Architecture of Explanatory Inference in the Human Prefrontal Cortex

PubMed Central

Barbey, Aron K.; Patterson, Richard

2011-01-01

Causal reasoning is a ubiquitous feature of human cognition. We continuously seek to understand, at least implicitly and often explicitly, the causal scenarios in which we live, so that we may anticipate what will come next, plan a potential response and envision its outcome, decide among possible courses of action in light of their probable outcomes, make midstream adjustments in our goal-related activities as our situation changes, and so on. A considerable body of research shows that the lateral prefrontal cortex (PFC) is crucial for causal reasoning, but also that there are significant differences in the manner in which ventrolateral PFC, dorsolateral PFC, and anterolateral PFC support causal reasoning. We propose, on the basis of research on the evolution, architecture, and functional organization of the lateral PFC, a general framework for understanding its roles in the many and varied sorts of causal reasoning carried out by human beings. Specifically, the ventrolateral PFC supports the generation of basic causal explanations and inferences; dorsolateral PFC supports the evaluation of these scenarios in light of some given normative standard (e.g., of plausibility or correctness in light of real or imagined causal interventions); and anterolateral PFC supports explanation and inference at an even higher level of complexity, coordinating the processes of generation and evaluation with further cognitive processes, and especially with computations of hedonic value and emotional implications of possible behavioral scenarios – considerations that are often critical both for understanding situations causally and for deciding about our own courses of action. PMID:21845182

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.

Discriminant analysis of functional optical topography for schizophrenia diagnosis

NASA Astrophysics Data System (ADS)

Chuang, Ching-Cheng; Nakagome, Kazuyuki; Pu, Shenghong; Lan, Tsuo-Hung; Lee, Chia-Yen; Sun, Chia-Wei

2014-01-01

Abnormal prefrontal function plays a central role in the cognition deficits of schizophrenic patients; however, the character of the relationship between discriminant analysis and prefrontal activation remains undetermined. Recently, evidence of low prefrontal cortex (PFC) activation in individuals with schizophrenia has also been found during verbal fluency tests (VFT) and other cognitive tests with several neuroimaging methods. The purpose of this study is to assess the hemodynamic changes of the PFC and discriminant analysis between schizophrenia patients and healthy controls during VFT task by utilizing functional optical topography. A total of 99 subjects including 53 schizophrenic patients and 46 age- and gender-matched healthy controls were studied. The results showed that the healthy group had larger activation in the right and left PFC than in the middle PFC. Besides, the schizophrenic group showed weaker task performance and lower activation in the whole PFC than the healthy group. The result of the discriminant analysis showed a significant difference with P value <0.001 in six channels (CH 23, 29, 31, 40, 42, 52) between the schizophrenic and healthy groups. Finally, 68.69% and 71.72% of subjects are correctly classified as being schizophrenic or healthy with all 52 channels and six significantly different channels, respectively. Our findings suggest that the left PFC can be a feature region for discriminant analysis of schizophrenic diagnosis.

Anxiety Evokes Hypofrontality and Disrupts Rule-Relevant Encoding by Dorsomedial Prefrontal Cortex Neurons.

