parcellation and functional connectivity mature along different developmental trajectories, with adult-like boundaries between LLPC areas established in school-age children prior to adult-like functional connectivity. PMID:21810781

Neuroscience of inhibition for addiction medicine: From prediction of initiation to prediction of relapse

PubMed Central

Moeller, Scott J.; Bederson, Lucia; Alia-Klein, Nelly; Goldstein, Rita Z.

2017-01-01

A core deficit in drug addiction is the inability to inhibit maladaptive drug-seeking behavior. Consistent with this deficit, drug-addicted individuals show reliable cross-sectional differences from healthy non-addicted controls during tasks of response inhibition accompanied by brain activation abnormalities as revealed by functional neuroimaging. However, it is less clear whether inhibition-related deficits predate the transition to problematic use, and, in turn, whether these deficits predict the transition out of problematic substance use. Here, we review longitudinal studies of response inhibition in children/adolescents with little substance experience and longitudinal studies of already-addicted individuals attempting to sustain abstinence. Results show that response inhibition, and its underlying neural correlates, predict both substance use outcomes (onset and abstinence). Neurally, key roles were observed for multiple regions of the frontal cortex (e.g., inferior frontal gyrus, dorsal anterior cingulate cortex, and dorsolateral prefrontal cortex). In general, less activation of these regions during response inhibition predicted not only the onset of substance use, but interestingly, also better abstinence-related outcomes among individuals already addicted. The role of subcortical areas, although potentially important, is less clear because of inconsistent results and because these regions are less classically reported in studies of healthy response inhibition. Overall, this review indicates that response inhibition is not simply a manifestation of current drug addiction, but rather a core neurocognitive dimension that predicts key substance use outcomes. Early intervention in inhibitory deficits could have high clinical and public health relevance. PMID:26806776

Functional connectivity of the ventral tegmental area and avolition in subjects with schizophrenia: a resting state functional MRI study.

PubMed

Giordano, Giulia Maria; Stanziano, Mario; Papa, Michele; Mucci, Armida; Prinster, Anna; Soricelli, Andrea; Galderisi, Silvana

2018-04-10

Avolition, a deficit in goal-directed behavior, is a key aspect of negative symptoms. It is highly prevalent in schizophrenia and is associated to poor functional outcome and to measures of real life motivation, indicating that central to the concept is the lack of interest and motivation. In this study we tested the hypothesis that avolition is related to altered connectivity within dopaminergic cortico-striatal circuits involved in motivation processes. Since dopamine input to these circuits derives mostly from the ventro-tegmental area (VTA), we investigated the relationships between the resting-state functional connectivity (RS-FC) of the VTA and avolition in twenty-six subjects with schizophrenia (SCZ), treated with second-generation antipsychotics only, compared to twenty-two healthy controls (HC). SCZ, in comparison to HC, showed significantly reduced RS-FC of the VTA with bilateral ventro-lateral prefrontal cortex (VLPFC), bilateral insular cortex (IC) and right (R) lateral occipital complex (LOC) and increased RS-FC of the VTA with bilateral dorso-lateral prefrontal cortex (DLPFC). Significant negative correlations were found between avolition and RS-FC of the VTA with the bilateral IC, R VLPFC and R LOC. According to our findings, avolition is linked to a disconnectivity of the VTA from several key cortical regions involved in the integration of value information with action selection. These findings are in line with translational animal models of "auto-activation apathy". Copyright © 2018 Elsevier B.V. and ECNP. All rights reserved.

Crosstalk between intracellular and extracellular signals regulating interneuron production, migration and integration into the cortex.

PubMed

Peyre, Elise; Silva, Carla G; Nguyen, Laurent

2015-01-01

During embryogenesis, cortical interneurons are generated by ventral progenitors located in the ganglionic eminences of the telencephalon. They travel along multiple tangential paths to populate the cortical wall. As they reach this structure they undergo intracortical dispersion to settle in their final destination. At the cellular level, migrating interneurons are highly polarized cells that extend and retract processes using dynamic remodeling of microtubule and actin cytoskeleton. Different levels of molecular regulation contribute to interneuron migration. These include: (1) Extrinsic guidance cues distributed along migratory streams that are sensed and integrated by migrating interneurons; (2) Intrinsic genetic programs driven by specific transcription factors that grant specification and set the timing of migration for different subtypes of interneurons; (3) Adhesion molecules and cytoskeletal elements/regulators that transduce molecular signalings into coherent movement. These levels of molecular regulation must be properly integrated by interneurons to allow their migration in the cortex. The aim of this review is to summarize our current knowledge of the interplay between microenvironmental signals and cell autonomous programs that drive cortical interneuron porduction, tangential migration, and intergration in the developing cerebral cortex.

Monosialotetrahexosylganglioside Inhibits the Expression of p-CREB and NR2B in the Auditory Cortex in Rats with Salicylate-Induced Tinnitus.

PubMed

Song, Rui-Biao; Lou, Wei-Hua

2015-01-01

This study investigated the effects of monosialotetrahexosylganglioside (GM1) on the expression of N-methyl-D-aspartate receptor subunit 2B (NR2B) and phosphorylated (p)-cyclic AMP response element-binding protein (CREB) in the auditory cortex of rats with tinnitus. Tinnitus-like behavior in rats was tested with the gap prepulse inhibition of acoustic startle paradigm. We then investigated the NR2B mRNA and protein and p-CREB protein levels in the auditory cortex of tinnitus rats compared with normal rats. Rats treated for 4 days with salicylate exhibited tinnitus. NR2B mRNA and protein and p-CREB protein levels were upregulated in these animals, with expression returning to normal levels 14 days after cessation of treatment; baseline levels of NR2B and p-CREB were also restored by GM1 administration. These data suggest that chronic salicylate administration induces tinnitus via upregulation of p-CREB and NR2B expression, and that GM1 can potentially be used to treat tinnitus.

Imaging of metal bioaccumulation in hay-scented fern (Dennstaedtia punctilobula) rhizomes growing on contaminated soils by laser ablation ICP-MS.

PubMed

Koelmel, Jeremy; Amarasiriwardena, Dulasiri

2012-09-01

Understanding Pb removal from the translocation stream is vital to engineering Pb hyperaccumulation in above ground organs, which would enhance the economic feasibility of Pb phytoextraction technologies. We investigated Cu, Pb, Sb and Zn distributions in Hay-scented fern (Dennstaedtia punctilobula) rhizomes on shooting range soils by laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS), analyzing digested rhizomes, stems, and fronds using ICP-MS. Nutrients Cu and Zn concentrated in fronds while toxic elements Pb and Sb did not, showing potential Pb and Sb sequestration in the rhizome. Frond and rhizome concentration of Pb was 0.17 ± 0.10% and 0.32 ± 0.21% of dry biomass, respectively. The 208Pb/13C and 121Sb/13C determined by LA-ICP-MS increased from inner sclerotic cortex to the epidermis, while Pb concentrated in the starchy cortex only in contaminated sites. These results suggest that concentration dependent bioaccumulation in the rhizome outer cortex removes Pb from the vascular transport stream. Copyright © 2012 Elsevier Ltd. All rights reserved.

Regional cerebral metabolic alterations in dementia of the Alzheimer type: positron emission tomography with (/sup 18/F)fluorodeoxyglucose

DOE Office of Scientific and Technical Information (OSTI.GOV)

Friedland, R.P.; Budinger, T.F.; Ganz, E.

1983-08-01

Alzheimer disease is the most common cause of dementia in adults. Despite recent advances in our understanding of its anatomy and chemistry, we remain largely ignorant of its pathogenesis, physiology, diagnosis, and treatment. Dynamic positron emission tomography using (/sup 18/F)fluorodeoxyglucose (FDG) was performed on the Donner 280-crystal ring in 10 subjects with dementia of the Alzheimer type and six healthy age-matched controls. Ratios comparing mean counts per resolution element in frontal, temporoparietal, and entire cortex regions in brain sections 10 mm thick obtained 40-70 min following FDG injection showed relatively less FDG uptake in the temporoparietal cortex bilaterally in allmore » the Alzheimer subjects (p less than 0.01). Left-right alterations were less prominent than the anteroposterior changes. This diminished uptake was due to lowered rates of FDG use and suggests that the metabolic effects of Alzheimer disease are most concentrated in the temporoparietal cortex. Positron emission tomography is a most powerful tool for the noninvasive in vivo assessment of cerebral pathophysiology in dementia.« less

The differential contributions of pFC and temporo-parietal cortex to multimodal semantic control: exploring refractory effects in semantic aphasia.

PubMed

Gardner, Hannah E; Lambon Ralph, Matthew A; Dodds, Naomi; Jones, Theresa; Ehsan, Sheeba; Jefferies, Elizabeth

2012-04-01

Aphasic patients with multimodal semantic impairment following pFC or temporo-parietal (TP) cortex damage (semantic aphasia [SA]) have deficits characterized by poor control of semantic activation/retrieval, as opposed to loss of semantic knowledge per se. In line with this, SA patients show "refractory effects"; that is, declining accuracy in cyclical word-picture matching tasks when semantically related sets are presented rapidly and repeatedly. This is argued to follow a build-up of competition between targets and distractors. However, the link between poor semantic control and refractory effects is still controversial for two reasons. (1) Some theories propose that refractory effects are specific to verbal or auditory tasks, yet SA patients show poor control over semantic processing in both word and picture semantic tasks. (2) SA can result from lesions to either the left pFC or TP cortex, yet previous work suggests that refractory effects are specifically linked to the left inferior frontal cortex. For the first time, verbal, visual, and nonverbal auditory refractory effects were explored in nine SA patients who had pFC (pFC+) or TP cortex (TP-only) lesions. In all modalities, patient accuracy declined significantly over repetitions. This refractory effect at the group level was driven by pFC+ patients and was not shown by individuals with TP-only lesions. These findings support the theory that SA patients have reduced control over multimodal semantic retrieval and, additionally, suggest there may be functional specialization within the posterior versus pFC elements of the semantic control network.

Aptamer-functionalized Fe3 O4 magnetic nanoparticles as a solid-phase extraction adsorbent for the selective extraction of berberine from Cortex phellodendri.

PubMed

Jiang, Ling-Feng; Chen, Bo-Cheng; Chen, Ben; Li, Xue-Jian; Liao, Hai-Lin; Zhang, Wen-Yan; Wu, Lin

2017-07-01

The extraction adsorbent was fabricated by immobilizing the highly specific recognition and binding of aptamer onto the surface of Fe 3 O 4 magnetic nanoparticles, which not only acted as recognition elements to recognize and capture the target molecule berberine from the extract of Cortex phellodendri, but also could favor the rapid separation and purification of the bound berberine by using an external magnet. The developed solid-phase extraction method in this work was useful for the selective extraction and determination of berberine in Cortex phellodendri extracts. Various conditions such as the amount of aptamer-functionalized Fe 3 O 4 magnetic nanoparticles, extraction time, temperature, pH value, Mg 2+ concentration, elution time and solvent were optimized for the solid-phase extraction of berberine. Under optimal conditions, the purity of berberine extracted from Cortex phellodendri was as high as 98.7% compared with that of 4.85% in the extract, indicating that aptamer-functionalized Fe 3 O 4 magnetic nanoparticles-based solid-phase extraction method was very effective for berberine enrichment and separation from a complex herb extract. The applicability and reliability of the developed solid-phase extraction method were demonstrated by separating berberine from nine different concentrations of one Cortex phellodendri extract. The relative recoveries of the spiked solutions of all the samples were between 95.4 and 111.3%, with relative standard deviations ranging between 0.57 and 1.85%. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Scopolamine into the anterior cingulate cortex diminishes nociception in a neuropathic pain model in the rat: an interruption of 'nociception-related memory acquisition'?

PubMed

Ortega-Legaspi, J Manuel; López-Avila, Alberto; Coffeen, Ulises; del Angel, Rosendo; Pellicer, Francisco

2003-01-01

The cingulate cortex plays a key role in the affective component related to pain perception. This structure receives cholinergic projections and also plays a role in memory processing. Therefore, we propose that the cholinergic system in the anterior cingulate cortex is involved in the nociceptive memory process. We used scopolamine (10 microg in 0.25 mircrol/saline) microinjected into the anterior cingulate cortex, either before thermonociception followed by a sciatic denervation, between thermonociception and denervation or after both procedures (n=10 each). The vehicle group (saline solution 0.9%, n=14) was microinjected before thermonociception. Chronic nociception was measured by the autotomy score, which onset and incidence were also determined. Group scopolamine-thermonociception-denervation (STD) presented the lowest autotomy score as compared to vehicle and group thermonociception-denervation-scopolamine (TDS) (vehicle vs. STD, p=0.002, STD vs. TDS, p=0.001). Group thermonociception-scopolamine-denervation (TSD) showed a diminished autotomy score when compared to TDS (p=0.053). STD group showed a delay in the onset of AB as compared to the rest of the groups. Group TSD presented a significative delay (p=0.048) in AB onset when compared to group TDS. There were no differences in the incidence between groups. The results show that nociception-related memory processed in the anterior cingulate cortex is susceptible of being modified by the cholinergic transmission blockade. When scopolamine is microinjected prior to the nociceptive stimuli, nociception-related memory acquisition is prevented. The evidence obtained in this study shows the role of the anterior cingulate cortex in the acquisition of nociception-related memory.

Neurocognitive development of the ability to manipulate information in working memory.

PubMed

Crone, Eveline A; Wendelken, Carter; Donohue, Sarah; van Leijenhorst, Linda; Bunge, Silvia A

2006-06-13

The ability to manipulate information in working memory is a key factor in cognitive development. Here, we used event-related functional MRI to test the hypothesis that developmental improvements in manipulation, relative to pure maintenance, are associated with increased recruitment of dorsolateral (DL) prefrontal cortex (PFC) and superior parietal cortex. Three age groups (8-12 years old, 13-17 years old, and 18-25 years old) performed an object-working memory task with separate maintenance and manipulation conditions. We found that 8- to 12-year-olds did not perform the task as well as adolescents or adults, particularly on trials requiring manipulation in addition to maintenance. In this study, no age differences were observed in the activation profile of ventrolateral PFC, a region associated with online maintenance. In contrast, unlike the older participants, 8- to 12-year-olds failed to recruit right DL PFC and bilateral superior parietal cortex during the delay period for manipulation relative to maintenance. This group difference was observed specifically during the delay period, while participants reordered items in working memory, and could not be accounted for by group differences in performance. Across participants, activation levels in right DL PFC and superior parietal cortex, but not ventrolateral PFC, were positively correlated with performance on manipulation trials. These results indicate that increased recruitment of right DL PFC and bilateral parietal cortex during adolescence is associated with improvements in the ability to work with object representations.

Schizophrenia: a tale of two critical periods for prefrontal cortical development

PubMed Central

Selemon, L D; Zecevic, N

2015-01-01

Schizophrenia is a disease of abnormal brain development. Considerable evidence now indicates that environmental factors have a causative role in schizophrenia. Elevated incidence of the disease has been linked to a wide range of disturbances in the prenatal environment and to social factors and drug intake during adolescence. Here we examine neurodevelopment of the prefrontal cortex in the first trimester of gestation and during adolescence to gain further insight into the neurodevelopmental processes that may be vulnerable in schizophrenia. Early embryonic development of the prefrontal cortex is characterized by cell proliferation, including renewal of progenitor cells, generation of early transient cell populations and neurogenesis of subcortical populations. Animal models show that curtailing early gestational cell proliferation produces schizophrenia-like pathology in the prefrontal cortex and mimics key behavioral and cognitive symptoms of the disease. At the other end of the spectrum, elimination of excitatory synapses is the fundamental process occurring during adolescent maturation in the prefrontal cortex. Adverse social situations that elevate stress increase dopamine stimulation of the mesocortical pathway and may lead to exaggerated synaptic pruning during adolescence. In a non-human primate model, dopamine hyperstimulation has been shown to decrease prefrontal pyramidal cell spine density and to be associated with profound cognitive dysfunction. Development of the prefrontal cortex in its earliest stage in gestation and in its final stage in adolescence represents two critical periods of vulnerability for schizophrenia in which cell proliferation and synaptic elimination, respectively, may be influenced by environmental factors. PMID:26285133

Strategies for tonal and atonal musical interpretation in blind and normally sighted children: an fMRI study.

PubMed

Guerrero Arenas, Coral; Hidalgo Tobón, Silvia S; Dies Suarez, Pilar; Barragán Pérez, Eduardo; Castro Sierra, Eduardo; García, Julio; de Celis Alonso, Benito

2016-04-01

Early childhood is known to be a period when cortical plasticity phenomena are at a maximum. Music is a stimulus known to modulate these mechanisms. On the other hand, neurological impairments like blindness are also known to affect cortical plasticity. Here, we address how tonal and atonal musical stimuli are processed in control and blind young children. We aimed to understand the differences between the two groups when processing this physiological information. Atonal stimuli produced larger activations in cerebellum, fusiform, and temporal lobe structures than tonal. In contrast, tonal stimuli induced larger frontal lobe representations than atonal. Control participants presented large activations in cerebellum, fusiform, and temporal lobe. A correlation/connectivity study showed that the blind group incorporated larger amounts of perceptual information (somatosensory and motor) into tonal processing through the function of the anterior prefrontal cortex (APC). They also used the visual cortex in conjunction with the Wernicke's area to process this information. In contrast, controls processed sound with perceptual stimuli from auditory cortex structures (including Wernicke's area). In this case, information was processed through the dorsal posterior cingulate cortex and not the APC. The orbitofrontal cortex also played a key role for atonal interpretation in this group. Wernicke's area, known to be involved in speech, was heavily involved for both groups and all stimuli. The two groups presented clear differences in strategies for music processing, with very different recruitment of brain regions.

Structural neuroplasticity in the sensorimotor network of professional female ballet dancers.

PubMed

Hänggi, Jürgen; Koeneke, Susan; Bezzola, Ladina; Jäncke, Lutz

2010-08-01

Evidence suggests that motor, sensory, and cognitive training modulates brain structures involved in a specific practice. Functional neuroimaging revealed key brain structures involved in dancing such as the putamen and the premotor cortex. Intensive ballet dance training was expected to modulate the structures of the sensorimotor network, for example, the putamen, premotor cortex, supplementary motor area (SMA), and the corticospinal tracts. We investigated gray (GM) and white matter (WM) volumes, fractional anisotropy (FA), and mean diffusivity (MD) using magnetic resonance-based morphometry and diffusion tensor imaging in 10 professional female ballet dancers compared with 10 nondancers. In dancers compared with nondancers, decreased GM volumes were observed in the left premotor cortex, SMA, putamen, and superior frontal gyrus, and decreased WM volumes in both corticospinal tracts, both internal capsules, corpus callosum, and left anterior cingulum. FA was lower in the WM underlying the dancers' left and right premotor cortex. There were no significant differences in MD between the groups. Age of dance commencement was negatively correlated with GM and WM volume in the right premotor cortex and internal capsule, respectively, and positively correlated with WM volume in the left precentral gyrus and corpus callosum. Results were not influenced by the significantly lower body mass index of the dancers. The present findings complement the results of functional imaging studies in experts that revealed reduced neural activity in skilled compared with nonskilled subjects. Reductions in brain activity are accompanied by local decreases in GM and WM volumes and decreased FA. 2009 Wiley-Liss, Inc.

Behavioral and neurophysiological correlates of regret in rat decision-making on a neuroeconomic task

PubMed Central

Steiner, Adam P.; Redish, A. David

2014-01-01

Summary Disappointment entails the recognition that one did not get the value one expected. In contrast, regret entails the recognition that an alternate (counterfactual) action would have produced a more valued outcome. Thus, the key to identifying regret is the representation of that counterfactual option in situations in which a mistake has been made. In humans, the orbitofrontal cortex is active during expressions of regret, and humans with damage to the orbitofrontal cortex do not express regret. In rats and non-human primates, both the orbitofrontal cortex and the ventral striatum have been implicated in decision-making, particularly in representations of expectations of reward. In order to examine representations of regretful situations, we recorded neural ensembles from orbitofrontal cortex and ventral striatum in rats encountering a spatial sequence of wait/skip choices for delayed delivery of different food flavors. We were able to measure preferences using an economic framework. Rats occasionally skipped low-cost choices and then encountered a high-cost choice. This sequence economically defines a potential regret-inducing instance. In these situations, rats looked backwards towards the lost option, the cells within the orbitofrontal cortex and ventral striatum represented that missed action, rats were more likely to wait for the long delay, and rats rushed through eating the food after that delay. That these situations drove rats to modify their behavior suggests that regret-like processes modify decision-making in non-human mammals. PMID:24908102

HCN channels segregate stimulation‐evoked movement responses in neocortex and allow for coordinated forelimb movements in rodents

PubMed Central

Farrell, Jordan S.; Palmer, Laura A.; Singleton, Anna C.; Pittman, Quentin J.; Teskey, G. Campbell

2016-01-01

Key points The present study tested whether HCN channels contribute to the organization of motor cortex and to skilled motor behaviour during a forelimb reaching task.Experimental reductions in HCN channel signalling increase the representation of complex multiple forelimb movements in motor cortex as assessed by intracortical microstimulation.Global HCN1KO mice exhibit reduced reaching accuracy and atypical movements during a single‐pellet reaching task relative to wild‐type controls.Acute pharmacological inhibition of HCN channels in forelimb motor cortex decreases reaching accuracy and increases atypical movements during forelimb reaching. Abstract The mechanisms by which distinct movements of a forelimb are generated from the same area of motor cortex have remained elusive. Here we examined a role for HCN channels, given their ability to alter synaptic integration, in the expression of forelimb movement responses during intracortical microstimulation (ICMS) and movements of the forelimb on a skilled reaching task. We used short‐duration high‐resolution ICMS to evoke forelimb movements following pharmacological (ZD7288), experimental (electrically induced cortical seizures) or genetic approaches that we confirmed with whole‐cell patch clamp to substantially reduce I h current. We observed significant increases in the number of multiple movement responses evoked at single sites in motor maps to all three experimental manipulations in rats or mice. Global HCN1 knockout mice were less successful and exhibited atypical movements on a skilled‐motor learning task relative to wild‐type controls. Furthermore, in reaching‐proficient rats, reaching accuracy was reduced and forelimb movements were altered during infusion of ZD7288 within motor cortex. Thus, HCN channels play a critical role in the separation of overlapping movement responses and allow for successful reaching behaviours. These data provide a novel mechanism for the encoding of multiple movement responses within shared networks of motor cortex. This mechanism supports a viewpoint of primary motor cortex as a site of dynamic integration for behavioural output. PMID:27568501

"Visual" Cortex Responds to Spoken Language in Blind Children.

PubMed

Bedny, Marina; Richardson, Hilary; Saxe, Rebecca

2015-08-19

Plasticity in the visual cortex of blind individuals provides a rare window into the mechanisms of cortical specialization. In the absence of visual input, occipital ("visual") brain regions respond to sound and spoken language. Here, we examined the time course and developmental mechanism of this plasticity in blind children. Nineteen blind and 40 sighted children and adolescents (4-17 years old) listened to stories and two auditory control conditions (unfamiliar foreign speech, and music). We find that "visual" cortices of young blind (but not sighted) children respond to sound. Responses to nonlanguage sounds increased between the ages of 4 and 17. By contrast, occipital responses to spoken language were maximal by age 4 and were not related to Braille learning. These findings suggest that occipital plasticity for spoken language is independent of plasticity for Braille and for sound. We conclude that in the absence of visual input, spoken language colonizes the visual system during brain development. Our findings suggest that early in life, human cortex has a remarkably broad computational capacity. The same cortical tissue can take on visual perception and language functions. Studies of plasticity provide key insights into how experience shapes the human brain. The "visual" cortex of adults who are blind from birth responds to touch, sound, and spoken language. To date, all existing studies have been conducted with adults, so little is known about the developmental trajectory of plasticity. We used fMRI to study the emergence of "visual" cortex responses to sound and spoken language in blind children and adolescents. We find that "visual" cortex responses to sound increase between 4 and 17 years of age. By contrast, responses to spoken language are present by 4 years of age and are not related to Braille-learning. These findings suggest that, early in development, human cortex can take on a strikingly wide range of functions. Copyright © 2015 the authors 0270-6474/15/3511674-08$15.00/0.

Correlation-based model of artificially induced plasticity in motor cortex by a bidirectional brain-computer interface.

PubMed

Lajoie, Guillaume; Krouchev, Nedialko I; Kalaska, John F; Fairhall, Adrienne L; Fetz, Eberhard E

2017-02-01

Experiments show that spike-triggered stimulation performed with Bidirectional Brain-Computer-Interfaces (BBCI) can artificially strengthen connections between separate neural sites in motor cortex (MC). When spikes from a neuron recorded at one MC site trigger stimuli at a second target site after a fixed delay, the connections between sites eventually strengthen. It was also found that effective spike-stimulus delays are consistent with experimentally derived spike-timing-dependent plasticity (STDP) rules, suggesting that STDP is key to drive these changes. However, the impact of STDP at the level of circuits, and the mechanisms governing its modification with neural implants remain poorly understood. The present work describes a recurrent neural network model with probabilistic spiking mechanisms and plastic synapses capable of capturing both neural and synaptic activity statistics relevant to BBCI conditioning protocols. Our model successfully reproduces key experimental results, both established and new, and offers mechanistic insights into spike-triggered conditioning. Using analytical calculations and numerical simulations, we derive optimal operational regimes for BBCIs, and formulate predictions concerning the efficacy of spike-triggered conditioning in different regimes of cortical activity.

Correlation-based model of artificially induced plasticity in motor cortex by a bidirectional brain-computer interface

PubMed Central

Lajoie, Guillaume; Kalaska, John F.; Fairhall, Adrienne L.; Fetz, Eberhard E.

2017-01-01

Experiments show that spike-triggered stimulation performed with Bidirectional Brain-Computer-Interfaces (BBCI) can artificially strengthen connections between separate neural sites in motor cortex (MC). When spikes from a neuron recorded at one MC site trigger stimuli at a second target site after a fixed delay, the connections between sites eventually strengthen. It was also found that effective spike-stimulus delays are consistent with experimentally derived spike-timing-dependent plasticity (STDP) rules, suggesting that STDP is key to drive these changes. However, the impact of STDP at the level of circuits, and the mechanisms governing its modification with neural implants remain poorly understood. The present work describes a recurrent neural network model with probabilistic spiking mechanisms and plastic synapses capable of capturing both neural and synaptic activity statistics relevant to BBCI conditioning protocols. Our model successfully reproduces key experimental results, both established and new, and offers mechanistic insights into spike-triggered conditioning. Using analytical calculations and numerical simulations, we derive optimal operational regimes for BBCIs, and formulate predictions concerning the efficacy of spike-triggered conditioning in different regimes of cortical activity. PMID:28151957

Counterfactual thinking affects the excitability of the motor cortex.

PubMed

Vicario, Carmelo M; Rafal, Robert D; Avenanti, Alessio

2015-04-01

Evidence suggests that monetary reward and affective experiences induce activity in the cortical motor system. Nevertheless, it is unclear whether counterfactual thinking related to wrong choices that lead to monetary loss and regret affects motor excitability. Using transcranial magnetic stimulation (TMS) of the motor cortex, we measured corticospinal excitability of 2 groups of healthy humans asked to actively guess the winning key among two possible alternatives (choice group); or passively assist to monetary outcomes randomly selected by the computer program (follow group). Results document a selective increment of the corticospinal excitability when a monetary loss outcome followed the key selection (i.e., in the choice group). On the other hand, no change in corticospinal excitability was found when participants passively assisted to a monetary loss randomly selected by the computer program (i.e., follow group). These findings suggest that counterfactual thinking and the negative emotional experiences arising from choices causing monetary loss--i.e., "I would have won instead of lost money if I'd made a different choice"--are mapped in the motor system. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Neurotransmission in developmental disorders].

PubMed

Takeuchi, Yoshihiro

2008-11-01

Attention deficit/hyperactivity disorder (AD/HD) is a heterogeneous developmental disorder with an etiology that is not fully understood. AD/HD has been considered to occur due to a disturbance in cathecholaminergic neurotransmission, with particular emphasis on dopamine. The neurotransmission of dopamine in subcortical regions such as the basal ganglia and limbic areas is synaptic; on the other hand, dopamine neurotransmission in the frontal cortex is quite different, because there are very few dopamine transporters (DAT) in the frontal cortex that allow dopamine to diffuse away from the dopamine synapse ("volume transmission"). It is now clear that noradrenergic neurons play a key regulatory role in dopaminergic function in the frontal cortex. Furthermore, serotonergic neurons exert an inhibitory effect on midbrain dopamine cell bodies, and they have an influence on dopamine release in terminal regions. There is accumulating neurobiological evidence pointing toward a role of the serotonin system in AD/HD. The etiology of autism spectrum disorders (ASD) is still unclear, but information from genetics, neuropathology, brain imaging, and basic neuroscience has provided insights into the understanding of this developmental disorder. In addition to abnormal circuitry in specific limbic and neocortical areas of the cerebral cortex, impairments in brainstem, cerebellar, thalamic, and basal ganglia connections have been reported. Numerous studies have pointed to abnormalities in serotonin and glutamate neurotransmission. Three important aspects involved in the pathophysiology of ASD have been proposed. The first is cell migration, the second is unbalanced excitatory-inhibitory networks, and the third is synapse formation and pruning, the key factors being reelin, neurexin, and neuroligin. Serotonin is considered to play an important role in all of these aspects of the pathophysiology of ASD. Finally, I would like to emphasize that it is crucial in the field of child neurology medical examination and treatment should be based on the basic neuroscience, always taking "neurons" into consideration.

The neural mechanisms of semantic and response conflicts: an fMRI study of practice-related effects in the Stroop task.

PubMed

Chen, Zhencai; Lei, Xu; Ding, Cody; Li, Hong; Chen, Antao

2013-02-01

Previous studies have demonstrated that there are separate neural mechanisms underlying semantic and response conflicts in the Stroop task. However, the practice effects of these conflicts need to be elucidated and the possible involvements of common neural mechanisms are yet to be established. We employed functional magnetic resonance imaging (fMRI) in a 4-2 mapping practice-related Stroop task to determine the neural substrates under these conflicts. Results showed that different patterns of brain activations are associated with practice in the attentional networks (e.g., dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), and posterior parietal cortex (PPC)) for both conflicts, response control regions (e.g., inferior frontal junction (IFJ), inferior frontal gyrus (IFG)/insula, and pre-supplementary motor areas (pre-SMA)) for semantic conflict, and posterior cortex for response conflict. We also found areas of common activation in the left hemisphere within the attentional networks, for the early practice stage in semantic conflict and the late stage in "pure" response conflict using conjunction analysis. The different practice effects indicate that there are distinct mechanisms underlying these two conflict types: semantic conflict practice effects are attributable to the automation of stimulus processing, conflict and response control; response conflict practice effects are attributable to the proportional increase of conflict-related cognitive resources. In addition, the areas of common activation suggest that the semantic conflict effect may contain a partial response conflict effect, particularly at the beginning of the task. These findings indicate that there are two kinds of response conflicts contained in the key-pressing Stroop task: the vocal-level (mainly in the early stage) and key-pressing (mainly in the late stage) response conflicts; thus, the use of the subtraction method for the exploration of semantic and response conflicts may need to be further examined. Copyright © 2012 Elsevier Inc. All rights reserved.

Apoptosis of rat kidney cells after 241-americium administration.

PubMed

Labéjof, L; Berry, J P; Duchambon, P; Poncy, J L; Galle, P

1998-01-01

Tumors induction by americium is well known but there are no data on the biological effects of this radionucleide at subcellular level. In order to study the possible ultrastructural lesions induced by this element, a group of rats were injected with 241-Americium-citrate (9 kBq), once a week for five weeks and sacrificed 7 days after the last injection. We describe the alterations observed in the cortex kidney using cytochemical (TUNEL reaction) and histochemical (PAS staining) methods for light microscopy as well as electron microscopy techniques. Various types of lesions were detected: condensation of nuclear chromatine, fragmentation of the nuclei, swollen mitochondria, disappearance of mitochondrial crests and skrinking of the cytoplasm. This study clearly demonstrated the induction of apoptosis by americium in rat cortex kidney cells.

Neural substrates of decision-making.

PubMed

Broche-Pérez, Y; Herrera Jiménez, L F; Omar-Martínez, E

2016-06-01

Decision-making is the process of selecting a course of action from among 2 or more alternatives by considering the potential outcomes of selecting each option and estimating its consequences in the short, medium and long term. The prefrontal cortex (PFC) has traditionally been considered the key neural structure in decision-making process. However, new studies support the hypothesis that describes a complex neural network including both cortical and subcortical structures. The aim of this review is to summarise evidence on the anatomical structures underlying the decision-making process, considering new findings that support the existence of a complex neural network that gives rise to this complex neuropsychological process. Current evidence shows that the cortical structures involved in decision-making include the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), and dorsolateral prefrontal cortex (DLPFC). This process is assisted by subcortical structures including the amygdala, thalamus, and cerebellum. Findings to date show that both cortical and subcortical brain regions contribute to the decision-making process. The neural basis of decision-making is a complex neural network of cortico-cortical and cortico-subcortical connections which includes subareas of the PFC, limbic structures, and the cerebellum. Copyright © 2014 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

Creative brains: designing in the real world†

PubMed Central

Goel, Vinod

2014-01-01

The process of designing artifacts is a creative activity. It is proposed that, at the cognitive level, one key to understanding design creativity is to understand the array of symbol systems designers utilize. These symbol systems range from being vague, imprecise, abstract, ambiguous, and indeterminate (like conceptual sketches), to being very precise, concrete, unambiguous, and determinate (like contract documents). The former types of symbol systems support associative processes that facilitate lateral (or divergent) transformations that broaden the problem space, while the latter types of symbol systems support inference processes facilitating vertical (or convergent) transformations that deepen of the problem space. The process of artifact design requires the judicious application of both lateral and vertical transformations. This leads to a dual mechanism model of design problem-solving comprising of an associative engine and an inference engine. It is further claimed that this dual mechanism model is supported by an interesting hemispheric dissociation in human prefrontal cortex. The associative engine and neural structures that support imprecise, ambiguous, abstract, indeterminate representations are lateralized in the right prefrontal cortex, while the inference engine and neural structures that support precise, unambiguous, determinant representations are lateralized in the left prefrontal cortex. At the brain level, successful design of artifacts requires a delicate balance between the two hemispheres of prefrontal cortex. PMID:24817846

No evidence of somatotopic place of articulation feature mapping in motor cortex during passive speech perception.

PubMed

Arsenault, Jessica S; Buchsbaum, Bradley R

2016-08-01

The motor theory of speech perception has experienced a recent revival due to a number of studies implicating the motor system during speech perception. In a key study, Pulvermüller et al. (2006) showed that premotor/motor cortex differentially responds to the passive auditory perception of lip and tongue speech sounds. However, no study has yet attempted to replicate this important finding from nearly a decade ago. The objective of the current study was to replicate the principal finding of Pulvermüller et al. (2006) and generalize it to a larger set of speech tokens while applying a more powerful statistical approach using multivariate pattern analysis (MVPA). Participants performed an articulatory localizer as well as a speech perception task where they passively listened to a set of eight syllables while undergoing fMRI. Both univariate and multivariate analyses failed to find evidence for somatotopic coding in motor or premotor cortex during speech perception. Positive evidence for the null hypothesis was further confirmed by Bayesian analyses. Results consistently show that while the lip and tongue areas of the motor cortex are sensitive to movements of the articulators, they do not appear to preferentially respond to labial and alveolar speech sounds during passive speech perception.

Differential functional connectivity of rostral anterior cingulate cortex during emotional interference

PubMed Central

Szekely, Akos; Silton, Rebecca L.; Heller, Wendy; Miller, Gregory A.

2017-01-01

Abstract The rostral-ventral subdivision of the anterior cingulate cortex (rACC) plays a key role in the regulation of emotional processing. Although rACC has strong anatomical connections with anterior insular cortex (AIC), amygdala, prefrontal cortex and striatal brain regions, it is unclear whether the functional connectivity of rACC with these regions changes when regulating emotional processing. Furthermore, it is not known whether this connectivity changes with deficits in emotion regulation seen in different kinds of anxiety and depression. To address these questions regarding rACC functional connectivity, non-patients high in self-reported anxious apprehension (AP), anxious arousal (AR), anhedonic depression (AD) or none (CON) indicated the ink color of pleasant, neutral and unpleasant words during functional magnetic resonance imaging. While ignoring task-irrelevant unpleasant words, AD and CON showed an increase in the functional connectivity of rACC with AIC, putamen, caudate and ventral pallidum. There was a decrease in this connectivity in AP and AR, with AP showing greater reduction than AR. These findings provide support for the role of rACC in integrating interoceptive, emotional and cognitive functions via interactions with insula and striatal regions during effective emotion regulation in healthy individuals and a failure of this integration that may be specific to anxiety, particularly AP. PMID:27998997

Anodal Transcranial Direct Current Stimulation Reduces Psychophysically Measured Surround Suppression in the Human Visual Cortex

PubMed Central

Spiegel, Daniel P.; Hansen, Bruce C.; Byblow, Winston D.; Thompson, Benjamin

2012-01-01

Transcranial direct current stimulation (tDCS) is a safe, non-invasive technique for transiently modulating the balance of excitation and inhibition within the human brain. It has been reported that anodal tDCS can reduce both GABA mediated inhibition and GABA concentration within the human motor cortex. As GABA mediated inhibition is thought to be a key modulator of plasticity within the adult brain, these findings have broad implications for the future use of tDCS. It is important, therefore, to establish whether tDCS can exert similar effects within non-motor brain areas. The aim of this study was to assess whether anodal tDCS could reduce inhibitory interactions within the human visual cortex. Psychophysical measures of surround suppression were used as an index of inhibition within V1. Overlay suppression, which is thought to originate within the lateral geniculate nucleus (LGN), was also measured as a control. Anodal stimulation of the occipital poles significantly reduced psychophysical surround suppression, but had no effect on overlay suppression. This effect was specific to anodal stimulation as cathodal stimulation had no effect on either measure. These psychophysical results provide the first evidence for tDCS-induced reductions of intracortical inhibition within the human visual cortex. PMID:22563485

Mindful attention to breath regulates emotions via increased amygdala-prefrontal cortex connectivity.

PubMed

Doll, Anselm; Hölzel, Britta K; Mulej Bratec, Satja; Boucard, Christine C; Xie, Xiyao; Wohlschläger, Afra M; Sorg, Christian

2016-07-01

Mindfulness practice is beneficial for emotion regulation; however, the neural mechanisms underlying this effect are poorly understood. The current study focuses on effects of attention-to-breath (ATB) as a basic mindfulness practice on aversive emotions at behavioral and brain levels. A key finding across different emotion regulation strategies is the modulation of amygdala and prefrontal activity. It is unclear how ATB relevant brain areas in the prefrontal cortex integrate with amygdala activation during emotional stimulation. We proposed that, during emotional stimulation, ATB down-regulates activation in the amygdala and increases its integration with prefrontal regions. To address this hypothesis, 26 healthy controls were trained in mindfulness-based attention-to-breath meditation for two weeks and then stimulated with aversive pictures during both attention-to-breath and passive viewing while undergoing fMRI. Data were controlled for breathing frequency. Results indicate that (1) ATB was effective in regulating aversive emotions. (2) Left dorso-medial prefrontal cortex was associated with ATB in general. (3) A fronto-parietal network was additionally recruited during emotional stimulation. (4) ATB down regulated amygdala activation and increased amygdala-prefrontal integration, with such increased integration being associated with mindfulness ability. Results suggest amygdala-dorsal prefrontal cortex integration as a potential neural pathway of emotion regulation by mindfulness practice. Copyright © 2016 Elsevier Inc. All rights reserved.

Healthy versus Entorhinal Cortical Atrophy Identification in Asymptomatic APOE4 Carriers at Risk for Alzheimer’s Disease

PubMed Central

Konishi, Kyoko; Joober, Ridha; Poirier, Judes; MacDonald, Kathleen; Chakravarty, Mallar; Patel, Raihaan; Breitner, John; Bohbot, Véronique D.

2018-01-01

Early detection of Alzheimer’s disease (AD) has been challenging as current biomarkers are invasive and costly. Strong predictors of future AD diagnosis include lower volume of the hippocampus and entorhinal cortex, as well as the ɛ4 allele of the Apolipoprotein E gene (APOE) gene. Therefore, studying functions that are critically mediated by the hippocampus and entorhinal cortex, such as spatial memory, in APOE ɛ4 allele carriers, may be key to the identification of individuals at risk of AD, prior to the manifestation of cognitive impairments. Using a virtual navigation task developed in-house, specifically designed to assess spatial versus non-spatial strategies, the current study is the first to differentiate functional and structural differences within APOE ɛ4 allele carriers. APOE ɛ4 allele carriers that predominantly use non-spatial strategies have decreased fMRI activity in the hippocampus and increased atrophy in the hippocampus, entorhinal cortex, and fimbria compared to APOE ɛ4 allele carriers who use spatial strategies. In contrast, APOE ɛ4 allele carriers who use spatial strategies have grey matter levels comparable to non-APOE ɛ4 allele carriers. Furthermore, in a leave-one-out analysis, grey matter in the entorhinal cortex could predict navigational strategy with 92% accuracy. PMID:29278888

The Mediodorsal Thalamus Drives Feedforward Inhibition in the Anterior Cingulate Cortex via Parvalbumin Interneurons

PubMed Central

Delevich, Kristen; Tucciarone, Jason; Huang, Z. Josh

2015-01-01

Although the medial prefrontal cortex (mPFC) is classically defined by its reciprocal connections with the mediodorsal thalamic nucleus (MD), the nature of information transfer between MD and mPFC is poorly understood. In sensory thalamocortical pathways, thalamic recruitment of feedforward inhibition mediated by fast-spiking, putative parvalbumin-expressing (PV) interneurons is a key feature that enables cortical neurons to represent sensory stimuli with high temporal fidelity. Whether a similar circuit mechanism is in place for the projection from the MD (a higher-order thalamic nucleus that does not receive direct input from the periphery) to the mPFC is unknown. Here we show in mice that inputs from the MD drive disynaptic feedforward inhibition in the dorsal anterior cingulate cortex (dACC) subregion of the mPFC. In particular, we demonstrate that axons arising from MD neurons directly synapse onto and excite PV interneurons that in turn mediate feedforward inhibition of pyramidal neurons in layer 3 of the dACC. This feedforward inhibition in the dACC limits the time window during which pyramidal neurons integrate excitatory synaptic inputs and fire action potentials, but in a manner that allows for greater flexibility than in sensory cortex. These findings provide a foundation for understanding the role of MD-PFC circuit function in cognition. PMID:25855185

Feedforward and feedback frequency-dependent interactions in a large-scale laminar network of the primate cortex.

PubMed

Mejias, Jorge F; Murray, John D; Kennedy, Henry; Wang, Xiao-Jing

2016-11-01

Interactions between top-down and bottom-up processes in the cerebral cortex hold the key to understanding attentional processes, predictive coding, executive control, and a gamut of other brain functions. However, the underlying circuit mechanism remains poorly understood and represents a major challenge in neuroscience. We approached this problem using a large-scale computational model of the primate cortex constrained by new directed and weighted connectivity data. In our model, the interplay between feedforward and feedback signaling depends on the cortical laminar structure and involves complex dynamics across multiple (intralaminar, interlaminar, interareal, and whole cortex) scales. The model was tested by reproducing, as well as providing insights into, a wide range of neurophysiological findings about frequency-dependent interactions between visual cortical areas, including the observation that feedforward pathways are associated with enhanced gamma (30 to 70 Hz) oscillations, whereas feedback projections selectively modulate alpha/low-beta (8 to 15 Hz) oscillations. Furthermore, the model reproduces a functional hierarchy based on frequency-dependent Granger causality analysis of interareal signaling, as reported in recent monkey and human experiments, and suggests a mechanism for the observed context-dependent hierarchy dynamics. Together, this work highlights the necessity of multiscale approaches and provides a modeling platform for studies of large-scale brain circuit dynamics and functions.

Feedforward and feedback frequency-dependent interactions in a large-scale laminar network of the primate cortex

PubMed Central

Mejias, Jorge F.; Murray, John D.; Kennedy, Henry; Wang, Xiao-Jing

2016-01-01

Interactions between top-down and bottom-up processes in the cerebral cortex hold the key to understanding attentional processes, predictive coding, executive control, and a gamut of other brain functions. However, the underlying circuit mechanism remains poorly understood and represents a major challenge in neuroscience. We approached this problem using a large-scale computational model of the primate cortex constrained by new directed and weighted connectivity data. In our model, the interplay between feedforward and feedback signaling depends on the cortical laminar structure and involves complex dynamics across multiple (intralaminar, interlaminar, interareal, and whole cortex) scales. The model was tested by reproducing, as well as providing insights into, a wide range of neurophysiological findings about frequency-dependent interactions between visual cortical areas, including the observation that feedforward pathways are associated with enhanced gamma (30 to 70 Hz) oscillations, whereas feedback projections selectively modulate alpha/low-beta (8 to 15 Hz) oscillations. Furthermore, the model reproduces a functional hierarchy based on frequency-dependent Granger causality analysis of interareal signaling, as reported in recent monkey and human experiments, and suggests a mechanism for the observed context-dependent hierarchy dynamics. Together, this work highlights the necessity of multiscale approaches and provides a modeling platform for studies of large-scale brain circuit dynamics and functions. PMID:28138530

Healthy versus Entorhinal Cortical Atrophy Identification in Asymptomatic APOE4 Carriers at Risk for Alzheimer's Disease.