PubMed

Park, Junchol; Wood, Jesse; Bondi, Corina; Del Arco, Alberto; Moghaddam, Bita

2016-03-16

Anxiety is a debilitating symptom of most psychiatric disorders, including major depression, post-traumatic stress disorder, schizophrenia, and addiction. A detrimental aspect of anxiety is disruption of prefrontal cortex (PFC)-mediated executive functions, such as flexible decision making. Here we sought to understand how anxiety modulates PFC neuronal encoding of flexible shifting between behavioral strategies. We used a clinically substantiated anxiogenic treatment to induce sustained anxiety in rats and recorded from dorsomedial PFC (dmPFC) and orbitofrontal cortex (OFC) neurons while they were freely moving in a home cage and while they performed a PFC-dependent task that required flexible switches between rules in two distinct perceptual dimensions. Anxiety elicited a sustained background "hypofrontality" in dmPFC and OFC by reducing the firing rate of spontaneously active neuronal subpopulations. During task performance, the impact of anxiety was subtle, but, consistent with human data, behavior was selectively impaired when previously correct conditions were presented as conflicting choices. This impairment was associated with reduced recruitment of dmPFC neurons that selectively represented task rules at the time of action. OFC rule representation was not affected by anxiety. These data indicate that a neural substrate of the decision-making deficits in anxiety is diminished dmPFC neuronal encoding of task rules during conflict-related actions. Given the translational relevance of the model used here, the data provide a neuronal encoding mechanism for how anxiety biases decision making when the choice involves overcoming a conflict. They also demonstrate that PFC encoding of actions, as opposed to cues or outcome, is especially vulnerable to anxiety. A debilitating aspect of anxiety is its impact on decision making and flexible control of behavior. These cognitive constructs depend on proper functioning of the prefrontal cortex (PFC). Understanding how anxiety affects PFC encoding of cognitive events is of great clinical and evolutionary significance. Using a clinically valid experimental model, we find that, under anxiety, decision making may be skewed by salient and conflicting environmental stimuli at the expense of flexible top-down guided choices. We also find that anxiety suppresses spontaneous activity of PFC neurons, and weakens encoding of task rules by dorsomedial PFC neurons. These data provide a neuronal encoding scheme for how anxiety disengages PFC during decision making. Copyright © 2016 the authors 0270-6474/16/363322-14$15.00/0.

The role of ventromedial prefrontal cortex volume in the association of expressive suppression and externally oriented thinking.

PubMed

Li, Xu; Lu, Jiamei; Li, Bingbing; Li, Haijiang; Jin, Li; Qiu, Jiang

2017-11-01

Studies have suggested that expressive suppression (ES) is linked to externally oriented thinking (EOT) through the ventromedial prefrontal cortex (vmPFC), and there are gender differences in their association. The present structural magnetic resonance imaging study was to investigate the neural bases of ES and EOT and their association in females versus males in a Chinese college sample. A total of 142 participants (83 females) were enrolled, and they completed the ES subscale of the Emotion Regulation Questionnaire, 20-item Toronto Alexithymia Scale, and anatomical scanning. Voxel-based morphometry, region of interest, and whole brain analyses with peak-level significance (family-wise error corrected at p < .05) were conducted to investigate the association of gray matter volume (GMV) variations with ES and EOT. A bootstrapping analysis was conducted to examine the role of vmPFC volume in the ES-EOT association. The ES scores were positively linked to the GMV of the vmPFC in females and negatively related to right dorsolateral PFC volume in males. The EOT scores were positively correlated with the GMV of the vmPFC in females and supplementary motor area in males. Furthermore, vmPFC volume mediated the relationship between ES and EOT LIMITATIONS: The cross-sectional design limited causal conclusions. The vmPFC may be the only neural base of ES and EOT and their association. In addition, these results were sex-specific. Copyright © 2017 Elsevier B.V. All rights reserved.

A prototype of volume-controlled tidal liquid ventilator using independent piston pumps.

PubMed

Robert, Raymond; Micheau, Philippe; Cyr, Stéphane; Lesur, Olivier; Praud, Jean-Paul; Walti, Hervé

2006-01-01

Liquid ventilation using perfluorochemicals (PFC) offers clear theoretical advantages over gas ventilation, such as decreased lung damage, recruitment of collapsed lung regions, and lavage of inflammatory debris. We present a total liquid ventilator designed to ventilate patients with completely filled lungs with a tidal volume of PFC liquid. The two independent piston pumps are volume controlled and pressure limited. Measurable pumping errors are corrected by a programmed supervisor module, which modifies the inserted or withdrawn volume. Pump independence also allows easy functional residual capacity modifications during ventilation. The bubble gas exchanger is divided into two sections such that the PFC exiting the lungs is not in contact with the PFC entering the lungs. The heating system is incorporated into the metallic base of the gas exchanger, and a heat-sink-type condenser is placed on top of the exchanger to retrieve PFC vapors. The prototype was tested on 5 healthy term newborn lambs (<5 days old). The results demonstrate the efficiency and safety of the prototype in maintaining adequate gas exchange, normal acido-basis equilibrium, and cardiovascular stability during a short, 2-hour total liquid ventilator. Airway pressure, lung volume, and ventilation scheme were maintained in the targeted range.