PubMed

Konishi, Kyoko; Joober, Ridha; Poirier, Judes; MacDonald, Kathleen; Chakravarty, Mallar; Patel, Raihaan; Breitner, John; Bohbot, Véronique D

2018-01-01

Early detection of Alzheimer's disease (AD) has been challenging as current biomarkers are invasive and costly. Strong predictors of future AD diagnosis include lower volume of the hippocampus and entorhinal cortex, as well as the ɛ4 allele of the Apolipoprotein E gene (APOE) gene. Therefore, studying functions that are critically mediated by the hippocampus and entorhinal cortex, such as spatial memory, in APOE ɛ4 allele carriers, may be key to the identification of individuals at risk of AD, prior to the manifestation of cognitive impairments. Using a virtual navigation task developed in-house, specifically designed to assess spatial versus non-spatial strategies, the current study is the first to differentiate functional and structural differences within APOE ɛ4 allele carriers. APOE ɛ4 allele carriers that predominantly use non-spatial strategies have decreased fMRI activity in the hippocampus and increased atrophy in the hippocampus, entorhinal cortex, and fimbria compared to APOE ɛ4 allele carriers who use spatial strategies. In contrast, APOE ɛ4 allele carriers who use spatial strategies have grey matter levels comparable to non-APOE ɛ4 allele carriers. Furthermore, in a leave-one-out analysis, grey matter in the entorhinal cortex could predict navigational strategy with 92% accuracy.

CREB regulates memory allocation in the insular cortex

PubMed Central

Sano, Yoshitake; Shobe, Justin L.; Zhou, Miou; Huang, Shan; Shuman, Tristan; Cai, Denise J.; Golshani, Peyman; Kamata, Masakazu; Silva, Alcino J.

2016-01-01

Summary The molecular and cellular mechanisms of memory storage have attracted a great deal of attention. By comparison, little is known about memory allocation, the process that determines which specific neurons in a neural network will store a given memory [1, 2]. Previous studies demonstrated that memory allocation is not random in the amygdala; these studies showed that amygdala neurons with higher levels of the cAMP response element binding protein (CREB) are more likely to be recruited into encoding and storing fear memory [3–6]. To determine whether specific mechanisms also regulate memory allocation in other brain regions, and whether CREB also has a role in this process, we studied insular cortical memory representations for conditioned taste aversion (CTA). In this task, an animal learns to associate a taste (CS) with the experience of malaise (such as that induced by LiCl; US). The insular cortex is required for CTA memory formation and retrieval [7–12]. CTA learning activates a subpopulation of neurons in this structure [13–15], and the insular cortex and the basolateral amygdala (BLA) interact during CTA formation [16, 17]. Here, we used a combination of approaches, including viral vector transfections of insular cortex, arc Fluorescence In Situ Hybridization (FISH) and Designer Receptors Exclusively Activated by Designer Drugs (DREADD) system, to show that CREB levels determine which insular cortical neurons go on to encode a given conditioned taste memory. PMID:25454591

Preparing Our Schools for the 21st Century. 1999 ASCD Yearbook.

ERIC Educational Resources Information Center

Marsh, David D., Ed.

This yearbook offers a view of the key elements of schooling in the 21st century, outlining the nature of the change process that will be needed to create such schools. These key elements are drawn from the experience of educational reform in several countries and reflect a growing consensus about which elements will help all schools achieve both…

More than skin deep: body representation beyond primary somatosensory cortex.

PubMed

Longo, Matthew R; Azañón, Elena; Haggard, Patrick

2010-02-01

The neural circuits underlying initial sensory processing of somatic information are relatively well understood. In contrast, the processes that go beyond primary somatosensation to create more abstract representations related to the body are less clear. In this review, we focus on two classes of higher-order processing beyond somatosensation. Somatoperception refers to the process of perceiving the body itself, and particularly of ensuring somatic perceptual constancy. We review three key elements of somatoperception: (a) remapping information from the body surface into an egocentric reference frame, (b) exteroceptive perception of objects in the external world through their contact with the body, and (c) interoceptive percepts about the nature and state of the body itself. Somatorepresentation, in contrast, refers to the essentially cognitive process of constructing semantic knowledge and attitudes about the body, including: (d) lexical-semantic knowledge about bodies generally and one's own body specifically, (e) configural knowledge about the structure of bodies, (f) emotions and attitudes directed towards one's own body, and (g) the link between physical body and psychological self. We review a wide range of neuropsychological, neuroimaging and neurophysiological data to explore the dissociation between these different aspects of higher somatosensory function. 2009 Elsevier Ltd. All rights reserved.

The rat corticospinal system is functionally and anatomically segregated.

PubMed

Olivares-Moreno, Rafael; Moreno-Lopez, Yunuen; Concha, Luis; Martínez-Lorenzana, Guadalupe; Condés-Lara, Miguel; Cordero-Erausquin, Matilde; Rojas-Piloni, Gerardo

2017-12-01

The descending corticospinal (CS) projection has been considered a key element for motor control, which results from direct and indirect modulation of spinal cord pre-motor interneurons in the intermediate gray matter of the spinal cord, which, in turn, influences motoneurons in the ventral horn. The CS tract (CST) is also involved in a selective and complex modulation of sensory information in the dorsal horn. However, little is known about the spinal network engaged by the CST and the organization of CS projections that may encode different cortical outputs to the spinal cord. This study addresses the issue of whether the CS system exerts parallel control on different spinal networks, which together participate in sensorimotor integration. Here, we show that in the adult rat, two different and partially intermingled CS neurons in the sensorimotor cortex activate, with different time latencies, distinct spinal cord neurons located in the dorsal horn and intermediate zone of the same segment. The fact that different populations of CS neurons project in a segregated manner suggests that CST is composed of subsystems controlling different spinal cord circuits that modulate motor outputs and sensory inputs in a coordinated manner.

Inhibition of phosphodiesterase10A attenuates morphine-induced conditioned place preference.

PubMed

Mu, Ying; Ren, Zhaoxiang; Jia, Jia; Gao, Bo; Zheng, Longtai; Wang, Guanghui; Friedman, Eitan; Zhen, Xuechu

2014-09-25

Phosphodiesterase (PDE) 10A is selectively expressed in medium spiny neurons of the striatum. Nucleus accumbens (NAc) is a key region that mediates drug reward and addiction-related behaviors. To investigate the potential role of PDE10A in the reinforcement properties of morphine, we tested the effect of MP-10, a selective inhibitor of PDE10A, on acquisition, expression, and extinction of morphine-induced conditioned place preference (CPP). The results show that 2.5 mg/kg MP-10, administered subcutaneously, significantly inhibited the acquisition of morphine-induced CPP. The same dose of MP-10 alone did not result in the CPP. Moreover, MP-10 did not alter the expression of morphine-induced CPP, but did accelerate the extinction of morphine-induced CPP. Additionally, chronic treatment with 2.5 mg/kg MP-10 decreased expression of phosphorylated CREB (pCREB), activated cAMP response element binding protein, in dorsomedial striatum, in shell of NAc, and in anterior cingulate cortex (ACC) as well as decreased expression of ΔFosB in the shell of NAc and ACC. The results suggest that inhibition of PDE10A may have therapeutic potential in the treatment of opioid addiction.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chu, Heng-Hsuan; Car, Suzana; Socha, Amanda L.

Understanding how seeds obtain and store nutrients is key to developing crops with higher agronomic and nutritional value. We have uncovered unique patterns of micronutrient localization in seeds using synchrotron X-ray fluorescence (SXRF). Although all four members of the Arabidopsis thaliana Mn-CDF family can transport Mn, here we show that only mtp8-2 has an altered Mn distribution pattern in seeds. In an mtp8-2 mutant, Mn no longer accumulates in hypocotyl cortex cells and sub-epidermal cells of the embryonic cotyledons, but rather accumulates with Fe in the cells surrounding the vasculature, a pattern previously shown to be determined by the vacuolarmore » transporter VIT1. We also show that MTP8, unlike the other three Mn-CDF family members, can transport Fe and is responsible for localization of Fe to the same cells that store Mn. When both the VIT1 and MTP8 transporters are non-functional, there is no accumulation of Fe or Mn in specific cell types; rather these elements are distributed amongst all cell types in the seed. Finally, disruption of the putative Fe binding sites in MTP8 resulted in loss of ability to transport Fe but did not affect the ability to transport Mn.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chu, Heng-Hsuan; Car, Suzana; Socha, Amanda L.

Understanding how seeds obtain and store nutrients is key to developing crops with higher agronomic and nutritional value. We have uncovered unique patterns of micronutrient localization in seeds using synchrotron X-ray fluorescence (SXRF). Although all four members of the Arabidopsis thaliana Mn-CDF family can transport Mn, here we show that only mtp8-2 has an altered Mn distribution pattern in seeds. In an mtp8-2 mutant, Mn no longer accumulates in hypocotyl cortex cells and sub-epidermal cells of the embryonic cotyledons, but rather accumulates with Fe in the cells surrounding the vasculature, a pattern previously shown to be determined by the vacuolarmore » transporter VIT1. We also show that MTP8, unlike the other three Mn-CDF family members, can transport Fe and is responsible for localization of Fe to the same cells that store Mn. When both the VIT1 and MTP8 transporters are non-functional, there is no accumulation of Fe or Mn in specific cell types; rather these elements are distributed amongst all cell types in the seed. Disruption of the putative Fe binding sites in MTP8 resulted in loss of ability to transport Fe but did not affect the ability to transport Mn.« less

A spiking network model of cerebellar Purkinje cells and molecular layer interneurons exhibiting irregular firing

PubMed Central

Lennon, William; Hecht-Nielsen, Robert; Yamazaki, Tadashi

2014-01-01

While the anatomy of the cerebellar microcircuit is well-studied, how it implements cerebellar function is not understood. A number of models have been proposed to describe this mechanism but few emphasize the role of the vast network Purkinje cells (PKJs) form with the molecular layer interneurons (MLIs)—the stellate and basket cells. We propose a model of the MLI-PKJ network composed of simple spiking neurons incorporating the major anatomical and physiological features. In computer simulations, the model reproduces the irregular firing patterns observed in PKJs and MLIs in vitro and a shift toward faster, more regular firing patterns when inhibitory synaptic currents are blocked. In the model, the time between PKJ spikes is shown to be proportional to the amount of feedforward inhibition from an MLI on average. The two key elements of the model are: (1) spontaneously active PKJs and MLIs due to an endogenous depolarizing current, and (2) adherence to known anatomical connectivity along a parasagittal strip of cerebellar cortex. We propose this model to extend previous spiking network models of the cerebellum and for further computational investigation into the role of irregular firing and MLIs in cerebellar learning and function. PMID:25520646

A quantitative metric to identify critical elements within seafood supply networks.

PubMed

Plagányi, Éva E; van Putten, Ingrid; Thébaud, Olivier; Hobday, Alistair J; Innes, James; Lim-Camacho, Lilly; Norman-López, Ana; Bustamante, Rodrigo H; Farmery, Anna; Fleming, Aysha; Frusher, Stewart; Green, Bridget; Hoshino, Eriko; Jennings, Sarah; Pecl, Gretta; Pascoe, Sean; Schrobback, Peggy; Thomas, Linda

2014-01-01

A theoretical basis is required for comparing key features and critical elements in wild fisheries and aquaculture supply chains under a changing climate. Here we develop a new quantitative metric that is analogous to indices used to analyse food-webs and identify key species. The Supply Chain Index (SCI) identifies critical elements as those elements with large throughput rates, as well as greater connectivity. The sum of the scores for a supply chain provides a single metric that roughly captures both the resilience and connectedness of a supply chain. Standardised scores can facilitate cross-comparisons both under current conditions as well as under a changing climate. Identification of key elements along the supply chain may assist in informing adaptation strategies to reduce anticipated future risks posed by climate change. The SCI also provides information on the relative stability of different supply chains based on whether there is a fairly even spread in the individual scores of the top few key elements, compared with a more critical dependence on a few key individual supply chain elements. We use as a case study the Australian southern rock lobster Jasus edwardsii fishery, which is challenged by a number of climate change drivers such as impacts on recruitment and growth due to changes in large-scale and local oceanographic features. The SCI identifies airports, processors and Chinese consumers as the key elements in the lobster supply chain that merit attention to enhance stability and potentially enable growth. We also apply the index to an additional four real-world Australian commercial fishery and two aquaculture industry supply chains to highlight the utility of a systematic method for describing supply chains. Overall, our simple methodological approach to empirically-based supply chain research provides an objective method for comparing the resilience of supply chains and highlighting components that may be critical.

A Quantitative Metric to Identify Critical Elements within Seafood Supply Networks

PubMed Central

Plagányi, Éva E.; van Putten, Ingrid; Thébaud, Olivier; Hobday, Alistair J.; Innes, James; Lim-Camacho, Lilly; Norman-López, Ana; Bustamante, Rodrigo H.; Farmery, Anna; Fleming, Aysha; Frusher, Stewart; Green, Bridget; Hoshino, Eriko; Jennings, Sarah; Pecl, Gretta; Pascoe, Sean; Schrobback, Peggy; Thomas, Linda

2014-01-01

A theoretical basis is required for comparing key features and critical elements in wild fisheries and aquaculture supply chains under a changing climate. Here we develop a new quantitative metric that is analogous to indices used to analyse food-webs and identify key species. The Supply Chain Index (SCI) identifies critical elements as those elements with large throughput rates, as well as greater connectivity. The sum of the scores for a supply chain provides a single metric that roughly captures both the resilience and connectedness of a supply chain. Standardised scores can facilitate cross-comparisons both under current conditions as well as under a changing climate. Identification of key elements along the supply chain may assist in informing adaptation strategies to reduce anticipated future risks posed by climate change. The SCI also provides information on the relative stability of different supply chains based on whether there is a fairly even spread in the individual scores of the top few key elements, compared with a more critical dependence on a few key individual supply chain elements. We use as a case study the Australian southern rock lobster Jasus edwardsii fishery, which is challenged by a number of climate change drivers such as impacts on recruitment and growth due to changes in large-scale and local oceanographic features. The SCI identifies airports, processors and Chinese consumers as the key elements in the lobster supply chain that merit attention to enhance stability and potentially enable growth. We also apply the index to an additional four real-world Australian commercial fishery and two aquaculture industry supply chains to highlight the utility of a systematic method for describing supply chains. Overall, our simple methodological approach to empirically-based supply chain research provides an objective method for comparing the resilience of supply chains and highlighting components that may be critical. PMID:24633147

How Many Words Does a Picture Really Tell? Cross-sectional Descriptive Study of Pictogram Evaluation by Youth.

PubMed

Korenevsky, Artyom; Vaillancourt, Régis; Pouliot, Annie; Revol, Marine; Steed, Evan; Besançon, Luc; Wahrendorf, Marit-Saskia; Patel, Jaimisha R

2013-07-01

Communicating health-related instructions with pictograms is useful, but such graphics can be interpreted in different ways. It is crucial to understand which pictogram components are best for accurate communication. To catalogue pictograms used to label drugs in clinical practice; to identify the common graphic elements for defined categories of pictograms, by performing a semiotic analysis (studying how signs are perceived and how they should be designed); to identify the key graphic elements common to pictograms preferred by users; and to develop suggestions for future pictogram design on the basis of users' input. Literature and Internet searches were performed to identify pictograms and pictogram categories. A call for pictograms was also circulated through the International Pharmaceutical Federation (FIP). Youth at a Canadian pediatric hospital were asked to rate pictograms (including storyboards and prescription labels generated by FIP pictogram software) in terms of how best they represented their intended meanings. Pictograms for which at least 80% of participants "somewhat agreed", "agreed", or "strongly agreed" that the graphic conveyed the intended meaning were designated as "preferred" and were selected for analysis. Elements appearing in at least 50% of these preferred pictograms were highlighted as key graphic elements for design of future pictograms. In total, 21 categories were identified for pictograms used in clinical practice, and a total of 204 pictograms were analyzed. Eighty-six participants took part in the survey. For each pictogram category, certain elements were identified as "preferred" and as "key graphic elements", whereas other elements met neither designation. For all 21 pictogram categories, at least 80% of survey respondents agreed that the FIP storyboard conveyed the intended meaning. Certain key, preferred graphic elements are required for pharmaceutical pictograms to convey their intended meaning. The overlap between preferred and key pictogram elements indicates that both must be considered in development of future pictograms. Redesign of existing pictograms with consideration of the best semiotic elements is in progress.

The Dynamic Brain: From Spiking Neurons to Neural Masses and Cortical Fields

PubMed Central

Deco, Gustavo; Jirsa, Viktor K.; Robinson, Peter A.; Breakspear, Michael; Friston, Karl

2008-01-01

The cortex is a complex system, characterized by its dynamics and architecture, which underlie many functions such as action, perception, learning, language, and cognition. Its structural architecture has been studied for more than a hundred years; however, its dynamics have been addressed much less thoroughly. In this paper, we review and integrate, in a unifying framework, a variety of computational approaches that have been used to characterize the dynamics of the cortex, as evidenced at different levels of measurement. Computational models at different space–time scales help us understand the fundamental mechanisms that underpin neural processes and relate these processes to neuroscience data. Modeling at the single neuron level is necessary because this is the level at which information is exchanged between the computing elements of the brain; the neurons. Mesoscopic models tell us how neural elements interact to yield emergent behavior at the level of microcolumns and cortical columns. Macroscopic models can inform us about whole brain dynamics and interactions between large-scale neural systems such as cortical regions, the thalamus, and brain stem. Each level of description relates uniquely to neuroscience data, from single-unit recordings, through local field potentials to functional magnetic resonance imaging (fMRI), electroencephalogram (EEG), and magnetoencephalogram (MEG). Models of the cortex can establish which types of large-scale neuronal networks can perform computations and characterize their emergent properties. Mean-field and related formulations of dynamics also play an essential and complementary role as forward models that can be inverted given empirical data. This makes dynamic models critical in integrating theory and experiments. We argue that elaborating principled and informed models is a prerequisite for grounding empirical neuroscience in a cogent theoretical framework, commensurate with the achievements in the physical sciences. PMID:18769680

Shape perception simultaneously up- and downregulates neural activity in the primary visual cortex.

PubMed

Kok, Peter; de Lange, Floris P

2014-07-07

An essential part of visual perception is the grouping of local elements (such as edges and lines) into coherent shapes. Previous studies have shown that this grouping process modulates neural activity in the primary visual cortex (V1) that is signaling the local elements [1-4]. However, the nature of this modulation is controversial. Some studies find that shape perception reduces neural activity in V1 [2, 5, 6], while others report increased V1 activity during shape perception [1, 3, 4, 7-10]. Neurocomputational theories that cast perception as a generative process [11-13] propose that feedback connections carry predictions (i.e., the generative model), while feedforward connections signal the mismatch between top-down predictions and bottom-up inputs. Within this framework, the effect of feedback on early visual cortex may be either enhancing or suppressive, depending on whether the feedback signal is met by congruent bottom-up input. Here, we tested this hypothesis by quantifying the spatial profile of neural activity in V1 during the perception of illusory shapes using population receptive field mapping. We find that shape perception concurrently increases neural activity in regions of V1 that have a receptive field on the shape but do not receive bottom-up input and suppresses activity in regions of V1 that receive bottom-up input that is predicted by the shape. These effects were not modulated by task requirements. Together, these findings suggest that shape perception changes lower-order sensory representations in a highly specific and automatic manner, in line with theories that cast perception in terms of hierarchical generative models. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effects of rolipram, a phosphodiesterase 4 inhibitor, in combination with imipramine on depressive behavior, CRE-binding activity and BDNF level in learned helplessness rats.

PubMed

Itoh, Tetsuji; Tokumura, Miwa; Abe, Kohji

2004-09-13

The brain cAMP regulating system and its downstream elements play a pivotal role in the therapeutic effects of antidepressants. We previously reported the increase in activities of phosphodiesterase 4, a major phosphodiesterase isozyme hydrolyzing cAMP, in the frontal cortex and hippocampus of learned helplessness rats, an animal model for depression. The present study was undertaken to examine the combination of effects of rolipram, a phosphodiesterase 4 inhibitor, with imipramine, a typical tricyclic antidepressant, on depressive behavior in learned helplessness rats. Concurrently, cAMP-response element (CRE)-binding activity and brain-derived neurotrophic factor (BDNF) levels related to the therapeutic effects of antidepressants were determined. Repeated administration of imipramine (1.25-10 mg/kg, i.p.) or rolipram (1.25 mg/kg, i.p.) reduced the number of escape failures in learned helplessness rats. Imipramine could not completely ameliorate the escape behavior to a level similar to that of non-stressed rats even at 10 mg/kg. However, repeated coadministration of rolipram with imipramine (1.25 and 2.5 mg/kg, respectively) almost completely eliminated the escape failures in learned helplessness rats. The reduction of CRE-binding activities and BDNF levels in the frontal cortex or hippocampus in learned helplessness rats were ameliorated by treatment with imipramine or rolipram alone. CRE-binding activities and/or BDNF levels of the frontal cortex and hippocampus were significantly increased by treatment with a combination of rolipram and imipramine compared to those in imipramine-treated rats. These results indicated that coadministration of phosphodiesterase type 4 inhibitors with antidepressants may be more effective for depression therapy and suggest that elevation of the cAMP signal transduction pathway is involved in the antidepressive effects.

Paired motor cortex and cervical epidural electrical stimulation timed to converge in the spinal cord promotes lasting increases in motor responses

PubMed Central

Mishra, Asht M.; Pal, Ajay; Gupta, Disha

2017-01-01

Key points Pairing motor cortex stimulation and spinal cord epidural stimulation produced large augmentation in motor cortex evoked potentials if they were timed to converge in the spinal cord.The modulation of cortical evoked potentials by spinal cord stimulation was largest when the spinal electrodes were placed over the dorsal root entry zone.Repeated pairing of motor cortex and spinal cord stimulation caused lasting increases in evoked potentials from both sites, but only if the time between the stimuli was optimal.Both immediate and lasting effects of paired stimulation are likely mediated by convergence of descending motor circuits and large diameter afferents onto common interneurons in the cervical spinal cord. Abstract Convergent activity in neural circuits can generate changes at their intersection. The rules of paired electrical stimulation are best understood for protocols that stimulate input circuits and their targets. We took a different approach by targeting the interaction of descending motor pathways and large diameter afferents in the spinal cord. We hypothesized that pairing stimulation of motor cortex and cervical spinal cord would strengthen motor responses through their convergence. We placed epidural electrodes over motor cortex and the dorsal cervical spinal cord in rats; motor evoked potentials (MEPs) were measured from biceps. MEPs evoked from motor cortex were robustly augmented with spinal epidural stimulation delivered at an intensity below the threshold for provoking an MEP. Augmentation was critically dependent on the timing and position of spinal stimulation. When the spinal stimulation was timed to coincide with the descending volley from motor cortex stimulation, MEPs were more than doubled. We then tested the effect of repeated pairing of motor cortex and spinal stimulation. Repetitive pairing caused strong augmentation of cortical MEPs and spinal excitability that lasted up to an hour after just 5 min of pairing. Additional physiology experiments support the hypothesis that paired stimulation is mediated by convergence of descending motor circuits and large diameter afferents in the spinal cord. The large effect size of this protocol and the conservation of the circuits being manipulated between rats and humans makes it worth pursuing for recovery of sensorimotor function after injury to the central nervous system. PMID:28752624

Introduction to the special section on "translational models of prefrontal cortical function".

PubMed

Baxter, Mark G

2011-06-01

Impaired functioning of the prefrontal cortex is particularly prominent in many forms of psychopathology and in degenerative brain diseases. Because it is challenging to draw causal links between specific brain abnormalities and impaired cognition in these conditions, research using nonhuman animals has a key role to play in elucidating the neurobiological mechanisms of prefrontal cortex function and aiding the search for treatments. This role is clearly illustrated in the review articles and original research reports in this special section. Taken together, these papers demonstrate the insights that have already been gained from research with nonhuman animals as well as the work that still needs to be done to attain the goal of understanding human prefrontal cortical function in both health and disease.

A neurocomputational system for relational reasoning.

PubMed

Knowlton, Barbara J; Morrison, Robert G; Hummel, John E; Holyoak, Keith J

2012-07-01

The representation and manipulation of structured relations is central to human reasoning. Recent work in computational modeling and neuroscience has set the stage for developing more detailed neurocomputational models of these abilities. Several key neural findings appear to dovetail with computational constraints derived from a model of analogical processing, 'Learning and Inference with Schemas and Analogies' (LISA). These include evidence that (i) coherent oscillatory activity in the gamma and theta bands enables long-distance communication between the prefrontal cortex and posterior brain regions where information is stored; (ii) neurons in prefrontal cortex can rapidly learn to represent abstract concepts; (iii) a rostral-caudal abstraction gradient exists in the PFC; and (iv) the inferior frontal gyrus exerts inhibitory control over task-irrelevant information. Copyright © 2012. Published by Elsevier Ltd.

Dysfunction of the prefrontal cortex in addiction: neuroimaging findings and clinical implications.

PubMed

Goldstein, Rita Z; Volkow, Nora D

2011-10-20

The loss of control over drug intake that occurs in addiction was initially believed to result from disruption of subcortical reward circuits. However, imaging studies in addictive behaviours have identified a key involvement of the prefrontal cortex (PFC) both through its regulation of limbic reward regions and its involvement in higher-order executive function (for example, self-control, salience attribution and awareness). This Review focuses on functional neuroimaging studies conducted in the past decade that have expanded our understanding of the involvement of the PFC in drug addiction. Disruption of the PFC in addiction underlies not only compulsive drug taking but also accounts for the disadvantageous behaviours that are associated with addiction and the erosion of free will.

Dysfunction of the prefrontal cortex in addiction: neuroimaging findings and clinical implications

PubMed Central

Goldstein, Rita Z.; Volkow, Nora D.

2012-01-01

The loss of control over drug intake that occurs in addiction was initially believed to result from disruption of subcortical reward circuits. However, imaging studies in addictive behaviours have identified a key involvement of the prefrontal cortex (PFC) both through its regulation of limbic reward regions and its involvement in higher-order executive function (for example, self-control, salience attribution and awareness). This Review focuses on functional neuroimaging studies conducted in the past decade that have expanded our understanding of the involvement of the PFC in drug addiction. Disruption of the PFC in addiction underlies not only compulsive drug taking but also accounts for the disadvantageous behaviours that are associated with addiction and the erosion of free will. PMID:22011681

The Contribution of Object Shape and Surface Properties to Object Ensemble Representation in Anterior-medial Ventral Visual Cortex.

PubMed

Cant, Jonathan S; Xu, Yaoda

2017-02-01

Our visual system can extract summary statistics from large collections of objects without forming detailed representations of the individual objects in the ensemble. In a region in ventral visual cortex encompassing the collateral sulcus and the parahippocampal gyrus and overlapping extensively with the scene-selective parahippocampal place area (PPA), we have previously reported fMRI adaptation to object ensembles when ensemble statistics repeated, even when local image features differed across images (e.g., two different images of the same strawberry pile). We additionally showed that this ensemble representation is similar to (but still distinct from) how visual texture patterns are processed in this region and is not explained by appealing to differences in the color of the elements that make up the ensemble. To further explore the nature of ensemble representation in this brain region, here we used PPA as our ROI and investigated in detail how the shape and surface properties (i.e., both texture and color) of the individual objects constituting an ensemble affect the ensemble representation in anterior-medial ventral visual cortex. We photographed object ensembles of stone beads that varied in shape and surface properties. A given ensemble always contained beads of the same shape and surface properties (e.g., an ensemble of star-shaped rose quartz beads). A change to the shape and/or surface properties of all the beads in an ensemble resulted in a significant release from adaptation in PPA compared with conditions in which no ensemble feature changed. In contrast, in the object-sensitive lateral occipital area (LO), we only observed a significant release from adaptation when the shape of the ensemble elements varied, and found no significant results in additional scene-sensitive regions, namely, the retrosplenial complex and occipital place area. Together, these results demonstrate that the shape and surface properties of the individual objects comprising an ensemble both contribute significantly to object ensemble representation in anterior-medial ventral visual cortex and further demonstrate a functional dissociation between object- (LO) and scene-selective (PPA) visual cortical regions and within the broader scene-processing network itself.

Environmental Novelty is Associated with a Selective Increase in Fos Expression in the Output Elements of the Hippocampal Formation and the Perirhinal Cortex

ERIC Educational Resources Information Center

VanElzakker, Michael; Fevurly, Rebecca D.; Breindel, Tressa; Spencer, Robert L.

2008-01-01

If the hippocampus plays a role in the detection of novel environmental features, then novelty should be associated with altered hippocampal neural activity and perhaps also measures of neuroplasticity. We examined Fos protein expression within subregions of rat hippocampal formation as an indicator of recent increases in neuronal excitation and…

Youthful Brains in Older Adults: Preserved Neuroanatomy in the Default Mode and Salience Networks Contributes to Youthful Memory in Superaging.

PubMed

Sun, Felicia W; Stepanovic, Michael R; Andreano, Joseph; Barrett, Lisa Feldman; Touroutoglou, Alexandra; Dickerson, Bradford C

2016-09-14

Decline in cognitive skills, especially in memory, is often viewed as part of "normal" aging. Yet some individuals "age better" than others. Building on prior research showing that cortical thickness in one brain region, the anterior midcingulate cortex, is preserved in older adults with memory performance abilities equal to or better than those of people 20-30 years younger (i.e., "superagers"), we examined the structural integrity of two large-scale intrinsic brain networks in superaging: the default mode network, typically engaged during memory encoding and retrieval tasks, and the salience network, typically engaged during attention, motivation, and executive function tasks. We predicted that superagers would have preserved cortical thickness in critical nodes in these networks. We defined superagers (60-80 years old) based on their performance compared to young adults (18-32 years old) on the California Verbal Learning Test Long Delay Free Recall test. We found regions within the networks of interest where the cerebral cortex of superagers was thicker than that of typical older adults, and where superagers were anatomically indistinguishable from young adults; hippocampal volume was also preserved in superagers. Within the full group of older adults, thickness of a number of regions, including the anterior temporal cortex, rostral medial prefrontal cortex, and anterior midcingulate cortex, correlated with memory performance, as did the volume of the hippocampus. These results indicate older adults with youthful memory abilities have youthful brain regions in key paralimbic and limbic nodes of the default mode and salience networks that support attentional, executive, and mnemonic processes subserving memory function. Memory performance typically declines with age, as does cortical structural integrity, yet some older adults maintain youthful memory. We tested the hypothesis that superagers (older individuals with youthful memory performance) would exhibit preserved neuroanatomy in key brain networks subserving memory. We found that superagers not only perform similarly to young adults on memory testing, they also do not show the typical patterns of brain atrophy in certain regions. These regions are contained largely within two major intrinsic brain networks: the default mode network, implicated in memory encoding, storage, and retrieval, and the salience network, associated with attention and executive processes involved in encoding and retrieval. Preserved neuroanatomical integrity in these networks is associated with better memory performance among older adults. Copyright © 2016 Sun, Stepanovic et al.

Aging Affects Acquisition and Reversal of Reward-Based Associative Learning

ERIC Educational Resources Information Center

Weiler, Julia A.; Bellebaum, Christian; Daum, Irene

2008-01-01

Reward-based associative learning is mediated by a distributed network of brain regions that are dependent on the dopaminergic system. Age-related changes in key regions of this system, the striatum and the prefrontal cortex, may adversely affect the ability to use reward information for the guidance of behavior. The present study investigated the…

Optogenetic Activation of Presynaptic Inputs in Lateral Amygdala Forms Associative Fear Memory

ERIC Educational Resources Information Center

Kwon, Jeong-Tae; Nakajima, Ryuichi; Hyung-Su, Kim; Jeong, Yire; Augustine, George J.; Han, Jin-Hee

2014-01-01

In Pavlovian fear conditioning, the lateral amygdala (LA) has been highlighted as a key brain site for association between sensory cues and aversive stimuli. However, learning-related changes are also found in upstream sensory regions such as thalamus and cortex. To isolate the essential neural circuit components for fear memory association, we…

Neuroscience of inhibition for addiction medicine: from prediction of initiation to prediction of relapse.

PubMed

Moeller, Scott J; Bederson, Lucia; Alia-Klein, Nelly; Goldstein, Rita Z

2016-01-01

A core deficit in drug addiction is the inability to inhibit maladaptive drug-seeking behavior. Consistent with this deficit, drug-addicted individuals show reliable cross-sectional differences from healthy nonaddicted controls during tasks of response inhibition accompanied by brain activation abnormalities as revealed by functional neuroimaging. However, it is less clear whether inhibition-related deficits predate the transition to problematic use, and, in turn, whether these deficits predict the transition out of problematic substance use. Here, we review longitudinal studies of response inhibition in children/adolescents with little substance experience and longitudinal studies of already addicted individuals attempting to sustain abstinence. Results show that response inhibition and its underlying neural correlates predict both substance use outcomes (onset and abstinence). Neurally, key roles were observed for multiple regions of the frontal cortex (e.g., inferior frontal gyrus, dorsal anterior cingulate cortex, and dorsolateral prefrontal cortex). In general, less activation of these regions during response inhibition predicted not only the onset of substance use, but interestingly also better abstinence-related outcomes among individuals already addicted. The role of subcortical areas, although potentially important, is less clear because of inconsistent results and because these regions are less classically reported in studies of healthy response inhibition. Overall, this review indicates that response inhibition is not simply a manifestation of current drug addiction, but rather a core neurocognitive dimension that predicts key substance use outcomes. Early intervention in inhibitory deficits could have high clinical and public health relevance. © 2016 Elsevier B.V. All rights reserved.

Decreased functional connectivity to posterior cingulate cortex in major depressive disorder.

PubMed

Yang, Rui; Gao, Chengge; Wu, Xiaoping; Yang, Junle; Li, Shengbin; Cheng, Hu

2016-09-30

The default mode network (DMN) and its interaction with other key networks such as the salience network and executive network are keys to understand psychiatric and neurological disorders including major depressive disorder (MDD). In this study, we combined independent component analysis and seed based connectivity analysis to study the posterior default mode network between 20 patients with MDD and 25 normal controls, as well as pre-treatment and post-treatment conditions of the patients. Both correlated and anti-correlated networks centered at the posterior cingulate cortex (PCC) were examined (PCC+ and PCC-). Our results showed aberrant functional connectivity of the PCC+ and PCC- networks between patients and normal controls. Specifically, normal controls exhibited significantly higher connectivity between the PCC and frontal/temporal regions for the PCC+ network and stronger connectivity strength between the PCC and the insula/middle frontal cortex for the PCC- network. The overall connectivity strength of the PCC+ and PCC- networks was also significantly lower in MDD. Because the PCC is a hub in the DMN that interacts with other networks, our result suggested a stronger interaction between the DMN and the salience network but a weak interaction between the DMN and the executive network in MDD. The treatment using sertraline did increase the functional connectivity strength, especially in the PCC+ network. Despite a large inter-subject variability in the overall connectivity strengths and change of the PCC network in response to the treatment, a high correlation between change of connectivity strength and the Hamilton depression score was observed for both the PCC+ and PCC- network. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Activation of the Basal Forebrain by the Orexin/Hypocretin Neurons: Orexin International Symposium

PubMed Central

Arrigoni, Elda; Mochizuki, Takatoshi; Scammell, Thomas E.

2010-01-01

The orexin neurons play an essential role in driving arousal and in maintaining normal wakefulness. Lack of orexin neurotransmission produces a chronic state of hypoarousal characterized by excessive sleepiness, frequent transitions between wake and sleep, and episodes of cataplexy. A growing body of research now suggests that the basal forebrain (BF) may be a key site through which the orexin-producing neurons promote arousal. Here we review anatomical, pharmacological and electrophysiological studies on how the orexin neurons may promote arousal by exciting cortically-projecting neurons of the BF. Orexin fibers synapse on BF cholinergic neurons and orexin-A is released in the BF during waking. Local application of orexins excites BF cholinergic neurons, induces cortical release of acetylcholine, and promotes wakefulness. The orexin neurons also contain and probably co-release the inhibitory neuropeptide dynorphin. We found that orexin-A and dynorphin have specific effects on different classes of BF neurons that project to the cortex. Cholinergic neurons were directly excited by orexin-A, but did not respond to dynorphin. Non-cholinergic BF neurons that project to the cortex seem to comprise at least two populations with some directly excited by orexin that may represent wake-active, GABAergic neurons, whereas others did not respond to orexin but were inhibited by dynorphin and may be sleep-active, GABAergic neurons. This evidence suggests that the BF is a key site through which orexins activate the cortex and promotes behavioral arousal. In addition, orexins and dynorphin may act synergistically in the BF to promote arousal and improve cognitive performance. PMID:19723027

Proteomic analysis of trans-hemispheric motor cortex reorganization following contralateral C7 nerve transfer

PubMed Central

Yuan, Yin; Xu, Xiu-yue; Lao, Jie; Zhao, Xin

2018-01-01

Nerve transfer is the most common treatment for total brachial plexus avulsion injury. After nerve transfer, the movement of the injured limb may be activated by certain movements of the healthy limb at the early stage of recovery, i.e., trans-hemispheric reorganization. Previous studies have focused on functional magnetic resonance imaging and changes in brain-derived neurotrophic factor and growth associated protein 43, but there have been no proteomics studies. In this study, we designed a rat model of total brachial plexus avulsion injury involving contralateral C7 nerve transfer. Isobaric tags for relative and absolute quantitation and western blot assay were then used to screen differentially expressed proteins in bilateral motor cortices. We found that most differentially expressed proteins in both cortices of upper limb were associated with nervous system development and function (including neuron differentiation and development, axonogenesis, and guidance), microtubule and cytoskeleton organization, synapse plasticity, and transmission of nerve impulses. Two key differentially expressed proteins, neurofilament light (NFL) and Thy-1, were identified. In contralateral cortex, the NFL level was upregulated 2 weeks after transfer and downregulated at 1 and 5 months. The Thy-1 level was upregulated from 1 to 5 months. In the affected cortex, the NFL level increased gradually from 1 to 5 months. Western blot results of key differentially expressed proteins were consistent with the proteomic findings. These results indicate that NFL and Thy-1 play an important role in trans-hemispheric organization following total brachial plexus root avulsion and contralateral C7 nerve transfer. PMID:29557385

Model Cortical Association Fields Account for the Time Course and Dependence on Target Complexity of Human Contour Perception

PubMed Central

Gintautas, Vadas; Ham, Michael I.; Kunsberg, Benjamin; Barr, Shawn; Brumby, Steven P.; Rasmussen, Craig; George, John S.; Nemenman, Ilya; Bettencourt, Luís M. A.; Kenyon, Garret T.

2011-01-01

Can lateral connectivity in the primary visual cortex account for the time dependence and intrinsic task difficulty of human contour detection? To answer this question, we created a synthetic image set that prevents sole reliance on either low-level visual features or high-level context for the detection of target objects. Rendered images consist of smoothly varying, globally aligned contour fragments (amoebas) distributed among groups of randomly rotated fragments (clutter). The time course and accuracy of amoeba detection by humans was measured using a two-alternative forced choice protocol with self-reported confidence and variable image presentation time (20-200 ms), followed by an image mask optimized so as to interrupt visual processing. Measured psychometric functions were well fit by sigmoidal functions with exponential time constants of 30-91 ms, depending on amoeba complexity. Key aspects of the psychophysical experiments were accounted for by a computational network model, in which simulated responses across retinotopic arrays of orientation-selective elements were modulated by cortical association fields, represented as multiplicative kernels computed from the differences in pairwise edge statistics between target and distractor images. Comparing the experimental and the computational results suggests that each iteration of the lateral interactions takes at least ms of cortical processing time. Our results provide evidence that cortical association fields between orientation selective elements in early visual areas can account for important temporal and task-dependent aspects of the psychometric curves characterizing human contour perception, with the remaining discrepancies postulated to arise from the influence of higher cortical areas. PMID:21998562

Valproate selectively reduces EEG activity in anterior parts of the cortex in patients with idiopathic generalized epilepsy. A low resolution electromagnetic tomography (LORETA) study.

PubMed

Béla, Clemens; Mónika, Bessenyei; Márton, Tóth; István, Kondákor

2007-07-01

To localize the cortical area where the anticonvulsive drug valproate (VPA) exerts its effect in patients with idiopathic generalized epilepsy (IGE). In a prior study we investigated 15 IGE patients in the untreated condition and compared their low resolution electromagnetic tomography (LORETA) results to a normal control group. The investigation of these patients was continued in the present study. All the 15 patients were treated with VPA and were followed by the authors. EEG was recorded after 3 months of VPA treatment in the seizure-free patients. A total of 2min of 19-channels, common reference-recorded, waking-relaxed background activity (without paroxysmal and other, non-stationary elements) was analyzed. "Activity" (current density, amper/meters squared) was given in four frequency bands (delta, theta, alpha, beta). Band-related group differences between the present LORETA results (treated condition) and the prior LORETA results (untreated condition) were computed for all the 2394 voxels by t-tests for interdependent datasets. The statistically significant (p<0.01, uncorrected) differences of activity were projected to real cortical anatomy using the Talairach Brain Atlas. Statistically significant differences between the untreated and treated condition emerged in the delta and theta bands. VPA decreased delta and theta activity in the entire frontal cortex, insula, anterior temporal cortex and hippocampus, and in the anterior part of the parietal cortex. VPA decreased activity in parts of the cortex that display ictogenic properties and contribute to seizure generation in IGE. Furthermore, the anatomical distribution of the drug effect exactly corresponded to the VPA-related accumulation of neuroprotective proteins reported in experimental papers.

Heavy metals translocation and accumulation from the rhizosphere soils to the edible parts of the medicinal plant Fengdan (Paeonia ostii) grown on a metal mining area, China.

PubMed

Shen, Zhang Jun; Xu, De Cong; Chen, Yan Song; Zhang, Zhen

2017-09-01

Fengdan (Paeonia ostii) is one of Chinese 34 famous medicinal materials. This study investigated the concentrations of Arsenic (As), Chromium (Cr), Cadmium (Cd), Copper (Cu), Lead (Pb), Iron (Fe), Manganese (Mn), and Zinc (Zn) in rhizosphere soils, cortex mouton and seeds of Fengdan planted in a metal mining area, China. The mean concentrations of As, Cd, Cu, and Zn in the rhizosphere soils were above the limits set by the Chinese Soil Environmental Quality Standard (GB 15618-1995). The contamination factor (CF) of Cd was >5, while it was >2for As, Cu, Pb, and Zn in all the soils. The integrated pollution index for all the soils was >3 and ˂ 5. Metal concentrations in the edible parts of Fengdan were in the following decreasing order: Mn>Fe>Zn>Cu>Pb>As>Cr≥Cd. The transfer factor mean values for As, Cu, Cd and Fe in the cortex moutan of old Fengdan (over 6 years) were significantly higher than in young Fengdan. Available metal concentrations, pH and soil organic matter content influenced the metal concentrations of the cortex moutan. The results indicated that mining and smelting operations have led to heavy metals contamination of soils and medicinal parts of Fengdan. The major metal pollutants were elemental Cd, Cu, Pb, and Zn. Heavy metals mainly accumulated in the cortex moutan of Fengdan. The mean concentrations of Cd, Cu, and Pb in the old cortex moutan (over 6 years) were above those of the Chinese Green Trade Standards for Medicinal Plants and Preparations in Foreign Trade (WM/T2-2004). Copyright © 2017. Published by Elsevier Inc.

Advances in the behavioural testing and network imaging of rodent recognition memory

PubMed Central

Kinnavane, Lisa; Albasser, Mathieu M.; Aggleton, John P.

2015-01-01

Research into object recognition memory has been galvanised by the introduction of spontaneous preference tests for rodents. The standard task, however, contains a number of inherent shortcomings that reduce its power. Particular issues include the problem that individual trials are time consuming, so limiting the total number of trials in any condition. In addition, the spontaneous nature of the behaviour and the variability between test objects add unwanted noise. To combat these issues, the ‘bow-tie maze’ was introduced. Although still based on the spontaneous preference of novel over familiar stimuli, the ability to give multiple trials within a session without handling the rodents, as well as using the same objects as both novel and familiar samples on different trials, overcomes key limitations in the standard task. Giving multiple trials within a single session also creates new opportunities for functional imaging of object recognition memory. A series of studies are described that examine the expression of the immediate-early gene, c-fos. Object recognition memory is associated with increases in perirhinal cortex and area Te2 c-fos activity. When rats explore novel objects the pathway from the perirhinal cortex to lateral entorhinal cortex, and then to the dentate gyrus and CA3, is engaged. In contrast, when familiar objects are explored the pathway from the perirhinal cortex to lateral entorhinal cortex, and then to CA1, takes precedence. The switch to the perforant pathway (novel stimuli) from the temporoammonic pathway (familiar stimuli) may assist the enhanced associative learning promoted by novel stimuli. PMID:25106740

Development and Function of the Human Fetal Adrenal Cortex: A Key Component in the Feto-Placental Unit

PubMed Central

Ishimoto, Hitoshi

2011-01-01

Continuous efforts have been devoted to unraveling the biophysiology and development of the human fetal adrenal cortex, which is structurally and functionally unique from other species. It plays a pivotal role, mainly through steroidogenesis, in the regulation of intrauterine homeostasis and in fetal development and maturation. The steroidogenic activity is characterized by early transient cortisol biosynthesis, followed by its suppressed synthesis until late gestation, and extensive production of dehydroepiandrosterone and its sulfate, precursors of placental estrogen, during most of gestation. The gland rapidly grows through processes including cell proliferation and angiogenesis at the gland periphery, cellular migration, hypertrophy, and apoptosis. Recent studies employing modern technologies such as gene expression profiling and laser capture microdissection have revealed that development and/or function of the fetal adrenal cortex may be regulated by a panoply of molecules, including transcription factors, extracellular matrix components, locally produced growth factors, and placenta-derived CRH, in addition to the primary regulator, fetal pituitary ACTH. The role of the fetal adrenal cortex in human pregnancy and parturition appears highly complex, probably due to redundant and compensatory mechanisms regulating these events. Mounting evidence indicates that actions of hormones operating in the human feto-placental unit are likely mediated by mechanisms including target tissue responsiveness, local metabolism, and bioavailability, rather than changes only in circulating levels. Comprehensive study of such molecular mechanisms and the newly identified factors implicated in adrenal development should help crystallize our understanding of the development and physiology of the human fetal adrenal cortex. PMID:21051591

Dopamine D2-receptor blockade enhances decoding of prefrontal signals in humans.

PubMed

Kahnt, Thorsten; Weber, Susanna C; Haker, Helene; Robbins, Trevor W; Tobler, Philippe N

2015-03-04

The prefrontal cortex houses representations critical for ongoing and future behavior expressed in the form of patterns of neural activity. Dopamine has long been suggested to play a key role in the integrity of such representations, with D2-receptor activation rendering them flexible but weak. However, it is currently unknown whether and how D2-receptor activation affects prefrontal representations in humans. In the current study, we use dopamine receptor-specific pharmacology and multivoxel pattern-based functional magnetic resonance imaging to test the hypothesis that blocking D2-receptor activation enhances prefrontal representations. Human subjects performed a simple reward prediction task after double-blind and placebo controlled administration of the D2-receptor antagonist amisulpride. Using a whole-brain searchlight decoding approach we show that D2-receptor blockade enhances decoding of reward signals in the medial orbitofrontal cortex. Examination of activity patterns suggests that amisulpride increases the separation of activity patterns related to reward versus no reward. Moreover, consistent with the cortical distribution of D2 receptors, post hoc analyses showed enhanced decoding of motor signals in motor cortex, but not of visual signals in visual cortex. These results suggest that D2-receptor blockade enhances content-specific representations in frontal cortex, presumably by a dopamine-mediated increase in pattern separation. These findings are in line with a dual-state model of prefrontal dopamine, and provide new insights into the potential mechanism of action of dopaminergic drugs. Copyright © 2015 the authors 0270-6474/15/354104-08$15.00/0.

Association of Optic Radiation Integrity with Cortical Thickness in Children with Anisometropic Amblyopia.

PubMed

Qi, Shun; Mu, Yun-Feng; Cui, Long-Biao; Li, Rong; Shi, Mei; Liu, Ying; Xu, Jun-Qing; Zhang, Jian; Yang, Jian; Yin, Hong

2016-02-01

Previous studies have indicated regional abnormalities of both gray and white matter in amblyopia. However, alterations of cortical thickness associated with changes in white matter integrity have rarely been reported. In this study, structural magnetic resonance imaging and diffusion tensor imaging (DTI) data were obtained from 15 children with anisometropic amblyopia and 15 age- and gender-matched children with normal sight. Combining DTI and surface-based morphometry, we examined a potential linkage between disrupted white matter integrity and altered cortical thickness. The fractional anisotropy (FA) values in the optic radiations (ORs) of children with anisometropic amblyopia were lower than in controls (P < 0.05). The cortical thickness in amblyopic children was lower than controls in the following subregions: lingual cortex, lateral occipitotemporal gyrus, cuneus, occipital lobe, inferior parietal lobe, and temporal lobe (P < 0.05, corrected), but was higher in the calcarine gyrus (P < 0.05, corrected). Node-by-node correlation analysis of changes in cortical thickness revealed a significant association between a lower FA value in the OR and diminished cortical thickness in the following subregions: medial lingual cortex, lateral occipitotemporal gyrus, lateral, superior, and medial occipital cortex, and lunate cortex. We also found a relationship between changes of cortical thickness and white matter OR integrity in amblyopia. These findings indicate that developmental changes occur simultaneously in the OR and visual cortex in amblyopia, and provide key information on complex damage of brain networks in anisometropic amblyopia. Our results also support the hypothesis that the pathogenesis of anisometropic amblyopia is neurodevelopmental.

Distinct development of the cerebral cortex in platypus and echidna.

PubMed

Ashwell, Ken W S; Hardman, Craig D

2012-01-01

Both lineages of the modern monotremes have distinctive features in the cerebral cortex, but the developmental mechanisms that produce such different adult cortical architecture remain unknown. Similarly, nothing is known about the differences and/or similarities between monotreme and therian cortical development. We have used material from the Hill embryological collection to try to answer key questions concerning cortical development in monotremes. Our findings indicate that gyrencephaly begins to emerge in the echidna brain shortly before birth (crown-rump length 12.5 mm), whereas the cortex of the platypus remains lissencephalic throughout development. The cortices of both monotremes are very immature at the time of hatching, much like that seen in marsupials, and both have a subventricular zone (SubV) within both the striatum and pallium during post-hatching development. It is particularly striking that in the platypus, this region has an extension from the palliostriatal angle beneath the developing trigeminoreceptive part of the somatosensory cortex of the lateral cortex. The putative SubV beneath the trigeminal part of S1 appears to accommodate at least two distinct types of cell and many mitotic figures and (particularly in the platypus) appears to be traversed by large numbers of thalamocortical axons as these grow in. The association with putative thalamocortical fibres suggests that this region may also serve functions similar to the subplate zone of Eutheria. These findings suggest that cortical development in each monotreme follows distinct paths from at least the time of birth, consistent with a long period of independent and divergent cortical evolution. Copyright © 2011 S. Karger AG, Basel.

Taking a gamble or playing by the rules: Dissociable prefrontal systems implicated in probabilistic versus deterministic rule-based decisions

PubMed Central

Bhanji, Jamil P.; Beer, Jennifer S.; Bunge, Silvia A.

2014-01-01

A decision may be difficult because complex information processing is required to evaluate choices according to deterministic decision rules and/or because it is not certain which choice will lead to the best outcome in a probabilistic context. Factors that tax decision making such as decision rule complexity and low decision certainty should be disambiguated for a more complete understanding of the decision making process. Previous studies have examined the brain regions that are modulated by decision rule complexity or by decision certainty but have not examined these factors together in the context of a single task or study. In the present functional magnetic resonance imaging study, both decision rule complexity and decision certainty were varied in comparable decision tasks. Further, the level of certainty about which choice to make (choice certainty) was varied separately from certainty about the final outcome resulting from a choice (outcome certainty). Lateral prefrontal cortex, dorsal anterior cingulate cortex, and bilateral anterior insula were modulated by decision rule complexity. Anterior insula was engaged more strongly by low than high choice certainty decisions, whereas ventromedial prefrontal cortex showed the opposite pattern. These regions showed no effect of the independent manipulation of outcome certainty. The results disambiguate the influence of decision rule complexity, choice certainty, and outcome certainty on activity in diverse brain regions that have been implicated in decision making. Lateral prefrontal cortex plays a key role in implementing deterministic decision rules, ventromedial prefrontal cortex in probabilistic rules, and anterior insula in both. PMID:19781652

Neural progenitor fate decision defects, cortical hypoplasia and behavioral impairment in Celsr1-deficient mice.

PubMed

Boucherie, C; Boutin, C; Jossin, Y; Schakman, O; Goffinet, A M; Ris, L; Gailly, P; Tissir, F

2018-03-01

The development of the cerebral cortex is a tightly regulated process that relies on exquisitely coordinated actions of intrinsic and extrinsic cues. Here, we show that the communication between forebrain meninges and apical neural progenitor cells (aNPC) is essential to cortical development, and that the basal compartment of aNPC is key to this communication process. We found that Celsr1, a cadherin of the adhesion G protein coupled receptor family, controls branching of aNPC basal processes abutting the meninges and thereby regulates retinoic acid (RA)-dependent neurogenesis. Loss-of-function of Celsr1 results in a decreased number of endfeet, modifies RA-dependent transcriptional activity and biases aNPC commitment toward self-renewal at the expense of basal progenitor and neuron production. The mutant cortex has a reduced number of neurons, and Celsr1 mutant mice exhibit microcephaly and behavioral abnormalities. Our results uncover an important role for Celsr1 protein and for the basal compartment of neural progenitor cells in fate decision during the development of the cerebral cortex.

Neural progenitor fate decision defects, cortical hypoplasia and behavioral impairment in Celsr1-deficient mice

PubMed Central

Boucherie, C; Boutin, C; Jossin, Y; Schakman, O; Goffinet, A M; Ris, L; Gailly, P; Tissir, F

2018-01-01

The development of the cerebral cortex is a tightly regulated process that relies on exquisitely coordinated actions of intrinsic and extrinsic cues. Here, we show that the communication between forebrain meninges and apical neural progenitor cells (aNPC) is essential to cortical development, and that the basal compartment of aNPC is key to this communication process. We found that Celsr1, a cadherin of the adhesion G protein coupled receptor family, controls branching of aNPC basal processes abutting the meninges and thereby regulates retinoic acid (RA)-dependent neurogenesis. Loss-of-function of Celsr1 results in a decreased number of endfeet, modifies RA-dependent transcriptional activity and biases aNPC commitment toward self-renewal at the expense of basal progenitor and neuron production. The mutant cortex has a reduced number of neurons, and Celsr1 mutant mice exhibit microcephaly and behavioral abnormalities. Our results uncover an important role for Celsr1 protein and for the basal compartment of neural progenitor cells in fate decision during the development of the cerebral cortex. PMID:29257130

Microbiota-driven transcriptional changes in prefrontal cortex override genetic differences in social behavior

PubMed Central

Gacias, Mar; Gaspari, Sevasti; Santos, Patricia-Mae G; Tamburini, Sabrina; Andrade, Monica; Zhang, Fan; Shen, Nan; Tolstikov, Vladimir; Kiebish, Michael A; Dupree, Jeffrey L; Zachariou, Venetia; Clemente, Jose C; Casaccia, Patrizia

2016-01-01

Gene-environment interactions impact the development of neuropsychiatric disorders, but the relative contributions are unclear. Here, we identify gut microbiota as sufficient to induce depressive-like behaviors in genetically distinct mouse strains. Daily gavage of vehicle (dH2O) in nonobese diabetic (NOD) mice induced a social avoidance behavior that was not observed in C57BL/6 mice. This was not observed in NOD animals with depleted microbiota via oral administration of antibiotics. Transfer of intestinal microbiota, including members of the Clostridiales, Lachnospiraceae and Ruminococcaceae, from vehicle-gavaged NOD donors to microbiota-depleted C57BL/6 recipients was sufficient to induce social avoidance and change gene expression and myelination in the prefrontal cortex. Metabolomic analysis identified increased cresol levels in these mice, and exposure of cultured oligodendrocytes to this metabolite prevented myelin gene expression and differentiation. Our results thus demonstrate that the gut microbiota modifies the synthesis of key metabolites affecting gene expression in the prefrontal cortex, thereby modulating social behavior. DOI: http://dx.doi.org/10.7554/eLife.13442.001 PMID:27097105

Molecular and Epigenetic Mechanisms for the Complex Effects of Stress on Synaptic Physiology and Cognitive Functions

PubMed Central

Yuen, Eunice Y.; Wei, Jing

2017-01-01

Abstract Evidence over the past decades has found that stress, particularly through the corticosterone stress hormones, produces complex changes in glutamatergic signaling in prefrontal cortex, which leads to the alteration of cognitive processes medicated by this brain region. Interestingly, the effects of stress on glutamatergic transmission appear to be “U-shaped,” depending upon the duration and severity of the stressor. These biphasic effects of acute vs chronic stress represent the adaptive vs maladaptive responses to stressful stimuli. Animal studies suggest that the stress-induced modulation of excitatory synaptic transmission involves changes in presynaptic glutamate release, postsynaptic glutamate receptor membrane trafficking and degradation, spine structure and cytoskeleton network, and epigenetic control of gene expression. This review will discuss current findings on the key molecules involved in the stress-induced regulation of prefrontal cortex synaptic physiology and prefrontal cortex-mediated functions. Understanding the molecular and epigenetic mechanisms that underlie the complex effects of stress will help to develop novel strategies to cope with stress-related mental disorders. PMID:29016816

Molecular and Epigenetic Mechanisms for the Complex Effects of Stress on Synaptic Physiology and Cognitive Functions.

PubMed

Yuen, Eunice Y; Wei, Jing; Yan, Zhen

2017-11-01

Evidence over the past decades has found that stress, particularly through the corticosterone stress hormones, produces complex changes in glutamatergic signaling in prefrontal cortex, which leads to the alteration of cognitive processes medicated by this brain region. Interestingly, the effects of stress on glutamatergic transmission appear to be "U-shaped," depending upon the duration and severity of the stressor. These biphasic effects of acute vs chronic stress represent the adaptive vs maladaptive responses to stressful stimuli. Animal studies suggest that the stress-induced modulation of excitatory synaptic transmission involves changes in presynaptic glutamate release, postsynaptic glutamate receptor membrane trafficking and degradation, spine structure and cytoskeleton network, and epigenetic control of gene expression. This review will discuss current findings on the key molecules involved in the stress-induced regulation of prefrontal cortex synaptic physiology and prefrontal cortex-mediated functions. Understanding the molecular and epigenetic mechanisms that underlie the complex effects of stress will help to develop novel strategies to cope with stress-related mental disorders. © The Author 2017. Published by Oxford University Press on behalf of CINP.

White matter structural connectivity and episodic memory in early childhood.

PubMed

Ngo, Chi T; Alm, Kylie H; Metoki, Athanasia; Hampton, William; Riggins, Tracy; Newcombe, Nora S; Olson, Ingrid R

2017-12-01

Episodic memory undergoes dramatic improvement in early childhood; the reason for this is poorly understood. In adults, episodic memory relies on a distributed neural network. Key brain regions that supporting these processes include the hippocampus, portions of the parietal cortex, and portions of prefrontal cortex, each of which shows different developmental profiles. Here we asked whether developmental differences in the axonal pathways connecting these regions may account for the robust gains in episodic memory in young children. Using diffusion weighted imaging, we examined whether white matter connectivity between brain regions implicated in episodic memory differed with age, and were associated with memory performance differences in 4- and 6-year-old children. Results revealed that white matter connecting the hippocampus to the inferior parietal lobule significantly predicted children's performance on episodic memory tasks. In contrast, variation in the white matter connecting the hippocampus to the medial prefrontal cortex did not relate to memory performance. These findings suggest that structural connectivity between the hippocampus and lateral parietal regions is relevant to the development of episodic memory. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Signal or noise: brain network interactions underlying the experience and training of mindfulness.

PubMed

Mooneyham, Benjamin W; Mrazek, Michael D; Mrazek, Alissa J; Schooler, Jonathan W

2016-04-01

A broad set of brain regions has been associated with the experience and training of mindfulness. Many of these regions lie within key intrinsic brain networks, including the executive control, salience, and default networks. In this paper, we review the existing literature on the cognitive neuroscience of mindfulness through the lens of network science. We describe the characteristics of the intrinsic brain networks implicated in mindfulness and summarize the relevant findings pertaining to changes in functional connectivity (FC) within and between these networks. Convergence across these findings suggests that mindfulness may be associated with increased FC between two regions within the default network: the posterior cingulate cortex and the ventromedial prefrontal cortex. Additionally, extensive meditation experience may be associated with increased FC between the insula and the dorsolateral prefrontal cortex. However, little consensus has emerged within the existing literature owing to the diversity of operational definitions of mindfulness, neuroimaging methods, and network characterizations. We describe several challenges to develop a coherent cognitive neuroscience of mindfulness and to provide detailed recommendations for future research. © 2016 New York Academy of Sciences.

White Matter Structural Connectivity and Episodic Memory in Early Childhood

PubMed Central

Ngo, Chi T.; Alm, Kylie H.; Metoki, Athanasia; Hampton, William; Riggins, Tracy; Newcombe, Nora S.; Olson, Ingrid R.

2018-01-01

Episodic memory undergoes dramatic improvement in early childhood; the reason for this is poorly understood. In adults, episodic memory relies on a distributed neural network. Key brain regions that supporting these processes include the hippocampus, portions of the parietal cortex, and portions of prefrontal cortex, each of which shows different developmental profiles. Here we asked whether developmental differences in the axonal pathways connecting these regions may account for the robust gains in episodic memory in young children. Using diffusion weighted imaging, we examined whether white matter connectivity between brain regions implicated in episodic memory differed with age, and were associated with memory performance differences in 4- and 6-year-old children. Results revealed that white matter connecting the hippocampus to the inferior parietal lobule significantly predicted children’s performance on episodic memory tasks. In contrast, variation in the white matter connecting the hippocampus to the medial prefrontal cortex did not relate to memory performance. These findings suggest that structural connectivity between the hippocampus and lateral parietal regions is relevant to the development of episodic memory PMID:29175538

Institutional analysis of milkfish supply chain using interpretive structural modelling (ISM) (case study of UD. Bunda Foods, Sidoarjo District)

NASA Astrophysics Data System (ADS)

Silalahi, R. L. R.; Mustaniroh, S. A.; Ikasari, D. M.; Sriulina, R. P.

2018-03-01

UD. Bunda Foods is an SME located in the district of Sidoarjo. UD. Bunda Foods has problems of maintaining its milkfish’s quality assurance and developing marketing strategies. Improving those problems enables UD. Bunda Foods to compete with other similar SMEs and to market its product for further expansion of their business. The objectives of this study were to determine the model of the institutional structure of the milkfish supply chain, to determine the elements, the sub-elements, and the relationship among each element. The method used in this research was Interpretive Structural Modeling (ISM), involving 5 experts as respondents consisting of 1 practitioner, 1 academician, and 3 government organisation employees. The results showed that there were two key elements include requirement and goals elements. Based on the Drive Power-Dependence (DP-D) matrix, the key sub-elements of requirement element, consisted of raw material continuity, appropriate marketing strategy, and production capital, were positioned in the Linkage sector quadrant. The DP-D matrix for the key sub-elements of the goal element also showed a similar position. The findings suggested several managerial implications to be carried out by UD. Bunda Foods include establishing good relationships with all involved institutions, obtaining capital assistance, and attending the marketing training provided by the government.

Effects of valerian consumption during pregnancy on cortical volume and the levels of zinc and copper in the brain tissue of mouse fetus.

PubMed

Mahmoudian, Alireza; Rajaei, Ziba; Haghir, Hossein; Banihashemian, Shahaboldin; Hami, Javad

2012-04-01

The aim of the present study was to determine the effects of valerian (Valeriana officinalis) consumption in pregnancy on cortical volume and the levels of zinc and copper, two essential elements that affect brain development and function, in the brain tissues of mouse fetuses. Pregnant female mice were treated with either saline or 1.2 g/kg body weight valerian extract intraperitoneally daily on gestation days (GD) 7 to 17. On GD 20, mice were sacrificed and their fetuses were collected. Fetal brains were dissected, weighed and processed for histological analysis. The volume of cerebral cortex was estimated by the Cavalieri principle. The levels of zinc and copper in the brain tissues were measured by atomic absorption spectroscopy. The results indicated that valerian consumption in pregnancy had no significant effect on brain weight, cerebral cortex volume and copper level in fetal brain. However,it significantly decreased the level of zinc in the brain (P<0.05). Using valerian during midgestation do not have an adverse effect on cerebral cortex; however,it caused a significant decrease in zinc level in the fetal brain. This suggests that valerian use should be limited during pregnancy.

The effects of physical activity on functional MRI activation associated with cognitive control in children: a randomized controlled intervention

PubMed Central

Chaddock-Heyman, Laura; Erickson, Kirk I.; Voss, Michelle W.; Knecht, Anya M.; Pontifex, Matthew B.; Castelli, Darla M.; Hillman, Charles H.; Kramer, Arthur F.

2013-01-01

This study used functional magnetic resonance imaging (fMRI) to examine the influence of a 9-month physical activity program on task-evoked brain activation during childhood. The results demonstrated that 8- to 9-year-old children who participated in 60+ min of physical activity, 5 days per week, for 9 months, showed decreases in fMRI brain activation in the right anterior prefrontal cortex coupled with within-group improvements in performance on a task of attentional and interference control. Children assigned to a wait-list control group did not show changes in brain function. Furthermore, at post-test, children in the physical activity group showed similar anterior frontal brain patterns and incongruent accuracy rates to a group of college-aged young adults. Children in the wait-list control group still differed from the young adults in terms of anterior prefrontal activation and performance at post-test. There were no significant changes in fMRI activation in the anterior cingulate cortex (ACC) for either group. These results suggest that physical activity during childhood may enhance specific elements of prefrontal cortex function involved in cognitive control. PMID:23487583

Crosstalk between intracellular and extracellular signals regulating interneuron production, migration and integration into the cortex

PubMed Central

Peyre, Elise; Silva, Carla G.; Nguyen, Laurent

2015-01-01

During embryogenesis, cortical interneurons are generated by ventral progenitors located in the ganglionic eminences of the telencephalon. They travel along multiple tangential paths to populate the cortical wall. As they reach this structure they undergo intracortical dispersion to settle in their final destination. At the cellular level, migrating interneurons are highly polarized cells that extend and retract processes using dynamic remodeling of microtubule and actin cytoskeleton. Different levels of molecular regulation contribute to interneuron migration. These include: (1) Extrinsic guidance cues distributed along migratory streams that are sensed and integrated by migrating interneurons; (2) Intrinsic genetic programs driven by specific transcription factors that grant specification and set the timing of migration for different subtypes of interneurons; (3) Adhesion molecules and cytoskeletal elements/regulators that transduce molecular signalings into coherent movement. These levels of molecular regulation must be properly integrated by interneurons to allow their migration in the cortex. The aim of this review is to summarize our current knowledge of the interplay between microenvironmental signals and cell autonomous programs that drive cortical interneuron porduction, tangential migration, and intergration in the developing cerebral cortex. PMID:25926769

Enhancing long-term memory with stimulation tunes visual attention in one trial.

PubMed

Reinhart, Robert M G; Woodman, Geoffrey F

2015-01-13

Scientists have long proposed that memory representations control the mechanisms of attention that focus processing on the task-relevant objects in our visual field. Modern theories specifically propose that we rely on working memory to store the object representations that provide top-down control over attentional selection. Here, we show that the tuning of perceptual attention can be sharply accelerated after 20 min of noninvasive brain stimulation over medial-frontal cortex. Contrary to prevailing theories of attention, these improvements did not appear to be caused by changes in the nature of the working memory representations of the search targets. Instead, improvements in attentional tuning were accompanied by changes in an electrophysiological signal hypothesized to index long-term memory. We found that this pattern of effects was reliably observed when we stimulated medial-frontal cortex, but when we stimulated posterior parietal cortex, we found that stimulation directly affected the perceptual processing of the search array elements, not the memory representations providing top-down control. Our findings appear to challenge dominant theories of attention by demonstrating that changes in the storage of target representations in long-term memory may underlie rapid changes in the efficiency with which humans can find targets in arrays of objects.

Texture Segregation Causes Early Figure Enhancement and Later Ground Suppression in Areas V1 and V4 of Visual Cortex

PubMed Central

Poort, Jasper; Self, Matthew W.; van Vugt, Bram; Malkki, Hemi; Roelfsema, Pieter R.

2016-01-01

Segregation of images into figures and background is fundamental for visual perception. Cortical neurons respond more strongly to figural image elements than to background elements, but the mechanisms of figure–ground modulation (FGM) are only partially understood. It is unclear whether FGM in early and mid-level visual cortex is caused by an enhanced response to the figure, a suppressed response to the background, or both. We studied neuronal activity in areas V1 and V4 in monkeys performing a texture segregation task. We compared texture-defined figures with homogeneous textures and found an early enhancement of the figure representation, and a later suppression of the background. Across neurons, the strength of figure enhancement was independent of the strength of background suppression. We also examined activity in the different V1 layers. Both figure enhancement and ground suppression were strongest in superficial and deep layers and weaker in layer 4. The current–source density profiles suggested that figure enhancement was caused by stronger synaptic inputs in feedback-recipient layers 1, 2, and 5 and ground suppression by weaker inputs in these layers, suggesting an important role for feedback connections from higher level areas. These results provide new insights into the mechanisms for figure–ground organization. PMID:27522074

An approach to separating the levels of hierarchical structure building in language and mathematics.

PubMed

Makuuchi, Michiru; Bahlmann, Jörg; Friederici, Angela D

2012-07-19

We aimed to dissociate two levels of hierarchical structure building in language and mathematics, namely 'first-level' (the build-up of hierarchical structure with externally given elements) and 'second-level' (the build-up of hierarchical structure with internally represented elements produced by first-level processes). Using functional magnetic resonance imaging, we investigated these processes in three domains: sentence comprehension, arithmetic calculation (using Reverse Polish notation, which gives two operands followed by an operator) and a working memory control task. All tasks required the build-up of hierarchical structures at the first- and second-level, resulting in a similar computational hierarchy across language and mathematics, as well as in a working memory control task. Using a novel method that estimates the difference in the integration cost for conditions of different trial durations, we found an anterior-to-posterior functional organization in the prefrontal cortex, according to the level of hierarchy. Common to all domains, the ventral premotor cortex (PMv) supports first-level hierarchy building, while the dorsal pars opercularis (POd) subserves second-level hierarchy building, with lower activation for language compared with the other two tasks. These results suggest that the POd and the PMv support domain-general mechanisms for hierarchical structure building, with the POd being uniquely efficient for language.

Investigation of Chemical and Physical Changes to Bioapatite During Fossilization Using Trace Element Geochemistry, Infrared Spectroscopy and Stable Isotopes

NASA Astrophysics Data System (ADS)

Suarez, C. A.; Kohn, M. J.

2013-12-01

Bioapatite in the form of vertebrate bone can be used for a wide variety of paleo-proxies, from determination of ancient diet to the isotopic composition of meteoric water. Bioapatite alteration during diagenesis is a constant barrier to the use of fossil bone as a paleo-proxy. To elucidate the physical and chemical alteration of bone apatite during fossilization, we analyzed an assortment of fossil bones of different ages for trace elements, using LA-ICP-MS, stable isotopes, and reflected IR spectroscopy. One set of fossil bones from the Pleistocene of Idaho show a diffusion recrystallization profile, however, rare earth element (REE) profiles indicate diffusion adsorption. This suggests that REE diffusion is controlled by changing (namely decreasing) boundary conditions (i.e. decreasing concentration of REE in surrounding pore fluids). Reflected IR analysis along this concentration profile reveal that areas high in U have lost type A carbonate from the crystal structure in addition to water and organics. Stable isotopic analysis of carbon and oxygen will determine what, if any, change in the isotopic composition of the carbonate component of apatite has occurred do to the diffusion and recrystallization process. Analysis of much older bone from the Cretaceous of China reveal shallow REE and U concentration profiles and very uniform reflected IR spectra with a significant loss of type A carbonate throughout the entire bone cortex. Analysis of stable isotopes through the bone cortex will be compared to the stable isotopes collected from the Pleistocene of Idaho.

Magnetoencephalography evidence for different brain subregions serving two musical cultures.

PubMed

Matsunaga, Rie; Yokosawa, Koichi; Abe, Jun-ichi

2012-12-01

Individuals who have been exposed to two different musical cultures (bimusicals) can be differentiated from those exposed to only one musical culture (monomusicals). Just as bilingual speakers handle the distinct language-syntactic rules of each of two languages, bimusical listeners handle two distinct musical-syntactic rules (e.g., tonal schemas) in each musical culture. This study sought to determine specific brain activities that contribute to differentiating two culture-specific tonal structures. We recorded magnetoencephalogram (MEG) responses of bimusical Japanese nonmusicians and amateur musicians as they monitored unfamiliar Western melodies and unfamiliar, but traditional, Japanese melodies, both of which contained tonal deviants (out-of-key tones). Previous studies with Western monomusicals have shown that tonal deviants elicit an early right anterior negativity (mERAN) originating in the inferior frontal cortex. In the present study, tonal deviants in both Western and Japanese melodies elicited mERANs with characteristics fitted by dipoles around the inferior frontal gyrus in the right hemisphere and the premotor cortex in the left hemisphere. Comparisons of the nature of mERAN activity to Western and Japanese melodies showed differences in the dipoles' locations but not in their peak latency or dipole strength. These results suggest that the differentiation between a tonal structure of one culture and that of another culture correlates with localization differences in brain subregions around the inferior frontal cortex and the premotor cortex. Copyright © 2012 Elsevier Ltd. All rights reserved.

Development and function of human cerebral cortex neural networks from pluripotent stem cells in vitro

PubMed Central

Kirwan, Peter; Turner-Bridger, Benita; Peter, Manuel; Momoh, Ayiba; Arambepola, Devika; Robinson, Hugh P. C.; Livesey, Frederick J.

2015-01-01

A key aspect of nervous system development, including that of the cerebral cortex, is the formation of higher-order neural networks. Developing neural networks undergo several phases with distinct activity patterns in vivo, which are thought to prune and fine-tune network connectivity. We report here that human pluripotent stem cell (hPSC)-derived cerebral cortex neurons form large-scale networks that reflect those found in the developing cerebral cortex in vivo. Synchronised oscillatory networks develop in a highly stereotyped pattern over several weeks in culture. An initial phase of increasing frequency of oscillations is followed by a phase of decreasing frequency, before giving rise to non-synchronous, ordered activity patterns. hPSC-derived cortical neural networks are excitatory, driven by activation of AMPA- and NMDA-type glutamate receptors, and can undergo NMDA-receptor-mediated plasticity. Investigating single neuron connectivity within PSC-derived cultures, using rabies-based trans-synaptic tracing, we found two broad classes of neuronal connectivity: most neurons have small numbers (<10) of presynaptic inputs, whereas a small set of hub-like neurons have large numbers of synaptic connections (>40). These data demonstrate that the formation of hPSC-derived cortical networks mimics in vivo cortical network development and function, demonstrating the utility of in vitro systems for mechanistic studies of human forebrain neural network biology. PMID:26395144

Histamine H3 receptor density is negatively correlated with neural activity related to working memory in humans.

PubMed

Ito, Takehito; Kimura, Yasuyuki; Seki, Chie; Ichise, Masanori; Yokokawa, Keita; Kawamura, Kazunori; Takahashi, Hidehiko; Higuchi, Makoto; Zhang, Ming-Rong; Suhara, Tetsuya; Yamada, Makiko

2018-06-14

The histamine H 3 receptor is regarded as a drug target for cognitive impairments in psychiatric disorders. H 3 receptors are expressed in neocortical areas, including the prefrontal cortex, the key region of cognitive functions such as working memory. However, the role of prefrontal H 3 receptors in working memory has not yet been clarified. Therefore, using functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) techniques, we aimed to investigate the association between the neural activity of working memory and the density of H 3 receptors in the prefrontal cortex. Ten healthy volunteers underwent both fMRI and PET scans. The N-back task was used to assess the neural activities related to working memory. H 3 receptor density was measured with the selective PET radioligand [ 11 C] TASP457. The neural activity of the right dorsolateral prefrontal cortex during the performance of the N-back task was negatively correlated with the density of H 3 receptors in this region. Higher neural activity of working memory was associated with lower H 3 receptor density in the right dorsolateral prefrontal cortex. This finding elucidates the role of H 3 receptors in working memory and indicates the potential of H 3 receptors as a therapeutic target for the cognitive impairments associated with neuropsychiatric disorders.

Ghrelin Causes a Decline in GABA Release by Reducing Fatty Acid Oxidation in Cortex.

PubMed

Mir, Joan Francesc; Zagmutt, Sebastián; Lichtenstein, Mathieu P; García-Villoria, Judit; Weber, Minéia; Gracia, Ana; Fabriàs, Gemma; Casas, Josefina; López, Miguel; Casals, Núria; Ribes, Antònia; Suñol, Cristina; Herrero, Laura; Serra, Dolors

2018-02-02

Lipid metabolism, specifically fatty acid oxidation (FAO) mediated by carnitine palmitoyltransferase (CPT) 1A, has been described to be an important actor of ghrelin action in hypothalamus. However, it is not known whether CPT1A and FAO mediate the effect of ghrelin on the cortex. Here, we show that ghrelin produces a differential effect on CPT1 activity and γ-aminobutyric acid (GABA) metabolism in the hypothalamus and cortex of mice. In the hypothalamus, ghrelin enhances CPT1A activity while GABA transaminase (GABAT) activity, a key enzyme in GABA shunt metabolism, is unaltered. However, in cortex CPT1A activity and GABAT activity are reduced after ghrelin treatment. Furthermore, in primary cortical neurons, ghrelin reduces GABA release through a CPT1A reduction. By using CPT1A floxed mice, we have observed that genetic ablation of CPT1A recapitulates the effect of ghrelin on GABA release in cortical neurons, inducing reductions in mitochondrial oxygen consumption, cell content of citrate and α-ketoglutarate, and GABA shunt enzyme activity. Taken together, these observations indicate that ghrelin-induced changes in CPT1A activity modulate mitochondrial function, yielding changes in GABA metabolism. This evidence suggests that the action of ghrelin on GABA release is region specific within the brain, providing a basis for differential effects of ghrelin in the central nervous system.

Reduced frontal cortex thickness and cortical volume associated with pathological narcissism.

PubMed

Mao, Yu; Sang, Na; Wang, Yongchao; Hou, Xin; Huang, Hui; Wei, Dongtao; Zhang, Jinfu; Qiu, Jiang

2016-07-22

Pathological narcissism is often characterized by arrogant behavior, a lack of empathy, and willingness to exploit other individuals. Generally, individuals with high levels of narcissism are more likely to suffer mental disorders. However, the brain structural basis of individual pathological narcissism trait among healthy people has not yet been investigated with surface-based morphometry. Thus, in this study, we investigated the relationship between cortical thickness (CT), cortical volume (CV), and individual pathological narcissism in a large healthy sample of 176 college students. Multiple regression was used to analyze the correlation between regional CT, CV, and the total Pathological Narcissism Inventory (PNI) score, adjusting for age, sex, and total intracranial volume. The results showed that the PNI score was significantly negatively associated with CT and CV in the right dorsolateral prefrontal cortex (DLPFC, key region of the central executive network, CEN), which might be associated with impaired emotion regulation processes. Furthermore, the PNI score showed significant negative associations with CV in the right postcentral gyrus, left medial prefrontal cortex (MPFC), and the CT in the right inferior frontal cortex (IFG, overlap with social brain network), which may be related to impairments in social cognition. Together, these findings suggest a unique structural basis for individual differences in pathological narcissism, distributed across different gray matter regions of the social brain network and CEN. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Modulatory Effects of the Ipsi and Contralateral Ventral Premotor Cortex (PMv) on the Primary Motor Cortex (M1) Outputs to Intrinsic Hand and Forearm Muscles in Cebus apella

PubMed Central

Quessy, Stephan; Côté, Sandrine L.; Hamadjida, Adjia; Deffeyes, Joan; Dancause, Numa

2016-01-01

The ventral premotor cortex (PMv) is a key node in the neural network involved in grasping. One way PMv can carry out this function is by modulating the outputs of the primary motor cortex (M1) to intrinsic hand and forearm muscles. As many PMv neurons discharge when grasping with either arm, both PMv within the same hemisphere (ipsilateral; iPMv) and in the opposite hemisphere (contralateral; cPMv) could modulate M1 outputs. Our objective was to compare modulatory effects of iPMv and cPMv on M1 outputs to intrinsic hand and forearm muscles. We used paired-pulse protocols with intracortical microstimulations in capuchin monkeys. A conditioning stimulus was applied in either iPMv or cPMv simultaneously or prior to a test stimulus in M1 and the effects quantified in electromyographic signals. Modulatory effects from iPMv were predominantly facilitatory, and facilitation was much more common and powerful on intrinsic hand than forearm muscles. In contrast, while the conditioning of cPMv could elicit facilitatory effects, in particular to intrinsic hand muscles, it was much more likely to inhibit M1 outputs. These data show that iPMv and cPMv have very different modulatory effects on the outputs of M1 to intrinsic hand and forearm muscles. PMID:27473318

Development and function of human cerebral cortex neural networks from pluripotent stem cells in vitro.

PubMed

Kirwan, Peter; Turner-Bridger, Benita; Peter, Manuel; Momoh, Ayiba; Arambepola, Devika; Robinson, Hugh P C; Livesey, Frederick J

2015-09-15

A key aspect of nervous system development, including that of the cerebral cortex, is the formation of higher-order neural networks. Developing neural networks undergo several phases with distinct activity patterns in vivo, which are thought to prune and fine-tune network connectivity. We report here that human pluripotent stem cell (hPSC)-derived cerebral cortex neurons form large-scale networks that reflect those found in the developing cerebral cortex in vivo. Synchronised oscillatory networks develop in a highly stereotyped pattern over several weeks in culture. An initial phase of increasing frequency of oscillations is followed by a phase of decreasing frequency, before giving rise to non-synchronous, ordered activity patterns. hPSC-derived cortical neural networks are excitatory, driven by activation of AMPA- and NMDA-type glutamate receptors, and can undergo NMDA-receptor-mediated plasticity. Investigating single neuron connectivity within PSC-derived cultures, using rabies-based trans-synaptic tracing, we found two broad classes of neuronal connectivity: most neurons have small numbers (<10) of presynaptic inputs, whereas a small set of hub-like neurons have large numbers of synaptic connections (>40). These data demonstrate that the formation of hPSC-derived cortical networks mimics in vivo cortical network development and function, demonstrating the utility of in vitro systems for mechanistic studies of human forebrain neural network biology. © 2015. Published by The Company of Biologists Ltd.

Differential functional connectivity of rostral anterior cingulate cortex during emotional interference.

PubMed

Szekely, Akos; Silton, Rebecca L; Heller, Wendy; Miller, Gregory A; Mohanty, Aprajita

2017-03-01

The rostral-ventral subdivision of the anterior cingulate cortex (rACC) plays a key role in the regulation of emotional processing. Although rACC has strong anatomical connections with anterior insular cortex (AIC), amygdala, prefrontal cortex and striatal brain regions, it is unclear whether the functional connectivity of rACC with these regions changes when regulating emotional processing. Furthermore, it is not known whether this connectivity changes with deficits in emotion regulation seen in different kinds of anxiety and depression. To address these questions regarding rACC functional connectivity, non-patients high in self-reported anxious apprehension (AP), anxious arousal (AR), anhedonic depression (AD) or none (CON) indicated the ink color of pleasant, neutral and unpleasant words during functional magnetic resonance imaging. While ignoring task-irrelevant unpleasant words, AD and CON showed an increase in the functional connectivity of rACC with AIC, putamen, caudate and ventral pallidum. There was a decrease in this connectivity in AP and AR, with AP showing greater reduction than AR. These findings provide support for the role of rACC in integrating interoceptive, emotional and cognitive functions via interactions with insula and striatal regions during effective emotion regulation in healthy individuals and a failure of this integration that may be specific to anxiety, particularly AP. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

A Distributed Network for Social Cognition Enriched for Oxytocin Receptors

PubMed Central

Mitre, Mariela; Marlin, Bianca J.; Schiavo, Jennifer K.; Morina, Egzona; Norden, Samantha E.; Hackett, Troy A.; Aoki, Chiye J.

2016-01-01

Oxytocin is a neuropeptide important for social behaviors such as maternal care and parent–infant bonding. It is believed that oxytocin receptor signaling in the brain is critical for these behaviors, but it is unknown precisely when and where oxytocin receptors are expressed or which neural circuits are directly sensitive to oxytocin. To overcome this challenge, we generated specific antibodies to the mouse oxytocin receptor and examined receptor expression throughout the brain. We identified a distributed network of female mouse brain regions for maternal behaviors that are especially enriched for oxytocin receptors, including the piriform cortex, the left auditory cortex, and CA2 of the hippocampus. Electron microscopic analysis of the cerebral cortex revealed that oxytocin receptors were mainly expressed at synapses, as well as on axons and glial processes. Functionally, oxytocin transiently reduced synaptic inhibition in multiple brain regions and enabled long-term synaptic plasticity in the auditory cortex. Thus modulation of inhibition may be a general mechanism by which oxytocin can act throughout the brain to regulate parental behaviors and social cognition. SIGNIFICANCE STATEMENT Oxytocin is an important peptide hormone involved in maternal behavior and social cognition, but it has been unclear what elements of neural circuits express oxytocin receptors due to the paucity of suitable antibodies. Here, we developed new antibodies to the mouse oxytocin receptor. Oxytocin receptors were found in discrete brain regions and at cortical synapses for modulating excitatory-inhibitory balance and plasticity. These antibodies should be useful for future studies of oxytocin and social behavior. PMID:26911697

Compensatory activity in the extrastriate body area of Parkinson's disease patients.

PubMed

van Nuenen, Bart F L; Helmich, Rick C; Buenen, Noud; van de Warrenburg, Bart P C; Bloem, Bastiaan R; Toni, Ivan

2012-07-11

Compensatory mechanisms are a crucial component of the cerebral changes triggered by neurodegenerative disorders. Identifying such compensatory mechanisms requires at least two complementary approaches: localizing candidate areas using functional imaging, and showing that interference with these areas has behavioral consequences. Building on recent imaging evidence, we use this approach to test whether a visual region in the human occipito-temporal cortex-the extrastriate body area-compensates for altered dorsal premotor activity in Parkinson's disease (PD) during motor-related processes. We separately inhibited the extrastriate body area and dorsal premotor cortex in 11 PD patients and 12 healthy subjects, using continuous theta burst stimulation. Our goal was to test whether these areas are involved in motor compensatory processes. We used motor imagery to isolate a fundamental element of motor planning, namely subjects' ability to incorporate the current state of their body into a motor plan (mental hand rotation). We quantified this ability through a posture congruency effect (i.e., the improvement in subjects' performance when their current body posture is congruent to the imagined movement). Following inhibition of the right extrastriate body area, the posture congruency effect was lost in PD patients, but not in healthy subjects. In contrast, inhibition of the left dorsal premotor cortex reduced the posture congruency effect in healthy subjects, but not in PD patients. These findings suggest that the right extrastriate body area plays a compensatory role in PD by supporting a function that is no longer performed by the dorsal premotor cortex.

Hyperelastic modelling of the crystalline lens: Accommodation and presbyopia

PubMed Central

Lanchares, Elena; Navarro, Rafael; Calvo, Begoña

2012-01-01

Purpose The modification of the mechanical properties of the human crystalline lens with age can be a major cause of presbyopia. Since these properties cannot be measured in vivo, numerical simulation can be used to estimate them. We propose an inverse method to determine age-dependent change in the material properties of the tissues composing the human crystalline lens. Methods A finite element model of a 30-year-old lens in the accommodated state was developed. The force necessary to achieve full accommodation in a 30-year-old lens of known external geometry was computed using this model. Two additional numerical models of the lens corresponding to the ages of 40 and 50 years were then built. Assuming that the accommodative force applied to the lens remains constant with age, the material properties of nucleus and cortex were estimated by inverse analysis. Results The zonular force necessary to reshape the model of a 30-year-old lens from the accommodated to the unaccommodated geometry was 0.078 newton (N). Both nucleus and cortex became stiffer with age. The stiffness of the nucleus increased with age at a higher rate than the cortex. Conclusions In agreement with the classical theory of Helmholtz, on which we based our model, our results indicate that a major cause of presbyopia is that both nucleus and cortex become stiffer with age; therefore, a constant value of the zonular forces with aging does not achieve full accommodation, that is, the accommodation capability decreases.

Consensus Paper: Towards a Systems-Level View of Cerebellar Function: the Interplay Between Cerebellum, Basal Ganglia, and Cortex.

PubMed

Caligiore, Daniele; Pezzulo, Giovanni; Baldassarre, Gianluca; Bostan, Andreea C; Strick, Peter L; Doya, Kenji; Helmich, Rick C; Dirkx, Michiel; Houk, James; Jörntell, Henrik; Lago-Rodriguez, Angel; Galea, Joseph M; Miall, R Chris; Popa, Traian; Kishore, Asha; Verschure, Paul F M J; Zucca, Riccardo; Herreros, Ivan

2017-02-01

Despite increasing evidence suggesting the cerebellum works in concert with the cortex and basal ganglia, the nature of the reciprocal interactions between these three brain regions remains unclear. This consensus paper gathers diverse recent views on a variety of important roles played by the cerebellum within the cerebello-basal ganglia-thalamo-cortical system across a range of motor and cognitive functions. The paper includes theoretical and empirical contributions, which cover the following topics: recent evidence supporting the dynamical interplay between cerebellum, basal ganglia, and cortical areas in humans and other animals; theoretical neuroscience perspectives and empirical evidence on the reciprocal influences between cerebellum, basal ganglia, and cortex in learning and control processes; and data suggesting possible roles of the cerebellum in basal ganglia movement disorders. Although starting from different backgrounds and dealing with different topics, all the contributors agree that viewing the cerebellum, basal ganglia, and cortex as an integrated system enables us to understand the function of these areas in radically different ways. In addition, there is unanimous consensus between the authors that future experimental and computational work is needed to understand the function of cerebellar-basal ganglia circuitry in both motor and non-motor functions. The paper reports the most advanced perspectives on the role of the cerebellum within the cerebello-basal ganglia-thalamo-cortical system and illustrates other elements of consensus as well as disagreements and open questions in the field.

Linear summation of outputs in a balanced network model of motor cortex.

PubMed

Capaday, Charles; van Vreeswijk, Carl

2015-01-01

Given the non-linearities of the neural circuitry's elements, we would expect cortical circuits to respond non-linearly when activated. Surprisingly, when two points in the motor cortex are activated simultaneously, the EMG responses are the linear sum of the responses evoked by each of the points activated separately. Additionally, the corticospinal transfer function is close to linear, implying that the synaptic interactions in motor cortex must be effectively linear. To account for this, here we develop a model of motor cortex composed of multiple interconnected points, each comprised of reciprocally connected excitatory and inhibitory neurons. We show how non-linearities in neuronal transfer functions are eschewed by strong synaptic interactions within each point. Consequently, the simultaneous activation of multiple points results in a linear summation of their respective outputs. We also consider the effects of reduction of inhibition at a cortical point when one or more surrounding points are active. The network response in this condition is linear over an approximately two- to three-fold decrease of inhibitory feedback strength. This result supports the idea that focal disinhibition allows linear coupling of motor cortical points to generate movement related muscle activation patterns; albeit with a limitation on gain control. The model also explains why neural activity does not spread as far out as the axonal connectivity allows, whilst also explaining why distant cortical points can be, nonetheless, functionally coupled by focal disinhibition. Finally, we discuss the advantages that linear interactions at the cortical level afford to motor command synthesis.

Photoinduced Regeneration of an Aptamer-Based Electrochemical Sensor for Sensitively Detecting Adenosine Triphosphate.