Association of stigma resistance with emotion regulation - functional magnetic resonance imaging and neuropsychological findings.

PubMed

Raij, Tuukka T; Korkeila, Jyrki; Joutsenniemi, Kaisla; Saarni, Samuli I; Riekki, Tapani J J

2014-04-01

[corrected] Personal characteristics contribute to whether negative attitudes in society are internalized as deteriorating self-stigma. Studies in healthy subjects suggest that resilience is associated with the regulation of amygdala activation by the medial prefrontal cortex (mPFC), but little is known about the factors that contribute to individual stigma resistance in psychiatric patients. We assessed stigma (by measuring association strengths between social inferiority and schizophrenia by an implicit association test) in 20 patients with schizophrenia and in 16 age- and sex-matched healthy control subjects. The brain activation strengths were measured by functional magnetic resonance imaging during evaluation of schizophrenia-related statements and of control statements. Association strengths between social inferiority and schizophrenia were inversely related to the strength of the activation of the rostro-ventral mPFC. This inverse correlation survived adjustment for global functioning, depression symptom scores, and insight. Activation of the rostro-ventral mPFC was negatively correlated with activation of the amygdala. The association strengths between social inferiority and schizophrenia correlated with the compromised performance in a Stroop task, which is a measure of cognitive regulation. Our findings suggest that individual stigma resistance is associated with emotion regulation. These findings may help to understand better stigma resistance and thereby aid the development of patient interventions that add to the public anti-stigma work in reducing devastating effects of stigma. © 2014.

Amygdala-prefrontal cortex resting-state functional connectivity varies with first depressive or manic episode in bipolar disorder.

PubMed

Wei, Shengnan; Geng, Haiyang; Jiang, Xiaowei; Zhou, Qian; Chang, Miao; Zhou, Yifang; Xu, Ke; Tang, Yanqing; Wang, Fei

2017-02-22

Bipolar disorder (BD) is one of the most complex mental illnesses, characterized by interactive depressive and manic states that are 2 contrary symptoms of disease states. The bilateral amygdala and prefrontal cortex (PFC) appear to play critical roles in BD; however, abnormalities seem to manifest differently in the 2 states and may provide further insight into underlying mechanisms. Sixteen participants with first-episode depressive and 13 participants with first-episode manic states of bipolar disorder as well as 30 healthy control (HC) participants underwent resting-state functional magnetic resonance imaging (fMRI). Resting-state functional connectivity (rsFC) between the bilateral amygdala and PFC was compared among the 3 groups. Compared with depressive state participants of the BD group, manic state participants of the BD group showed a significant decrease in rsFC between the amygdala and right orbital frontal cortex (p<0.05, corrected). In addition, rsFC between the amygdala and left middle frontal cortex was significantly decreased in depressive and manic state participants of the BD group when compared with the HC group (p<0.05, corrected). Our findings suggest that mood state during the first episodes of BD may be related to abnormality in hemispheric lateralization. The abnormalities in amygdala- left PFC functional connectivity might present the trait feature for BD, while deficits in amygdala- right PFC functional connectivity might be specific to manic episode, compared to depressive episode. Copyright © 2017 Elsevier B.V. All rights reserved.

Metal Surface Decontamination by the PFC Solution

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

Hui-Jun Won; Gye-Nam Kim; Wang-Kyu Choi

2006-07-01

PFC (per-fluorocarbon) spray decontamination equipment was fabricated and its decontamination behavior was investigated. Europium oxide powder was mixed with the isotope solution which contains Co-60 and Cs-137. The different shape of metal specimens artificially contaminated with europium oxide powder was used as the surrogate contaminants. Before and after the application of the PFC spray decontamination method, the radioactivity of the metal specimens was measured by MCA. The decontamination factors were in the range from 9.6 to 62.4. The spent PFC solution was recycled by distillation. Before and after distillation, the turbidity of PFC solution was also measured. From the testmore » results, it was found that more than 98% of the PFC solution could be recycled by a distillation. (authors)« less

Risk factors associated with cognitions for late-onset depression based on anterior and posterior default mode sub-networks.

PubMed

Liu, Rui; Yue, Yingying; Hou, Zhenghua; Yuan, Yonggui; Wang, Qiao

2018-08-01

Abnormal functional connectivity (FC) in the default mode network (DMN) plays an important role in late-onset depression (LOD) patients. In this study, the risk predictors of LOD based on anterior and posterior DMN are explored. A total of 27 LOD patients and 40 healthy controls (HC) underwent resting-state functional magnetic resonance imaging and cognitive assessments. Firstly, FCs within DMN sub-networks were determined by placing seeds in the ventral medial prefrontal cortex (vmPFC) and posterior cingulate cortex (PCC). Secondly, multivariable logistic regression was used to identify risk factors for LOD patients. Finally, correlation analysis was performed to investigate the relationship between risk factors and the cognitive value. Multivariable logistic regression showed that the FCs between the vmPFC and right middle temporal gyrus (MTG) (vmPFC-MTG_R), FCs between the vmPFC and left precuneus (PCu), and FCs between the PCC and left PCu (PCC-PCu_L) were the risk factors for LOD. Furthermore, FCs of the vmPFC-MTG_R and PCC-PCu_L correlated with processing speed (R = 0.35, P = 0.002; R = 0.32, P = 0.009), and FCs of the vmPFC-MTG_R correlated with semantic memory (R = 0.41, P = 0.001). The study was a cross-sectional study. The results may be potentially biased because of a small sample. In this study, we confirmed that LOD patients mainly present cognitive deficits in processing speed and semantic memory. Moreover, our findings further suggested that FCs within DMN sub-networks associated with cognitions were risk factors, which may be used for the prediction of LOD. Copyright © 2018 Elsevier B.V. All rights reserved.

Parallel processing of cognitive and physical demands in left and right prefrontal cortices during smartphone use while walking.

PubMed

Takeuchi, Naoyuki; Mori, Takayuki; Suzukamo, Yoshimi; Tanaka, Naofumi; Izumi, Shin-Ichi

2016-02-01

Smartphone use while walking is becoming a public concern owing to an increased risk of falling that can result from cognitive-motor interference. We evaluated prefrontal cortex (PFC) activity in participants playing a smartphone game while walking, in order to elucidate the role of the PFC in the allocation of attention between physical and cognitive demands. Sixteen young and 15 older adults participated in this study. Participants were instructed to perform a touch number-selecting game on a smartphone while walking. The numbers of correct and mistake responses were analyzed as a measure of cognitive performance. Linear trunk accelerations were measured by another smartphone and analyzed for step time and acceleration magnitude as an assay of gait performance. PFC activity during the task was measured using a wearable 16-channel near-infrared spectroscopy system. Smartphone game playing while walking decreased the cognitive and gait performances compared with performances of single-task condition in older group more than in young group. There was no difference in PFC activation during smartphone use while walking between young and older groups, but age appeared to mediate correlation magnitude between PFC activation and changes in performance. In young adults, multiple regression analysis revealed an association of the right PFC with a reduction in acceleration magnitude (β = 0.581, p = 0.023), and an association of the left PFC with an increase in game-playing mistakes (β = -0.556, p = 0.032) during smartphone use while walking. In older adults, multiple regression analysis revealed an association of the middle PFC with a prolongation of step time (β = -0.550, p = 0.042) and of the left PFC with a reduction in acceleration magnitude (β = -0.648, p = 0.012). In young adults, the left PFC inhibited inappropriate action and the right PFC stabilized gait performance. In older adults, a less-lateralized PFC activity pattern suppressed the deterioration of gait performance, but this resulted in impairment on a simultaneous cognitive task. These results suggest that lateralization of motor and cognitive tasks aids in efficient task completion during a complex action such as using a smartphone while walking.