PubMed

Zhang, Xiaoyu; Song, Chunxia; Yang, Ke; Hong, Wenwen; Lu, Ying; Yu, Ping; Mao, Lanqun

2018-04-17

Electrochemical aptasensors generally include three elements, that is, recognition element, signal-transformation element, and regeneration element. In this study, a new adenosine triphosphate (ATP) aptasensor is developed by combining three elements into one DNA oligonucleotide chain. In the DNA oligonucleotide chain, DNA aptamer is used as the recognition element, ferrocene group attached at the 3'-end of the aptamer is used as the signal-transformation element, and azobenzene moiety embedded into the DNA chain is used as the regeneration element. In addition to the similar analytical properties with the traditional ones, the aptasensor developed here is easily regenerated with UV-light irradiation. The current response recorded on the aptasensor increases with increasing the concentration of ATP in the incubation solution and is linear with the logarithm of ATP concentration in the range from 1 nM to 100 μM. The limit of detection is 0.5 nM (S/N = 3). The basal level of ATP in the rat brain cortex microdialysate is determined to be 21.33 ± 4.1 nM ( n = 3). After being challenged with ATP, the aptasensor could be readily regenerated by UV-light irradiation for more than seven cycles. The regeneration of the aptasensor is proposed to be regulated by conversing azobenzene from its trans to cis form under UV irradiation.

Application of fractal dimension method of functional MRI time-series to limbic dysregulation in anxiety study.

PubMed

Olejarczyk, Elzbieta

2007-01-01

Functional magnetic resonance imaging (fMRI) allows to investigate the amplitude of activation in neural networks of brain. In this work we present the results of fMRI time-series analysis performed to identify the process of dysregulation of dynamic interaction between different limbic system regions in healthy adults in state of increased anxiety. The results obtain for 65 healthy adults using nonlinear dynamics methods like fractal dimension confirm the key roles of the bilateral amygdala, bilateral hippocampus, BA9 (dorsolateral prefrontal cortex), and BA45 (ventromedial prefrontal cortex) in modulating emotional response in healthy adults. For different regions of interest (ROIs) significant correlations were found not only for the neutral respective rest but also for fear and angry contrasts.

Encoding of frequency-modulation (FM) rates in human auditory cortex.

PubMed

Okamoto, Hidehiko; Kakigi, Ryusuke

2015-12-14

Frequency-modulated sounds play an important role in our daily social life. However, it currently remains unclear whether frequency modulation rates affect neural activity in the human auditory cortex. In the present study, using magnetoencephalography, we investigated the auditory evoked N1m and sustained field responses elicited by temporally repeated and superimposed frequency-modulated sweeps that were matched in the spectral domain, but differed in frequency modulation rates (1, 4, 16, and 64 octaves per sec). The results obtained demonstrated that the higher rate frequency-modulated sweeps elicited the smaller N1m and the larger sustained field responses. Frequency modulation rate had a significant impact on the human brain responses, thereby providing a key for disentangling a series of natural frequency-modulated sounds such as speech and music.

Differential Olfactory Identification in Children with Autism and Asperger's Disorder: A Comparative and Longitudinal Study

ERIC Educational Resources Information Center

May, Tamara; Brewer, Warrick J.; Rinehart, Nicole J.; Enticott, Peter G.; Brereton, Avril V.; Tonge, Bruce J.

2011-01-01

Key theories of autism implicate orbitofrontal cortex (OFC) compromise, while olfactory identification (OI) deficits are associated with OFC dysfunction. This study aimed to complete a 5-year follow-up of children with high-functioning autism (HFA) who previously lacked the normal age-OI association; and compare unirhinal-OI in children with HFA,…

Left Inferior Frontal Cortex and Syntax: Function, Structure and Behaviour in Patients with Left Hemisphere Damage

ERIC Educational Resources Information Center

Tyler, Lorraine K.; Marslen-Wilson, William D.; Randall, Billi; Wright, Paul; Devereux, Barry J.; Zhuang, Jie; Papoutsi, Marina; Stamatakis, Emmanuel A.

2011-01-01

For the past 150 years, neurobiological models of language have debated the role of key brain regions in language function. One consistently debated set of issues concern the role of the left inferior frontal gyrus in syntactic processing. Here we combine measures of functional activity, grey matter integrity and performance in patients with left…

Self-affirmation activates brain systems associated with self-related processing and reward and is reinforced by future orientation

PubMed Central

O’Donnell, Matthew Brook; Tinney, Francis J.; Lieberman, Matthew D.; Taylor, Shelley E.; Strecher, Victor J.; Falk, Emily B.

2016-01-01

Self-affirmation theory posits that people are motivated to maintain a positive self-view and that threats to perceived self-competence are met with resistance. When threatened, self-affirmations can restore self-competence by allowing individuals to reflect on sources of self-worth, such as core values. Many questions exist, however, about the underlying mechanisms associated with self-affirmation. We examined the neural mechanisms of self-affirmation with a task developed for use in a functional magnetic resonance imaging environment. Results of a region of interest analysis demonstrated that participants who were affirmed (compared with unaffirmed participants) showed increased activity in key regions of the brain’s self-processing (medial prefrontal cortex + posterior cingulate cortex) and valuation (ventral striatum + ventral medial prefrontal cortex) systems when reflecting on future-oriented core values (compared with everyday activities). Furthermore, this neural activity went on to predict changes in sedentary behavior consistent with successful affirmation in response to a separate physical activity intervention. These results highlight neural processes associated with successful self-affirmation, and further suggest that key pathways may be amplified in conjunction with prospection. PMID:26541373

Differential recruitment of the sensorimotor putamen and frontoparietal cortex during motor chunking in humans

PubMed Central

Wymbs, Nicholas F.; Bassett, Danielle S.; Mucha, Peter J.; Porter, Mason A.; Grafton, Scott T.

2012-01-01

Motor chunking facilitates movement production by combining motor elements into integrated units of behavior. Previous research suggests that chunking involves two processes: concatenation, aimed at the formation of motor-motor associations between elements or sets of elements; and segmentation, aimed at the parsing of multiple contiguous elements into shorter action sets. We used fMRI to measure the trial-wise recruitment of brain regions associated with these chunking processes as healthy subjects performed a cued sequence production task. A novel dynamic network analysis identified chunking structure for a set of motor sequences acquired during fMRI and collected on three days of training. Activity in the bilateral sensorimotor putamen positively correlated with chunk concatenation, whereas a left hemisphere frontoparietal network was correlated with chunk segmentation. Across subjects, there was an aggregate increase in chunk strength (concatenation) with training, suggesting that subcortical circuits play a direct role in the creation of fluid transitions across chunks. PMID:22681696

Differential recruitment of the sensorimotor putamen and frontoparietal cortex during motor chunking in humans.

PubMed

Wymbs, Nicholas F; Bassett, Danielle S; Mucha, Peter J; Porter, Mason A; Grafton, Scott T

2012-06-07

Motor chunking facilitates movement production by combining motor elements into integrated units of behavior. Previous research suggests that chunking involves two processes: concatenation, aimed at the formation of motor-motor associations between elements or sets of elements, and segmentation, aimed at the parsing of multiple contiguous elements into shorter action sets. We used fMRI to measure the trial-wise recruitment of brain regions associated with these chunking processes as healthy subjects performed a cued-sequence production task. A dynamic network analysis identified chunking structure for a set of motor sequences acquired during fMRI and collected over 3 days of training. Activity in the bilateral sensorimotor putamen positively correlated with chunk concatenation, whereas a left-hemisphere frontoparietal network was correlated with chunk segmentation. Across subjects, there was an aggregate increase in chunk strength (concatenation) with training, suggesting that subcortical circuits play a direct role in the creation of fluid transitions across chunks. Copyright © 2012 Elsevier Inc. All rights reserved.

The impact of hypoglycaemia awareness status on regional brain responses to acute hypoglycaemia in men with type 1 diabetes.

PubMed

Dunn, Joel T; Choudhary, Pratik; Teh, Ming Ming; Macdonald, Ian; Hunt, Katharine F; Marsden, Paul K; Amiel, Stephanie A

2018-05-12

Impaired awareness of hypoglycaemia (IAH) in type 1 diabetes increases the risk of severe hypoglycaemia sixfold and can be resistant to intervention. We explored the impact of IAH on central responses to hypoglycaemia to investigate the mechanisms underlying barriers to therapeutic intervention. We conducted [ 15 O]water positron emission tomography studies of regional brain perfusion during euglycaemia (target 5 mmol/l), hypoglycaemia (achieved level, 2.4 mmol/l) and recovery (target 5 mmol/l) in 17 men with type 1 diabetes: eight with IAH, and nine with intact hypoglycaemia awareness (HA). Hypoglycaemia with HA was associated with increased activation in brain regions including the thalamus, insula, globus pallidus (GP), anterior cingulate cortex (ACC), orbital cortex, dorsolateral frontal (DLF) cortex, angular gyrus and amygdala; deactivation occurred in the temporal and parahippocampal regions. IAH was associated with reduced catecholamine and symptom responses to hypoglycaemia vs HA (incremental AUC: autonomic scores, 26.2 ± 35.5 vs 422.7 ± 237.1; neuroglycopenic scores, 34.8 ± 88.8 vs 478.9 ± 311.1; both p < 0.002). There were subtle differences (p < 0.005, k ≥ 50 voxels) in brain activation at hypoglycaemia, including early differences in the right central operculum, bilateral medial orbital (MO) cortex, and left posterior DLF cortex, with additional differences in the ACC, right GP and post- and pre-central gyri in established hypoglycaemia, and lack of deactivation in temporal regions in established hypoglycaemia. Differences in activation in the post- and pre-central gyri may be expected in people with reduced subjective responses to hypoglycaemia. Alterations in the activity of regions involved in the drive to eat (operculum), emotional salience (MO cortex), aversion (GP) and recall (temporal) suggest differences in the perceived importance and urgency of responses to hypoglycaemia in IAH compared with HA, which may be key to the persistence of the condition.

Apoptotic microtubules delimit an active caspase free area in the cellular cortex during the execution phase of apoptosis.

PubMed

Oropesa-Ávila, M; Fernández-Vega, A; de la Mata, M; Maraver, J G; Cordero, M D; Cotán, D; de Miguel, M; Calero, C P; Paz, M V; Pavón, A D; Sánchez, M A; Zaderenko, A P; Ybot-González, P; Sánchez-Alcázar, J A

2013-03-07

Apoptotic microtubule network (AMN) is organized during apoptosis, forming a cortical structure beneath plasma membrane, which has an important role in preserving cell morphology and plasma membrane permeability. The aim of this study was to examine the role of AMN in maintaining plasma membrane integrity during the execution phase of apoptosis. We demonstrated in camptothecin-induced apoptosis in H460 cells that AMN delimits an active caspase free area beneath plasma membrane that permits the preservation of cellular cortex and transmembrane proteins. AMN depolymerization in apoptotic cells by a short exposure to colchicine allowed active caspases to reach the cellular cortex and cleave many key proteins involved in plasma membrane structural support, cell adhesion and ionic homeostasis. Cleavage of cellular cortex and plasma membrane proteins, such as α-spectrin, paxilin, focal adhesion kinase (FAK), E-cadherin and integrin subunit β4 was associated with cell collapse and cell detachment. Otherwise, cleavage-mediated inactivation of calcium ATPase pump (PMCA-4) and Na(+)/Ca(2+) exchanger (NCX) involved in cell calcium extrusion resulted in calcium overload. Furthermore, cleavage of Na(+)/K(+) pump subunit β was associated with altered sodium homeostasis. Cleavage of cell cortex and plasma membrane proteins in apoptotic cells after AMN depolymerization increased plasma permeability, ionic imbalance and bioenergetic collapse, leading apoptotic cells to secondary necrosis. The essential role of caspase-mediated cleavage in this process was demonstrated because the concomitant addition of colchicine that induces AMN depolymerization and the pan-caspase inhibitor z-VAD avoided the cleavage of cortical and plasma membrane proteins and prevented apoptotic cells to undergo secondary necrosis. Furthermore, the presence of AMN was also critical for proper phosphatidylserine externalization and apoptotic cell clearance by macrophages. These results indicate that AMN is essential to preserve an active caspase free area in the cellular cortex of apoptotic cells that allows plasma membrane integrity during the execution phase of apoptosis.

Apoptotic microtubules delimit an active caspase free area in the cellular cortex during the execution phase of apoptosis

PubMed Central

Oropesa-Ávila, M; Fernández-Vega, A; de la Mata, M; Maraver, J G; Cordero, M D; Cotán, D; de Miguel, M; Calero, C P; Paz, M V; Pavón, A D; Sánchez, M A; Zaderenko, A P; Ybot-González, P; Sánchez-Alcázar, J A

2013-01-01

Apoptotic microtubule network (AMN) is organized during apoptosis, forming a cortical structure beneath plasma membrane, which has an important role in preserving cell morphology and plasma membrane permeability. The aim of this study was to examine the role of AMN in maintaining plasma membrane integrity during the execution phase of apoptosis. We demonstrated in camptothecin-induced apoptosis in H460 cells that AMN delimits an active caspase free area beneath plasma membrane that permits the preservation of cellular cortex and transmembrane proteins. AMN depolymerization in apoptotic cells by a short exposure to colchicine allowed active caspases to reach the cellular cortex and cleave many key proteins involved in plasma membrane structural support, cell adhesion and ionic homeostasis. Cleavage of cellular cortex and plasma membrane proteins, such as α-spectrin, paxilin, focal adhesion kinase (FAK), E-cadherin and integrin subunit β4 was associated with cell collapse and cell detachment. Otherwise, cleavage-mediated inactivation of calcium ATPase pump (PMCA-4) and Na+/Ca2+ exchanger (NCX) involved in cell calcium extrusion resulted in calcium overload. Furthermore, cleavage of Na+/K+ pump subunit β was associated with altered sodium homeostasis. Cleavage of cell cortex and plasma membrane proteins in apoptotic cells after AMN depolymerization increased plasma permeability, ionic imbalance and bioenergetic collapse, leading apoptotic cells to secondary necrosis. The essential role of caspase-mediated cleavage in this process was demonstrated because the concomitant addition of colchicine that induces AMN depolymerization and the pan-caspase inhibitor z-VAD avoided the cleavage of cortical and plasma membrane proteins and prevented apoptotic cells to undergo secondary necrosis. Furthermore, the presence of AMN was also critical for proper phosphatidylserine externalization and apoptotic cell clearance by macrophages. These results indicate that AMN is essential to preserve an active caspase free area in the cellular cortex of apoptotic cells that allows plasma membrane integrity during the execution phase of apoptosis. PMID:23470534

Comparative Analysis of the Subventricular Zone in Rat, Ferret and Macaque: Evidence for an Outer Subventricular Zone in Rodents

PubMed Central

Camacho, Jasmin; Antczak, Jared L.; Prakash, Anish N.; Cziep, Matthew E.; Walker, Anita I.; Noctor, Stephen C.

2012-01-01

The mammalian cerebral cortex arises from precursor cells that reside in a proliferative region surrounding the lateral ventricles of the developing brain. Recent work has shown that precursor cells in the subventricular zone (SVZ) provide a major contribution to prenatal cortical neurogenesis, and that the SVZ is significantly thicker in gyrencephalic mammals such as primates than it is in lissencephalic mammals including rodents. Identifying characteristics that are shared by or that distinguish cortical precursor cells across mammalian species will shed light on factors that regulate cortical neurogenesis and may point toward mechanisms that underlie the evolutionary expansion of the neocortex in gyrencephalic mammals. We immunostained sections of the developing cerebral cortex from lissencephalic rats, and from gyrencephalic ferrets and macaques to compare the distribution of precursor cell types in each species. We also performed time-lapse imaging of precursor cells in the developing rat neocortex. We show that the distribution of Pax6+ and Tbr2+ precursor cells is similar in lissencephalic rat and gyrencephalic ferret, and different in the gyrencephalic cortex of macaque. We show that mitotic Pax6+ translocating radial glial cells (tRG) are present in the cerebral cortex of each species during and after neurogenesis, demonstrating that the function of Pax6+ tRG cells is not restricted to neurogenesis. Furthermore, we show that Olig2 expression distinguishes two distinct subtypes of Pax6+ tRG cells. Finally we present a novel method for discriminating the inner and outer SVZ across mammalian species and show that the key cytoarchitectural features and cell types that define the outer SVZ in developing primates are present in the developing rat neocortex. Our data demonstrate that the developing rat cerebral cortex possesses an outer subventricular zone during late stages of cortical neurogenesis and that the developing rodent cortex shares important features with that of primates. PMID:22272298

Altered Structural and Functional Connectivity in Late Preterm Preadolescence: An Anatomic Seed-Based Study of Resting State Networks Related to the Posteromedial and Lateral Parietal Cortex.

PubMed

Degnan, Andrew J; Wisnowski, Jessica L; Choi, SoYoung; Ceschin, Rafael; Bhushan, Chitresh; Leahy, Richard M; Corby, Patricia; Schmithorst, Vincent J; Panigrahy, Ashok

2015-01-01

Late preterm birth confers increased risk of developmental delay, academic difficulties and social deficits. The late third trimester may represent a critical period of development of neural networks including the default mode network (DMN), which is essential to normal cognition. Our objective is to identify functional and structural connectivity differences in the posteromedial cortex related to late preterm birth. Thirty-eight preadolescents (ages 9-13; 19 born in the late preterm period (≥32 weeks gestational age) and 19 at term) without access to advanced neonatal care were recruited from a low socioeconomic status community in Brazil. Participants underwent neurocognitive testing, 3-dimensional T1-weighted imaging, diffusion-weighted imaging and resting state functional MRI (RS-fMRI). Seed-based probabilistic diffusion tractography and RS-fMRI analyses were performed using unilateral seeds within the posterior DMN (posterior cingulate cortex, precuneus) and lateral parietal DMN (superior marginal and angular gyri). Late preterm children demonstrated increased functional connectivity within the posterior default mode networks and increased anti-correlation with the central-executive network when seeded from the posteromedial cortex (PMC). Key differences were demonstrated between PMC components with increased anti-correlation with the salience network seen only with posterior cingulate cortex seeding but not with precuneus seeding. Probabilistic tractography showed increased streamlines within the right inferior longitudinal fasciculus and inferior fronto-occipital fasciculus within late preterm children while decreased intrahemispheric streamlines were also observed. No significant differences in neurocognitive testing were demonstrated between groups. Late preterm preadolescence is associated with altered functional connectivity from the PMC and lateral parietal cortex to known distributed functional cortical networks despite no significant executive neurocognitive differences. Selective increased structural connectivity was observed in the setting of decreased posterior interhemispheric connections. Future work is needed to determine if these findings represent a compensatory adaptation employing alternate neural circuitry or could reflect subtle pathology resulting in emotional processing deficits not seen with neurocognitive testing.

Blood-brain barrier and intestinal epithelial barrier alterations in autism spectrum disorders.

PubMed

Fiorentino, Maria; Sapone, Anna; Senger, Stefania; Camhi, Stephanie S; Kadzielski, Sarah M; Buie, Timothy M; Kelly, Deanna L; Cascella, Nicola; Fasano, Alessio

2016-01-01

Autism spectrum disorders (ASD) are complex conditions whose pathogenesis may be attributed to gene-environment interactions. There are no definitive mechanisms explaining how environmental triggers can lead to ASD although the involvement of inflammation and immunity has been suggested. Inappropriate antigen trafficking through an impaired intestinal barrier, followed by passage of these antigens or immune-activated complexes through a permissive blood-brain barrier (BBB), can be part of the chain of events leading to these disorders. Our goal was to investigate whether an altered BBB and gut permeability is part of the pathophysiology of ASD. Postmortem cerebral cortex and cerebellum tissues from ASD, schizophrenia (SCZ), and healthy subjects (HC) and duodenal biopsies from ASD and HC were analyzed for gene and protein expression profiles. Tight junctions and other key molecules associated with the neurovascular unit integrity and function and neuroinflammation were investigated. Claudin ( CLDN )-5 and -12 were increased in the ASD cortex and cerebellum. CLDN-3 , tricellulin , and MMP-9 were higher in the ASD cortex. IL-8 , tPA , and IBA-1 were downregulated in SCZ cortex; IL-1b was increased in the SCZ cerebellum. Differences between SCZ and ASD were observed for most of the genes analyzed in both brain areas. CLDN-5 protein was increased in ASD cortex and cerebellum, while CLDN-12 appeared reduced in both ASD and SCZ cortexes. In the intestine, 75% of the ASD samples analyzed had reduced expression of barrier-forming TJ components ( CLDN-1 , OCLN , TRIC ), whereas 66% had increased pore-forming CLDNs ( CLDN-2 , -10 , -15 ) compared to controls. In the ASD brain, there is an altered expression of genes associated with BBB integrity coupled with increased neuroinflammation and possibly impaired gut barrier integrity. While these findings seem to be specific for ASD, the possibility of more distinct SCZ subgroups should be explored with additional studies.

Comparative analysis of the subventricular zone in rat, ferret and macaque: evidence for an outer subventricular zone in rodents.

PubMed

Martínez-Cerdeño, Verónica; Cunningham, Christopher L; Camacho, Jasmin; Antczak, Jared L; Prakash, Anish N; Cziep, Matthew E; Walker, Anita I; Noctor, Stephen C

2012-01-01

The mammalian cerebral cortex arises from precursor cells that reside in a proliferative region surrounding the lateral ventricles of the developing brain. Recent work has shown that precursor cells in the subventricular zone (SVZ) provide a major contribution to prenatal cortical neurogenesis, and that the SVZ is significantly thicker in gyrencephalic mammals such as primates than it is in lissencephalic mammals including rodents. Identifying characteristics that are shared by or that distinguish cortical precursor cells across mammalian species will shed light on factors that regulate cortical neurogenesis and may point toward mechanisms that underlie the evolutionary expansion of the neocortex in gyrencephalic mammals. We immunostained sections of the developing cerebral cortex from lissencephalic rats, and from gyrencephalic ferrets and macaques to compare the distribution of precursor cell types in each species. We also performed time-lapse imaging of precursor cells in the developing rat neocortex. We show that the distribution of Pax6+ and Tbr2+ precursor cells is similar in lissencephalic rat and gyrencephalic ferret, and different in the gyrencephalic cortex of macaque. We show that mitotic Pax6+ translocating radial glial cells (tRG) are present in the cerebral cortex of each species during and after neurogenesis, demonstrating that the function of Pax6+ tRG cells is not restricted to neurogenesis. Furthermore, we show that Olig2 expression distinguishes two distinct subtypes of Pax6+ tRG cells. Finally we present a novel method for discriminating the inner and outer SVZ across mammalian species and show that the key cytoarchitectural features and cell types that define the outer SVZ in developing primates are present in the developing rat neocortex. Our data demonstrate that the developing rat cerebral cortex possesses an outer subventricular zone during late stages of cortical neurogenesis and that the developing rodent cortex shares important features with that of primates.

AIDS and HIV Training and Education in Criminal Justice Agencies. AIDS Bulletin.

ERIC Educational Resources Information Center

Hammett, Theodore M.

This bulletin summarizes key elements of an effective AIDS training and education program for law enforcement and corrections personnel. First, these key elements of training and education for criminal justice personnel are discussed: staff participation in materials development; timely and frequent training; mandatory training; live training by…

LHX2 Interacts with the NuRD Complex and Regulates Cortical Neuron Subtype Determinants Fezf2 and Sox11.

PubMed

Muralidharan, Bhavana; Khatri, Zeba; Maheshwari, Upasana; Gupta, Ritika; Roy, Basabdatta; Pradhan, Saurabh J; Karmodiya, Krishanpal; Padmanabhan, Hari; Shetty, Ashwin S; Balaji, Chinthapalli; Kolthur-Seetharam, Ullas; Macklis, Jeffrey D; Galande, Sanjeev; Tole, Shubha

2017-01-04

In the developing cerebral cortex, sequential transcriptional programs take neuroepithelial cells from proliferating progenitors to differentiated neurons with unique molecular identities. The regulatory changes that occur in the chromatin of the progenitors are not well understood. During deep layer neurogenesis, we show that transcription factor LHX2 binds to distal regulatory elements of Fezf2 and Sox11, critical determinants of neuron subtype identity in the mouse neocortex. We demonstrate that LHX2 binds to the nucleosome remodeling and histone deacetylase histone remodeling complex subunits LSD1, HDAC2, and RBBP4, which are proximal regulators of the epigenetic state of chromatin. When LHX2 is absent, active histone marks at the Fezf2 and Sox11 loci are increased. Loss of LHX2 produces an increase, and overexpression of LHX2 causes a decrease, in layer 5 Fezf2 and CTIP2-expressing neurons. Our results provide mechanistic insight into how LHX2 acts as a necessary and sufficient regulator of genes that control cortical neuronal subtype identity. The functional complexity of the cerebral cortex arises from an array of distinct neuronal subtypes with unique connectivity patterns that are produced from common progenitors. This study reveals that transcription factor LHX2 regulates the numbers of specific cortical output neuron subtypes by controlling the genes that are required to produce them. Loss or increase in LHX2 during neurogenesis is sufficient to increase or decrease, respectively, a particular subcerebrally projecting population. Mechanistically, LHX2 interacts with chromatin modifying protein complexes to edit the chromatin landscape of its targets Fezf2 and Sox11, which regulates their expression and consequently the identities of the neurons produced. Thus, LHX2 is a key component of the control network for producing neurons that will participate in cortical circuitry. Copyright © 2017 Muralidharan et al.

Recruitment of the prefrontal cortex and cerebellum in Parkinsonian rats following skilled aerobic exercise.

PubMed

Wang, Zhuo; Guo, Yumei; Myers, Kalisa G; Heintz, Ryan; Holschneider, Daniel P

2015-05-01

Exercise modality and complexity play a key role in determining neurorehabilitative outcome in Parkinson's disease (PD). Exercise training (ET) that incorporates both motor skill training and aerobic exercise has been proposed to synergistically improve cognitive and automatic components of motor control in PD patients. Here we introduced such a skilled aerobic ET paradigm in a rat model of dopaminergic deafferentation. Rats with bilateral, intra-striatal 6-hydroxydopamine lesions were exposed to forced ET for 4weeks, either on a simple running wheel (non-skilled aerobic exercise, NSAE) or on a complex wheel with irregularly spaced rungs (skilled aerobic exercise, SAE). Cerebral perfusion was mapped during horizontal treadmill walking or at rest using [(14)C]-iodoantipyrine 1week after the completion of ET. Regional cerebral blood flow (rCBF) was quantified by autoradiography and analyzed in 3-dimensionally reconstructed brains by statistical parametric mapping. SAE compared to NSAE resulted in equal or greater recovery in motor deficits, as well as greater increases in rCBF during walking in the prelimbic area of the prefrontal cortex, broad areas of the somatosensory cortex, and the cerebellum. NSAE compared to SAE animals showed greater activation in the dorsal caudate-putamen and dorsal hippocampus. Seed correlation analysis revealed enhanced functional connectivity in SAE compared to NSAE animals between the prelimbic cortex and motor areas, as well as altered functional connectivity between midline cerebellum and sensorimotor regions. Our study provides the first evidence for functional brain reorganization following skilled aerobic exercise in Parkinsonian rats, and suggests that SAE compared to NSAE results in enhancement of prefrontal cortex- and cerebellum-mediated control of motor function. Copyright © 2015 Elsevier Inc. All rights reserved.

Recruitment of the prefrontal cortex and cerebellum in Parkinsonian rats following skilled aerobic exercise

PubMed Central

Wang, Zhuo; Guo, Yumei; Myers, Kalisa G.; Heintz, Ryan; Holschneider, Daniel P.

2015-01-01

Exercise modality and complexity play a key role in determining neurorehabilitative outcome in Parkinson’s disease (PD). Exercise training (ET) that incorporates both motor skill training and aerobic exercise has been proposed to synergistically improve cognitive and automatic components of motor control in PD patients. Here we introduced such a skilled aerobic ET paradigm in a rat model of dopaminergic deafferentation. Rats with bilateral, intra-striatal 6-hydroxydopamine lesions were exposed to forced ET for 4 weeks, either on a simple running wheel (non-skilled aerobic exercise, NSAE) or on a complex wheel with irregularly spaced rungs (skilled aerobic exercise, SAE). Cerebral perfusion was mapped during horizontal treadmill walking or at rest using [14C]-iodoantipyrine 1 week after the completion of ET. Regional cerebral blood flow (rCBF) was quantified by autoradiography and analyzed in 3-dimensionally reconstructed brains by statistical parametric mapping. SAE compared to NSAE resulted in equal or greater recovery in motor deficits, as well as greater increases in rCBF during walking in the prelimbic area of the prefrontal cortex, broad areas of the somatosensory cortex, and the cerebellum. NSAE compared to SAE animals showed greater activation in the dorsal caudate-putamen and dorsal hippocampus. Seed correlation analysis revealed enhanced functional connectivity in SAE compared to NSAE animals between the prelimbic cortex and motor areas, as well as altered functional connectivity between midline cerebellum and sensorimotor regions. Our study provides the first evidence for functional brain reorganization following skilled aerobic exercise in Parkinsonian rats, and suggests that SAE compared to NSAE results in enhancement of prefrontal cortex- and cerebellum-mediated control of motor function. PMID:25747184

Age-Dependent Brain Gene Expression and Copy Number Anomalies in Autism Suggest Distinct Pathological Processes at Young Versus Mature Ages

PubMed Central

Winn, Mary E.; Barnes, Cynthia Carter; Li, Hai-Ri; Weiss, Lauren; Fan, Jian-Bing; Murray, Sarah; April, Craig; Belinson, Haim; Fu, Xiang-Dong; Wynshaw-Boris, Anthony; Schork, Nicholas J.; Courchesne, Eric

2012-01-01

Autism is a highly heritable neurodevelopmental disorder, yet the genetic underpinnings of the disorder are largely unknown. Aberrant brain overgrowth is a well-replicated observation in the autism literature; but association, linkage, and expression studies have not identified genetic factors that explain this trajectory. Few studies have had sufficient statistical power to investigate whole-genome gene expression and genotypic variation in the autistic brain, especially in regions that display the greatest growth abnormality. Previous functional genomic studies have identified possible alterations in transcript levels of genes related to neurodevelopment and immune function. Thus, there is a need for genetic studies involving key brain regions to replicate these findings and solidify the role of particular functional pathways in autism pathogenesis. We therefore sought to identify abnormal brain gene expression patterns via whole-genome analysis of mRNA levels and copy number variations (CNVs) in autistic and control postmortem brain samples. We focused on prefrontal cortex tissue where excess neuron numbers and cortical overgrowth are pronounced in the majority of autism cases. We found evidence for dysregulation in pathways governing cell number, cortical patterning, and differentiation in young autistic prefrontal cortex. In contrast, adult autistic prefrontal cortex showed dysregulation of signaling and repair pathways. Genes regulating cell cycle also exhibited autism-specific CNVs in DNA derived from prefrontal cortex, and these genes were significantly associated with autism in genome-wide association study datasets. Our results suggest that CNVs and age-dependent gene expression changes in autism may reflect distinct pathological processes in the developing versus the mature autistic prefrontal cortex. Our results raise the hypothesis that genetic dysregulation in the developing brain leads to abnormal regional patterning, excess prefrontal neurons, cortical overgrowth, and neural dysfunction in autism. PMID:22457638

Age-dependent brain gene expression and copy number anomalies in autism suggest distinct pathological processes at young versus mature ages.

PubMed

Chow, Maggie L; Pramparo, Tiziano; Winn, Mary E; Barnes, Cynthia Carter; Li, Hai-Ri; Weiss, Lauren; Fan, Jian-Bing; Murray, Sarah; April, Craig; Belinson, Haim; Fu, Xiang-Dong; Wynshaw-Boris, Anthony; Schork, Nicholas J; Courchesne, Eric

2012-01-01

Autism is a highly heritable neurodevelopmental disorder, yet the genetic underpinnings of the disorder are largely unknown. Aberrant brain overgrowth is a well-replicated observation in the autism literature; but association, linkage, and expression studies have not identified genetic factors that explain this trajectory. Few studies have had sufficient statistical power to investigate whole-genome gene expression and genotypic variation in the autistic brain, especially in regions that display the greatest growth abnormality. Previous functional genomic studies have identified possible alterations in transcript levels of genes related to neurodevelopment and immune function. Thus, there is a need for genetic studies involving key brain regions to replicate these findings and solidify the role of particular functional pathways in autism pathogenesis. We therefore sought to identify abnormal brain gene expression patterns via whole-genome analysis of mRNA levels and copy number variations (CNVs) in autistic and control postmortem brain samples. We focused on prefrontal cortex tissue where excess neuron numbers and cortical overgrowth are pronounced in the majority of autism cases. We found evidence for dysregulation in pathways governing cell number, cortical patterning, and differentiation in young autistic prefrontal cortex. In contrast, adult autistic prefrontal cortex showed dysregulation of signaling and repair pathways. Genes regulating cell cycle also exhibited autism-specific CNVs in DNA derived from prefrontal cortex, and these genes were significantly associated with autism in genome-wide association study datasets. Our results suggest that CNVs and age-dependent gene expression changes in autism may reflect distinct pathological processes in the developing versus the mature autistic prefrontal cortex. Our results raise the hypothesis that genetic dysregulation in the developing brain leads to abnormal regional patterning, excess prefrontal neurons, cortical overgrowth, and neural dysfunction in autism.

Gray-matter volume, midbrain dopamine D2/D3 receptors and drug craving in methamphetamine users.

PubMed

Morales, A M; Kohno, M; Robertson, C L; Dean, A C; Mandelkern, M A; London, E D

2015-06-01

Dysfunction of the mesocorticolimbic system has a critical role in clinical features of addiction. Despite evidence suggesting that midbrain dopamine receptors influence amphetamine-induced dopamine release and that dopamine is involved in methamphetamine-induced neurotoxicity, associations between dopamine receptors and gray-matter volume have been unexplored in methamphetamine users. Here we used magnetic resonance imaging and [(18)F]fallypride positron emission tomography, respectively, to measure gray-matter volume (in 58 methamphetamine users) and dopamine D2/D3 receptor availability (binding potential relative to nondisplaceable uptake of the radiotracer, BPnd) (in 31 methamphetamine users and 37 control participants). Relationships between these measures and self-reported drug craving were examined. Although no difference in midbrain D2/D3 BPnd was detected between methamphetamine and control groups, midbrain D2/D3 BPnd was positively correlated with gray-matter volume in the striatum, prefrontal cortex, insula, hippocampus and temporal cortex in methamphetamine users, but not in control participants (group-by-midbrain D2/D3 BPnd interaction, P<0.05 corrected for multiple comparisons). Craving for methamphetamine was negatively associated with gray-matter volume in the insula, prefrontal cortex, amygdala, temporal cortex, occipital cortex, cerebellum and thalamus (P<0.05 corrected for multiple comparisons). A relationship between midbrain D2/D3 BPnd and methamphetamine craving was not detected. Lower midbrain D2/D3 BPnd may increase vulnerability to deficits in gray-matter volume in mesocorticolimbic circuitry in methamphetamine users, possibly reflecting greater dopamine-induced toxicity. Identifying factors that influence prefrontal and limbic volume, such as midbrain BPnd, may be important for understanding the basis of drug craving, a key factor in the maintenance of substance-use disorders.

Reduction of RPT6/S8 (a Proteasome Component) and Proteasome Activity in the Cortex is Associated with Cognitive Impairment in Lewy Body Dementia

PubMed Central

Alghamdi, Amani; Vallortigara, Julie; Howlett, David R.; Broadstock, Martin; Hortobágyi, Tibor; Ballard, Clive; Thomas, Alan J.; O’Brien, John T.; Aarsland, Dag; Attems, Johannes; Francis, Paul T.; Whitfield, David R.

2017-01-01

Lewy body dementia is the second most common neurodegenerative dementia and is pathologically characterized by α-synuclein positive cytoplasmic inclusions, with varying amounts of amyloid-β (Aβ) and hyperphosphorylated tau (tau) aggregates in addition to synaptic loss. A dysfunctional ubiquitin proteasome system (UPS), the major proteolytic pathway responsible for the clearance of short lived proteins, may be a mediating factor of disease progression and of the development of α-synuclein aggregates. In the present study, protein expression of a key component of the UPS, the RPT6 subunit of the 19S regulatory complex was determined. Furthermore, the main proteolytic-like (chymotrypsin- and PGPH-) activities have also been analyzed. The middle frontal (Brodmann, BA9), inferior parietal (BA40), and anterior cingulate (BA24) gyrus’ cortex were selected as regions of interest from Parkinson’s disease dementia (PDD, n = 31), dementia with Lewy bodies (DLB, n = 44), Alzheimer’s disease (AD, n = 16), and control (n = 24) brains. Clinical and pathological data available included the MMSE score. DLB, PDD, and AD were characterized by significant reductions of RPT6 (one-way ANOVA, p < 0.001; Bonferroni post hoc test) in prefrontal cortex and parietal cortex compared with controls. Strong associations were observed between RPT6 levels in prefrontal, parietal cortex, and anterior cingulate gyrus and cognitive impairment (p = 0.001, p = 0.001, and p = 0.008, respectively). These findings highlight the involvement of the UPS in Lewy body dementia and indicate that targeting the UPS may have the potential to slow down or reduce the progression of cognitive impairment in DLB and PDD. PMID:28269775

Gray-Matter Volume, Midbrain Dopamine D2/D3 Receptors and Drug Craving in Methamphetamine Users

PubMed Central

Morales, Angelica A.; Kohno, Milky; Robertson, Chelsea L.; Dean, Andy C.; Mandelkern, Mark A.; London, Edythe D.

2015-01-01

Dysfunction of the mesocorticolimbic system plays a critical role in clinical features of addiction. Despite evidence suggesting that midbrain dopamine receptors influence amphetamine-induced dopamine release and that dopamine is involved in methamphetamine-induced neurotoxicity, associations between dopamine receptors and gray-matter volume have been unexplored in methamphetamine users. Here we used magnetic resonance imaging and [18F]fallypride positron emission tomography, respectively, to measure gray-matter volume (in 58 methamphetamine users) and dopamine D2/D3 receptor availability (binding potential relative to nondisplaceable uptake of the radiotracer, BPnd) (in 31 methamphetamine users and 37 control participants). Relationships between these measures and self-reported drug craving were examined. Although no difference in midbrain D2/D3 BPnd was detected between methamphetamine and control groups, midbrain D2/D3 BPnd was positively correlated with gray-matter volume in the striatum, prefrontal cortex, insula, hippocampus and temporal cortex in methamphetamine users, but not in control participants (group-by-midbrain D2/D3 BPnd interaction, p<0.05 corrected for multiple comparisons). Craving for methamphetamine was negatively associated with gray-matter volume in the insula, prefrontal cortex, amygdala, temporal cortex, occipital cortex, cerebellum, and thalamus (p<0.05 corrected for multiple comparisons). A relationship between midbrain D2/D3 BPnd and methamphetamine craving was not detected. Lower midbrain D2/D3 BPnd may increase vulnerability to deficits in gray-matter volume in mesocorticolimbic circuitry in methamphetamine users, possibly reflecting greater dopamine-induced toxicity. Identifying factors that influence prefrontal and limbic volume, such as midbrain BPnd, may be important for understanding the basis of drug craving, a key factor in the maintenance of substance use disorders. PMID:25896164

Alterations of resting state networks and structural connectivity in relation to the prefrontal and anterior cingulate cortices in late prematurity.

PubMed

Degnan, Andrew J; Wisnowski, Jessica L; Choi, SoYoung; Ceschin, Rafael; Bhushan, Chitresh; Leahy, Richard M; Corby, Patricia; Schmithorst, Vincent J; Panigrahy, Ashok

2015-01-07

Late preterm birth is increasingly recognized as a risk factor for cognitive and social deficits. The prefrontal cortex is particularly vulnerable to injury in late prematurity because of its protracted development and extensive cortical connections. Our study examined children born late preterm without access to advanced postnatal care to assess structural and functional connectivity related to the prefrontal cortex. Thirty-eight preadolescents [19 born late preterm (34-36 /7 weeks gestational age) and 19 at term] were recruited from a developing community in Brazil. Participants underwent neuropsychological testing. Individuals underwent three-dimensional T1-weighted, diffusion-weighted, and resting state functional MRI. Probabilistic tractography and functional connectivity analyses were carried out using unilateral seeds combining the medial prefrontal cortex and the anterior cingulate cortex. Late preterm children showed increased functional connectivity within regions of the default mode, salience, and central-executive networks from both right and left frontal cortex seeds. Decreased functional connectivity was observed within the right parahippocampal region from left frontal seeding. Probabilistic tractography showed a pattern of decreased streamlines in frontal white matter pathways and the corpus callosum, but also increased streamlines in the left orbitofrontal white matter and the right frontal white matter when seeded from the right. Late preterm children and term control children scored similarly on neuropsychological testing. Prefrontal cortical connectivity is altered in late prematurity, with hyperconnectivity observed in key resting state networks in the absence of neuropsychological deficits. Abnormal structural connectivity indicated by probabilistic tractography suggests subtle changes in white matter development, implying disruption of normal maturation during the late gestational period.

Ovarian Function Modulates the Effects of Long-Chain Polyunsaturated Fatty Acids on the Mouse Cerebral Cortex.

PubMed

Herrera, Jose L; Ordoñez-Gutierrez, Lara; Fabrias, Gemma; Casas, Josefina; Morales, Araceli; Hernandez, Guadalberto; Acosta, Nieves G; Rodriguez, Covadonga; Prieto-Valiente, Luis; Garcia-Segura, Luis M; Alonso, Rafael; Wandosell, Francisco G

2018-01-01

Different dietary ratios of n -6/ n -3 long-chain polyunsaturated fatty acids (LC-PUFAs) may alter brain lipid profile, neural activity, and brain cognitive function. To determine whether ovarian hormones influence the effect of diet on the brain, ovariectomized and sham-operated mice continuously treated with placebo or estradiol were fed for 3 months with diets containing low or high n -6/ n -3 LC-PUFA ratios. The fatty acid (FA) profile and expression of key neuronal proteins were analyzed in the cerebral cortex, with intact female mice on standard diet serving as internal controls of brain lipidome composition. Diets containing different concentrations of LC-PUFAs greatly modified total FAs, sphingolipids, and gangliosides in the cerebral cortex. Some of these changes were dependent on ovarian hormones, as they were not detected in ovariectomized animals, and in the case of complex lipids, the effect of ovariectomy was partially or totally reversed by continuous administration of estradiol. However, even though differential dietary LC-PUFA content modified the expression of neuronal proteins such as synapsin and its phosphorylation level, PSD-95, amyloid precursor protein (APP), or glial proteins such as glial fibrillary acidic protein (GFAP), an effect also dependent on the presence of the ovary, chronic estradiol treatment was unable to revert the dietary effects on brain cortex synaptic proteins. These results suggest that, in addition to stable estradiol levels, other ovarian hormones such as progesterone and/or cyclic ovarian secretory activity could play a physiological role in the modulation of dietary LC-PUFAs on the cerebral cortex, which may have clinical implications for post-menopausal women on diets enriched with different proportions of n -3 and n -6 LC-PUFAs.

Ovarian Function Modulates the Effects of Long-Chain Polyunsaturated Fatty Acids on the Mouse Cerebral Cortex

PubMed Central

Herrera, Jose L.; Ordoñez-Gutierrez, Lara; Fabrias, Gemma; Casas, Josefina; Morales, Araceli; Hernandez, Guadalberto; Acosta, Nieves G.; Rodriguez, Covadonga; Prieto-Valiente, Luis; Garcia-Segura, Luis M.; Alonso, Rafael; Wandosell, Francisco G.

2018-01-01

Different dietary ratios of n−6/n−3 long-chain polyunsaturated fatty acids (LC-PUFAs) may alter brain lipid profile, neural activity, and brain cognitive function. To determine whether ovarian hormones influence the effect of diet on the brain, ovariectomized and sham-operated mice continuously treated with placebo or estradiol were fed for 3 months with diets containing low or high n−6/n−3 LC-PUFA ratios. The fatty acid (FA) profile and expression of key neuronal proteins were analyzed in the cerebral cortex, with intact female mice on standard diet serving as internal controls of brain lipidome composition. Diets containing different concentrations of LC-PUFAs greatly modified total FAs, sphingolipids, and gangliosides in the cerebral cortex. Some of these changes were dependent on ovarian hormones, as they were not detected in ovariectomized animals, and in the case of complex lipids, the effect of ovariectomy was partially or totally reversed by continuous administration of estradiol. However, even though differential dietary LC-PUFA content modified the expression of neuronal proteins such as synapsin and its phosphorylation level, PSD-95, amyloid precursor protein (APP), or glial proteins such as glial fibrillary acidic protein (GFAP), an effect also dependent on the presence of the ovary, chronic estradiol treatment was unable to revert the dietary effects on brain cortex synaptic proteins. These results suggest that, in addition to stable estradiol levels, other ovarian hormones such as progesterone and/or cyclic ovarian secretory activity could play a physiological role in the modulation of dietary LC-PUFAs on the cerebral cortex, which may have clinical implications for post-menopausal women on diets enriched with different proportions of n−3 and n−6 LC-PUFAs. PMID:29740285

Anthocyanins protect against LPS-induced oxidative stress-mediated neuroinflammation and neurodegeneration in the adult mouse cortex.

PubMed

Khan, Muhammad Sohail; Ali, Tahir; Kim, Min Woo; Jo, Myeung Hoon; Jo, Min Gi; Badshah, Haroon; Kim, Myeong Ok

2016-11-01

Several studies provide evidence that reactive oxygen species (ROS) are key mediators of various neurological disorders. Anthocyanins are polyphenolic compounds and are well known for their anti-oxidant and neuroprotective effects. In this study, we investigated the neuroprotective effects of anthocyanins (extracted from black soybean) against lipopolysaccharide (LPS)-induced ROS-mediated neuroinflammation and neurodegeneration in the adult mouse cortex. Intraperitoneal injection of LPS (250 μg/kg) for 7 days triggers elevated ROS and oxidative stress, which induces neuroinflammation and neurodegeneration in the adult mouse cortex. Treatment with 24 mg/kg/day of anthocyanins for 14 days in LPS-injected mice (7 days before and 7 days co-treated with LPS) attenuated elevated ROS and oxidative stress compared to mice that received LPS-injection alone. The immunoblotting results showed that anthocyanins reduced the level of the oxidative stress kinase phospho-c-Jun N-terminal Kinase 1 (p-JNK). The immunoblotting and morphological results showed that anthocyanins treatment significantly reduced LPS-induced-ROS-mediated neuroinflammation through inhibition of various inflammatory mediators, such as IL-1β, TNF-α and the transcription factor NF- k B. Anthocyanins treatment also reduced activated astrocytes and microglia in the cortex of LPS-injected mice, as indicated by reductions in GFAP and Iba-1, respectively. Anthocyanins also prevent overexpression of various apoptotic markers, i.e., Bax, cytosolic cytochrome C, cleaved caspase-3 and PARP-1. Immunohistochemical fluoro-jade B (FJB) and Nissl staining indicated that anthocyanins prevent LPS-induced neurodegeneration in the mouse cortex. Our results suggest that dietary flavonoids, such as anthocyanins, have antioxidant and neuroprotective activities that could be beneficial to various neurological disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

Elucidating the underlying components of food valuation in the human orbitofrontal cortex.