Distinct roles of three frontal cortical areas in reward-guided behavior

PubMed Central

Noonan, M.P.; Mars, R.B.; Rushworth, M.F.S

2011-01-01

Functional magnetic resonance imaging (fMRI) was used to measure activity in three frontal cortical areas, lateral orbitofrontal cortex (lOFC), medial orbitofrontal cortex/ventromedial frontal cortex (mOFC/vmPFC), and anterior cingulate cortex (ACC) when expectations about type of reward, and not just reward presence or absence, could be learned. Two groups of human subjects learned twelve stimulus-response pairings. In one group (Consistent), correct performances of a given pairing were always reinforced with a specific reward outcome whereas in the other group (Inconsistent), correct performances were reinforced with randomly selected rewards. MOFC/vmPFC and lOFC were not distinguished by simple differences in relative preference for positive and negative outcomes. Instead lOFC activity reflected updating of reward-related associations specific to reward type; lOFC was active whenever informative outcomes allowed updating of reward-related associations regardless of whether the outcomes were positive or negative and the effects were greater when consistent stimulus-outcome and response-outcome mappings were present. A psycho-physiological interaction (PPI) analysis demonstrated changed coupling between lOFC and brain areas for visual object representation, such as perirhinal cortex, and reward-guided learning, such as amygdala, ventral striatum, and habenula /mediodorsal thalamus. By contrast mOFC/vmPFC activity reflected expected values of outcomes and occurrence of positive outcomes, irrespective of consistency of outcome mappings. The third frontal cortical region, ACC, reflected the use of reward type information to guide response selection. ACC activity reflected the probability of selecting the correct response, was greater when consistent outcome mappings were present, and was related to individual differences in propensity to select the correct response. PMID:21976525

Parental influence on children with attention-deficit/hyperactivity disorder: II. Results of a pilot intervention training parents as friendship coaches for children.

PubMed

Mikami, Amori Yee; Lerner, Matthew D; Griggs, Marissa Swaim; McGrath, Alison; Calhoun, Casey D

2010-08-01

We report findings from a pilot intervention that trained parents to be "friendship coaches" for their children with Attention-Deficit/Hyperactivity Disorder (ADHD). Parents of 62 children with ADHD (ages 6-10; 68% male) were randomly assigned to receive the parental friendship coaching (PFC) intervention, or to be in a no-treatment control group. Families of 62 children without ADHD were included as normative comparisons. PFC was administered in eight, 90-minute sessions to parents; there was no child treatment component. Parents were taught to arrange a social context in which their children were optimally likely to develop good peer relationships. Receipt of PFC predicted improvements in children's social skills and friendship quality on playdates as reported by parents, and peer acceptance and rejection as reported by teachers unaware of treatment status. PFC also predicted increases in observed parental facilitation and corrective feedback, and reductions in criticism during the child's peer interaction, which mediated the improvements in children's peer relationships. However, no effects for PFC were found on the number of playdates hosted or on teacher report of child social skills. Findings lend initial support to a treatment model that targets parental behaviors to address children's peer problems.

Vaporization dynamics of volatile perfluorocarbon droplets: A theoretical model and in vitro validation

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

Doinikov, Alexander A., E-mail: doinikov@bsu.by; Bouakaz, Ayache; Sheeran, Paul S.