PubMed

Suzuki, Shinsuke; Cross, Logan; O'Doherty, John P

2017-12-01

The valuation of food is a fundamental component of our decision-making. Yet little is known about how value signals for food and other rewards are constructed by the brain. Using a food-based decision task in human participants, we found that subjective values can be predicted from beliefs about constituent nutritive attributes of food: protein, fat, carbohydrates and vitamin content. Multivariate analyses of functional MRI data demonstrated that, while food value is represented in patterns of neural activity in both medial and lateral parts of the orbitofrontal cortex (OFC), only the lateral OFC represents the elemental nutritive attributes. Effective connectivity analyses further indicate that information about the nutritive attributes represented in the lateral OFC is integrated within the medial OFC to compute an overall value. These findings provide a mechanistic account for the construction of food value from its constituent nutrients.

Temporal tuning in the bat auditory cortex is sharper when studied with natural echolocation sequences.

PubMed

Beetz, M Jerome; Hechavarría, Julio C; Kössl, Manfred

2016-06-30

Precise temporal coding is necessary for proper acoustic analysis. However, at cortical level, forward suppression appears to limit the ability of neurons to extract temporal information from natural sound sequences. Here we studied how temporal processing can be maintained in the bats' cortex in the presence of suppression evoked by natural echolocation streams that are relevant to the bats' behavior. We show that cortical neurons tuned to target-distance actually profit from forward suppression induced by natural echolocation sequences. These neurons can more precisely extract target distance information when they are stimulated with natural echolocation sequences than during stimulation with isolated call-echo pairs. We conclude that forward suppression does for time domain tuning what lateral inhibition does for selectivity forms such as auditory frequency tuning and visual orientation tuning. When talking about cortical processing, suppression should be seen as a mechanistic tool rather than a limiting element.

Parvalbumin-positive interneurons of the prefrontal cortex support working memory and cognitive flexibility

PubMed Central

Murray, Andrew J.; Woloszynowska-Fraser, Marta U.; Ansel-Bollepalli, Laura; Cole, Katy L. H.; Foggetti, Angelica; Crouch, Barry; Riedel, Gernot; Wulff, Peer

2015-01-01

Dysfunction of parvalbumin (PV)-positive GABAergic interneurons (PVIs) within the prefrontal cortex (PFC) has been implicated in schizophrenia pathology. It is however unclear, how impaired signaling of these neurons may contribute to PFC dysfunction. To identify how PVIs contribute to PFC-dependent behaviors we inactivated PVIs in the PFC in mice using region- and cell-type-selective expression of tetanus toxin light chain (TeLC) and compared the functional consequences of this manipulation with non-cell-type-selective perturbations of the same circuitry. By sampling for behavioral alterations that map onto distinct symptom categories in schizophrenia, we show that dysfunction of PVI signaling in the PFC specifically produces deficits in the cognitive domain, but does not give rise to PFC-dependent correlates of negative or positive symptoms. Our results suggest that distinct aspects of the complex symptomatology of PFC dysfunction in schizophrenia can be attributed to specific prefrontal circuit elements. PMID:26608841

Sensory Prioritization in Rats: Behavioral Performance and Neuronal Correlates.

PubMed

Lee, Conrad C Y; Diamond, Mathew E; Arabzadeh, Ehsan

2016-03-16

Operating with some finite quantity of processing resources, an animal would benefit from prioritizing the sensory modality expected to provide key information in a particular context. The present study investigated whether rats dedicate attentional resources to the sensory modality in which a near-threshold event is more likely to occur. We manipulated attention by controlling the likelihood with which a stimulus was presented from one of two modalities. In a whisker session, 80% of trials contained a brief vibration stimulus applied to whiskers and the remaining 20% of trials contained a brief change of luminance. These likelihoods were reversed in a visual session. When a stimulus was presented in the high-likelihood context, detection performance increased and was faster compared with the same stimulus presented in the low-likelihood context. Sensory prioritization was also reflected in neuronal activity in the vibrissal area of primary somatosensory cortex: single units responded differentially to the whisker vibration stimulus when presented with higher probability compared with lower probability. Neuronal activity in the vibrissal cortex displayed signatures of multiplicative gain control and enhanced response to vibration stimuli during the whisker session. In conclusion, rats allocate priority to the more likely stimulus modality and the primary sensory cortex may participate in the redistribution of resources. Detection of low-amplitude events is critical to survival; for example, to warn prey of predators. To formulate a response, decision-making systems must extract minute neuronal signals from the sensory modality that provides key information. Here, we identify the behavioral and neuronal correlates of sensory prioritization in rats. Rats were trained to detect whisker vibrations or visual flickers. Stimuli were embedded in two contexts in which either visual or whisker modality was more likely to occur. When a stimulus was presented in the high-likelihood context, detection was faster and more reliable. Neuronal recording from the vibrissal cortex revealed enhanced representation of vibrations in the prioritized context. These results establish the rat as an alternative model organism to primates for studying attention. Copyright © 2016 the authors 0270-6474/16/363243-11$15.00/0.

Effective Connectivity within the Default Mode Network: Dynamic Causal Modeling of Resting-State fMRI Data.

PubMed

Sharaev, Maksim G; Zavyalova, Viktoria V; Ushakov, Vadim L; Kartashov, Sergey I; Velichkovsky, Boris M

2016-01-01

The Default Mode Network (DMN) is a brain system that mediates internal modes of cognitive activity, showing higher neural activation when one is at rest. Nowadays, there is a lot of interest in assessing functional interactions between its key regions, but in the majority of studies only association of Blood-oxygen-level dependent (BOLD) activation patterns is measured, so it is impossible to identify causal influences. There are some studies of causal interactions (i.e., effective connectivity), however often with inconsistent results. The aim of the current work is to find a stable pattern of connectivity between four DMN key regions: the medial prefrontal cortex (mPFC), the posterior cingulate cortex (PCC), left and right intraparietal cortex (LIPC and RIPC). For this purpose functional magnetic resonance imaging (fMRI) data from 30 healthy subjects (1000 time points from each one) was acquired and spectral dynamic causal modeling (DCM) on a resting-state fMRI data was performed. The endogenous brain fluctuations were explicitly modeled by Discrete Cosine Set at the low frequency band of 0.0078-0.1 Hz. The best model at the group level is the one where connections from both bilateral IPC to mPFC and PCC are significant and symmetrical in strength (p < 0.05). Connections between mPFC and PCC are bidirectional, significant in the group and weaker than connections originating from bilateral IPC. In general, all connections from LIPC/RIPC to other DMN regions are much stronger. One can assume that these regions have a driving role within the DMN. Our results replicate some data from earlier works on effective connectivity within the DMN as well as provide new insights on internal DMN relationships and brain's functioning at resting state.

Brain structures and functional connectivity associated with individual differences in Internet tendency in healthy young adults.

PubMed

Li, Weiwei; Li, Yadan; Yang, Wenjing; Zhang, Qinglin; Wei, Dongtao; Li, Wenfu; Hitchman, Glenn; Qiu, Jiang

2015-04-01

Internet addiction (IA) incurs significant social and financial costs in the form of physical side-effects, academic and occupational impairment, and serious relationship problems. The majority of previous studies on Internet addiction disorders (IAD) have focused on structural and functional abnormalities, while few studies have simultaneously investigated the structural and functional brain alterations underlying individual differences in IA tendencies measured by questionnaires in a healthy sample. Here we combined structural (regional gray matter volume, rGMV) and functional (resting-state functional connectivity, rsFC) information to explore the neural mechanisms underlying IAT in a large sample of 260 healthy young adults. The results showed that IAT scores were significantly and positively correlated with rGMV in the right dorsolateral prefrontal cortex (DLPFC, one key node of the cognitive control network, CCN), which might reflect reduced functioning of inhibitory control. More interestingly, decreased anticorrelations between the right DLPFC and the medial prefrontal cortex/rostral anterior cingulate cortex (mPFC/rACC, one key node of the default mode network, DMN) were associated with higher IAT scores, which might be associated with reduced efficiency of the CCN and DMN (e.g., diminished cognitive control and self-monitoring). Furthermore, the Stroop interference effect was positively associated with the volume of the DLPFC and with the IA scores, as well as with the connectivity between DLPFC and mPFC, which further indicated that rGMV variations in the DLPFC and decreased anticonnections between the DLPFC and mPFC may reflect addiction-related reduced inhibitory control and cognitive efficiency. These findings suggest the combination of structural and functional information can provide a valuable basis for further understanding of the mechanisms and pathogenesis of IA. Copyright © 2015 Elsevier Ltd. All rights reserved.

Disruption of Functional Organization Within the Primary Motor Cortex in Children With Autism

PubMed Central

Nebel, Mary Beth; Joel, Suresh E.; Muschelli, John; Barber, Anita D.; Caffo, Brian S.; Pekar, James J.; Mostofsky, Stewart H.

2013-01-01

Accumulating evidence suggests that motor impairments are prevalent in autism spectrum disorder (ASD), relate to the social and communicative deficits at the core of the diagnosis and may reflect abnormal connectivity within brain networks underlying motor control and learning. Parcellation of resting-state functional connectivity data using spectral clustering approaches has been shown to be an effective means of visualizing functional organization within the brain but has most commonly been applied to explorations of normal brain function. This article presents a parcellation of a key area of the motor network, the primary motor cortex (M1), a key area of the motor control network, in adults, typically developing (TD) children and children with ASD and introduces methods for selecting the number of parcels, matching parcels across groups and testing group differences. The parcellation is based solely on patterns of connectivity between individual M1 voxels and all voxels outside of M1, and within all groups, a gross dorsomedial to ventrolateral organization emerged within M1 which was left–right symmetric. Although this gross organizational scheme was present in both groups of children, statistically significant group differences in the size and segregation of M1 parcels within regions of the motor homunculus corresponding to the upper and lower limbs were observed. Qualitative comparison of the M1 parcellation for children with ASD with that of younger and older TD children suggests that these organizational differences, with a lack of differentiation between lower limb/trunk regions and upper limb/hand regions, may be due, at least in part, to a delay in functional specialization within the motor cortex. PMID:23118015

Cortical neurons sensitive to combinations of information-bearing elements of biosonar signals in the mustache bat.

PubMed

Suga, N; O'Neill, W E; Manabe, T

1978-05-19

The auditory cortex of the mustache bat, Pteronotus parnellii rubiginosus, is composed of functional divisions which are differently organized to be suited for processing the elements of its biosonar signal according to their biological significance. Unlike the Doppler-shifted-CF (constant frequency) processing area, the area processing the frequency-modulated components does not show clear tonotopic and amplitopic representations, but consists of several clusters of neurons, each of which is sensitive to a particular combination (or combinations) of information-bearing elements of the biosonar signal and echoes. The response properties of neurons in the major clusters indicate that processing of information carried by the frequency-modulated components of echoes is facilitated by the first harmonic of the emitted biosonar signal. The properties of some of these neurons suggest that they are tuned to a target which has a particular cross-sectional area and which is located at a particular distance.

How Many Words Does a Picture Really Tell? Cross-sectional Descriptive Study of Pictogram Evaluation by Youth

PubMed Central

Korenevsky, Artyom; Vaillancourt, Régis; Pouliot, Annie; Revol, Marine; Steed, Evan; Besançon, Luc; Wahrendorf, Marit-Saskia; Patel, Jaimisha R

2013-01-01

Background Communicating health-related instructions with pictograms is useful, but such graphics can be interpreted in different ways. It is crucial to understand which pictogram components are best for accurate communication. Objectives: To catalogue pictograms used to label drugs in clinical practice; to identify the common graphic elements for defined categories of pictograms, by performing a semiotic analysis (studying how signs are perceived and how they should be designed); to identify the key graphic elements common to pictograms preferred by users; and to develop suggestions for future pictogram design on the basis of users’ input. Methods: Literature and Internet searches were performed to identify pictograms and pictogram categories. A call for pictograms was also circulated through the International Pharmaceutical Federation (FIP). Youth at a Canadian pediatric hospital were asked to rate pictograms (including storyboards and prescription labels generated by FIP pictogram software) in terms of how best they represented their intended meanings. Pictograms for which at least 80% of participants “somewhat agreed”, “agreed”, or “strongly agreed” that the graphic conveyed the intended meaning were designated as “preferred” and were selected for analysis. Elements appearing in at least 50% of these preferred pictograms were highlighted as key graphic elements for design of future pictograms. Results: In total, 21 categories were identified for pictograms used in clinical practice, and a total of 204 pictograms were analyzed. Eighty-six participants took part in the survey. For each pictogram category, certain elements were identified as “preferred” and as “key graphic elements”, whereas other elements met neither designation. For all 21 pictogram categories, at least 80% of survey respondents agreed that the FIP storyboard conveyed the intended meaning. Conclusions: Certain key, preferred graphic elements are required for pharmaceutical pictograms to convey their intended meaning. The overlap between preferred and key pictogram elements indicates that both must be considered in development of future pictograms. Redesign of existing pictograms with consideration of the best semiotic elements is in progress. PMID:23950605

76 FR 6496 - Special Flight Rules Area in the Vicinity of Grand Canyon National Park, Draft Environmental...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-04

... being considered include: Alternative A Current Condition: Key elements are corridors open year round, annual allocation cap of 93,971, and no quiet technology incentive. Current tours for helicopters and... to quiet technology aircraft. Alternative F Modified Current Condition: Key elements are similar to...

The Secret to Finland's Success: Educating Teachers. Research Brief

ERIC Educational Resources Information Center

Sahlberg, Pasi

2010-01-01

In the last decade, Finland has emerged as the leading OECD country in educational achievement. In examining the sources of Finland's dramatic rise to the top, research shows one key element that has impacted Finland's success above all others: excellent teachers. This policy brief details the key elements of Finland's successful system, examining…

The occipital place area represents the local elements of scenes

PubMed Central

Kamps, Frederik S.; Julian, Joshua B.; Kubilius, Jonas; Kanwisher, Nancy; Dilks, Daniel D.

2016-01-01

Neuroimaging studies have identified three scene-selective regions in human cortex: parahippocampal place area (PPA), retrosplenial complex (RSC), and occipital place area (OPA). However, precisely what scene information each region represents in not clear, especially for the least studied, more posterior OPA. Here we hypothesized that OPA represents local elements of scenes within two independent, yet complementary scene descriptors: spatial boundary (i.e., the layout of external surfaces) and scene content (e.g., internal objects). If OPA processes the local elements of spatial boundary information, then it should respond to these local elements (e.g., walls) themselves, regardless of their spatial arrangement. Indeed, we found OPA, but not PPA or RSC, responded similarly to images of intact rooms and these same rooms in which the surfaces were fractured and rearranged, disrupting the spatial boundary. Next, if OPA represents the local elements of scene content information, then it should respond more when more such local elements (e.g., furniture) are present. Indeed, we found that OPA, but not PPA or RSC, responded more to multiple than single pieces of furniture. Taken together, these findings reveal that OPA analyzes local scene elements – both in spatial boundary and scene content representation – while PPA and RSC represent global scene properties. PMID:26931815

The occipital place area represents the local elements of scenes.

PubMed

Kamps, Frederik S; Julian, Joshua B; Kubilius, Jonas; Kanwisher, Nancy; Dilks, Daniel D

2016-05-15

Neuroimaging studies have identified three scene-selective regions in human cortex: parahippocampal place area (PPA), retrosplenial complex (RSC), and occipital place area (OPA). However, precisely what scene information each region represents is not clear, especially for the least studied, more posterior OPA. Here we hypothesized that OPA represents local elements of scenes within two independent, yet complementary scene descriptors: spatial boundary (i.e., the layout of external surfaces) and scene content (e.g., internal objects). If OPA processes the local elements of spatial boundary information, then it should respond to these local elements (e.g., walls) themselves, regardless of their spatial arrangement. Indeed, we found that OPA, but not PPA or RSC, responded similarly to images of intact rooms and these same rooms in which the surfaces were fractured and rearranged, disrupting the spatial boundary. Next, if OPA represents the local elements of scene content information, then it should respond more when more such local elements (e.g., furniture) are present. Indeed, we found that OPA, but not PPA or RSC, responded more to multiple than single pieces of furniture. Taken together, these findings reveal that OPA analyzes local scene elements - both in spatial boundary and scene content representation - while PPA and RSC represent global scene properties. Copyright © 2016 Elsevier Inc. All rights reserved.

Respective Role of the Dorsal Hippocampus and the Entorhinal Cortex during the Recombination of Previously Learned Olfactory-Tactile Associations in the Rat

ERIC Educational Resources Information Center

Boisselier, Lise; Ferry, Barbara; Gervais, Rémi

2017-01-01

The hippocampal formation has been extensively described as a key component for object recognition in conjunction with place and context. The present study aimed at describing neural mechanisms in the hippocampal formation that support olfactory-tactile (OT) object discrimination in a task where space and context were not taken into account. The…

Southern Great Plains Rapid Ecoregional Assessment: pre-assessment report

USGS Publications Warehouse

Assal, Timothy J.; Melcher, Cynthia P.; Carr, Natasha B.

2015-01-01

An overview on the ecology and management issues for each Conservation Element is provided, including distribution and ecology, landscape structure and dynamics, and associated species of management concern affiliated with each Conservation Element. For each Conservation Element, effects of the Change Agents are described. An overview of potential key ecological attributes and potential Change Agents are summarized by conceptual models and tables. The tables provide an organizational framework and background information for evaluating the key ecological attributes and Change Agents in Phase II.

A matter of definition--key elements identified in a discourse analysis of definitions of palliative care.

PubMed

Pastrana, T; Jünger, S; Ostgathe, C; Elsner, F; Radbruch, L

2008-04-01

For more than 30 years, the term "palliative care" has been used. From the outset, the term has undergone a series of transformations in its definitions and consequently in its tasks and goals. There remains a lack of consensus on a definition. The aim of this article is to analyse the definitions of palliative care in the specialist literature and to identify the key elements of palliative care using discourse analysis: a qualitative methodology. The literature search focused on definitions of the term 'palliative medicine' and 'palliative care' in the World Wide Web and medical reference books in English and German. A total of 37 English and 26 German definitions were identified and analysed. Our study confirmed the lack of a consistent meaning concerning the investigated terms, reflecting on-going discussion about the nature of the field among palliative care practitioners. Several common key elements were identified. Four main categories emerged from the discourse analysis of the definition of palliative care: target groups, structure, tasks and expertise. In addition, the theoretical principles and goals of palliative care were discussed and found to be key elements, with relief and prevention of suffering and improvement of quality of life as main goals. The identified key elements can contribute to the definition of the concept 'palliative care'. Our study confirms the importance of semantic and ethical influences on palliative care that should be considered in future research on semantics in different languages.

High baseline activity in inferior temporal cortex improves neural and behavioral discriminability during visual categorization

PubMed Central

Emadi, Nazli; Rajimehr, Reza; Esteky, Hossein

2014-01-01

Spontaneous firing is a ubiquitous property of neural activity in the brain. Recent literature suggests that this baseline activity plays a key role in perception. However, it is not known how the baseline activity contributes to neural coding and behavior. Here, by recording from the single neurons in the inferior temporal cortex of monkeys performing a visual categorization task, we thoroughly explored the relationship between baseline activity, the evoked response, and behavior. Specifically we found that a low-frequency (<8 Hz) oscillation in the spike train, prior and phase-locked to the stimulus onset, was correlated with increased gamma power and neuronal baseline activity. This enhancement of the baseline activity was then followed by an increase in the neural selectivity and the response reliability and eventually a higher behavioral performance. PMID:25404900

Synaptic molecular imaging in spared and deprived columns of mouse barrel cortex with array tomography

PubMed Central

Weiler, Nicholas C; Collman, Forrest; Vogelstein, Joshua T; Burns, Randal; Smith, Stephen J

2014-01-01

A major question in neuroscience is how diverse subsets of synaptic connections in neural circuits are affected by experience dependent plasticity to form the basis for behavioral learning and memory. Differences in protein expression patterns at individual synapses could constitute a key to understanding both synaptic diversity and the effects of plasticity at different synapse populations. Our approach to this question leverages the immunohistochemical multiplexing capability of array tomography (ATomo) and the columnar organization of mouse barrel cortex to create a dataset comprising high resolution volumetric images of spared and deprived cortical whisker barrels stained for over a dozen synaptic molecules each. These dataset has been made available through the Open Connectome Project for interactive online viewing, and may also be downloaded for offline analysis using web, Matlab, and other interfaces. PMID:25977797

Synaptic molecular imaging in spared and deprived columns of mouse barrel cortex with array tomography.

PubMed

Weiler, Nicholas C; Collman, Forrest; Vogelstein, Joshua T; Burns, Randal; Smith, Stephen J

2014-01-01

A major question in neuroscience is how diverse subsets of synaptic connections in neural circuits are affected by experience dependent plasticity to form the basis for behavioral learning and memory. Differences in protein expression patterns at individual synapses could constitute a key to understanding both synaptic diversity and the effects of plasticity at different synapse populations. Our approach to this question leverages the immunohistochemical multiplexing capability of array tomography (ATomo) and the columnar organization of mouse barrel cortex to create a dataset comprising high resolution volumetric images of spared and deprived cortical whisker barrels stained for over a dozen synaptic molecules each. These dataset has been made available through the Open Connectome Project for interactive online viewing, and may also be downloaded for offline analysis using web, Matlab, and other interfaces.

Practical private database queries based on a quantum-key-distribution protocol

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jakobi, Markus; Humboldt-Universitaet zu Berlin, D-10117 Berlin; Simon, Christoph

2011-02-15

Private queries allow a user, Alice, to learn an element of a database held by a provider, Bob, without revealing which element she is interested in, while limiting her information about the other elements. We propose to implement private queries based on a quantum-key-distribution protocol, with changes only in the classical postprocessing of the key. This approach makes our scheme both easy to implement and loss tolerant. While unconditionally secure private queries are known to be impossible, we argue that an interesting degree of security can be achieved by relying on fundamental physical principles instead of unverifiable security assumptions inmore » order to protect both the user and the database. We think that the scope exists for such practical private queries to become another remarkable application of quantum information in the footsteps of quantum key distribution.« less

Developing Cognitive Control: Three Key Transitions

PubMed Central

Munakata, Yuko; Snyder, Hannah R.; Chatham, Christopher H.

2012-01-01

The ability to flexibly break out of routine behaviors develops gradually and is essential for success in life. We discuss three key developmental transitions toward more flexible behavior. First, children develop an increasing ability to overcome habits by engaging cognitive control in response to environmental signals. Second, children shift from recruiting cognitive control reactively, as needed in the moment, to recruiting cognitive control proactively, in preparation for needing it. Third, children shift from relying on environmental signals for engaging cognitive control to becoming more self-directed. All three transitions can be understood in terms of the development of increasingly active and abstract goal representations in prefrontal cortex. PMID:22711982

The Arabidopsis MTP8 transporter determines the localization of manganese and iron in seeds

DOE PAGES

Chu, Heng-Hsuan; Car, Suzana; Socha, Amanda L.; ...

2017-09-08

Understanding how seeds obtain and store nutrients is key to developing crops with higher agronomic and nutritional value. We have uncovered unique patterns of micronutrient localization in seeds using synchrotron X-ray fluorescence (SXRF). Although all four members of the Arabidopsis thaliana Mn-CDF family can transport Mn, here we show that only mtp8-2 has an altered Mn distribution pattern in seeds. In an mtp8-2 mutant, Mn no longer accumulates in hypocotyl cortex cells and sub-epidermal cells of the embryonic cotyledons, but rather accumulates with Fe in the cells surrounding the vasculature, a pattern previously shown to be determined by the vacuolarmore » transporter VIT1. We also show that MTP8, unlike the other three Mn-CDF family members, can transport Fe and is responsible for localization of Fe to the same cells that store Mn. When both the VIT1 and MTP8 transporters are non-functional, there is no accumulation of Fe or Mn in specific cell types; rather these elements are distributed amongst all cell types in the seed. Finally, disruption of the putative Fe binding sites in MTP8 resulted in loss of ability to transport Fe but did not affect the ability to transport Mn.« less

Insidious adrenocortical insufficiency underlies neuroendocrine dysregulation in TIF-2 deficient mice.

PubMed

Patchev, Alexandre V; Fischer, Dieter; Wolf, Siegmund S; Herkenham, Miles; Götz, Franziska; Gehin, Martine; Chambon, Pierre; Patchev, Vladimir K; Almeida, Osborne F X

2007-01-01

The transcription-intermediary-factor-2 (TIF-2) is a coactivator of the glucocorticoid receptor (GR), and its disruption would be expected to influence glucocorticoid-mediated control of the hypothalamo-pituitary-adrenal (HPA) axis. Here, we show that its targeted deletion in mice is associated with altered expression of several glucocorticoid-dependent components of HPA regulation (e.g., corticotropin-releasing hormone, vasopressin, ACTH, glucocorticoid receptors), suggestive of hyperactivity under basal conditions. At the same time, TIF-2(-/-) mice display significantly lower basal corticosterone levels and a sluggish and blunted initial secretory response to brief emotional and prolonged physical stress. Subsequent analysis revealed this discrepancy to result from pronounced aberrations in the structure and function of the adrenal gland, including the cytoarchitectural organization of the zona fasciculata and basal and stress-induced expression of key elements of steroid hormone synthesis, such as the steroidogenic acute regulatory (StAR) protein and 3beta-hydroxysteroid dehydrogenase (3beta-HSD). In addition, altered expression levels of two nuclear receptors, DAX-1 and steroidogenic factor 1 (SF-1), in the adrenal cortex strengthen the view that TIF-2 deletion disrupts adrenocortical development and steroid biosynthesis. Thus, hyperactivity of the hypothalamo-pituitary unit is ascribed to insidious adrenal insufficiency and impaired glucocorticoid feedback.

Information processing in echo state networks at the edge of chaos.

PubMed

Boedecker, Joschka; Obst, Oliver; Lizier, Joseph T; Mayer, N Michael; Asada, Minoru

2012-09-01

We investigate information processing in randomly connected recurrent neural networks. It has been shown previously that the computational capabilities of these networks are maximized when the recurrent layer is close to the border between a stable and an unstable dynamics regime, the so called edge of chaos. The reasons, however, for this maximized performance are not completely understood. We adopt an information-theoretical framework and are for the first time able to quantify the computational capabilities between elements of these networks directly as they undergo the phase transition to chaos. Specifically, we present evidence that both information transfer and storage in the recurrent layer are maximized close to this phase transition, providing an explanation for why guiding the recurrent layer toward the edge of chaos is computationally useful. As a consequence, our study suggests self-organized ways of improving performance in recurrent neural networks, driven by input data. Moreover, the networks we study share important features with biological systems such as feedback connections and online computation on input streams. A key example is the cerebral cortex, which was shown to also operate close to the edge of chaos. Consequently, the behavior of model systems as studied here is likely to shed light on reasons why biological systems are tuned into this specific regime.

Anillin acts as a bifunctional linker coordinating midbody ring biogenesis during cytokinesis

PubMed Central

Kechad, Amel; Jananji, Silvana; Ruella, Yvonne; Hickson, Gilles R. X.

2013-01-01

Summary Animal cell cytokinesis proceeds via constriction of an actomyosin-based contractile ring (CR) [1, 2]. Upon reaching a diameter of ~1 μm [3], a midbody ring (MR) forms to stabilize the intercellular bridge until abscission [4-6]. How MR formation is coupled to CR closure and how plasma membrane anchoring is maintained at this key transition is unknown. Time-lapse microscopy of Drosophila S2 cells depleted of the scaffold protein, Anillin [7-9], revealed that Anillin is required for complete closure of the CR and formation of the MR. Truncation analysis revealed that Anillin N-termini connected with the actomyosin CR and supported formation of stable MR-like structures, but these could not maintain anchoring of the plasma membrane. Conversely, Anillin C-termini failed to connect with the CR or MR but recruited the septin, Peanut, to ectopic structures at the equatorial cortex. Peanut depletion mimicked truncation of the Anillin C-terminus, resulting in MR-like structures that failed to anchor the membrane. These data demonstrate that Anillin coordinates the transition from CR to MR, and that it does so by linking two distinct cortical cytoskeletal elements. One apparently acts as the core structural template for MR assembly, while the other ensures stable anchoring of the plasma membrane beyond the CR stage. PMID:22226749

Sparse orthogonal population representation of spatial context in the retrosplenial cortex.

PubMed

Mao, Dun; Kandler, Steffen; McNaughton, Bruce L; Bonin, Vincent

2017-08-15

Sparse orthogonal coding is a key feature of hippocampal neural activity, which is believed to increase episodic memory capacity and to assist in navigation. Some retrosplenial cortex (RSC) neurons convey distributed spatial and navigational signals, but place-field representations such as observed in the hippocampus have not been reported. Combining cellular Ca 2+ imaging in RSC of mice with a head-fixed locomotion assay, we identified a population of RSC neurons, located predominantly in superficial layers, whose ensemble activity closely resembles that of hippocampal CA1 place cells during the same task. Like CA1 place cells, these RSC neurons fire in sequences during movement, and show narrowly tuned firing fields that form a sparse, orthogonal code correlated with location. RSC 'place' cell activity is robust to environmental manipulations, showing partial remapping similar to that observed in CA1. This population code for spatial context may assist the RSC in its role in memory and/or navigation.Neurons in the retrosplenial cortex (RSC) encode spatial and navigational signals. Here the authors use calcium imaging to show that, similar to the hippocampus, RSC neurons also encode place cell-like activity in a sparse orthogonal representation, partially anchored to the allocentric cues on the linear track.

Midbrain response to milkshake correlates with ad libitum milkshake intake in the absence of hunger.

PubMed

Nolan-Poupart, Sarah; Veldhuizen, Maria G; Geha, Paul; Small, Dana M

2013-01-01

There is now widespread agreement that individual variation in the neural circuits representing the reinforcing properties of foods may be associated with risk for overeating and obesity. What is currently unknown is how and whether brain response to a food is related to immediate subsequent intake of that food. Here we used functional magnetic resonance imaging (fMRI) to test whether response to a palatable milkshake is associated with subsequent ad libitum milkshake consumption. We predicted that enhanced responses in key reward regions (insula, striatum, midbrain, medial orbitofrontal cortex) and decreased responses in regions implicated in self-control (lateral prefrontal and lateral orbitofrontal cortex) would be associated with greater intake. We found a significant positive association between response to milkshake in the periaqueductal gray region of the midbrain and ad libitum milkshake intake. Although strong bilateral insular responses were observed during consumption of the milkshake this response did not correlate with subsequent intake. The associations observed in the midbrain and orbitofrontal cortex were uninfluenced by ratings of hunger, which were near neutral. We conclude that midbrain response to a palatable food is related to eating in the absence of hunger. Copyright © 2012 Elsevier Ltd. All rights reserved.

Cues, context, and long-term memory: the role of the retrosplenial cortex in spatial cognition

PubMed Central

Miller, Adam M. P.; Vedder, Lindsey C.; Law, L. Matthew; Smith, David M.

2014-01-01

Spatial navigation requires memory representations of landmarks and other navigation cues. The retrosplenial cortex (RSC) is anatomically positioned between limbic areas important for memory formation, such as the hippocampus (HPC) and the anterior thalamus, and cortical regions along the dorsal stream known to contribute importantly to long-term spatial representation, such as the posterior parietal cortex. Damage to the RSC severely impairs allocentric representations of the environment, including the ability to derive navigational information from landmarks. The specific deficits seen in tests of human and rodent navigation suggest that the RSC supports allocentric representation by processing the stable features of the environment and the spatial relationships among them. In addition to spatial cognition, the RSC plays a key role in contextual and episodic memory. The RSC also contributes importantly to the acquisition and consolidation of long-term spatial and contextual memory through its interactions with the HPC. Within this framework, the RSC plays a dual role as part of the feedforward network providing sensory and mnemonic input to the HPC and as a target of the hippocampal-dependent systems consolidation of long-term memory. PMID:25140141

Posterior Parietal Cortex Drives Inferotemporal Activations During Three-Dimensional Object Vision.

PubMed

Van Dromme, Ilse C; Premereur, Elsie; Verhoef, Bram-Ernst; Vanduffel, Wim; Janssen, Peter

2016-04-01

The primate visual system consists of a ventral stream, specialized for object recognition, and a dorsal visual stream, which is crucial for spatial vision and actions. However, little is known about the interactions and information flow between these two streams. We investigated these interactions within the network processing three-dimensional (3D) object information, comprising both the dorsal and ventral stream. Reversible inactivation of the macaque caudal intraparietal area (CIP) during functional magnetic resonance imaging (fMRI) reduced fMRI activations in posterior parietal cortex in the dorsal stream and, surprisingly, also in the inferotemporal cortex (ITC) in the ventral visual stream. Moreover, CIP inactivation caused a perceptual deficit in a depth-structure categorization task. CIP-microstimulation during fMRI further suggests that CIP projects via posterior parietal areas to the ITC in the ventral stream. To our knowledge, these results provide the first causal evidence for the flow of visual 3D information from the dorsal stream to the ventral stream, and identify CIP as a key area for depth-structure processing. Thus, combining reversible inactivation and electrical microstimulation during fMRI provides a detailed view of the functional interactions between the two visual processing streams.

Posterior Parietal Cortex Drives Inferotemporal Activations During Three-Dimensional Object Vision

PubMed Central

Van Dromme, Ilse C.; Premereur, Elsie; Verhoef, Bram-Ernst; Vanduffel, Wim; Janssen, Peter

2016-01-01

The primate visual system consists of a ventral stream, specialized for object recognition, and a dorsal visual stream, which is crucial for spatial vision and actions. However, little is known about the interactions and information flow between these two streams. We investigated these interactions within the network processing three-dimensional (3D) object information, comprising both the dorsal and ventral stream. Reversible inactivation of the macaque caudal intraparietal area (CIP) during functional magnetic resonance imaging (fMRI) reduced fMRI activations in posterior parietal cortex in the dorsal stream and, surprisingly, also in the inferotemporal cortex (ITC) in the ventral visual stream. Moreover, CIP inactivation caused a perceptual deficit in a depth-structure categorization task. CIP-microstimulation during fMRI further suggests that CIP projects via posterior parietal areas to the ITC in the ventral stream. To our knowledge, these results provide the first causal evidence for the flow of visual 3D information from the dorsal stream to the ventral stream, and identify CIP as a key area for depth-structure processing. Thus, combining reversible inactivation and electrical microstimulation during fMRI provides a detailed view of the functional interactions between the two visual processing streams. PMID:27082854

Lateral Prefrontal Cortex Subregions Make Dissociable Contributions during Fluid Reasoning

PubMed Central

Thompson, Russell; Duncan, John; Owen, Adrian M.

2011-01-01

Reasoning is a key component of adaptable “executive” behavior and is known to depend on a network of frontal and parietal brain regions. However, the mechanisms by which this network supports reasoning and adaptable behavior remain poorly defined. Here, we examine the relationship between reasoning, executive control, and frontoparietal function in a series of nonverbal reasoning experiments. Our results demonstrate that, in accordance with previous studies, a network of frontal and parietal brain regions is recruited during reasoning. Our results also reveal that this network can be fractionated according to how different subregions respond when distinct reasoning demands are manipulated. While increased rule complexity modulates activity within a right lateralized network including the middle frontal gyrus and the superior parietal cortex, analogical reasoning demand—or the requirement to remap rules on to novel features—recruits the left inferior rostrolateral prefrontal cortex and the lateral occipital complex. In contrast, the posterior extent of the inferior frontal gyrus, associated with simpler executive demands, is not differentially sensitive to rule complexity or analogical demand. These findings accord well with the hypothesis that different reasoning demands are supported by different frontal and parietal subregions. PMID:20483908

Contribution of Genoarchitecture to Understanding Hippocampal Evolution and Development.

PubMed

Medina, Loreta; Abellán, Antonio; Desfilis, Ester

2017-01-01

The hippocampal formation is a highly conserved structure of the medial pallium that works in association with the entorhinal cortex, playing a key role in memory formation and spatial navigation. Although it has been described in several vertebrates, the presence of comparable subdivisions across species remained unclear. This panorama has started to change in recent years thanks to the identification of some of the genes that regulate the development of the hippocampal formation in the mouse and help to delineate its subdivisions based on molecular features. Some of these genes have been used to try to identify subdivisions in chicken and lizards comparable to those of the mammalian hippocampal formation and the entorhinal cortex. Here, we review some of these data, which suggest the existence of fields comparable to the dentate gyrus, CA3, CA1, subiculum, as well as medial and lateral parts of the entorhinal cortex in all amniotes. We also analyze available data suggesting the existence of serial connections between these fields, speculate on the possible existence of auto-associative loops in CA3, and discuss general principles governing the formation of the connections. © 2017 S. Karger AG, Basel.

The neural substrates of action identification.

PubMed

Marsh, Abigail A; Kozak, Megan N; Wegner, Daniel M; Reid, Marguerite E; Yu, Henry H; Blair, R J R

2010-12-01

Mentalization is the process by which an observer views a target as possessing higher cognitive faculties such as goals, intentions and desires. Mentalization can be assessed using action identification paradigms, in which observers choose mentalistic (goals-focused) or mechanistic (action-focused) descriptions of targets' actions. Neural structures that play key roles in inferring goals and intentions from others' observed or imagined actions include temporo-parietal junction, ventral premotor cortex and extrastriate body area. We hypothesized that these regions play a role in action identification as well. Data collected using functional magnetic resonance imaging (fMRI) confirmed our predictions that activity in ventral premotor cortex and middle temporal gyrus near the extrastriate body area varies both as a function of the valence of the target and the extent to which actions are identified as goal-directed. In addition, the inferior parietal lobule is preferentially engaged when participants identify the actions of mentalized targets. Functional connectivity analyses suggest support from other regions, including the medial prefrontal cortex and amygdala, during mentalization. We found correlations between action identification and Autism Quotient scores, suggesting that understanding the neural correlates of action identification may enhance our understanding of the underpinnings of essential social cognitive processes.

What makes the dorsomedial frontal cortex active during reading the mental states of others?

PubMed Central

Isoda, Masaki; Noritake, Atsushi

2013-01-01

The dorsomedial frontal part of the cerebral cortex is consistently activated when people read the mental states of others, such as their beliefs, desires, and intentions, the ability known as having a theory of mind (ToM) or mentalizing. This ubiquitous finding has led many researchers to conclude that the dorsomedial frontal cortex (DMFC) constitutes a core component in mentalizing networks. Despite this, it remains unclear why the DMFC becomes active during ToM tasks. We argue that key psychological and behavioral aspects in mentalizing are closely associated with DMFC functions. These include executive inhibition, distinction between self and others, prediction under uncertainty, and perception of intentions, all of which are important for predicting others' intention and behavior. We review the literature supporting this claim, ranging in fields from developmental psychology to human neuroimaging and macaque electrophysiology. Because perceiving intentions in others' actions initiates mentalizing and forms the basis of virtually all types of social interaction, the fundamental issue in social neuroscience is to determine the aspects of physical entities that make an observer perceive that they are intentional beings and to clarify the neurobiological underpinnings of the perception of intentionality in others' actions. PMID:24367287

Remodeling of Dendritic Spines in the Avian Vocal Motor Cortex Following Deafening Depends on the Basal Ganglia Circuit.

PubMed

Zhou, Xin; Fu, Xin; Lin, Chun; Zhou, Xiaojuan; Liu, Jin; Wang, Li; Zhang, Xinwen; Zuo, Mingxue; Fan, Xiaolong; Li, Dapeng; Sun, Yingyu

2017-05-01

Deafening elicits a deterioration of learned vocalization, in both humans and songbirds. In songbirds, learned vocal plasticity has been shown to depend on the basal ganglia-cortical circuit, but the underlying cellular basis remains to be clarified. Using confocal imaging and electron microscopy, we examined the effect of deafening on dendritic spines in avian vocal motor cortex, the robust nucleus of the arcopallium (RA), and investigated the role of the basal ganglia circuit in motor cortex plasticity. We found rapid structural changes to RA dendritic spines in response to hearing loss, accompanied by learned song degradation. In particular, the morphological characters of RA spine synaptic contacts between 2 major pathways were altered differently. However, experimental disruption of the basal ganglia circuit, through lesions in song-specialized basal ganglia nucleus Area X, largely prevented both the observed changes to RA dendritic spines and the song deterioration after hearing loss. Our results provide cellular evidence to highlight a key role of the basal ganglia circuit in the motor cortical plasticity that underlies learned vocal plasticity. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The developmental switch in GABA polarity is delayed in fragile X mice.

PubMed

He, Qionger; Nomura, Toshihiro; Xu, Jian; Contractor, Anis

2014-01-08

Delays in synaptic and neuronal development in the cortex are key hallmarks of fragile X syndrome, a prevalent neurodevelopmental disorder that causes intellectual disability and sensory deficits and is the most common known cause of autism. Previous studies have demonstrated that the normal progression of plasticity and synaptic refinement during the critical period is altered in the cortex of fragile X mice. Although the disruptions in excitatory synapses are well documented in fragile X, there is less known about inhibitory neurotransmission during the critical period. GABAergic transmission plays a crucial trophic role in cortical development through its early depolarizing action. At the end of cortical critical period, response properties of GABA transform into their mature hyperpolarizing type due to developmental changes in intracellular chloride homeostasis. We found that the timing of the switch from depolarizing to hyperpolarizing GABA is delayed in the cortex of fragile X mice and there is a concurrent alteration in the expression of the neuronal chloride cotransporter NKCC1 that promotes the accumulation of intracellular chloride. Disruption of the trophic effects of GABA during cortical development could contribute to the altered trajectory of synaptic maturation in fragile X syndrome.

Gender Differences in Behavioral and Neural Responses to Unfairness Under Social Pressure.

PubMed

Zheng, Li; Ning, Reipeng; Li, Lin; Wei, Chunli; Cheng, Xuemei; Zhou, Chu; Guo, Xiuyan

2017-10-18

Numerous studies have revealed the key role of social pressure on individuals' decision-making processes. However, the impact of social pressure on unfairness-related decision-making processes remains unclear. In the present study, we investigated how social pressure modulated men's and women's responses in an ultimatum game. Twenty women and eighteen men played the ultimatum game as responders in the scanner, where fair and unfair offers were tendered by proposers acting alone (low pressure) or by proposers endorsed by three supporters (high pressure). Results showed that men rejected more, whereas women accepted more unfair offers in the high versus low pressure context. Neurally, pregenual anterior cingulate cortex activation in women positively predicted their acceptance rate difference between contexts. In men, stronger right anterior insula activation and increased connectivity between right anterior insula and dorsal anterior cingulate cortex were observed when they receiving unfair offers in the high than low pressure context. Furthermore, more bilateral anterior insula and left dorsolateral prefrontal cortex activations were found when men rejected (relative to accepted) unfair offers in the high than low pressure context. These findings highlighted gender differences in the modulation of behavioral and neural responses to unfairness by social pressure.

A biologically based model for the integration of sensory-motor contingencies in rules and plans: a prefrontal cortex based extension of the Distributed Adaptive Control architecture.

PubMed

Duff, Armin; Fibla, Marti Sanchez; Verschure, Paul F M J

2011-06-30

Intelligence depends on the ability of the brain to acquire and apply rules and representations. At the neuronal level these properties have been shown to critically depend on the prefrontal cortex. Here we present, in the context of the Distributed Adaptive Control architecture (DAC), a biologically based model for flexible control and planning based on key physiological properties of the prefrontal cortex, i.e. reward modulated sustained activity and plasticity of lateral connectivity. We test the model in a series of pertinent tasks, including multiple T-mazes and the Tower of London that are standard experimental tasks to assess flexible control and planning. We show that the model is both able to acquire and express rules that capture the properties of the task and to quickly adapt to changes. Further, we demonstrate that this biomimetic self-contained cognitive architecture generalizes to planning. In addition, we analyze the extended DAC architecture, called DAC 6, as a model that can be applied for the creation of intelligent and psychologically believable synthetic agents. Copyright © 2010 Elsevier Inc. All rights reserved.

Quantitative microlocalization of diffusible ions in normal and galactose cataractous rat lens by secondary ion mass spectrometry.

PubMed

Burns, M S; File, D M

1986-11-01

Secondary ion mass spectrometry (SIMS) is a surface analytical technique with high sensitivity for elemental detection and microlocalization capabilities within the micrometre range. Quantitative analysis of epoxy resins and gelatin have been reported (Burns-Bellhorn & File, 1979). We report here the first application of this technique to quantitative microlocalization in the context of a physiological problem--analyses of sodium, potassium and calcium in normal and galactose-induced cataract in rat lens. It is known that during the development of galactose-induced cataract the whole lens content of potassium is decreased, sodium is increased and, in late stages, calcium concentration increases. Whether these alterations in diffusible ions occur homogeneously or heterogeneously is not known. Standard curves were generated from epoxy resins containing known concentrations of sodium, potassium or calcium organometallic compounds using the Cameca IMS 300 Secondary Ion Mass Spectrometer. Normal and cataractous lenses were prepared by freezing in isopentane in a liquid nitrogen bath followed by freeze-drying at -30 degrees C. After dry embedding in epoxy resin, 10 microns thick sections of lens were pressure mounted on silicon wafers, overcoated with gold, and ion emission measured under the same instrumental conditions used to obtain the standard curves. Quantitative analysis of an area 27 microns in diameter, or a total analysed volume of 1.1 microns3, was performed by using a mechanical aperture in the ion optical system. Ion images provided qualitative microanalysis with a lateral resolution of 1 micron. Control rat lenses gave values for sodium and potassium content with a precision of +/- 17% or less. These values were compared to flame photometry and atomic absorption measurements of normal lenses and were accurate within 25%. Analysis of serum and blood also gave accurate and precise measurements of these elements. Normal rat lenses had a gradient of sodium, and, to a lesser degree, of potassium from the cortex to the nucleus. Development of galactose-induced cataract was heterogeneous by morphological criteria, beginning at the lens equator and spreading from the cortex into the nucleus. However, the loss of potassium and increase in sodium concentration occurred at early stages in both the cortex and nucleus cells, possibly because these cells are interconnected by gap junctions. There is a local alteration in elemental content prior to morphologically demonstrable cataract formation.(ABSTRACT TRUNCATED AT 400 WORDS)

Regional expression and ultrastructural localization of EphA7 in the hippocampus and cerebellum of adult rat.

PubMed

Amegandjin, Clara A; Jammow, Wafaa; Laforest, Sylvie; Riad, Mustapha; Baharnoori, Moogeh; Badeaux, Frédérique; DesGroseillers, Luc; Murai, Keith K; Pasquale, Elena B; Drolet, Guy; Doucet, Guy

2016-08-15

EphA7 is expressed in the adult central nervous system (CNS), where its roles are yet poorly defined. We mapped its distribution using in situ hybridization (ISH) and immunohistochemistry (IHC) combined with light (LM) and electron microscopy (EM) in adult rat and mouse brain. The strongest ISH signal was in the hippocampal pyramidal and granule cell layers. Moderate levels were detected in habenula, striatum, amygdala, the cingulate, piriform and entorhinal cortex, and in cerebellum, notably the Purkinje cell layer. The IHC signal distribution was consistent with ISH results, with transport of the protein to processes, as exemplified in the hippocampal neuropil layers and weakly stained pyramidal cell layers. In contrast, in the cerebellum, the Purkinje cell bodies were the most strongly immunolabeled elements. EM localized the cell surface-expression of EphA7 essentially in postsynaptic densities (PSDs) of dendritic spines and shafts, and on some astrocytic leaflets, in both hippocampus and cerebellum. Perikaryal and dendritic labeling was mostly intracellular, associated with the synthetic and trafficking machineries. Immunopositive vesicles were also observed in axons and axon terminals. Quantitative analysis in EM showed significant differences in the frequency of labeled elements between regions. Notably, labeled dendrites were ∼3-5 times less frequent in cerebellum than in hippocampus, but they were individually endowed with ∼10-40 times higher frequencies of PSDs, on their shafts and spines. The cell surface localization of EphA7, being preferentially in PSDs, and in perisynaptic astrocytic leaflets, provides morphologic evidence that EphA7 plays key roles in adult CNS synaptic maintenance, plasticity, or function. J. Comp. Neurol. 524:2462-2478, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Acute stress exposure preceding transient global brain ischemia exacerbates the decrease in cortical remodeling potential in the rat retrosplenial cortex.

PubMed

Kutsuna, Nobuo; Yamashita, Akiko; Eriguchi, Takashi; Oshima, Hideki; Suma, Takeshi; Sakatani, Kaoru; Yamamoto, Takamitsu; Yoshino, Atsuo; Katayama, Yoichi

2014-01-01

Doublecortin (DCX)-immunoreactive (-ir) cells are candidates that play key roles in adult cortical remodeling. We have previously reported that DCX-ir cells decrease after stress exposure or global brain ischemia (GBI) in the cingulate cortex (Cg) of rats. Herein, we investigate whether the decrease in DCX-ir cells is exacerbated after GBI due to acute stress exposure preconditioning. Twenty rats were divided into 3 groups: acute stress exposure before GBI (Group P), non-stress exposure before GBI (Group G), and controls (Group C). Acute stress or GBI was induced by a forced swim paradigm or by transient bilateral common carotid artery occlusion, respectively. DCX-ir cells were investigated in the anterior cingulate cortex (ACC) and retrosplenial cortex (RS). The number of DCX-ir cells per unit area (mm(2)) decreased after GBI with or without stress preconditioning in the ACC and in the RS (ANOVA followed by a Tukey-type test, P<0.001). Moreover, compared to Group G, the number in Group P decreased significantly in RS (P<0.05), though not significantly in ACC. Many of the DCX-ir cells were co-localized with the GABAergic neuronal marker parvalbumin. The present study indicates that cortical remodeling potential of GABAergic neurons of Cg decreases after GBI, and moreover, the ratio of the decrease is exacerbated by acute stress preconditioning in the RS. Copyright © 2013 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Perfusion functional MRI reveals cerebral blood flow pattern under psychological stress

NASA Astrophysics Data System (ADS)

Wang, Jiongjiong; Rao, Hengyi; Wetmore, Gabriel S.; Furlan, Patricia M.; Korczykowski, Marc; Dinges, David F.; Detre, John A.

2005-12-01

Despite the prevalence of stress in everyday life and its impact on happiness, health, and cognition, little is known about the neural substrate of the experience of everyday stress in humans. We use a quantitative and noninvasive neuroimaging technique, arterial spin-labeling perfusion MRI, to measure cerebral blood flow (CBF) changes associated with mild to moderate stress induced by a mental arithmetic task with performance monitoring. Elicitation of stress was verified by self-report of stress and emotional state and measures of heart rate and salivary-cortisol level. The change in CBF induced by the stress task was positively correlated with subjective stress rating in the ventral right prefrontal cortex (RPFC) and left insula/putamen area. The ventral RPFC along with right insula/putamen and anterior cingulate showed sustained activation after task completion in subjects reporting a high stress level during arithmetic tasks. Additionally, variations of baseline CBF in the ventral RPFC and right orbitofrontal cortex were found to correlate with changes in salivary-cortisol level and heart rate caused by undergoing stress tasks. We further demonstrated that the observed right prefrontal activation could not be attributed to increased cognitive demand accompanying stress tasks and extended beyond neural pathways associated with negative emotions. Our results provide neuroimaging evidence that psychological stress induces negative emotion and vigilance and that the ventral RPFC plays a key role in the central stress response. anterior cingulate cortex | arterial spin labeling | right prefrontal cortex

Focal expression of mutated tau in entorhinal cortex neurons of rats impairs spatial working memory.

PubMed

Ramirez, Julio J; Poulton, Winona E; Knelson, Erik; Barton, Cole; King, Michael A; Klein, Ronald L

2011-01-01

Entorhinal cortex neuropathology begins very early in Alzheimer's disease (AD), a disorder characterized by severe memory disruption. Indeed, loss of entorhinal volume is predictive of AD and two of the hallmark neuroanatomical markers of AD, amyloid plaques and neurofibrillary tangles (NFTs), are particularly prevalent in the entorhinal area of AD-afflicted brains. Gene transfer techniques were used to create a model neurofibrillary tauopathy by injecting a recombinant adeno-associated viral vector with a mutated human tau gene (P301L) into the entorhinal cortex of adult rats. The objective of the present investigation was to determine whether adult onset, spatially restricted tauopathy could be sufficient to reproduce progressive deficits in mnemonic function. Spatial memory on a Y-maze was tested for approximately 3 months post-surgery. Upon completion of behavioral testing the brains were assessed for expression of human tau and evidence of tauopathy. Rats injected with the tau vector became persistently impaired on the task after about 6 weeks of postoperative testing, whereas the control rats injected with a green fluorescent protein vector performed at criterion levels during that period. Histological analysis confirmed the presence of hyperphosphorylated tau and NFTs in the entorhinal cortex and neighboring retrohippocampal areas as well as limited synaptic degeneration of the perforant path. Thus, highly restricted vector-induced tauopathy in retrohippocampal areas is sufficient for producing progressive impairment in mnemonic ability in rats, successfully mimicking a key aspect of tauopathies such as AD. Copyright © 2010 Elsevier B.V. All rights reserved.

Post-transcriptional regulation in corticogenesis: how RNA-binding proteins help build the brain

PubMed Central

Pilaz, Louis-Jan; Silver, Debra L.

2015-01-01

The cerebral cortex, the brain structure responsible for our higher cognitive functions, is built during embryonic development in a process called corticogenesis. During corticogenesis, neural stem cells generate distinct populations of progenitors and excitatory neurons. These new neurons migrate radially in the cortex, eventually forming neuronal layers and establishing synaptic connections with other neurons both within and outside the cortex. Perturbations to corticogenesis can result in severe neurodevelopmental disorders, thus emphasizing the need to better understand molecular regulation of brain development. Recent studies in both model organisms and humans have collectively highlighted roles for post-transcriptional regulation in virtually all steps of corticogenesis. Genomic approaches have revealed global RNA changes associated with spatial and temporal regulation of cortical development. Additionally, genetic studies have uncovered RNA-binding proteins (RBPs) critical for cell proliferation, differentiation, and migration within the developing neocortex. Many of these same RBPs play causal roles in neurodevelopmental pathologies. In the developing neocortex, RBPs influence diverse steps of mRNA metabolism, including splicing, stability, translation, and localization. With the advent of new technologies, researchers have begun to uncover key transcripts regulated by these RBPs. Given the complexity of the developing mammalian cortex, a major challenge for the future will be to understand how dynamic RNA regulation occurs within heterogeneous cell populations, across space and time. In sum, post-transcriptional regulation has emerged as a critical mechanism for driving corticogenesis and exciting direction of future research. PMID:26088328

Age-related changes in mitochondrial antioxidant enzyme Trx2 and TXNIP-Trx2-ASK1 signal pathways in the auditory cortex of a mimetic aging rat model: changes to Trx2 in the auditory cortex.

PubMed

Sun, Hai-Ying; Hu, Yu-Juan; Zhao, Xue-Yan; Zhong, Yi; Zeng, Ling-Ling; Chen, Xu-Bo; Yuan, Jie; Wu, Jing; Sun, Yu; Kong, Wen; Kong, Wei-Jia

2015-07-01

Age-associated degeneration in the central auditory system, which is defined as central presbycusis, can impair sound localization and speech perception. Research has shown that oxidative stress plays a central role in the pathological process of central presbycusis. Thioredoxin 2 (Trx2), one member of thioredoxin family, plays a key role in regulating the homeostasis of cellular reactive oxygen species and anti-apoptosis. The purpose of this study was to explore the association between Trx2 and the phenotype of central presbycusis using a mimetic aging animal model induced by long-term exposure to d-galactose (d-Gal). We also explored changes in thioredoxin-interacting protein (TXNIP), apoptosis signal regulating kinase 1 (ASK1) and phosphorylated ASK1 (p-ASK1) expression, as well as the Trx2-TXNIP/Trx2-ASK1 binding complex in the auditory cortex of mimetic aging rats. Our results demonstrate that, compared with control groups, the levels of Trx2 and Trx2-ASK1 binding complex were significantly reduced, whereas TXNIP, ASK1 p-ASK1 expression, and Trx2-TXNIP binding complex were significantly increased in the auditory cortex of the mimetic aging groups. Our results indicated that changes in Trx2 and the TXNIP-Trx2-ASK1 signal pathway may participate in the pathogenesis of central presbycusis. © 2015 FEBS.

Egocentric and allocentric representations in auditory cortex

PubMed Central

Brimijoin, W. Owen; Bizley, Jennifer K.

2017-01-01

A key function of the brain is to provide a stable representation of an object’s location in the world. In hearing, sound azimuth and elevation are encoded by neurons throughout the auditory system, and auditory cortex is necessary for sound localization. However, the coordinate frame in which neurons represent sound space remains undefined: classical spatial receptive fields in head-fixed subjects can be explained either by sensitivity to sound source location relative to the head (egocentric) or relative to the world (allocentric encoding). This coordinate frame ambiguity can be resolved by studying freely moving subjects; here we recorded spatial receptive fields in the auditory cortex of freely moving ferrets. We found that most spatially tuned neurons represented sound source location relative to the head across changes in head position and direction. In addition, we also recorded a small number of neurons in which sound location was represented in a world-centered coordinate frame. We used measurements of spatial tuning across changes in head position and direction to explore the influence of sound source distance and speed of head movement on auditory cortical activity and spatial tuning. Modulation depth of spatial tuning increased with distance for egocentric but not allocentric units, whereas, for both populations, modulation was stronger at faster movement speeds. Our findings suggest that early auditory cortex primarily represents sound source location relative to ourselves but that a minority of cells can represent sound location in the world independent of our own position. PMID:28617796

Visually evoked responses in extrastriate area MT after lesions of striate cortex in early life.

PubMed

Yu, Hsin-Hao; Chaplin, Tristan A; Egan, Gregory W; Reser, David H; Worthy, Katrina H; Rosa, Marcello G P

2013-07-24

Lesions of striate cortex [primary visual cortex (V1)] in adult primates result in blindness. In contrast, V1 lesions in neonates typically allow much greater preservation of vision, including, in many human patients, conscious perception. It is presently unknown how this marked functional difference is related to physiological changes in cortical areas that are spared by the lesions. Here we report a study of the middle temporal area (MT) of adult marmoset monkeys that received unilateral V1 lesions within 6 weeks of birth. In contrast with observations after similar lesions in adult monkeys, we found that virtually all neurons in the region of MT that was deprived of V1 inputs showed robust responses to visual stimulation. These responses were very similar to those recorded in neurons with receptive fields outside the lesion projection zones in terms of firing rate, signal-to-noise ratio, and latency. In addition, the normal retinotopic organization of MT was maintained. Nonetheless, we found evidence of a very specific functional deficit: direction selectivity, a key physiological characteristic of MT that is known to be preserved in many cells after adult V1 lesions, was absent. These results demonstrate that lesion-induced reorganization of afferent pathways is sufficient to develop robust visual function in primate extrastriate cortex, highlighting a likely mechanism for the sparing of vision after neonatal V1 lesions. However, they also suggest that interactions with V1 in early postnatal life are critical for establishing stimulus selectivity in MT.

Multi-frequency localization of aberrant brain activity in autism spectrum disorder.

PubMed

Xiang, Jing; Korostenskaja, Milena; Molloy, Cynthia; deGrauw, Xinyao; Leiken, Kimberly; Gilman, Carley; Meinzen-Derr, Jareen; Fujiwara, Hisako; Rose, Douglas F; Mitchell, Terry; Murray, Donna S

2016-01-01

The abnormality of intrinsic brain activity in autism spectrum disorders (ASDs) is still inconclusive. Contradictory results have been found pointing towards hyper-activity or hypo-activity in various brain regions. The present research aims to investigate the spatial and spectral signatures of aberrant brain activity in an unprecedented frequency range of 1-2884 Hz at source levels in ASD using newly developed methods. Seven ASD subjects and age- and gender-matched controls were studied using a high-sampling rate magnetoencephalography (MEG) system. Brain activity in delta (1-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), beta (12-30 Hz), low gamma (30-55 Hz), high gamma (65-90 Hz), ripples (90-200 Hz), high-frequency oscillations (HFOs, 200-1000 Hz), and very high-frequency oscillations (VHFOs, 1000-2884 Hz) was volumetrically localized and measured using wavelet and beamforming. In comparison to controls, ASD subjects had significantly higher odds of alpha activity (8-12 Hz) in the sensorimotor cortex (mu rhythm), and generally high-frequency activity (90-2884 Hz) in the frontal cortex. The source power of HFOs (200-1000 Hz) in the frontal cortex in ASD was significantly elevated as compared with controls. The results suggest that ASD has significantly altered intrinsic brain activity in both low- and high-frequency ranges. Increased intrinsic high-frequency activity in the frontal cortex may play a key role in ASD. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Linear summation of outputs in a balanced network model of motor cortex

PubMed Central

Capaday, Charles; van Vreeswijk, Carl

2015-01-01

Given the non-linearities of the neural circuitry's elements, we would expect cortical circuits to respond non-linearly when activated. Surprisingly, when two points in the motor cortex are activated simultaneously, the EMG responses are the linear sum of the responses evoked by each of the points activated separately. Additionally, the corticospinal transfer function is close to linear, implying that the synaptic interactions in motor cortex must be effectively linear. To account for this, here we develop a model of motor cortex composed of multiple interconnected points, each comprised of reciprocally connected excitatory and inhibitory neurons. We show how non-linearities in neuronal transfer functions are eschewed by strong synaptic interactions within each point. Consequently, the simultaneous activation of multiple points results in a linear summation of their respective outputs. We also consider the effects of reduction of inhibition at a cortical point when one or more surrounding points are active. The network response in this condition is linear over an approximately two- to three-fold decrease of inhibitory feedback strength. This result supports the idea that focal disinhibition allows linear coupling of motor cortical points to generate movement related muscle activation patterns; albeit with a limitation on gain control. The model also explains why neural activity does not spread as far out as the axonal connectivity allows, whilst also explaining why distant cortical points can be, nonetheless, functionally coupled by focal disinhibition. Finally, we discuss the advantages that linear interactions at the cortical level afford to motor command synthesis. PMID:26097452

Neuronal network-based mathematical modeling of perceived verticality in acute unilateral vestibular lesions: from nerve to thalamus and cortex.

PubMed

Glasauer, S; Dieterich, M; Brandt, T

2018-05-29

Acute unilateral lesions of vestibular graviceptive pathways from the otolith organs and semicircular canals via vestibular nuclei and the thalamus to the parieto-insular vestibular cortex regularly cause deviations of perceived verticality in the frontal roll plane. These tilts are ipsilateral in peripheral and in ponto-medullary lesions and contralateral in ponto-mesencephalic lesions. Unilateral lesions of the vestibular thalamus or cortex cause smaller tilts of the perceived vertical, which may be either ipsilateral or contralateral. Using a neural network model, we previously explained why unilateral vestibular midbrain lesions rarely manifest with rotational vertigo. We here extend this approach, focussing on the direction-specific deviations of perceived verticality in the roll plane caused by acute unilateral vestibular lesions from the labyrinth to the cortex. Traditionally, the effect of unilateral peripheral lesions on perceived verticality has been attributed to a lesion-based bias of the otolith system. We here suggest, on the basis of a comparison of model simulations with patient data, that perceived visual tilt after peripheral lesions is caused by the effect of a torsional semicircular canal bias on the central gravity estimator. We further argue that the change of gravity coding from a peripheral/brainstem vectorial representation in otolith coordinates to a distributed population coding at thalamic and cortical levels can explain why unilateral thalamic and cortical lesions have a variable effect on perceived verticality. Finally, we propose how the population-coding network for gravity direction might implement the elements required for the well-known perceptual underestimation of the subjective visual vertical in tilted body positions.

The selection criteria elements of X-ray optics system

NASA Astrophysics Data System (ADS)

Plotnikova, I. V.; Chicherina, N. V.; Bays, S. S.; Bildanov, R. G.; Stary, O.

2018-01-01

At the design of new modifications of x-ray tomography there are difficulties in the right choice of elements of X-ray optical system. Now this problem is solved by practical consideration, selection of values of the corresponding parameters - tension on an x-ray tube taking into account the thickness and type of the studied material. For reduction of time and labor input of design it is necessary to create the criteria of the choice, to determine key parameters and characteristics of elements. In the article two main elements of X-ray optical system - an x-ray tube and the detector of x-ray radiation - are considered. Criteria of the choice of elements, their key characteristics, the main dependences of parameters, quality indicators and also recommendations according to the choice of elements of x-ray systems are received.

Spontaneous Up states in vitro: a single-metric index of the functional maturation and regional differentiation of the cerebral cortex.

PubMed

Rigas, Pavlos; Adamos, Dimitrios A; Sigalas, Charalambos; Tsakanikas, Panagiotis; Laskaris, Nikolaos A; Skaliora, Irini

2015-01-01

Understanding the development and differentiation of the neocortex remains a central focus of neuroscience. While previous studies have examined isolated aspects of cellular and synaptic organization, an integrated functional index of the cortical microcircuit is still lacking. Here we aimed to provide such an index, in the form of spontaneously recurring periods of persistent network activity -or Up states- recorded in mouse cortical slices. These coordinated network dynamics emerge through the orchestrated regulation of multiple cellular and synaptic elements and represent the default activity of the cortical microcircuit. To explore whether spontaneous Up states can capture developmental changes in intracortical networks we obtained local field potential recordings throughout the mouse lifespan. Two independent and complementary methodologies revealed that Up state activity is systematically modified by age, with the largest changes occurring during early development and adolescence. To explore possible regional heterogeneities we also compared the development of Up states in two distinct cortical areas and show that primary somatosensory cortex develops at a faster pace than primary motor cortex. Our findings suggest that in vitro Up states can serve as a functional index of cortical development and differentiation and can provide a baseline for comparing experimental and/or genetic mouse models.

Sensory Response of Transplanted Astrocytes in Adult Mammalian Cortex In Vivo

PubMed Central

Zhang, Kuan; Chen, Chunhai; Yang, Zhiqi; He, Wenjing; Liao, Xiang; Ma, Qinlong; Deng, Ping; Lu, Jian; Li, Jingcheng; Wang, Meng; Li, Mingli; Zheng, Lianghong; Zhou, Zhuan; Sun, Wei; Wang, Liting; Jia, Hongbo; Yu, Zhengping; Zhou, Zhou; Chen, Xiaowei

2016-01-01

Glial precursor transplantation provides a potential therapy for brain disorders. Before its clinical application, experimental evidence needs to indicate that engrafted glial cells are functionally incorporated into the existing circuits and become essential partners of neurons for executing fundamental brain functions. While previous experiments supporting for their functional integration have been obtained under in vitro conditions using slice preparations, in vivo evidence for such integration is still lacking. Here, we utilized in vivo two-photon Ca2+ imaging along with immunohistochemistry, fluorescent indicator labeling-based axon tracing and correlated light/electron microscopy to analyze the profiles and the functional status of glial precursor cell-derived astrocytes in adult mouse neocortex. We show that after being transplanted into somatosensory cortex, precursor-derived astrocytes are able to survive for more than a year and respond with Ca2+ signals to sensory stimulation. These sensory-evoked responses are mediated by functionally-expressed nicotinic receptors and newly-established synaptic contacts with the host cholinergic afferents. Our results provide in vivo evidence for a functional integration of transplanted astrocytes into adult mammalian neocortex, representing a proof-of-principle for sensory cortex remodeling through addition of essential neural elements. Moreover, we provide strong support for the use of glial precursor transplantation to understand glia-related neural development in vivo. PMID:27405333

Spontaneous Up states in vitro: a single-metric index of the functional maturation and regional differentiation of the cerebral cortex

PubMed Central

Rigas, Pavlos; Adamos, Dimitrios A.; Sigalas, Charalambos; Tsakanikas, Panagiotis; Laskaris, Nikolaos A.; Skaliora, Irini

2015-01-01

Understanding the development and differentiation of the neocortex remains a central focus of neuroscience. While previous studies have examined isolated aspects of cellular and synaptic organization, an integrated functional index of the cortical microcircuit is still lacking. Here we aimed to provide such an index, in the form of spontaneously recurring periods of persistent network activity -or Up states- recorded in mouse cortical slices. These coordinated network dynamics emerge through the orchestrated regulation of multiple cellular and synaptic elements and represent the default activity of the cortical microcircuit. To explore whether spontaneous Up states can capture developmental changes in intracortical networks we obtained local field potential recordings throughout the mouse lifespan. Two independent and complementary methodologies revealed that Up state activity is systematically modified by age, with the largest changes occurring during early development and adolescence. To explore possible regional heterogeneities we also compared the development of Up states in two distinct cortical areas and show that primary somatosensory cortex develops at a faster pace than primary motor cortex. Our findings suggest that in vitro Up states can serve as a functional index of cortical development and differentiation and can provide a baseline for comparing experimental and/or genetic mouse models. PMID:26528142

Key Elements in Successful Training A Comparative Study of Two Workplaces. Project Report, 2000-2001.

ERIC Educational Resources Information Center

Adult Literacy and Numeracy Australian Research Consortium, Alice Springs. Northern Territory Centre.

This publication presents case studies of two sites--one with and one without a history of involvement in Workplace English Language and Literacy (WELL)-funded training programs. Case study 1, "Partnership, Flexibility, and Experience: Key Elements in Successful Training" (Jenny McGuirk), investigates a food processing company in New South Wales…

Organic memristive device as key element for neuromorphic networks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Erokhin, Victor

Organic memristive device has three important properties allowing to consider it as a key element of neuromorphic systems. First, its electrical properties are somehow similar to those of synapses. Second, it can be easily transferred into an oscillator. Third, organic nature of the devices allow to assemble them into stochastic 3D networks capable to learning and adaptations.

Vital Collaboratives, Alliances, and Partnerships: A Search for Key Elements of an Effective Public-Private Partnership

ERIC Educational Resources Information Center

Young, Charles Keith

2010-01-01

Owing to the significant structural changes that have occurred in the global marketplace over the past 2 decades, a corresponding increase of public-private partnerships have been established among the business sector, local governments, and public community colleges. This qualitative project sought to identify and substantiate key elements that…

How Strategic Planning Keeps You Sane when Delivering Distance Programs

ERIC Educational Resources Information Center

MacNeil, Dixie; Luzius, Kim; Dunkin, Sonya

2010-01-01

This paper details the advantages of creating a strategic plan in the development and delivery of distance programs at the authors' own institution. The steps involved in the planning process and the three key elements of a successful strategic plan are addressed. The key elements include a program plan explaining the roles/responsibilities of…

Flexible Use of Predictive Cues beyond the Orbitofrontal Cortex: Role of the Submedius Thalamic Nucleus.

PubMed

Alcaraz, Fabien; Marchand, Alain R; Vidal, Elisa; Guillou, Alexandre; Faugère, Angélique; Coutureau, Etienne; Wolff, Mathieu

2015-09-23

The orbitofrontal cortex (OFC) is known to play a crucial role in learning the consequences of specific events. However, the contribution of OFC thalamic inputs to these processes is largely unknown. Using a tract-tracing approach, we first demonstrated that the submedius nucleus (Sub) shares extensive reciprocal connections with the OFC. We then compared the effects of excitotoxic lesions of the Sub or the OFC on the ability of rats to use outcome identity to direct responding. We found that neither OFC nor Sub lesions interfered with the basic differential outcomes effect. However, more specific tests revealed that OFC rats, but not Sub rats, were disproportionally relying on the outcome, rather than on the discriminative stimulus, to guide behavior, which is consistent with the view that the OFC integrates information about predictive cues. In subsequent experiments using a Pavlovian contingency degradation procedure, we found that both OFC and Sub lesions produced a severe deficit in the ability to update Pavlovian associations. Altogether, the submedius therefore appears as a functionally relevant thalamic component in a circuit dedicated to the integration of predictive cues to guide behavior, previously conceived as essentially dependent on orbitofrontal functions. Significance statement: In the present study, we identify a largely unknown thalamic region, the submedius nucleus, as a new functionally relevant component in a circuit supporting the flexible use of predictive cues. Such abilities were previously conceived as largely dependent on the orbitofrontal cortex. Interestingly, this echoes recent findings in the field showing, in research involving an instrumental setup, an additional involvement of another thalamic nuclei, the parafascicular nucleus, when correct responding requires an element of flexibility (Bradfield et al., 2013a). Therefore, the present contribution supports the emerging view that limbic thalamic nuclei may contribute critically to adaptive responding when an element of flexibility is required after the establishment of initial learning. Copyright © 2015 the authors 0270-6474/15/3513183-11$15.00/0.

The Coordinated Noninvasive Studies (CNS) Project. Phase 1. Appendices

DTIC Science & Technology

1991-12-01

34Bandwidth of three-element patterns and its effect on relative ear advantages," to Acoustical Society of America, Cincinnati. Abstract: J Acoust Soc Amer...Acoustical Society of America, Cincinnati. Abstract: J Acoust Soc Amer 73: S60. "Cerebral metabolic effects of auditory stimulation," to Brain Breakfast...Laboratory, Los Alamos NM. "PET and the cortex: the effects of auditory stimulation on cerebral blood flow," to Department of Speech and Hearing Sciences

Perceptual elements in brain mechanisms of acoustic communication in humans and nonhuman primates.

PubMed

Reser, David H; Rosa, Marcello

2014-12-01

Ackermann et al. outline a model for elaboration of subcortical motor outputs as a driving force for the development of the apparently unique behaviour of language in humans. They emphasize circuits in the striatum and midbrain, and acknowledge, but do not explore, the importance of the auditory perceptual pathway for evolution of verbal communication. We suggest that understanding the evolution of language will also require understanding of vocalization perception, especially in the auditory cortex.

Texture Segregation Causes Early Figure Enhancement and Later Ground Suppression in Areas V1 and V4 of Visual Cortex.

PubMed

Poort, Jasper; Self, Matthew W; van Vugt, Bram; Malkki, Hemi; Roelfsema, Pieter R

2016-10-01

Segregation of images into figures and background is fundamental for visual perception. Cortical neurons respond more strongly to figural image elements than to background elements, but the mechanisms of figure-ground modulation (FGM) are only partially understood. It is unclear whether FGM in early and mid-level visual cortex is caused by an enhanced response to the figure, a suppressed response to the background, or both.We studied neuronal activity in areas V1 and V4 in monkeys performing a texture segregation task. We compared texture-defined figures with homogeneous textures and found an early enhancement of the figure representation, and a later suppression of the background. Across neurons, the strength of figure enhancement was independent of the strength of background suppression.We also examined activity in the different V1 layers. Both figure enhancement and ground suppression were strongest in superficial and deep layers and weaker in layer 4. The current-source density profiles suggested that figure enhancement was caused by stronger synaptic inputs in feedback-recipient layers 1, 2, and 5 and ground suppression by weaker inputs in these layers, suggesting an important role for feedback connections from higher level areas. These results provide new insights into the mechanisms for figure-ground organization. © The Author 2016. Published by Oxford University Press.

Orientation dependent modulation of apparent speed: a model based on the dynamics of feed-forward and horizontal connectivity in V1 cortex.

PubMed

Seriès, Peggy; Georges, Sébastien; Lorenceau, Jean; Frégnac, Yves

2002-11-01

Psychophysical and physiological studies suggest that long-range horizontal connections in primary visual cortex participate in spatial integration and contour processing. Until recently, little attention has been paid to their intrinsic temporal properties. Recent physiological studies indicate, however, that the propagation of activity through long-range horizontal connections is slow, with time scales comparable to the perceptual scales involved in motion processing. Using a simple model of V1 connectivity, we explore some of the implications of this slow dynamics. The model predicts that V1 responses to a stimulus in the receptive field can be modulated by a previous stimulation, a few milliseconds to a few tens of milliseconds before, in the surround. We analyze this phenomenon and its possible consequences on speed perception, as a function of the spatio-temporal configuration of the visual inputs (relative orientation, spatial separation, temporal interval between the elements, sequence speed). We show that the dynamical interactions between feed-forward and horizontal signals in V1 can explain why the perceived speed of fast apparent motion sequences strongly depends on the orientation of their elements relative to the motion axis and can account for the range of speed for which this perceptual effect occurs (Georges, Seriès, Frégnac and Lorenceau, this issue).

Expression of small cytoplasmic transcripts of the rat identifier element in vivo and in cultured cells.

PubMed Central

McKinnon, R D; Danielson, P; Brow, M A; Bloom, F E; Sutcliffe, J G

1987-01-01

We examined the level of expression of small RNA transcripts hybridizing to a rodent repetitive DNA element, the identifier (ID) sequence, in a variety of cell types in vivo and in cultured mammalian cells. A 160-nucleotide (160n) cytoplasmic poly(A)+ RNA (BC1) appeared in late embryonic and early postnatal rat brain development, was enriched in the cerebral cortex, and appeared to be restricted to neural tissue and the anterior pituitary gland. A 110n RNA (BC2) was specifically enriched in brain, especially the postnatal cortex, but was detectable at low levels in peripheral tissues. A third, related 75n poly(A)- RNA (T3) was found in rat brain and at lower levels in peripheral tissues but was very abundant in the testes. The BC RNAs were found in a variety of rat cell lines, and their level of expression was dependent upon cell culture conditions. A rat ID probe detected BC-like RNAs in mouse brain but not liver and detected a 200n RNA in monkey brain but not liver at lower hybridization stringencies. These RNAs were expressed by mouse and primate cell lines. Thus, tissue-specific expression of small ID-sequence-related transcripts is conserved among mammals, but the tight regulation found in vivo is lost by cells in culture. Images PMID:2439903

Determinants of fluidlike behavior and effective viscosity in cross-linked actin networks.

PubMed

Kim, Taeyoon; Gardel, Margaret L; Munro, Ed

2014-02-04

The actin cortex has a well-documented ability to rapidly remodel and flow while maintaining long-range connectivity, but how this is achieved remains poorly understood. Here, we use computer simulations to explore how stress relaxation in cross-linked actin networks subjected to extensional stress depends on the interplay between network architecture and turnover. We characterize a regime in which a network response is nonaffine and stress relaxation is governed by the continuous dissipation of elastic energy via cyclic formation, elongation, and turnover of tension-bearing elements. Within this regime, for a wide range of network parameters, we observe a constant deformation (creep) rate that is linearly proportional to the rate of filament turnover, leading to a constant effective viscosity that is inversely proportional to turnover rate. Significantly, we observe a biphasic dependence of the creep rate on applied stress: below a critical stress threshold, the creep rate increases linearly with applied stress; above that threshold, the creep rate becomes independent of applied stress. We show that this biphasic stress dependence can be understood in terms of the nonlinear force-extension behavior of individual force-transmitting network elements. These results have important implications for understanding the origins and control of viscous flows both in the cortex of living cells and in other polymer networks. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Key ingredients of anti-stigma programs for health care providers: a data synthesis of evaluative studies.

PubMed

Knaak, Stephanie; Modgill, Geeta; Patten, Scott B

2014-10-01

As part of its ongoing effort to combat stigma against mental illness among health care providers, the Mental Health Commission of Canada partnered with organizations conducting anti-stigma interventions. Our objective was to evaluate program effectiveness and to better understand what makes some programs more effective than others. Our paper reports the elements of these programs found to be most strongly associated with favourable outcomes. Our study employed a multi-phased, mixed-methods design. First, a grounded theory qualitative study was undertaken to identify key program elements. Next, each program (n = 22) was coded according to the presence or absence of the identified key program ingredients. Then, random-effects, meta-regression modelling was used to examine the association between program outcomes and the key ingredients. The qualitative analysis led to a 6-ingredient model of key program elements. Results of the quantitative analysis showed that programs that included all 6 of these ingredients performed significantly better than those that did not. Individual analyses of each of the 6 ingredients showed that including multiple forms of social contact and emphasizing recovery were characteristics of the most effective programs. The results provide a validation of a 6-ingredient model of key program elements for anti-stigma programming for health care providers. Emphasizing recovery and including multiple types of social contact are of particular importance for maximizing the effectiveness of anti-stigma programs for health care providers.

A Transposon in Comt Generates mRNA Variants and Causes Widespread Expression and Behavioral Differences among Mice

PubMed Central

Wang, Xusheng; Miles, Michael F.; Lu, Lu; Williams, Robert W.

2010-01-01

Background Catechol-O-methyltransferase (COMT) is a key enzyme responsible for the degradation of dopamine and norepinephrine. COMT activity influences cognitive and emotional states in humans and aggression and drug responses in mice. This study identifies the key sequence variant that leads to differences in Comt mRNA and protein levels among mice, and that modulates synaptic function and pharmacological and behavioral traits. Methodology/Principal Findings We examined Comt expression in multiple tissues in over 100 diverse strains and several genetic crosses. Differences in expression map back to Comt and are generated by a 230 nt insertion of a B2 short interspersed element (B2 SINE) in the proximal 3′ UTR of Comt in C57BL/6J. This transposon introduces a premature polyadenylation signal and creates a short 3′ UTR isoform. The B2 SINE is shared by a subset of strains, including C57BL/6J, A/J, BALB/cByJ, and AKR/J, but is absent in others, including DBA/2J, FVB/NJ, SJL/J, and wild subspecies. The short isoform is associated with increased protein expression in prefrontal cortex and hippocampus relative to the longer ancestral isoform. The Comt variant causes downstream differences in the expression of genes involved in synaptic function, and also modulates phenotypes such as dopamine D1 and D2 receptor binding and pharmacological responses to haloperidol. Conclusions/Significance We have precisely defined the B2 SINE as the source of variation in Comt and demonstrated that a transposon in a 3′ UTR can alter mRNA isoform use and modulate behavior. The recent fixation of the variant in a subset of strains may have contributed to the rapid divergence of inbred strains. PMID:20808911

The neurobiology of emotion–cognition interactions: fundamental questions and strategies for future research

PubMed Central

Okon-Singer, Hadas; Hendler, Talma; Pessoa, Luiz; Shackman, Alexander J.

2015-01-01

Recent years have witnessed the emergence of powerful new tools for assaying the brain and a remarkable acceleration of research focused on the interplay of emotion and cognition. This work has begun to yield new insights into fundamental questions about the nature of the mind and important clues about the origins of mental illness. In particular, this research demonstrates that stress, anxiety, and other kinds of emotion can profoundly influence key elements of cognition, including selective attention, working memory, and cognitive control. Often, this influence persists beyond the duration of transient emotional challenges, partially reflecting the slower molecular dynamics of catecholamine and hormonal neurochemistry. In turn, circuits involved in attention, executive control, and working memory contribute to the regulation of emotion. The distinction between the ‘emotional’ and the ‘cognitive’ brain is fuzzy and context-dependent. Indeed, there is compelling evidence that brain territories and psychological processes commonly associated with cognition, such as the dorsolateral prefrontal cortex and working memory, play a central role in emotion. Furthermore, putatively emotional and cognitive regions influence one another via a complex web of connections in ways that jointly contribute to adaptive and maladaptive behavior. This work demonstrates that emotion and cognition are deeply interwoven in the fabric of the brain, suggesting that widely held beliefs about the key constituents of ‘the emotional brain’ and ‘the cognitive brain’ are fundamentally flawed. We conclude by outlining several strategies for enhancing future research. Developing a deeper understanding of the emotional-cognitive brain is important, not just for understanding the mind but also for elucidating the root causes of its disorders. PMID:25774129

Dorsolateral Prefrontal Contributions to Human Intelligence

PubMed Central

Barbey, Aron K.; Colom, Roberto; Grafman, Jordan

2012-01-01

Although cognitive neuroscience has made remarkable progress in understanding the involvement of the prefrontal cortex in executive control functions for human intelligence, the necessity of the dorsolateral prefrontal cortex (dlPFC) for key competencies of general intelligence and executive function remains to be well established. Here we studied human brain lesion patients with dlPFC lesions to investigate whether this region is computationally necessary for performance on neuropsychological tests of general intelligence and executive function, administering the Wechsler Adult Intelligence Scale (WAIS) and subtests of the Delis Kaplan Executive Function System (D-KEFS) to three groups: dlPFC lesions (n = 19), non-dlPFC lesions (n = 152), and no brain lesions (n = 55). The key results indicate that: (1) patients with focal dlPFC damage exhibit lower scores, at the latent variable level, than controls in general intelligence (g) and executive function; (2) dlPFC patients demonstrate lower scores than controls in several executive measures; and (3) these latter differences are no longer significant when the pervasive influence of the general factor of intelligence (g) is statistically removed. The observed findings support a central role for the dlPFC in general intelligence and make specific recommendations for the interpretation and application of the WAIS and D-KEFS to the study of high-level cognition in health and disease. PMID:22634247

Changes in Serial Optical Topography and TMS during Task Performance after Constraint-Induced Movement Therapy in Stroke: A Case Study

PubMed Central

Park, Si-Woon; Butler, Andrew J.; Cavalheiro, Vanessa; Alberts, Jay L.; Wolf, Steven L.

2013-01-01

The authors examined serial changes in optical topography in a stroke patient performing a functional task, as well as clinical and physiologic measures while undergoing constraint-induced therapy (CIT). A 73-year-old right hemiparetic patient, who had a subcortical stroke 4 months previously, received 2 weeks of CIT. During the therapy, daily optical topography imaging using near-infrared light was measured serially while the participant performed a functional key-turning task. Clinical outcome measures included the Wolf Motor Function Test (WMFT), Motor Activity Log (MAL), and functional key grip test. Transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) were also used to map cortical areas and hemodynamic brain responses, respectively. Optical topography measurement showed an overall decrease in oxy-hemoglobin concentration in both hemispheres as therapy progressed and the laterality index increased toward the contralateral hemisphere. An increased TMS motor map area was observed in the contralateral cortex following treatment. Posttreatment fMRI showed bilateral primary motor cortex activation, although slightly greater in the contralateral hemisphere, during affected hand movement. Clinical scores revealed marked improvement in functional activities. In one patient who suffered a stroke, 2 weeks of CIT led to improved function and cortical reorganization in the hemisphere contralateral to the affected hand. PMID:15228805

Neural foundations to moral reasoning and antisocial behavior

PubMed Central

Yang, Yaling

2006-01-01

A common feature of the antisocial, rule-breaking behavior that is central to criminal, violent and psychopathic individuals is the failure to follow moral guidelines. This review summarizes key findings from brain imaging research on both antisocial behavior and moral reasoning, and integrates these findings into a neural moral model of antisocial behavior. Key areas found to be functionally or structurally impaired in antisocial populations include dorsal and ventral regions of the prefrontal cortex (PFC), amygdala, hippocampus, angular gyrus, anterior cingulate and temporal cortex. Regions most commonly activated in moral judgment tasks consist of the polar/medial and ventral PFC, amygdala, angular gyrus and posterior cingulate. It is hypothesized that the rule-breaking behavior common to antisocial, violent and psychopathic individuals is in part due to impairments in some of the structures (dorsal and ventral PFC, amygdala and angular gyrus) subserving moral cognition and emotion. Impairments to the emotional component that comprises the feeling of what is moral is viewed as the primary deficit in antisocials, although some disruption to the cognitive and cognitive-emotional components of morality (particularly self-referential thinking and emotion regulation) cannot be ruled out. While this neurobiological predisposition is likely only one of several biosocial processes involved in the etiology of antisocial behavior, it raises significant moral issues for the legal system and neuroethics. PMID:18985107

Self-affirmation activates brain systems associated with self-related processing and reward and is reinforced by future orientation.

PubMed

Cascio, Christopher N; O'Donnell, Matthew Brook; Tinney, Francis J; Lieberman, Matthew D; Taylor, Shelley E; Strecher, Victor J; Falk, Emily B

2016-04-01

Self-affirmation theory posits that people are motivated to maintain a positive self-view and that threats to perceived self-competence are met with resistance. When threatened, self-affirmations can restore self-competence by allowing individuals to reflect on sources of self-worth, such as core values. Many questions exist, however, about the underlying mechanisms associated with self-affirmation. We examined the neural mechanisms of self-affirmation with a task developed for use in a functional magnetic resonance imaging environment. Results of a region of interest analysis demonstrated that participants who were affirmed (compared with unaffirmed participants) showed increased activity in key regions of the brain's self-processing (medial prefrontal cortex + posterior cingulate cortex) and valuation (ventral striatum + ventral medial prefrontal cortex) systems when reflecting on future-oriented core values (compared with everyday activities). Furthermore, this neural activity went on to predict changes in sedentary behavior consistent with successful affirmation in response to a separate physical activity intervention. These results highlight neural processes associated with successful self-affirmation, and further suggest that key pathways may be amplified in conjunction with prospection. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Cold Blooded: Evaluating Brain Temperature by MRI During Surface Cooling of Human Subjects.

PubMed

Curran, Eric J; Wolfson, Daniel L; Watts, Richard; Freeman, Kalev

2017-10-01

Targeted temperature management (TTM) confers neurological and survival benefits for post-cardiac arrest patients with return of spontaneous circulation (ROSC) who remain comatose. Specialized equipment for induction of hypothermia is not available in the prehospital setting, and there are no reliable methods for emergency medical services personnel to initiate TTM. We hypothesized that the application of surface cooling elements to the neck will decrease brain temperature and act as initiators of TTM. Magnetic resonance (MR) spectroscopy was used to evaluate the effect of a carotid surface cooling element on brain temperature in healthy adults. Six individuals completed this study. We measured a temperature drop of 0.69 ± 0.38 °C (95% CI) in the cortex of the brain following the application of the cooling element. Application of a room temperature element also caused a measurable decrease in brain temperature of 0.66 ± 0.41 °C (95% CI) which may be attributable to baroreceptor activation. The application of surface cooling elements to the neck decreased brain temperature and may serve as a method to initiate TTM in the prehospital setting.

Assessing the Role of Inhibition in Stabilizing Neocortical Networks Requires Large-Scale Perturbation of the Inhibitory Population

PubMed Central

Mrsic-Flogel, Thomas D.

2017-01-01

Neurons within cortical microcircuits are interconnected with recurrent excitatory synaptic connections that are thought to amplify signals (Douglas and Martin, 2007), form selective subnetworks (Ko et al., 2011), and aid feature discrimination. Strong inhibition (Haider et al., 2013) counterbalances excitation, enabling sensory features to be sharpened and represented by sparse codes (Willmore et al., 2011). This balance between excitation and inhibition makes it difficult to assess the strength, or gain, of recurrent excitatory connections within cortical networks, which is key to understanding their operational regime and the computations that they perform. Networks that combine an unstable high-gain excitatory population with stabilizing inhibitory feedback are known as inhibition-stabilized networks (ISNs) (Tsodyks et al., 1997). Theoretical studies using reduced network models predict that ISNs produce paradoxical responses to perturbation, but experimental perturbations failed to find evidence for ISNs in cortex (Atallah et al., 2012). Here, we reexamined this question by investigating how cortical network models consisting of many neurons behave after perturbations and found that results obtained from reduced network models fail to predict responses to perturbations in more realistic networks. Our models predict that a large proportion of the inhibitory network must be perturbed to reliably detect an ISN regime robustly in cortex. We propose that wide-field optogenetic suppression of inhibition under promoters targeting a large fraction of inhibitory neurons may provide a perturbation of sufficient strength to reveal the operating regime of cortex. Our results suggest that detailed computational models of optogenetic perturbations are necessary to interpret the results of experimental paradigms. SIGNIFICANCE STATEMENT Many useful computational mechanisms proposed for cortex require local excitatory recurrence to be very strong, such that local inhibitory feedback is necessary to avoid epileptiform runaway activity (an “inhibition-stabilized network” or “ISN” regime). However, recent experimental results suggest that this regime may not exist in cortex. We simulated activity perturbations in cortical networks of increasing realism and found that, to detect ISN-like properties in cortex, large proportions of the inhibitory population must be perturbed. Current experimental methods for inhibitory perturbation are unlikely to satisfy this requirement, implying that existing experimental observations are inconclusive about the computational regime of cortex. Our results suggest that new experimental designs targeting a majority of inhibitory neurons may be able to resolve this question. PMID:29074575

Student Voice in a Chinese Context: Investigating the Key Elements of Leadership That Enhance Student Voice

ERIC Educational Resources Information Center

Cheng, Annie Yan Ni

2012-01-01

This study examines the issues surrounding "student voice" in a specific Chinese context, and assesses the key elements of leadership that could enhance student voice in that context. It reports the results of a research conducted in a community-based educational centre in Hong Kong that provides after-school educational and social…

Drawing with Light and Clay: Teaching and Learning in the Art Studio as Pathways to Engagement

ERIC Educational Resources Information Center

Albertson, Constant; Davidson, Miriam

2007-01-01

In this essay, Albertson and Davidson explore the attributes of photography and ceramic arts education to identify eight key elements integral to engagement in these art studios for under-served and disenchanted learners. They suggest that these key elements can provide numerous clues as to how teachers and school communities might reimagine both…

California Charter Oversight: Key Elements and Actual Costs. CRB 12-001

ERIC Educational Resources Information Center

Blanton, Rebecca E.

2012-01-01

This study was mandated by SB537 (Simitian, Chapter 650, Stats. of 2007, codified at Ed. Code Section 47613), which requires the California Research Bureau (CRB) to prepare and submit to the Legislature a report on the key elements and actual costs of charter school oversight. Charter schools are public schools that are operated by entities other…

The long (LINEs) and the short (SINEs) of it: altered methylation as a precursor to toxicity.

PubMed

Carnell, Ammie N; Goodman, Jay I

2003-10-01

Although once thought of as "junk" DNA, the importance of interspersed elements in the genome has become increasingly appreciated in recent years. In a broad sense these are collectively referred to as transposable elements, which encompass both transposons and retrotransposons. The latter include long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs). Expression of these elements leads to genetic instability. Therefore, it is important that they remain transcriptionally silenced, and DNA methylation plays a key role in this regard. A framework for understanding the possible interplay between altered DNA methylation, an epigenetic change, and mutational events is presented. A case is made as to how retrotransposable elements, specifically LINEs and SINEs, are likely to emerge as key players in furthering our understanding of mechanisms underlying a variety of toxicities, including carcinogenesis but not limited to this endpoint.

Sex-dependent alterations in motor and anxiety-like behavior of aged bacterial peptidoglycan sensing molecule 2 knockout mice.

PubMed

Arentsen, Tim; Khalid, Roksana; Qian, Yu; Diaz Heijtz, Rochellys

2018-01-01

Peptidoglycan recognition proteins (PGRPs) are key sensing-molecules of the innate immune system that specifically detect bacterial peptidoglycan (PGN) and its derivates. PGRPs have recently emerged as potential key regulators of normal brain development and behavior. To test the hypothesis that PGRPs play a role in motor control and anxiety-like behavior in later life, we used 15-month old male and female peptidoglycan recognition protein 2 (Pglyrp2) knockout (KO) mice. Pglyrp2 is an N-acetylmuramyl-l-alanine amidase that hydrolyzes PGN between the sugar backbone and the peptide chain (which is unique among the mammalian PGRPs). Using a battery of behavioral tests, we demonstrate that Pglyrp2 KO male mice display decreased levels of anxiety-like behavior compared with wild type (WT) males. In contrast, Pglyrp2 KO female mice show reduced rearing activity and increased anxiety-like behavior compared to WT females. In the accelerated rotarod test, however, Pglyrp2 KO female mice performed better compared to WT females (i.e., they had longer latency to fall off the rotarod). Further, Pglyrp2 KO male mice exhibited decreased expression levels of synaptophysin, gephyrin, and brain-derived neurotrophic factor in the frontal cortex, but not in the amygdala. Pglyrp2 KO female mice exhibited increased expression levels of spinophilin and alpha-synuclein in the frontal cortex, while exhibiting decreased expression levels of synaptophysin, gephyrin and spinophilin in the amygdala. Our findings suggest a novel role for Pglyrp2asa key regulator of motor and anxiety-like behavior in late life. Copyright © 2017. Published by Elsevier Inc.

Ammonia mediates cortical hemichannel dysfunction in rodent models of chronic liver disease

PubMed Central

Hadjihambi, Anna; De Chiara, Francesco; Hosford, Patrick S.; Habtetion, Abeba; Karagiannis, Anastassios; Davies, Nathan

2017-01-01

The pathogenesis of hepatic encephalopathy (HE) in cirrhosis is multifactorial and ammonia is thought to play a key role. Astroglial dysfunction is known to be present in HE. Astrocytes are extensively connected by gap junctions formed of connexins, which also exist as functional hemichannels allowing exchange of molecules between the cytoplasm and the extracellular milieu. The astrocyte‐neuron lactate shuttle hypothesis suggests that neuronal activity is fueled (at least in part) by lactate provided by neighboring astrocytes. We hypothesized that in HE, astroglial dysfunction could impair metabolic communication between astrocytes and neurons. In this study, we determined whether hyperammonemia leads to hemichannel dysfunction and impairs lactate transport in the cerebral cortex using rat models of HE (bile duct ligation [BDL] and induced hyperammonemia) and also evaluated the effect of ammonia‐lowering treatment (ornithine phenylacetate [OP]). Plasma ammonia concentration in BDL rats was significantly reduced by OP treatment. Biosensor recordings demonstrated that HE is associated with a significant reduction in both tonic and hypoxia‐induced lactate release in the cerebral cortex, which was normalized by OP treatment. Cortical dye loading experiments revealed hemichannel dysfunction in HE with improvement following OP treatment, while the expression of key connexins was unaffected. Conclusion: The results of the present study demonstrate that HE is associated with central nervous system hemichannel dysfunction, with ammonia playing a key role. The data provide evidence of a potential neuronal energy deficit due to impaired hemichannel‐mediated lactate transport between astrocytes and neurons as a possible mechanism underlying pathogenesis of HE. (Hepatology 2017;65:1306‐1318) PMID:28066916

"Stress" is 80 Years Old: From Hans Selye Original Paper in 1936 to Recent Advances in GI Ulceration.

PubMed

Szabo, Sandor; Yoshida, Masashi; Filakovszky, Janos; Juhasz, Gyorgy

2017-01-01

The first scientific publication on 'general adaption syndrome', or as we know today 'biologic stress' has been published in Nature in 1936 by the 29-year old Hans Selye. His results in that short publication that contained no references or illustrations, were based on experiments in rats that were exposed to severe insults/ stressors, but his idea about a 'nonspecific bodily response' originated from his observations of sick patients whom he had seen as a medical student and young clinician. Autopsy of stressed rats revealed three major, grossly visible changes: hyperemia and enlargement of the adrenals, atrophy of the thymus and lymph nodes as well as hemorrhagic gastric erosions/ulcers (the "stress triad"). Based on this and additional observations, he concluded that the key master organ in stress reactions is the adrenal cortex (although he also accepted the limited and short lasting effect of catecholamines released from the adrenal medulla) which stimulated by an increased secretion of ACTH, secreted by the anterior pituitary gland. He thus identified the first molecular mediators of the stress reaction, i.e., steroids released from the adrenal cortex that we call today glucocorticoids, based on his classification and naming of steroids. At the end of a very productive life in experimental medicine, Selye recognized that under both unpleasant and demanding stressors as well as positive, rewarding stimuli adrenal cortex releases the same glucocorticoids and only certain brain structures may distinguish the stimuli under distress and eustress - terms he introduced in 1974, that also contained his last definition of stress: the nonspecific response of the body on any demand on it. After brief description of the history of stress research, the rest of this review is focused on one element of stress triad, i.e., gastroduodenal ulceration, especially its pathogenesis, prevention and treatment. Following a short description of acute gastroprotection, discovered by one of Selye's students, we discuss new molecular mediators of gastroduodenal ulceration like dopamine and new drugs that either only heal (very potently, on molar basis) or prevent and heal ulcers like sucralfate derivatives and the relatively new peptide BPC-157. We conclude that despite the extensive and multidisciplinary research on stress during the last 80 years, a lot of basic and clinical research is needed to better understand the manifestations, central and peripheral molecular regulators of stress response, especially the modes of prevention/management of distress or its transformation into eustress and the treatment of stress-related diseases. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Chemical thermodynamic data. 1. The concept of links to the chemical elements and the historical development of key thermodynamic data

NASA Astrophysics Data System (ADS)

Wolery, Thomas J.; Jové Colón, Carlos F.

2017-09-01

Chemical thermodynamic data remain a keystone for geochemical modeling and reactive transport simulation as applied to an increasing number of applications in the earth sciences, as well as applications in other areas including metallurgy, material science, and industrial process design. The last century has seen the development of a large body of thermodynamic data and a number of major compilations. The past several decades have seen the development of thermodynamic databases in digital form designed to support computer calculations. However, problems with thermodynamic data appear to be persistent. One problem pertains to the use of inconsistent primary key reference data. Such data pertain to elemental reference forms and key, stoichiometrically simple chemical species including metal oxides, CO2, water, and aqueous species such as Na+ and Cl-. A consistent set of primary key data (standard Gibbs energies, standard enthalpies, and standard entropies for key chemical species) for 298.15 K and 1 bar pressure is essential. Thermochemical convention is to define the standard Gibbs energy and the standard enthalpy of an individual chemical species in terms of formation from reference forms of the constituent chemical elements. We propose a formal concept of "links" to the elemental reference forms. This concept involves a documented understanding of all reactions and calculations leading to values for a formation property (standard Gibbs energy or enthalpy). A valid link consists of two parts: (a) the path of reactions and corrections and (b) the associated data, which are key data. Such a link differs from a bare "key" or "reference" datum in that it requires additional information. Some or all of its associated data may also be key data. In evaluating a reported thermodynamic datum, one should identify the links to the chemical elements, a process which can be time-consuming and which may lead to a dead end (an incomplete link). The use of two or more inconsistent links to the same elemental reference form in a thermodynamic database will result in an inconsistency in the database. Thus, in constructing a database, it is important to establish a set of reliable links (generally resulting in a set of primary reference data) and then correct all data adopted subsequently for consistency with that set. Recommended values of key data have not been constant through history. We review some of this history through the lens of major compilations and other influential reports, and note a number of problem areas. Finally, we illustrate the concepts developed in this paper by applying them to some key species of geochemical interest, including liquid water; quartz and aqueous silica; and gibbsite, corundum, and the aqueous aluminum ion.

A functional difference in information processing between orbitofrontal cortex and ventral striatum during decision-making behaviour.

PubMed

Stott, Jeffrey J; Redish, A David

2014-11-05

Both orbitofrontal cortex (OFC) and ventral striatum (vStr) have been identified as key structures that represent information about value in decision-making tasks. However, the dynamics of how this information is processed are not yet understood. We recorded ensembles of cells from OFC and vStr in rats engaged in the spatial adjusting delay-discounting task, a decision-making task that involves a trade-off between delay to and magnitude of reward. Ventral striatal neural activity signalled information about reward before the rat's decision, whereas such reward-related signals were absent in OFC until after the animal had committed to its decision. These data support models in which vStr is directly involved in action selection, but OFC processes decision-related information afterwards that can be used to compare the predicted and actual consequences of behaviour. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Reading a Suspenseful Literary Text Activates Brain Areas Related to Social Cognition and Predictive Inference

PubMed Central

Lehne, Moritz; Engel, Philipp; Rohrmeier, Martin; Menninghaus, Winfried; Jacobs, Arthur M.; Koelsch, Stefan

2015-01-01

Stories can elicit powerful emotions. A key emotional response to narrative plots (e.g., novels, movies, etc.) is suspense. Suspense appears to build on basic aspects of human cognition such as processes of expectation, anticipation, and prediction. However, the neural processes underlying emotional experiences of suspense have not been previously investigated. We acquired functional magnetic resonance imaging (fMRI) data while participants read a suspenseful literary text (E.T.A. Hoffmann's “The Sandman”) subdivided into short text passages. Individual ratings of experienced suspense obtained after each text passage were found to be related to activation in the medial frontal cortex, bilateral frontal regions (along the inferior frontal sulcus), lateral premotor cortex, as well as posterior temporal and temporo-parietal areas. The results indicate that the emotional experience of suspense depends on brain areas associated with social cognition and predictive inference. PMID:25946306

The piriform, perirhinal, and entorhinal cortex in seizure generation

PubMed Central

Vismer, Marta S.; Forcelli, Patrick A.; Skopin, Mark D.; Gale, Karen; Koubeissi, Mohamad Z.

2015-01-01

Understanding neural network behavior is essential to shed light on epileptogenesis and seizure propagation. The interconnectivity and plasticity of mammalian limbic and neocortical brain regions provide the substrate for the hypersynchrony and hyperexcitability associated with seizure activity. Recurrent unprovoked seizures are the hallmark of epilepsy, and limbic epilepsy is the most common type of medically-intractable focal epilepsy in adolescents and adults that necessitates surgical evaluation. In this review, we describe the role and relationships among the piriform (PIRC), perirhinal (PRC), and entorhinal cortex (ERC) in seizure-generation and epilepsy. The inherent function, anatomy, and histological composition of these cortical regions are discussed. In addition, the neurotransmitters, intrinsic and extrinsic connections, and the interaction of these regions are described. Furthermore, we provide evidence based on clinical research and animal models that suggest that these cortical regions may act as key seizure-trigger zones and, even, epileptogenesis. PMID:26074779

A high-fat diet decreases GABA concentration in the frontal cortex and hippocampus of rats.

PubMed

Sandoval-Salazar, Cuauhtemoc; Ramírez-Emiliano, Joel; Trejo-Bahena, Aurora; Oviedo-Solís, Cecilia I; Solís-Ortiz, Martha Silvia

2016-02-29

It has been proposed that the γ-aminobutyric acid (GABA) plays a key role in the regulation of food intake and body weight by controlling the excitability, plasticity and the synchronization of neuronal activity in the frontal cortex (FC). It has been also proposed that the high-fat diet (HFD) could disturb the metabolism of glutamate and consequently the GABA levels, but the mechanism is not yet clearly understood. Therefore, the aim of this study was to investigate the effect of a HFD on the GABA levels in the FC and hippocampus of rats. The HFD significantly increased weight gain and blood glucose levels, whereas decreased the GABA levels in the FC and hippocampus compared with standard diet-fed rats. HFD decreases GABA levels in the FC and hippocampus of rat, which likely disrupts the GABAergic inhibitory processes, underlying feeding behavior.

Frequency–specific network connectivity increases underlie accurate spatiotemporal memory retrieval

PubMed Central

Watrous, Andrew J.; Tandon, Nitin; Connor, Chris; Pieters, Thomas; Ekstrom, Arne D.

2013-01-01

The medial temporal lobes, prefrontal cortex, and parts of parietal cortex form the neural underpinnings of episodic memory, which includes remembering both where and when an event occurred. Yet how these three key regions interact during retrieval of spatial and temporal context remains largely untested. Here, we employed simultaneous electrocorticographical recordings across multiple lobular regions, employing phase synchronization as a measure of network functional connectivity, while patients retrieved spatial and temporal context associated with an episode. Successful memory retrieval was characterized by greater global connectivity compared to incorrect retrieval, with the MTL acting as a convergence hub for these interactions. Spatial vs. temporal context retrieval resulted in prominent differences in both the spectral and temporal patterns of network interactions. These results emphasize dynamic network interactions as central to episodic memory retrieval, providing novel insight into how multiple contexts underlying a single event can be recreated within the same network. PMID:23354333

Emergent processes in cognitive-emotional interactions

PubMed Central

Pessoa, Luiz

2010-01-01

Emotion and cognition have been viewed as largely separate entities in the brain. Within this framework, significant progress has been made in understanding specific aspects of behavior. Research in the past two decades, however, has started to paint a different picture of brain organization, one in which network interactions are key to understanding complex behaviors. From both basic and clinical perspectives, the characterization of cognitive-emotional interactions constitutes a fundamental issue in the investigation of the mind and brain. This review will highlight the interactive and integrative potential that exists in the brain to bring together the cognitive and emotional domains. First, anatomical evidence will be provided, focusing on structures such as hypothalamus, basal forebrain, amygdala, cingulate cortex, orbitofrontal cortex, and insula. Data on functional interactions will then be discussed, followed by a discussion of a dual competition framework, which describes cognitive-emotional interactions in terms of perceptual and cognitive competition mechanisms. PMID:21319489

Global dynamics of selective attention and its lapses in primary auditory cortex.

PubMed

Lakatos, Peter; Barczak, Annamaria; Neymotin, Samuel A; McGinnis, Tammy; Ross, Deborah; Javitt, Daniel C; O'Connell, Monica Noelle

2016-12-01

Previous research demonstrated that while selectively attending to relevant aspects of the external world, the brain extracts pertinent information by aligning its neuronal oscillations to key time points of stimuli or their sampling by sensory organs. This alignment mechanism is termed oscillatory entrainment. We investigated the global, long-timescale dynamics of this mechanism in the primary auditory cortex of nonhuman primates, and hypothesized that lapses of entrainment would correspond to lapses of attention. By examining electrophysiological and behavioral measures, we observed that besides the lack of entrainment by external stimuli, attentional lapses were also characterized by high-amplitude alpha oscillations, with alpha frequency structuring of neuronal ensemble and single-unit operations. Entrainment and alpha-oscillation-dominated periods were strongly anticorrelated and fluctuated rhythmically at an ultra-slow rate. Our results indicate that these two distinct brain states represent externally versus internally oriented computational resources engaged by large-scale task-positive and task-negative functional networks.

Reality of auditory verbal hallucinations.

PubMed

Raij, Tuukka T; Valkonen-Korhonen, Minna; Holi, Matti; Therman, Sebastian; Lehtonen, Johannes; Hari, Riitta

2009-11-01

Distortion of the sense of reality, actualized in delusions and hallucinations, is the key feature of psychosis but the underlying neuronal correlates remain largely unknown. We studied 11 highly functioning subjects with schizophrenia or schizoaffective disorder while they rated the reality of auditory verbal hallucinations (AVH) during functional magnetic resonance imaging (fMRI). The subjective reality of AVH correlated strongly and specifically with the hallucination-related activation strength of the inferior frontal gyri (IFG), including the Broca's language region. Furthermore, how real the hallucination that subjects experienced was depended on the hallucination-related coupling between the IFG, the ventral striatum, the auditory cortex, the right posterior temporal lobe, and the cingulate cortex. Our findings suggest that the subjective reality of AVH is related to motor mechanisms of speech comprehension, with contributions from sensory and salience-detection-related brain regions as well as circuitries related to self-monitoring and the experience of agency.

Reality of auditory verbal hallucinations

PubMed Central

Valkonen-Korhonen, Minna; Holi, Matti; Therman, Sebastian; Lehtonen, Johannes; Hari, Riitta

2009-01-01

Distortion of the sense of reality, actualized in delusions and hallucinations, is the key feature of psychosis but the underlying neuronal correlates remain largely unknown. We studied 11 highly functioning subjects with schizophrenia or schizoaffective disorder while they rated the reality of auditory verbal hallucinations (AVH) during functional magnetic resonance imaging (fMRI). The subjective reality of AVH correlated strongly and specifically with the hallucination-related activation strength of the inferior frontal gyri (IFG), including the Broca's language region. Furthermore, how real the hallucination that subjects experienced was depended on the hallucination-related coupling between the IFG, the ventral striatum, the auditory cortex, the right posterior temporal lobe, and the cingulate cortex. Our findings suggest that the subjective reality of AVH is related to motor mechanisms of speech comprehension, with contributions from sensory and salience-detection-related brain regions as well as circuitries related to self-monitoring and the experience of agency. PMID:19620178

Right Orbitofrontal Cortex Mediates Conscious Olfactory Perception

PubMed Central

Li, Wen; Lopez, Leonardo; Osher, Jason; Howard, James D.; Parrish, Todd B.; Gottfried, Jay A.

2013-01-01

Understanding how the human brain translates sensory impressions into conscious percepts is a key challenge of neuroscience research. Work in this area has overwhelmingly centered on the conscious experience of vision at the exclusion of the other senses—in particular, smell. We hypothesized that the orbitofrontal cortex (OFC) is a central substrate for olfactory conscious experience because of its privileged physiological role in odor processing. Combining functional magnetic resonance imaging, peripheral autonomic recordings, and olfactory psychophysics, we studied a case of complete anosmia (smell loss) in a patient with circumscribed traumatic brain injury to the right OFC. Despite a complete absence of conscious olfaction, the patient exhibited robust “blind smell,” as indexed by reliable odor-evoked neural activity in the left OFC and normal autonomic responses to odor hedonics during presentation of stimuli to the left nostril. These data highlight the right OFC’s critical role in subserving human olfactory consciousness. PMID:20817780

Physiology, anatomy, and plasticity of the cerebral cortex in relation to musical instrument performance

NASA Astrophysics Data System (ADS)

Tramo, Mark Jude

2004-05-01

The acquisition and maintenance of fine-motor skills underlying musical instrument performance rely on the development, integration, and plasticity of neural systems localized within specific subregions of the cerebral cortex. Cortical representations of a motor sequence, such as a sequence of finger movements along the keys of a saxophone, take shape before the figure sequence occurs. The temporal pattern and spatial coordinates are computed by networks of neurons before and during the movements. When a finger sequence is practiced over and over, performance gets faster and more accurate, probably because cortical neurons generating the sequence increase in spatial extent, their electrical discharges become more synchronous, or both. By combining experimental methods such as single- and multi-neuron recordings, focal stimulation, microanatomical tracers, gross morphometry, evoked potentials, and functional imaging in humans and nonhuman primates, neuroscientists are gaining insights into the cortical physiology, anatomy, and plasticity of musical instrument performance.

'Trampoline fracture' of the proximal tibia in children: report of 3 cases and review of literature.

PubMed

Bruyeer, E; Geusens, E; Catry, F; Vanstraelen, L; Vanhoenacker, F

2012-01-01

We present three cases of fracture of the proximal tibia in young children who were jumping on a trampoline. The typical radiological findings and the underlying mechanism of trauma are discussed. The key radiological features are: a transverse hairline fracture of the upper tibia often accompanied by a buckle fracture of the lateral or medial tibial cortex, buckling of the anterior upper tibial cortex and anterior tilting of the epiphyseal plate. New types of injuries related to specific recreational activities are recognized. It is often helpful to associate a typical injury with a particular activity. Trampoline related injuries have increased dramatically over the last years. The most common lesions are fractures and ligamentous injuries, in particular a transverse fracture of the proximal tibia. However the radiological findings can be very subtle and easily overlooked. It is therefore important to be aware of the typical history and radiological findings.

Altered Structural and Functional Connectivity in Late Preterm Preadolescence: An Anatomic Seed-Based Study of Resting State Networks Related to the Posteromedial and Lateral Parietal Cortex

PubMed Central

Degnan, Andrew J.; Wisnowski, Jessica L.; Choi, SoYoung; Ceschin, Rafael; Bhushan, Chitresh; Leahy, Richard M.; Corby, Patricia; Schmithorst, Vincent J.; Panigrahy, Ashok

2015-01-01

Objective Late preterm birth confers increased risk of developmental delay, academic difficulties and social deficits. The late third trimester may represent a critical period of development of neural networks including the default mode network (DMN), which is essential to normal cognition. Our objective is to identify functional and structural connectivity differences in the posteromedial cortex related to late preterm birth. Methods Thirty-eight preadolescents (ages 9–13; 19 born in the late preterm period (≥32 weeks gestational age) and 19 at term) without access to advanced neonatal care were recruited from a low socioeconomic status community in Brazil. Participants underwent neurocognitive testing, 3-dimensional T1-weighted imaging, diffusion-weighted imaging and resting state functional MRI (RS-fMRI). Seed-based probabilistic diffusion tractography and RS-fMRI analyses were performed using unilateral seeds within the posterior DMN (posterior cingulate cortex, precuneus) and lateral parietal DMN (superior marginal and angular gyri). Results Late preterm children demonstrated increased functional connectivity within the posterior default mode networks and increased anti-correlation with the central-executive network when seeded from the posteromedial cortex (PMC). Key differences were demonstrated between PMC components with increased anti-correlation with the salience network seen only with posterior cingulate cortex seeding but not with precuneus seeding. Probabilistic tractography showed increased streamlines within the right inferior longitudinal fasciculus and inferior fronto-occipital fasciculus within late preterm children while decreased intrahemispheric streamlines were also observed. No significant differences in neurocognitive testing were demonstrated between groups. Conclusion Late preterm preadolescence is associated with altered functional connectivity from the PMC and lateral parietal cortex to known distributed functional cortical networks despite no significant executive neurocognitive differences. Selective increased structural connectivity was observed in the setting of decreased posterior interhemispheric connections. Future work is needed to determine if these findings represent a compensatory adaptation employing alternate neural circuitry or could reflect subtle pathology resulting in emotional processing deficits not seen with neurocognitive testing. PMID:26098888

Interleukin-18 Expression Increases in Response to Neurovascular Damage Following Soman-induced Status Epilepticus in Rats

DTIC Science & Technology

2015-07-22

CONTRACT NUMBER soman-induced status epilepticus in rats 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Johnson, EA, Guignet, MA, Dao...See reprint. 15. SUBJECT TERMS Interleukin 18, Status epilepticus , Soman (GD), Macrophage, T-cell, Neutrophil, Piriform cortex, Hippocampus...following soman-induced status epilepticus in rats Erik A. Johnson1*, Michelle A. Guignet1, Thuy L. Dao1, Tracey A. Hamilton2 and Robert K. Kan1 Abstract

Element-topology-independent preconditioners for parallel finite element computations

NASA Technical Reports Server (NTRS)

Park, K. C.; Alexander, Scott

1992-01-01

A family of preconditioners for the solution of finite element equations are presented, which are element-topology independent and thus can be applicable to element order-free parallel computations. A key feature of the present preconditioners is the repeated use of element connectivity matrices and their left and right inverses. The properties and performance of the present preconditioners are demonstrated via beam and two-dimensional finite element matrices for implicit time integration computations.

Heat Switches for ADRs

NASA Technical Reports Server (NTRS)

DiPirro, M. J.; Shirron, P. J.

2014-01-01

Heat switches are key elements in the cyclic operation of Adiabatic Demagnetization Refrigerators (ADRs). Several of the types of heat switches that have been used for ADRs are described in this paper. Key elements in selection and design of these switches include not only ON/OFF switching ratio, but also method of actuation, size, weight, and structural soundness. Some of the trade-off are detailed in this paper.

Motor cortex and spinal cord neuromodulation promote corticospinal tract axonal outgrowth and motor recovery after cervical contusion spinal cord injury.

PubMed

Zareen, N; Shinozaki, M; Ryan, D; Alexander, H; Amer, A; Truong, D Q; Khadka, N; Sarkar, A; Naeem, S; Bikson, M; Martin, J H

2017-11-01

Cervical injuries are the most common form of SCI. In this study, we used a neuromodulatory approach to promote skilled movement recovery and repair of the corticospinal tract (CST) after a moderately severe C4 midline contusion in adult rats. We used bilateral epidural intermittent theta burst (iTBS) electrical stimulation of motor cortex to promote CST axonal sprouting and cathodal trans-spinal direct current stimulation (tsDCS) to enhance spinal cord activation to motor cortex stimulation after injury. We used Finite Element Method (FEM) modeling to direct tsDCS to the cervical enlargement. Combined iTBS-tsDCS was delivered for 30min daily for 10days. We compared the effect of stimulation on performance in the horizontal ladder and the Irvine Beattie and Bresnahan forepaw manipulation tasks and CST axonal sprouting in injury-only and injury+stimulation animals. The contusion eliminated the dorsal CST in all animals. tsDCS significantly enhanced motor cortex evoked responses after C4 injury. Using this combined spinal-M1 neuromodulatory approach, we found significant recovery of skilled locomotion and forepaw manipulation skills compared with injury-only controls. The spared CST axons caudal to the lesion in both animal groups derived mostly from lateral CST axons that populated the contralateral intermediate zone. Stimulation enhanced injury-dependent CST axonal outgrowth below and above the level of the injury. This dual neuromodulatory approach produced partial recovery of skilled motor behaviors that normally require integration of posture, upper limb sensory information, and intent for performance. We propose that the motor systems use these new CST projections to control movements better after injury. Copyright © 2017 Elsevier Inc. All rights reserved.

Teloplasm formation in a leech, Helobdella triserialis, is a microtubule-dependent process.

PubMed

Astrow, S H; Holton, B; Weisblat, D A

1989-10-01

Fertilized eggs of the leech Helobdella triserialis undergo a cytoplasmic reorganization which generates domains of nonyolky cytoplasm, called teloplasm, at the animal and vegetal poles. The segregation of teloplasm to one cell of the eight-cell embryo is responsible for a unique developmental fate of that cell, i.e., to give rise to segmental ectoderm and mesoderm. We have studied the cytoplasmic movements that generate teloplasm using time-lapse video microscopy; the formation and migration of rings of nonyolky cytoplasm were visualized using transmitted light, while the movements of mitochondria into these rings were monitored with epifluorescence after labeling embryos with rhodamine 123, a fluorescent mitochondrial dye. To examine the likelihood that cytoskeletal elements play a role in the mechanism of teloplasm formation in Helobdella, we examined the distribution of microtubules and microfilaments during the first cell cycle by indirect immunofluorescence and rhodamine-phalloidin labeling, respectively. The cortex of the early embryo contained a network of microtubules many of which were oriented parallel to the cell surface. As teloplasm formation ensued, microtubule networks became concentrated in the animal and the vegetal cortex relative to the equatorial cortex. More extensive microtubule arrays were found within the rings of teloplasm. Actin filaments appeared in the form of narrow rings in the cortex, but these varied apparently randomly from embryo to embryo in terms of number, size, and position. The role of microtubules and microfilaments in teloplasm formation was tested using depolymerizing agents. Teloplasm formation was blocked by microtubule inhibitors, but not by microfilament inhibitors. These results differ significantly from those obtained in embryos of the oligochaete Tubifex hattai, suggesting that the presumably homologous cytoplasmic reorganizations seen in these two annelids have different cytoskeletal dependencies.

The proprotein convertase PC2 is involved in the maturation of prosomatostatin to somatostatin-14 but not in the somatostatin deficit in Alzheimer's disease.

PubMed

Winsky-Sommerer, R; Grouselle, D; Rougeot, C; Laurent, V; David, J-P; Delacourte, A; Dournaud, P; Seidah, N G; Lindberg, I; Trottier, S; Epelbaum, J

2003-01-01

A somatostatin deficit occurs in the cerebral cortex of Alzheimer's disease patients without a major loss in somatostatin-containing neurons. This deficit could be related to a reduction in the rate of proteolytic processing of peptide precursors. Since the two proprotein convertases (PC)1 and PC2 are responsible for the processing of neuropeptide precursors directed to the regulated secretory pathway, we examined whether they are involved first in the proteolytic processing of prosomatostatin in mouse and human brain and secondly in somatostatin defect associated with Alzheimer's disease. By size exclusion chromatography, the cleavage of prosomatostatin to somatostatin-14 is almost totally abolished in the cortex of PC2 null mice, while the proportions of prosomatostatin and somatostatin-28 are increased. By immunohistochemistry, PC1 and PC2 were localized in many neuronal elements in human frontal and temporal cortex. The convertases levels were quantified by Western blot, as well as the protein 7B2 which is required for the production of active PC2. No significant change in PC1 levels was observed in Alzheimer's disease. In contrast, a marked decrease in the ratio of the PC2 precursor to the total enzymatic pool was observed in the frontal cortex of Alzheimer patients. This decrease coincides with an increase in the binding protein 7B2. However, the content and enzymatic activity of the PC2 mature form were similar in Alzheimer patients and controls. Therefore, the cortical somatostatin defect is not due to convertase alteration occuring during Alzheimer's disease. Further studies will be needed to assess the mechanisms involved in somatostatin deficiency in Alzheimer's disease.

PI3K/AKT pathway mutations cause a spectrum of brain malformations from megalencephaly to focal cortical dysplasia

PubMed Central

Mirzaa, Ghayda M.; Ishak, Gisele E.; O'Roak, Brian J.; Hiatt, Joseph B.; Roden, William H.; Gunter, Sonya A.; Christian, Susan L.; Collins, Sarah; Adams, Carissa; Rivière, Jean-Baptiste; St-Onge, Judith; Ojemann, Jeffrey G.; Shendure, Jay; Hevner, Robert F.; Dobyns, William B.

2015-01-01

Malformations of cortical development containing dysplastic neuronal and glial elements, including hemimegalencephaly and focal cortical dysplasia, are common causes of intractable paediatric epilepsy. In this study we performed multiplex targeted sequencing of 10 genes in the PI3K/AKT pathway on brain tissue from 33 children who underwent surgical resection of dysplastic cortex for the treatment of intractable epilepsy. Sequencing results were correlated with clinical, imaging, pathological and immunohistological phenotypes. We identified mosaic activating mutations in PIK3CA and AKT3 in this cohort, including cancer-associated hotspot PIK3CA mutations in dysplastic megalencephaly, hemimegalencephaly, and focal cortical dysplasia type IIa. In addition, a germline PTEN mutation was identified in a male with hemimegalencephaly but no peripheral manifestations of the PTEN hamartoma tumour syndrome. A spectrum of clinical, imaging and pathological abnormalities was found in this cohort. While patients with more severe brain imaging abnormalities and systemic manifestations were more likely to have detected mutations, routine histopathological studies did not predict mutation status. In addition, elevated levels of phosphorylated S6 ribosomal protein were identified in both neurons and astrocytes of all hemimegalencephaly and focal cortical dysplasia type II specimens, regardless of the presence or absence of detected PI3K/AKT pathway mutations. In contrast, expression patterns of the T308 and S473 phosphorylated forms of AKT and in vitro AKT kinase activities discriminated between mutation-positive dysplasia cortex, mutation-negative dysplasia cortex, and non-dysplasia epilepsy cortex. Our findings identify PI3K/AKT pathway mutations as an important cause of epileptogenic brain malformations and establish megalencephaly, hemimegalencephaly, and focal cortical dysplasia as part of a single pathogenic spectrum. PMID:25722288

Effects of pramipexole on the processing of rewarding and aversive taste stimuli.

PubMed

McCabe, Ciara; Harwood, James; Brouwer, Sietske; Harmer, Catherine J; Cowen, Philip J

2013-07-01

Pramipexole, a D2/D3 dopamine receptor agonist, has been implicated in the development of impulse control disorders in patients with Parkinson's disease. Investigation of single doses of pramipexole in healthy participants in reward-based learning tasks has shown inhibition of the neural processing of reward, presumptively through stimulation of dopamine autoreceptors. This study aims to examine the effects of pramipexole on the neural response to the passive receipt of rewarding and aversive sight and taste stimuli. We used functional magnetic resonance imaging to examine the neural responses to the sight and taste of pleasant (chocolate) and aversive (mouldy strawberry) stimuli in 16 healthy volunteers who received a single dose of pramipexole (0.25 mg) and placebo in a double-blind, within-subject, design. Relative to placebo, pramipexole treatment reduced blood oxygen level-dependent activation to the chocolate stimuli in the areas known to play a key role in reward, including the ventromedial prefrontal cortex, the orbitofrontal cortex, striatum, thalamus and dorsal anterior cingulate cortex. Pramipexole also reduced activation to the aversive condition in the dorsal anterior cingulate cortex. There were no effects of pramipexole on the subjective ratings of the stimuli. Our results are consistent with an ability of acute, low-dose pramipexole to diminish dopamine-mediated responses to both rewarding and aversive taste stimuli, perhaps through an inhibitory action of D2/3 autoreceptors on phasic burst activity of midbrain dopamine neurones. The ability of pramipexole to inhibit aversive processing might potentiate its adverse behavioural effects and could also play a role in its proposed efficacy in treatment-resistant depression.

Dynamic neural activity during stress signals resilient coping

PubMed Central

Sinha, Rajita; Lacadie, Cheryl M.; Constable, R. Todd; Seo, Dongju

2016-01-01

Active coping underlies a healthy stress response, but neural processes supporting such resilient coping are not well-known. Using a brief, sustained exposure paradigm contrasting highly stressful, threatening, and violent stimuli versus nonaversive neutral visual stimuli in a functional magnetic resonance imaging (fMRI) study, we show significant subjective, physiologic, and endocrine increases and temporally related dynamically distinct patterns of neural activation in brain circuits underlying the stress response. First, stress-specific sustained increases in the amygdala, striatum, hypothalamus, midbrain, right insula, and right dorsolateral prefrontal cortex (DLPFC) regions supported the stress processing and reactivity circuit. Second, dynamic neural activation during stress versus neutral runs, showing early increases followed by later reduced activation in the ventrolateral prefrontal cortex (VLPFC), dorsal anterior cingulate cortex (dACC), left DLPFC, hippocampus, and left insula, suggested a stress adaptation response network. Finally, dynamic stress-specific mobilization of the ventromedial prefrontal cortex (VmPFC), marked by initial hypoactivity followed by increased VmPFC activation, pointed to the VmPFC as a key locus of the emotional and behavioral control network. Consistent with this finding, greater neural flexibility signals in the VmPFC during stress correlated with active coping ratings whereas lower dynamic activity in the VmPFC also predicted a higher level of maladaptive coping behaviors in real life, including binge alcohol intake, emotional eating, and frequency of arguments and fights. These findings demonstrate acute functional neuroplasticity during stress, with distinct and separable brain networks that underlie critical components of the stress response, and a specific role for VmPFC neuroflexibility in stress-resilient coping. PMID:27432990

Primary motor cortex activity reduction under the regulation of SMA by real-time fMRI

NASA Astrophysics Data System (ADS)

Guo, Jia; Zhao, Xiaojie; Li, Yi; Yao, Li; Chen, Kewei

2012-03-01

Real-time fMRI (rtfMRI) is a new technology which allows human subjects to observe and control their own BOLD signal change from one or more localized brain regions during scanning. Current rtfMRI-neurofeedback studies mainly focused on the target region itself without considering other related regions influenced by the real-time feedback. However, there always exits important directional influence between many of cooperative regions. On the other hand, rtfMRI based on motor imagery mainly aimed at somatomotor cortex or primary motor area, whereas supplement motor area (SMA) was a relatively more integrated and pivotal region. In this study, we investigated whether the activities of SMA can be controlled utilizing different motor imagery strategies, and whether there exists any possible impact on an unregulated but related region, primary motor cortex (M1). SMA was first localized using overt finger tapping task, the activities of SMA were feedback to subjects visually on line during each of two subsequent imagery motor movement sessions. All thirteen healthy participants were found to be able to successfully control their SMA activities by self-fit imagery strategies which involved no actual motor movements. The activation of right M1 was also found to be significantly reduced in both intensity and extent with the neurofeedback process targeted at SMA, suggestive that not only the part of motor cortex activities were influenced under the regulation of a key region SMA, but also the increased difference between SMA and M1 might reflect the potential learning effect.

Effects of social isolation and re-socialization on cognition and ADAR1 (p110) expression in mice.

PubMed

Chen, Wei; An, Dong; Xu, Hong; Cheng, Xiaoxin; Wang, Shiwei; Yu, Weizhi; Yu, Deqin; Zhao, Dan; Sun, Yiping; Deng, Wuguo; Tang, Yiyuan; Yin, Shengming

2016-01-01

It has been reported that social isolation stress could be a key factor that leads to cognitive deficit for both humans and rodent models. However, detailed mechanisms are not yet clear. ADAR1 (Adenosine deaminase acting on RNA) is an enzyme involved in RNA editing that has a close relation to cognitive function. We have hypothesized that social isolation stress may impact the expression of ADAR1 in the brain of mice with cognitive deficit. To test our hypothesis, we evaluated the cognition ability of mice isolated for different durations (2, 4, and 8 weeks) using object recognition and object location tests; we also measured ADAR1 expression in hippocampus and cortex using immunohistochemistry and western blot. Our study showed that social isolation stress induced spatial and non-spatial cognition deficits of the tested mice. In addition, social isolation significantly increased both the immunoreactivity and protein expression of ADAR1 (p110) in the hippocampus and frontal cortex. Furthermore, re-socialization could not only recover the cognition deficits, but also bring ADAR1 (p110) immunoreactivity of hippocampus and frontal cortex, as well as ADAR1 (p110) protein expression of hippocampus back to the normal level for the isolated mice in adolescence. In conclusion, social isolation stress significantly increases ADAR1 (p110) expression in the hippocampus and frontal cortex of the mice with cognitive deficit. This finding may open a window to better understand the reasons (e.g., epigenetic change) that are responsible for social isolation-induced cognitive deficit and help the development of novel therapies for the resulted diseases.

Prefrontoparietal dysfunction during emotion regulation in anxiety disorder: a meta-analysis of functional magnetic resonance imaging studies.

PubMed

Wang, Hai-Yang; Zhang, Xiao-Xia; Si, Cui-Ping; Xu, Yang; Liu, Qian; Bian, He-Tao; Zhang, Bing-Wei; Li, Xue-Lin; Yan, Zhong-Rui

2018-01-01

Impairments in emotion regulation, and more specifically in cognitive reappraisal, are thought to play a key role in the pathogenesis of anxiety disorders. However, the available evidence on such deficits is inconsistent. To further illustrate the neurobiological underpinnings of anxiety disorder, the present meta-analysis summarizes functional magnetic resonance imaging (fMRI) findings for cognitive reappraisal tasks and investigates related brain areas. We performed a comprehensive series of meta-analyses of cognitive reappraisal fMRI studies contrasting patients with anxiety disorder with healthy control (HC) subjects, employing an anisotropic effect-size signed differential mapping approach. We also conducted a subgroup analysis of medication status, anxiety disorder subtype, data-processing software, and MRI field strengths. Meta-regression was used to explore the effects of demographics and clinical characteristics. Eight studies, with 11 datasets including 219 patients with anxiety disorder and 227 HC, were identified. Compared with HC, patients with anxiety disorder showed relatively decreased activation of the bilateral dorsomedial prefrontal cortex (dmPFC), bilateral dorsal anterior cingulate cortex (dACC), bilateral supplementary motor area (SMA), left ventromedial prefrontal cortex (vmPFC), bilateral parietal cortex, and left fusiform gyrus during cognitive reappraisal. The subgroup analysis, jackknife sensitivity analysis, heterogeneity analysis, and Egger's tests further confirmed these findings. Impaired cognitive reappraisal in anxiety disorder may be the consequence of hypo-activation of the prefrontoparietal network, consistent with insufficient top-down control. Our findings provide robust evidence that functional impairment in prefrontoparietal neuronal circuits may have a significant role in the pathogenesis of anxiety disorder.

Limited daily feeding and intermittent feeding have different effects on regional brain energy homeostasis during aging.

PubMed

Smiljanic, Kosara; Todorovic, Smilja; Mladenovic Djordjevic, Aleksandra; Vanmierlo, Tim; Lütjohann, Dieter; Ivkovic, Sanja; Kanazir, Selma

2018-04-01

Albeit aging is an inevitable process, the rate of aging is susceptible to modifications. Dietary restriction (DR) is a vigorous nongenetic and nonpharmacological intervention that is known to delay aging and increase healthspan in diverse species. This study aimed to compare the impact of different restricting feeding regimes such as limited daily feeding (LDF, 60% AL) and intermittent feeding (IF) on brain energy homeostasis during aging. The analysis was focused on the key molecules in glucose and cholesterol metabolism in the cortex and hippocampus of middle-aged (12-month-old) and aged (24-month-old) male Wistar rats. We measured the impact of different DRs on the expression levels of AMPK, glucose transporters (GLUT1, GLUT3, GLUT4), and the rate-limiting enzyme in the cholesterol synthesis pathway (HMGCR). Additionally, we assessed the changes in the amounts of cholesterol, its metabolite, and precursors following LDF and IF. IF decreased the levels of AMPK and pAMPK in the cortex while the increased levels were detected in the hippocampus. Glucose metabolism was more affected in the cortex, while cholesterol metabolism was more influenced in the hippocampus. Overall, the hippocampus was more resilient to the DRs, with fewer changes compared to the cortex. We showed that LDF and IF differently affected the brain energy homeostasis during aging and that specific brain regions exhibited distinct vulnerabilities towards DRs. Consequently, special attention should be paid to the DR application among elderly as different phases of aging do not respond equally to altered nutritional regimes.

Neural Systems Underlying Emotional and Non-emotional Interference Processing: An ALE Meta-Analysis of Functional Neuroimaging Studies

PubMed Central

Xu, Min; Xu, Guiping; Yang, Yang

2016-01-01

Understanding how the nature of interference might influence the recruitments of the neural systems is considered as the key to understanding cognitive control. Although, interference processing in the emotional domain has recently attracted great interest, the question of whether there are separable neural patterns for emotional and non-emotional interference processing remains open. Here, we performed an activation likelihood estimation meta-analysis of 78 neuroimaging experiments, and examined common and distinct neural systems for emotional and non-emotional interference processing. We examined brain activation in three domains of interference processing: emotional verbal interference in the face-word conflict task, non-emotional verbal interference in the color-word Stroop task, and non-emotional spatial interference in the Simon, SRC and Flanker tasks. Our results show that the dorsal anterior cingulate cortex (ACC) was recruited for both emotional and non-emotional interference. In addition, the right anterior insula, presupplementary motor area (pre-SMA), and right inferior frontal gyrus (IFG) were activated by interference processing across both emotional and non-emotional domains. In light of these results, we propose that the anterior insular cortex may serve to integrate information from different dimensions and work together with the dorsal ACC to detect and monitor conflicts, whereas pre-SMA and right IFG may be recruited to inhibit inappropriate responses. In contrast, the dorsolateral prefrontal cortex (DLPFC) and posterior parietal cortex (PPC) showed different degrees of activation and distinct lateralization patterns for different processing domains, which suggests that these regions may implement cognitive control based on the specific task requirements. PMID:27895564

Brain Activity during Mental Imagery of Gait Versus Gait-Like Plantar Stimulation: A Novel Combined Functional MRI Paradigm to Better Understand Cerebral Gait Control.

PubMed

Labriffe, Matthieu; Annweiler, Cédric; Amirova, Liubov E; Gauquelin-Koch, Guillemette; Ter Minassian, Aram; Leiber, Louis-Marie; Beauchet, Olivier; Custaud, Marc-Antoine; Dinomais, Mickaël

2017-01-01

Human locomotion is a complex sensorimotor behavior whose central control remains difficult to explore using neuroimaging method due to technical constraints, notably the impossibility to walk with a scanner on the head and/or to walk for real inside current scanners. The aim of this functional Magnetic Resonance Imaging (fMRI) study was to analyze interactions between two paradigms to investigate the brain gait control network: (1) mental imagery of gait, and (2) passive mechanical stimulation of the plantar surface of the foot with the Korvit boots. The Korvit stimulator was used through two different modes, namely an organized ("gait like") sequence and a destructured (chaotic) pattern. Eighteen right-handed young healthy volunteers were recruited (mean age, 27 ± 4.7 years). Mental imagery activated a broad neuronal network including the supplementary motor area-proper (SMA-proper), pre-SMA, the dorsal premotor cortex, ventrolateral prefrontal cortex, anterior insula, and precuneus/superior parietal areas. The mechanical plantar stimulation activated the primary sensorimotor cortex and secondary somatosensory cortex bilaterally. The paradigms generated statistically common areas of activity, notably bilateral SMA-proper and right pre-SMA, highlighting the potential key role of SMA in gait control. There was no difference between the organized and chaotic Korvit sequences, highlighting the difficulty of developing a walking-specific plantar stimulation paradigm. In conclusion, this combined-fMRI paradigm combining mental imagery and gait-like plantar stimulation provides complementary information regarding gait-related brain activity and appears useful for the assessment of high-level gait control.

Ventral aspect of the visual form pathway is not critical for the perception of biological motion

PubMed Central

Gilaie-Dotan, Sharon; Saygin, Ayse Pinar; Lorenzi, Lauren J.; Rees, Geraint; Behrmann, Marlene

2015-01-01

Identifying the movements of those around us is fundamental for many daily activities, such as recognizing actions, detecting predators, and interacting with others socially. A key question concerns the neurobiological substrates underlying biological motion perception. Although the ventral “form” visual cortex is standardly activated by biologically moving stimuli, whether these activations are functionally critical for biological motion perception or are epiphenomenal remains unknown. To address this question, we examined whether focal damage to regions of the ventral visual cortex, resulting in significant deficits in form perception, adversely affects biological motion perception. Six patients with damage to the ventral cortex were tested with sensitive point-light display paradigms. All patients were able to recognize unmasked point-light displays and their perceptual thresholds were not significantly different from those of three different control groups, one of which comprised brain-damaged patients with spared ventral cortex (n > 50). Importantly, these six patients performed significantly better than patients with damage to regions critical for biological motion perception. To assess the necessary contribution of different regions in the ventral pathway to biological motion perception, we complement the behavioral findings with a fine-grained comparison between the lesion location and extent, and the cortical regions standardly implicated in biological motion processing. This analysis revealed that the ventral aspects of the form pathway (e.g., fusiform regions, ventral extrastriate body area) are not critical for biological motion perception. We hypothesize that the role of these ventral regions is to provide enhanced multiview/posture representations of the moving person rather than to represent biological motion perception per se. PMID:25583504

Activation of cannabinoid system in anterior cingulate cortex and orbitofrontal cortex modulates cost-benefit decision making.

PubMed

Khani, Abbas; Kermani, Mojtaba; Hesam, Soghra; Haghparast, Abbas; Argandoña, Enrike G; Rainer, Gregor

2015-06-01

Despite the evidence for altered decision making in cannabis abusers, the role of the cannabinoid system in decision-making circuits has not been studied. Here, we examined the effects of cannabinoid modulation during cost-benefit decision making in the anterior cingulate cortex (ACC) and orbitofrontal cortex (OFC), key brain areas involved in decision making. We trained different groups of rats in a delay-based and an effort-based form of cost-benefit T-maze decision-making task. During test days, the rats received local injections of either vehicle or ACEA, a cannabinoid type-1 receptor (CB1R) agonist in the ACC or OFC. We measured spontaneous locomotor activity following the same treatments and characterized CB1Rs localization on different neuronal populations within these regions using immunohistochemistry. We showed that CB1R activation in the ACC impaired decision making such that rats were less willing to invest physical effort to gain high reward. Similarly, CB1R activation in the OFC induced impulsive pattern of choice such that rats preferred small immediate rewards to large delayed rewards. Control tasks ensured that the effects were specific for differential cost-benefit tasks. Furthermore, we characterized widespread colocalizations of CB1Rs on GABAergic axonal ends but few colocalizations on glutamatergic, dopaminergic, and serotonergic neuronal ends. These results provide first direct evidence that the cannabinoid system plays a critical role in regulating cost-benefit decision making in the ACC and OFC and implicate cannabinoid modulation of synaptic ends of predominantly interneurons and to a lesser degree other neuronal populations in these two frontal regions.

Effective connectivity of a reward network in obese women

PubMed Central

Stoeckel, Luke E.; Kim, Jieun; Weller, Rosalyn E.; Cox, James E.; Cook, Edwin W.; Horwitz, Barry

2012-01-01

Exaggerated reactivity to food cues in obese women appears to be mediated in part by a hyperactive reward system that includes the nucleus accumbens, amygdala, and orbitofrontal cortex. The present study used fMRI to investigate whether differences between 12 obese and 12 normal-weight women in reward-related brain activation in response to food images can be explained by changes in the functional interactions between key reward network regions. A two-step path analysis/General Linear Model approach was used to test whether there were group differences in network connections between nucleus accumbens, amygdala, and orbitofrontal cortex in response to high- and low-calorie food images. There was abnormal connectivity in the obese group in response to both high- and low-calorie food cues compared to normal-weight controls. Compared to controls, the obese group had a relative deficiency in the amygdala’s modulation of activation in both orbitofrontal cortex and nucleus accumbens, but excessive influence of orbitofrontal cortex’s modulation of activation in nucleus accumbens. The deficient projections from the amygdala might relate to suboptimal modulation of the affective/emotional aspects of a food’s reward value or an associated cue’s motivational salience, whereas increased orbitofrontal cortex to nucleus accumbens connectivity might contribute to a heightened drive to eat in response to a food cue. Thus, it is possible that not only greater activation of the reward system, but also differences in the interaction of regions in this network may contribute to the relatively increased motivational value of foods in obese individuals. PMID:19467298

Neuronal density, size and shape in the human anterior cingulate cortex: a comparison of Nissl and NeuN staining.

PubMed

Gittins, Rebecca; Harrison, Paul J

2004-03-15

There are an increasing number of quantitative morphometric studies of the human cerebral cortex, especially as part of comparative investigations of major psychiatric disorders. In this context, the present study had two aims. First, to provide quantitative data regarding key neuronal morphometric parameters in the anterior cingulate cortex. Second, to compare the results of conventional Nissl staining with those observed after immunostaining with NeuN, an antibody becoming widely used as a selective neuronal marker. We stained adjacent sections of area 24b from 16 adult brains with cresyl violet or NeuN. We measured the density of pyramidal and non-pyramidal neurons, and the size and shape of pyramidal neurons, in laminae II, III, Va, Vb and VI, using two-dimensional counting methods. Strong correlations between the two modes of staining were seen for all variables. However, NeuN gave slightly higher estimates of neuronal density and size, and a more circular perikaryal shape. Brain pH was correlated with neuronal size, measured with both methods, and with neuronal shape. Age and post-mortem interval showed no correlations with any parameter. These data confirm the value of NeuN as a tool for quantitative neuronal morphometric studies in routinely processed human brain tissue. Absolute values are highly correlated between NeuN and cresyl violet stains, but cannot be interchanged. NeuN may be particularly useful when it is important to distinguish small neurons from glia, such as in cytoarchitectural studies of the cerebral cortex in depression and schizophrenia.

Altered Intrinsic Functional Brain Architecture in Children at Familial Risk of Major Depression.

PubMed

Chai, Xiaoqian J; Hirshfeld-Becker, Dina; Biederman, Joseph; Uchida, Mai; Doehrmann, Oliver; Leonard, Julia A; Salvatore, John; Kenworthy, Tara; Brown, Ariel; Kagan, Elana; de Los Angeles, Carlo; Gabrieli, John D E; Whitfield-Gabrieli, Susan

2016-12-01

Neuroimaging studies of patients with major depression have revealed abnormal intrinsic functional connectivity measured during the resting state in multiple distributed networks. However, it is unclear whether these findings reflect the state of major depression or reflect trait neurobiological underpinnings of risk for major depression. We compared resting-state functional connectivity, measured with functional magnetic resonance imaging, between unaffected children of parents who had documented histories of major depression (at-risk, n = 27; 8-14 years of age) and age-matched children of parents with no lifetime history of depression (control subjects, n = 16). At-risk children exhibited hyperconnectivity between the default mode network and subgenual anterior cingulate cortex/orbital frontal cortex, and the magnitude of connectivity positively correlated with individual symptom scores. At-risk children also exhibited 1) hypoconnectivity within the cognitive control network, which also lacked the typical anticorrelation with the default mode network; 2) hypoconnectivity between left dorsolateral prefrontal cortex and subgenual anterior cingulate cortex; and 3) hyperconnectivity between the right amygdala and right inferior frontal gyrus, a key region for top-down modulation of emotion. Classification between at-risk children and control subjects based on resting-state connectivity yielded high accuracy with high sensitivity and specificity that was superior to clinical rating scales. Children at familial risk for depression exhibited atypical functional connectivity in the default mode, cognitive control, and affective networks. Such task-independent functional brain measures of risk for depression in children could be used to promote early intervention to reduce the likelihood of developing depression. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Punishing an error improves learning: the influence of punishment magnitude on error-related neural activity and subsequent learning.

PubMed

Hester, Robert; Murphy, Kevin; Brown, Felicity L; Skilleter, Ashley J

2010-11-17

Punishing an error to shape subsequent performance is a major tenet of individual and societal level behavioral interventions. Recent work examining error-related neural activity has identified that the magnitude of activity in the posterior medial frontal cortex (pMFC) is predictive of learning from an error, whereby greater activity in this region predicts adaptive changes in future cognitive performance. It remains unclear how punishment influences error-related neural mechanisms to effect behavior change, particularly in key regions such as pMFC, which previous work has demonstrated to be insensitive to punishment. Using an associative learning task that provided monetary reward and punishment for recall performance, we observed that when recall errors were categorized by subsequent performance--whether the failure to accurately recall a number-location association was corrected at the next presentation of the same trial--the magnitude of error-related pMFC activity predicted future correction. However, the pMFC region was insensitive to the magnitude of punishment an error received and it was the left insula cortex that predicted learning from the most aversive outcomes. These findings add further evidence to the hypothesis that error-related pMFC activity may reflect more than a prediction error in representing the value of an outcome. The novel role identified here for the insular cortex in learning from punishment appears particularly compelling for our understanding of psychiatric and neurologic conditions that feature both insular cortex dysfunction and a diminished capacity for learning from negative feedback or punishment.

Translational neurocardiology: preclinical models and cardioneural integrative aspects

PubMed Central

Andresen, M. C.; Armour, J. A.; Billman, G. E.; Chen, P.‐S.; Foreman, R. D.; Herring, N.; O'Leary, D. S.; Sabbah, H. N.; Schultz, H. D.; Sunagawa, K.; Zucker, I. H.

2016-01-01

Abstract Neuronal elements distributed throughout the cardiac nervous system, from the level of the insular cortex to the intrinsic cardiac nervous system, are in constant communication with one another to ensure that cardiac output matches the dynamic process of regional blood flow demand. Neural elements in their various ‘levels’ become differentially recruited in the transduction of sensory inputs arising from the heart, major vessels, other visceral organs and somatic structures to optimize neuronal coordination of regional cardiac function. This White Paper will review the relevant aspects of the structural and functional organization for autonomic control of the heart in normal conditions, how these systems remodel/adapt during cardiac disease, and finally how such knowledge can be leveraged in the evolving realm of autonomic regulation therapy for cardiac therapeutics. PMID:27098459

A Collaboration on Collaboration

NASA Technical Reports Server (NTRS)

Cobleigh, Brent

2004-01-01

NASA's 2003-2004 Leadership Development Program class recognized that effective collaborations are often the key to achieving mission success. Personal connections and common goals were key elements of their work together and key findings of their collaboration benchmarking within the agency.

Repetitive element transcripts are elevated in the brain of C9orf72 ALS/FTLD patients.

PubMed

Prudencio, Mercedes; Gonzales, Patrick K; Cook, Casey N; Gendron, Tania F; Daughrity, Lillian M; Song, Yuping; Ebbert, Mark T W; van Blitterswijk, Marka; Zhang, Yong-Jie; Jansen-West, Karen; Baker, Matthew C; DeTure, Michael; Rademakers, Rosa; Boylan, Kevin B; Dickson, Dennis W; Petrucelli, Leonard; Link, Christopher D

2017-09-01

Significant transcriptome alterations are detected in the brain of patients with amyotrophic lateral sclerosis (ALS), including carriers of the C9orf72 repeat expansion and C9orf72-negative sporadic cases. Recently, the expression of repetitive element transcripts has been associated with toxicity and, while increased repetitive element expression has been observed in several neurodegenerative diseases, little is known about their contribution to ALS. To assess whether aberrant expression of repetitive element sequences are observed in ALS, we analysed RNA sequencing data from C9orf72-positive and sporadic ALS cases, as well as healthy controls. Transcripts from multiple classes and subclasses of repetitive elements (LINEs, endogenous retroviruses, DNA transposons, simple repeats, etc.) were significantly increased in the frontal cortex of C9orf72 ALS patients. A large collection of patient samples, representing both C9orf72 positive and negative ALS, ALS/FTLD, and FTLD cases, was used to validate the levels of several repetitive element transcripts. These analyses confirmed that repetitive element expression was significantly increased in C9orf72-positive compared to C9orf72-negative or control cases. While previous studies suggest an important link between TDP-43 and repetitive element biology, our data indicate that TDP-43 pathology alone is insufficient to account for the observed changes in repetitive elements in ALS/FTLD. Instead, we found that repetitive element expression positively correlated with RNA polymerase II activity in postmortem brain, and pharmacologic modulation of RNA polymerase II activity altered repetitive element expression in vitro. We conclude that increased RNA polymerase II activity in ALS/FTLD may lead to increased repetitive element transcript expression, a novel pathological feature of ALS/FTLD. © The Author 2017. Published by Oxford University Press.

Societal-Equity-Enhancing Criteria and Facility-Host Incentives Supporting Five Key Elements in the January 2012 Blue Ribbon Commission Report - 13015

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eriksson, Leif G.; Dials, George E.; George, Critz H.

2013-07-01

In February 2009, the Obama Administration announced it would abandon USA's only candidate SNF/HLW-disposal facility since 1987. In 2010, all related activities were stopped and the Blue Ribbon Commission on America's Nuclear Future was established 'to recommend a new strategy for managing the back end of the nuclear fuel cycle', which it did in January 2012, emphasizing eight key elements. However, Key Element 1, 'A new, consent-based approach to siting future nuclear facilities', is qualitative/indeterminate rather than quantitative/measurable. It is thus highly-susceptible to semantic permutations that could extend rather than, as intended, expedite the siting of future nuclear facilities unlessmore » it also defines: a) Whose consent is needed?; and b) What constitutes consent? The following 'generic', radiation-risk- and societal-equity-based criteria address these questions: 1. Identify areas affected by projected radiation and other health risks from: a. The proposed nuclear facility (facility stakeholders); and b. The related nuclear-materials-transportation routes (transportation stakeholders); then 2. Surround each stakeholder area with a buffer zone and use this enlarged foot print to identify: a. Stakeholder hosts; and b. Areas not hosting any stakeholder category (interested parties). 3. Define 'consent-based' as being at least 60 percent of the 'population' in the respective stakeholder category and apply this yardstick to both 'in favor' and 'against' votes. Although criteria 1 and 2 also need facility-based definitions to make Key Element 1 measurable, the described siting approach, augmented by related facility-host incentives, would expedite the schedule and reduce the cost for achieving Key Elements 4-6 and 8, politics permitting. (authors)« less

Proteomic analysis of synaptoneurosomes highlights the relevant role of local translation in the hippocampus.

PubMed

Benito, Itziar; Casañas, Juan José; Montesinos, María Luz

2018-06-19

Several proteomic analyses have been performed on synaptic fractions isolated from cortex or even total brain, resulting in preparations with a high synaptic heterogeneity and complexity. Synaptoneurosomes (SNs) are subcellular membranous elements that contain sealed pre- and post-synaptic components. They are obtained by subcellular fractionation of brain homogenates and serve as a suitable model to study many aspects of the synapse physiology. Here we report the proteomic content of SNs isolated from hippocampus of adult mice, a brain region involved in memory that presents lower synaptic heterogeneity than cortex. Interestingly, in addition to pre- and post-synaptic proteins, we found that proteins involved in RNA binding and translation were overrepresented in our preparation. These results validate the protocol we previously reported for SNs isolation, and, as reported by other authors, highlight the relevance of local synaptic translation for hippocampal physiology. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Identification of Germ Plasm-Associated Transcripts by Microarray Analysis of Xenopus Vegetal Cortex RNA

PubMed Central

Cuykendall, Tawny N.; Houston, Douglas W.

2011-01-01

RNA localization is a common mechanism for regulating cell structure and function. Localized RNAs in Xenopus oocytes are critical for early development, including germline specification by the germ plasm. Despite the importance of these localized RNAs, only approximately 25 have been identified and fewer are functionally characterized. Using microarrays, we identified a large set of localized RNAs from the vegetal cortex. Overall, our results indicate a minimum of 275 localized RNAs in oocytes, or 2–3% of maternal transcripts, which are in general agreement with previous findings. We further validated vegetal localization for 24 candidates and further characterized three genes expressed in the germ plasm. We identified novel germ plasm expression for reticulon 3.1, exd2 (a novel exonuclease-domain encoding gene), and a putative noncoding RNA. Further analysis of these and other localized RNAs will likely identify new functions of germ plasm and facilitate the identification of cis-acting RNA localization elements. PMID:20503379

Separate elements of episodic memory subserved by distinct hippocampal-prefrontal connections.

PubMed

Barker, Gareth R I; Banks, Paul J; Scott, Hannah; Ralph, G Scott; Mitrophanous, Kyriacos A; Wong, Liang-Fong; Bashir, Zafar I; Uney, James B; Warburton, E Clea

2017-02-01

Episodic memory formation depends on information about a stimulus being integrated within a precise spatial and temporal context, a process dependent on the hippocampus and prefrontal cortex. Investigations of putative functional interactions between these regions are complicated by multiple direct and indirect hippocampal-prefrontal connections. Here application of a pharmacogenetic deactivation technique enabled us to investigate the mnemonic contributions of two direct hippocampal-medial prefrontal cortex (mPFC) pathways, one arising in the dorsal CA1 (dCA1) and the other in the intermediate CA1 (iCA1). While deactivation of either pathway impaired episodic memory, the resulting pattern of mnemonic deficits was different: deactivation of the dCA1→mPFC pathway selectively disrupted temporal order judgments while iCA1→mPFC pathway deactivation disrupted spatial memory. These findings reveal a previously unsuspected division of function among CA1 neurons that project directly to the mPFC. Such subnetworks may enable the distinctiveness of contextual information to be maintained in an episodic memory circuit.

Shell bone histology of the long-necked chelid Yaminuechelys (Testudines: Pleurodira) from the late Cretaceous—early Palaeocene of Patagonia with comments on the histogenesis of bone ornamentation

NASA Astrophysics Data System (ADS)

Jannello, Juan Marcos; Cerda, Ignacio A.; de la Fuente, Marcelo S.

2016-04-01

Yaminuechelys is a long-necked chelid turtle whose remains have been recovered from outcrops of the Santonian-Maastrichtian and Danian of South America. With the purpose of providing data about shell sculpturing origin and palaeoecology, the bone histology of several shell elements (including neural, costal, peripheral and plastral plates) of Yaminuechelys is described herein. Histological analysis reveals that Yaminuechelys shares with Chelidae the presence of interwoven structural fibre bundles in the external cortex, and parallel-fibred bone of the internal cortex. The presence of resorption lines in several samples indicates that the particular ornamentation of the external surfaces originated, at least in part, by focalized resorption and new bone deposition. This mechanism for ornamentation origin and maintenance is here described for the first time in a turtle. Compactness of the shell bones is consistent with an aquatic habitat, which supports previous hypothesis based on palaeoenvironmental and morphological data.

Dendritic branching angles of pyramidal cells across layers of the juvenile rat somatosensory cortex.

PubMed

Leguey, Ignacio; Bielza, Concha; Larrañaga, Pedro; Kastanauskaite, Asta; Rojo, Concepción; Benavides-Piccione, Ruth; DeFelipe, Javier

2016-09-01

The characterization of the structural design of cortical microcircuits is essential for understanding how they contribute to function in both health and disease. Since pyramidal neurons represent the most abundant neuronal type and their dendritic spines constitute the major postsynaptic elements of cortical excitatory synapses, our understanding of the synaptic organization of the neocortex largely depends on the available knowledge regarding the structure of pyramidal cells. Previous studies have identified several apparently common rules in dendritic geometry. We study the dendritic branching angles of pyramidal cells across layers to further shed light on the principles that determine the geometric shapes of these cells. We find that the dendritic branching angles of pyramidal cells from layers II-VI of the juvenile rat somatosensory cortex suggest common design principles, despite the particular morphological and functional features that are characteristic of pyramidal cells in each cortical layer. J. Comp. Neurol. 524:2567-2576, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Suppressive and enhancing effects in early visual cortex during illusory shape perception: A comment on.

PubMed

Moors, Pieter

2015-01-01

In a recent functional magnetic resonance imaging study, Kok and de Lange (2014) observed that BOLD activity for a Kanizsa illusory shape stimulus, in which pacmen-like inducers elicit an illusory shape percept, was either enhanced or suppressed relative to a nonillusory control configuration depending on whether the spatial profile of BOLD activity in early visual cortex was related to the illusory shape or the inducers, respectively. The authors argued that these findings fit well with the predictive coding framework, because top-down predictions related to the illusory shape are not met with bottom-up sensory input and hence the feedforward error signal is enhanced. Conversely, for the inducing elements, there is a match between top-down predictions and input, leading to a decrease in error. Rather than invoking predictive coding as the explanatory framework, the suppressive effect related to the inducers might be caused by neural adaptation to perceptually stable input due to the trial sequence used in the experiment.

Voluntary medical male circumcision: a qualitative study exploring the challenges of costing demand creation in eastern and southern Africa.

PubMed

Bertrand, Jane T; Njeuhmeli, Emmanuel; Forsythe, Steven; Mattison, Sarah K; Mahler, Hally; Hankins, Catherine A

2011-01-01

This paper proposes an approach to estimating the costs of demand creation for voluntary medical male circumcision (VMMC) scale-up in 13 countries of eastern and southern Africa. It addresses two key questions: (1) what are the elements of a standardized package for demand creation? And (2) what challenges exist and must be taken into account in estimating the costs of demand creation? We conducted a key informant study on VMMC demand creation using purposive sampling to recruit seven people who provide technical assistance to government programs and manage budgets for VMMC demand creation. Key informants provided their views on the important elements of VMMC demand creation and the most effective funding allocations across different types of communication approaches (e.g., mass media, small media, outreach/mobilization). The key finding was the wide range of views, suggesting that a standard package of core demand creation elements would not be universally applicable. This underscored the importance of tailoring demand creation strategies and estimates to specific country contexts before estimating costs. The key informant interviews, supplemented by the researchers' field experience, identified these issues to be addressed in future costing exercises: variations in the cost of VMMC demand creation activities by country and program, decisions about the quality and comprehensiveness of programming, and lack of data on critical elements needed to "trigger the decision" among eligible men. Based on this study's findings, we propose a seven-step methodological approach to estimate the cost of VMMC scale-up in a priority country, based on our key assumptions. However, further work is needed to better understand core components of a demand creation package and how to cost them. Notwithstanding the methodological challenges, estimating the cost of demand creation remains an essential element in deriving estimates of the total costs for VMMC scale-up in eastern and southern Africa.

Voluntary Medical Male Circumcision: A Qualitative Study Exploring the Challenges of Costing Demand Creation in Eastern and Southern Africa

PubMed Central

Bertrand, Jane T.; Njeuhmeli, Emmanuel; Forsythe, Steven; Mattison, Sarah K.; Mahler, Hally; Hankins, Catherine A.

2011-01-01

Background This paper proposes an approach to estimating the costs of demand creation for voluntary medical male circumcision (VMMC) scale-up in 13 countries of eastern and southern Africa. It addresses two key questions: (1) what are the elements of a standardized package for demand creation? And (2) what challenges exist and must be taken into account in estimating the costs of demand creation? Methods and Findings We conducted a key informant study on VMMC demand creation using purposive sampling to recruit seven people who provide technical assistance to government programs and manage budgets for VMMC demand creation. Key informants provided their views on the important elements of VMMC demand creation and the most effective funding allocations across different types of communication approaches (e.g., mass media, small media, outreach/mobilization). The key finding was the wide range of views, suggesting that a standard package of core demand creation elements would not be universally applicable. This underscored the importance of tailoring demand creation strategies and estimates to specific country contexts before estimating costs. The key informant interviews, supplemented by the researchers' field experience, identified these issues to be addressed in future costing exercises: variations in the cost of VMMC demand creation activities by country and program, decisions about the quality and comprehensiveness of programming, and lack of data on critical elements needed to “trigger the decision” among eligible men. Conclusions Based on this study's findings, we propose a seven-step methodological approach to estimate the cost of VMMC scale-up in a priority country, based on our key assumptions. However, further work is needed to better understand core components of a demand creation package and how to cost them. Notwithstanding the methodological challenges, estimating the cost of demand creation remains an essential element in deriving estimates of the total costs for VMMC scale-up in eastern and southern Africa. PMID:22140450

Parallel and serial grouping of image elements in visual perception.

PubMed

Houtkamp, Roos; Roelfsema, Pieter R

2010-12-01

The visual system groups image elements that belong to an object and segregates them from other objects and the background. Important cues for this grouping process are the Gestalt criteria, and most theories propose that these are applied in parallel across the visual scene. Here, we find that Gestalt grouping can indeed occur in parallel in some situations, but we demonstrate that there are also situations where Gestalt grouping becomes serial. We observe substantial time delays when image elements have to be grouped indirectly through a chain of local groupings. We call this chaining process incremental grouping and demonstrate that it can occur for only a single object at a time. We suggest that incremental grouping requires the gradual spread of object-based attention so that eventually all the object's parts become grouped explicitly by an attentional labeling process. Our findings inspire a new incremental grouping theory that relates the parallel, local grouping process to feedforward processing and the serial, incremental grouping process to recurrent processing in the visual cortex.

Assessing the significance of Palaeolithic engraved cortexes. A case study from the Mousterian site of Kiik-Koba, Crimea

PubMed Central

d’Errico, Francesco; Stepanchuk, Vadim

2018-01-01

Twenty-Seven Lower and Middle Paleolithic sites from Europe and the Middle East are reported in the literature to have yielded incised stones. At eleven of these sites incisions are present on flint cortexes. Even when it is possible to demonstrate that the engravings are ancient and human made, it is often difficult to distinguish incisions resulting from functional activities such as butchery or use as a cutting board, from those produced deliberately, and even more difficult to identify the scope of the latter. In this paper we present results of the analysis of an engraved cortical flint flake found at Kiik-Koba, a key Mousterian site from Crimea, and create an interpretative framework to guide the interpretation of incised cortexes. The frame of inference that we propose allows for a reasoned evaluation of the actions playing a role in the marking process and aims at narrowing down the interpretation of the evidence. The object comes from layer IV, the same layer in which a Neanderthal child burial was unearthed, which contains a para-Micoquian industry of Kiik-Koba type dated to between c.35 and 37 cal kyr BP. The microscopic analysis and 3D reconstruction of the grooves on the cortex of this small flint flake, demonstrate that the incisions represent a deliberate engraving made by a skilled craftsman, probably with two different points. The lines are nearly perfectly framed into the cortex, testifying of well controlled motions. This is especially the case considering the small size of the object, which makes this a difficult task. The production of the engraving required excellent neuromotor and volitional control, which implies focused attention. Evaluation of the Kiik-Koba evidence in the light of the proposed interpretative framework supports the view that the engraving was made with a representational intent. PMID:29718916

Assessing the significance of Palaeolithic engraved cortexes. A case study from the Mousterian site of Kiik-Koba, Crimea.

PubMed

Majkić, Ana; d'Errico, Francesco; Stepanchuk, Vadim

2018-01-01

Twenty-Seven Lower and Middle Paleolithic sites from Europe and the Middle East are reported in the literature to have yielded incised stones. At eleven of these sites incisions are present on flint cortexes. Even when it is possible to demonstrate that the engravings are ancient and human made, it is often difficult to distinguish incisions resulting from functional activities such as butchery or use as a cutting board, from those produced deliberately, and even more difficult to identify the scope of the latter. In this paper we present results of the analysis of an engraved cortical flint flake found at Kiik-Koba, a key Mousterian site from Crimea, and create an interpretative framework to guide the interpretation of incised cortexes. The frame of inference that we propose allows for a reasoned evaluation of the actions playing a role in the marking process and aims at narrowing down the interpretation of the evidence. The object comes from layer IV, the same layer in which a Neanderthal child burial was unearthed, which contains a para-Micoquian industry of Kiik-Koba type dated to between c.35 and 37 cal kyr BP. The microscopic analysis and 3D reconstruction of the grooves on the cortex of this small flint flake, demonstrate that the incisions represent a deliberate engraving made by a skilled craftsman, probably with two different points. The lines are nearly perfectly framed into the cortex, testifying of well controlled motions. This is especially the case considering the small size of the object, which makes this a difficult task. The production of the engraving required excellent neuromotor and volitional control, which implies focused attention. Evaluation of the Kiik-Koba evidence in the light of the proposed interpretative framework supports the view that the engraving was made with a representational intent.

Dynamics of Aerenchyma Distribution in the Cortex of Sulfate-deprived Adventitious Roots of Maize

PubMed Central

BOURANIS, DIMITRIS L.; CHORIANOPOULOU, STYLIANI N.; KOLLIAS, CHARALAMBOS; MANIOU, PHILIPPA; PROTONOTARIOS, VASSILIS E.; SIYIANNIS, VASSILIS F.; HAWKESFORD, MALCOLM J.

2006-01-01

• Background and Aims Aerenchyma formation in maize adventitious roots is induced in nutrient solution by the deprivation of sulfate (S) under well-oxygenated conditions. The aim of this research was to examine the extent of aerenchyma formation in the cortex of sulfate-deprived adventitious roots along the root axis, in correlation with the presence of reactive oxygen species (ROS), calcium levels and pH of cortex cells and root lignification. • Methods The morphometry of the second whorl of adventitious (W2) roots, subject to S-deprivation conditions throughout development, was recorded in terms of root length and lateral root length and distribution. W2 roots divided into sectors according to the mean length of lateral roots, and cross-sections of each were examined for aerenchyma. In-situ detection of alterations in ROS presence, calcium levels and pH were performed by means of fluorescence microscopy using H2DCF-DA, fluo-3AM and BCECF, respectively. Lignification was detected using the Wiesner test. • Key Results S-deprivation reduced shoot growth and enhanced root proliferation. Aerenchyma was found in the cortex of 77 % of the root length, particularly in the region of emerging or developing lateral roots. The basal and apical sectors had no aerenchyma and no aerenchyma connection was found with the shoot. S-deprivation resulted in alterations of ROS, calcium levels and pH in aerenchymatous sectors compared with the basal non-aerenchymatous region. Lignified epidermal layers were located at the basal and the proximal sectors. S-deprivation resulted in shorter lateral roots in the upper sectors and in a limited extension of the lignified layers towards the next lateral root carrying sector. • Conclusions Lateral root proliferation is accompanied by spatially localized induced cell death in the cortex of developing young maize adventitious roots during S-deprivation. PMID:16481362

Platinum Partitioning at Low Oxygen Fugacity: Implications for Core Formation Processes

NASA Technical Reports Server (NTRS)

Medard, E.; Martin, A. M.; Righter, K.; Lanziroti, A.; Newville, M.

2016-01-01

Highly siderophile elements (HSE = Au, Re, and the Pt-group elements) are tracers of silicate / metal interactions during planetary processes. Since most core-formation models involve some state of equilibrium between liquid silicate and liquid metal, understanding the partioning of highly siderophile elements (HSE) between silicate and metallic melts is a key issue for models of core / mantle equilibria and for core formation scenarios. However, partitioning models for HSE are still inaccurate due to the lack of sufficient experimental constraints to describe the variations of partitioning with key variable like temperature, pressure, and oxygen fugacity. In this abstract, we describe a self-consistent set of experiments aimed at determining the valence of platinum, one of the HSE, in silicate melts. This is a key information required to parameterize the evolution of platinum partitioning with oxygen fugacity.

Effect of continuous theta burst stimulation of the right dorsolateral prefrontal cortex on cerebral blood flow changes during decision making.

PubMed

Cho, Sang Soo; Pellecchia, Giovanna; Ko, Ji Hyun; Ray, Nicola; Obeso, Ignacio; Houle, Sylvain; Strafella, Antonio P

2012-04-01

Decision making is a cognitive function relaying on a complex neural network. In particular, the right dorsolateral prefrontal cortex (DLPFC) plays a key role within this network. We used positron emission tomography (PET) combined with continuous theta burst transcranial magnetic stimulation (cTBS) to investigate neuronal and behavioral changes in normal volunteers while performing a delay discounting (DD) task. We aimed to test whether stimulation of right DLPFC would modify the activation pattern of the neural circuit underlying decision making during the DD task and influence discounting behavior. We found that cTBS of the right DLPFC influenced decision making by reducing impulsivity and inducing participants to favor large but delayed rewards instead of immediate but small rewards. Stimulation also affected activation in several prefrontal areas associated with DD. In particular, we observed a reduced regional cerebral blood flow (rCBF) in the ipsilateral DLPFC (BA 46) extending into the rostral part of the prefrontal cortex (BA 10) as well as a disrupted relationship between impulsivity (k-value) and rCBF in these and other prefrontal areas. These findings suggest that transcranial magnetic stimulation of the DLPFC influences the neural network underlying impulsive decision making behavior. Copyright © 2012 Elsevier Inc. All rights reserved.

Spatially generalizable representations of facial expressions: Decoding across partial face samples.

PubMed

Greening, Steven G; Mitchell, Derek G V; Smith, Fraser W

2018-04-01

A network of cortical and sub-cortical regions is known to be important in the processing of facial expression. However, to date no study has investigated whether representations of facial expressions present in this network permit generalization across independent samples of face information (e.g., eye region vs mouth region). We presented participants with partial face samples of five expression categories in a rapid event-related fMRI experiment. We reveal a network of face-sensitive regions that contain information about facial expression categories regardless of which part of the face is presented. We further reveal that the neural information present in a subset of these regions: dorsal prefrontal cortex (dPFC), superior temporal sulcus (STS), lateral occipital and ventral temporal cortex, and even early visual cortex, enables reliable generalization across independent visual inputs (faces depicting the 'eyes only' vs 'eyes removed'). Furthermore, classification performance was correlated to behavioral performance in STS and dPFC. Our results demonstrate that both higher (e.g., STS, dPFC) and lower level cortical regions contain information useful for facial expression decoding that go beyond the visual information presented, and implicate a key role for contextual mechanisms such as cortical feedback in facial expression perception under challenging conditions of visual occlusion. Copyright © 2017 Elsevier Ltd. All rights reserved.

A specific area of olfactory cortex involved in stress hormone responses to predator odours.

PubMed

Kondoh, Kunio; Lu, Zhonghua; Ye, Xiaolan; Olson, David P; Lowell, Bradford B; Buck, Linda B

2016-04-07

Instinctive reactions to danger are critical to the perpetuation of species and are observed throughout the animal kingdom. The scent of predators induces an instinctive fear response in mice that includes behavioural changes, as well as a surge in blood stress hormones that mobilizes multiple body systems to escape impending danger. How the olfactory system routes predator signals detected in the nose to achieve these effects is unknown. Here we identify a specific area of the olfactory cortex in mice that induces stress hormone responses to volatile predator odours. Using monosynaptic and polysynaptic viral tracers, we found that multiple olfactory cortical areas transmit signals to hypothalamic corticotropin-releasing hormone (CRH) neurons, which control stress hormone levels. However, only one minor cortical area, the amygdalo-piriform transition area (AmPir), contained neurons upstream of CRH neurons that were activated by volatile predator odours. Chemogenetic stimulation of AmPir activated CRH neurons and induced an increase in blood stress hormones, mimicking an instinctive fear response. Moreover, chemogenetic silencing of AmPir markedly reduced the stress hormone response to predator odours without affecting a fear behaviour. These findings suggest that AmPir, a small area comprising <5% of the olfactory cortex, plays a key part in the hormonal component of the instinctive fear response to volatile predator scents.

Parasol cell mosaics are unlikely to drive the formation of structured orientation maps in primary visual cortex.

PubMed

Hore, Victoria R A; Troy, John B; Eglen, Stephen J

2012-11-01

The receptive fields of on- and off-center parasol cell mosaics independently tile the retina to ensure efficient sampling of visual space. A recent theoretical model represented the on- and off-center mosaics by noisy hexagonal lattices of slightly different density. When the two lattices are overlaid, long-range Moiré interference patterns are generated. These Moiré interference patterns have been suggested to drive the formation of highly structured orientation maps in visual cortex. Here, we show that noisy hexagonal lattices do not capture the spatial statistics of parasol cell mosaics. An alternative model based upon local exclusion zones, termed as the pairwise interaction point process (PIPP) model, generates patterns that are statistically indistinguishable from parasol cell mosaics. A key difference between the PIPP model and the hexagonal lattice model is that the PIPP model does not generate Moiré interference patterns, and hence stimulated orientation maps do not show any hexagonal structure. Finally, we estimate the spatial extent of spatial correlations in parasol cell mosaics to be only 200-350 μm, far less than that required to generate Moiré interference. We conclude that parasol cell mosaics are too disordered to drive the formation of highly structured orientation maps in visual cortex.

Neural Correlates of Temporal Complexity and Synchrony during Audiovisual Correspondence Detection.

PubMed

Baumann, Oliver; Vromen, Joyce M G; Cheung, Allen; McFadyen, Jessica; Ren, Yudan; Guo, Christine C

2018-01-01

We often perceive real-life objects as multisensory cues through space and time. A key challenge for audiovisual integration is to match neural signals that not only originate from different sensory modalities but also that typically reach the observer at slightly different times. In humans, complex, unpredictable audiovisual streams lead to higher levels of perceptual coherence than predictable, rhythmic streams. In addition, perceptual coherence for complex signals seems less affected by increased asynchrony between visual and auditory modalities than for simple signals. Here, we used functional magnetic resonance imaging to determine the human neural correlates of audiovisual signals with different levels of temporal complexity and synchrony. Our study demonstrated that greater perceptual asynchrony and lower signal complexity impaired performance in an audiovisual coherence-matching task. Differences in asynchrony and complexity were also underpinned by a partially different set of brain regions. In particular, our results suggest that, while regions in the dorsolateral prefrontal cortex (DLPFC) were modulated by differences in memory load due to stimulus asynchrony, areas traditionally thought to be involved in speech production and recognition, such as the inferior frontal and superior temporal cortex, were modulated by the temporal complexity of the audiovisual signals. Our results, therefore, indicate specific processing roles for different subregions of the fronto-temporal cortex during audiovisual coherence detection.

Altered intrinsic and extrinsic connectivity in schizophrenia.

PubMed

Zhou, Yuan; Zeidman, Peter; Wu, Shihao; Razi, Adeel; Chen, Cheng; Yang, Liuqing; Zou, Jilin; Wang, Gaohua; Wang, Huiling; Friston, Karl J

2018-01-01

Schizophrenia is a disorder characterized by functional dysconnectivity among distributed brain regions. However, it is unclear how causal influences among large-scale brain networks are disrupted in schizophrenia. In this study, we used dynamic causal modeling (DCM) to assess the hypothesis that there is aberrant directed (effective) connectivity within and between three key large-scale brain networks (the dorsal attention network, the salience network and the default mode network) in schizophrenia during a working memory task. Functional MRI data during an n-back task from 40 patients with schizophrenia and 62 healthy controls were analyzed. Using hierarchical modeling of between-subject effects in DCM with Parametric Empirical Bayes, we found that intrinsic (within-region) and extrinsic (between-region) effective connectivity involving prefrontal regions were abnormal in schizophrenia. Specifically, in patients (i) inhibitory self-connections in prefrontal regions of the dorsal attention network were decreased across task conditions; (ii) extrinsic connectivity between regions of the default mode network was increased; specifically, from posterior cingulate cortex to the medial prefrontal cortex; (iii) between-network extrinsic connections involving the prefrontal cortex were altered; (iv) connections within networks and between networks were correlated with the severity of clinical symptoms and impaired cognition beyond working memory. In short, this study revealed the predominance of reduced synaptic efficacy of prefrontal efferents and afferents in the pathophysiology of schizophrenia.

The motilin agonist erythromycin increases hunger by modulating homeostatic and hedonic brain circuits in healthy women: a randomized, placebo-controlled study.

PubMed

Zhao, Dongxing; Meyer-Gerspach, Anne Christin; Deloose, Eveline; Iven, Julie; Weltens, Nathalie; Depoortere, Inge; O'daly, Owen; Tack, Jan; Van Oudenhove, Lukas

2018-01-29

The motilin agonist, erythromycin, induces gastric phase III of the migrating motor complex, which in turn generates hunger peaks. To identify the brain mechanisms underlying these orexigenic effects, 14 healthy women participated in a randomized, placebo-controlled crossover study. Functional magnetic resonance brain images were acquired for 50 minutes interprandially. Intravenous infusion of erythromycin (40 mg) or saline started 10 minutes after the start of scanning. Blood samples (for glucose and hormone levels) and hunger ratings were collected at fixed timepoints. Thirteen volunteers completed the study, without any adverse events. Brain regions involved in homeostatic and hedonic control of appetite and food intake responded to erythromycin, including pregenual anterior cingulate cortex, anterior insula cortex, orbitofrontal cortex, amygdala, caudate, pallidum and putamen bilaterally, right accumbens, hypothalamus, and midbrain. Octanoylated ghrelin levels decreased, whereas both glucose and insulin increased after erythromycin. Hunger were higher after erythromycin, and these differences covaried with the brain response in most of the abovementioned regions. The motilin agonist erythromycin increases hunger by modulating neurocircuitry related to homeostatic and hedonic control of appetite and feeding. These results confirm recent behavioural findings identifying motilin as a key orexigenic hormone in humans, and identify the brain mechanisms underlying its effect.

Phylogeny and expression pattern of starch branching enzyme family genes in cassava (Manihot esculenta Crantz) under diverse environments.

PubMed

Pei, Jinli; Wang, Huijun; Xia, Zhiqiang; Liu, Chen; Chen, Xin; Ma, Pingan; Lu, Cheng; Wang, Wenquan

2015-08-01

Starch branching enzyme (SBE) is one of the key enzymes involved in starch biosynthetic metabolism. In this study, six SBE family genes were identified from the cassava genome. Phylogenetic analysis divided the MeSBE family genes into dicot family A, B, C, and the new group. Tissue-specific analysis showed that MeSBE2.2 was strongly expressed in leaves, stems cortex, and root stele, and MeSBE3 had high expression levels in stem cortex and root stele of plants in the rapid growth stage under field condition, whereas the expression levels of MeSBE2.1, MeSBE4, and MeSBE5 were low except for in stems cortex. The transcriptional activity of MeSBE2.2 and MeSBE3 was higher compared with other members and gradually increased in the storage roots during root growth process, while the other MeSBE members normally remained low expression levels. Expression of MeSBE2.2 could be induced by salt, drought, exogenous abscisic acid, jasmonic acid, and salicylic acid signals, while MeSBE3 had positive response to drought, salt, exogenous abscisic acid, and salicylic acid in leaves but not in storage root, indicating that they might be more important in starch biosynthesis pathway under diverse environments.

How demanding is the brain on a reversal task under day and night conditions?

PubMed

Arias, N; Fidalgo, C; Méndez, M; Arias, J L

2015-07-23

Reversal learning has been studied as the process of learning to inhibit previously rewarded actions. These behavioral studies are usually performed during the day, when animals are in their daily period rest. However, how day or night affects spatial reversal learning and the brain regions involved in the learning process are still unknown. We conducted two experiments using the Morris Water Maze under different light-conditions: naïve group (CN, n=8), day group (DY, n=8), control DY group (CDY, n=8) night group (NG, n=8), and control NG group (CNG, n=7). Distance covered, velocity and latencies to reach the platform were examined. After completing these tasks, cytochrome c-oxidase activity (CO) in several brain limbic system structures was compared between groups. There were no behavioral differences in the time of day when the animals were trained. However, the metabolic brain consumption was higher in rats trained in the day condition. This CO increase was supported by the prefrontal cortex, thalamus, dorsal and ventral striatum, hippocampus and entorhinal cortex, revealing their role in the performance of the spatial reversal learning task. Finally, the orbitofrontal cortex has been revealed as a key structure in reversal learning execution. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.