2014-10-15

Purpose: Perfluorocarbon (PFC) microdroplets, called phase-change contrast agents (PCCAs), are a promising tool in ultrasound imaging and therapy. Interest in PCCAs is motivated by the fact that they can be triggered to transition from the liquid state to the gas state by an externally applied acoustic pulse. This property opens up new approaches to applications in ultrasound medicine. Insight into the physics of vaporization of PFC droplets is vital for effective use of PCCAs and for anticipating bioeffects. PCCAs composed of volatile PFCs (with low boiling point) exhibit complex dynamic behavior: after vaporization by a short acoustic pulse, a PFCmore » droplet turns into a vapor bubble which undergoes overexpansion and damped radial oscillation until settling to a final diameter. This behavior has not been well described theoretically so far. The purpose of our study is to develop an improved theoretical model that describes the vaporization dynamics of volatile PFC droplets and to validate this model by comparison with in vitro experimental data. Methods: The derivation of the model is based on applying the mathematical methods of fluid dynamics and thermodynamics to the process of the acoustic vaporization of PFC droplets. The used approach corrects shortcomings of the existing models. The validation of the model is carried out by comparing simulated results with in vitro experimental data acquired by ultrahigh speed video microscopy for octafluoropropane (OFP) and decafluorobutane (DFB) microdroplets of different sizes. Results: The developed theory allows one to simulate the growth of a vapor bubble inside a PFC droplet until the liquid PFC is completely converted into vapor, and the subsequent overexpansion and damped oscillations of the vapor bubble, including the influence of an externally applied acoustic pulse. To evaluate quantitatively the difference between simulated and experimental results, the L2-norm errors were calculated for all cases where the simulated and experimental results are compared. These errors were found to be in the ranges of 0.043–0.067 and 0.037–0.088 for OFP and DFB droplets, respectively. These values allow one to consider agreement between the simulated and experimental results as good. This agreement is attained by varying only 2 of 16 model parameters which describe the material properties of gaseous and liquid PFCs and the liquid surrounding the PFC droplet. The fitting parameters are the viscosity and the surface tension of the surrounding liquid. All other model parameters are kept invariable. Conclusions: The good agreement between the theoretical and experimental results suggests that the developed model is able to correctly describe the key physical processes underlying the vaporization dynamics of volatile PFC droplets. The necessity of varying the parameters of the surrounding liquid for fitting the experimental curves can be explained by the fact that the parts of the initial phospholipid shell of PFC droplets remain on the surface of vapor bubbles at the oscillatory stage and their presence affects the bubble dynamics.« less

Individual Differences in Amygdala-Medial Prefrontal Anatomy Link Negative Affect, Impaired Social Functioning, and Polygenic Depression Risk

PubMed Central

Holmes, Avram J.; Lee, Phil H.; Hollinshead, Marisa O.; Bakst, Leah; Roffman, Joshua L.; Smoller, Jordan W.; Buckner, Randy L.

2013-01-01

Individual differences in affective and social processes may arise from variability in amygdala-medial prefrontal (mPFC) circuitry and related genetic heterogeneity. To explore this possibility in humans, we examined the structural correlates of trait negative affect in a sample of 1050 healthy young adults with no history of psychiatric illness. Analyses revealed that heightened negative affect was associated with increased amygdala volume and reduced thickness in a left mPFC region encompassing the subgenual and rostral anterior cingulate cortex. The most extreme individuals displayed an inverse correlation between amygdala volume and mPFC thickness, suggesting that imbalance between these structures is linked to negative affect in the general population. Subgroups of participants were further evaluated on social (n = 206) and emotional (n = 533) functions. Individuals with decreased mPFC thickness exhibited the poorest social cognition and were least able to correctly identify facial emotion. Given prior links between disrupted amygdala–mPFC circuitry and the presence of major depressive disorder (MDD), we explored whether the individual differences in anatomy observed here in healthy young adults were associated with polygenic risk for MDD (n = 438) using risk scores derived from a large genome-wide association analysis (n = 18,759). Analyses revealed associations between increasing polygenic burden for MDD and reduced cortical thickness in the left mPFC. These collective findings suggest that, within the healthy population, there is significant variability in amygdala–mPFC circuitry that is associated with poor functioning across affective and social domains. Individual differences in this circuitry may arise, in part, from common genetic variability that contributes to risk for MDD. PMID:23238724

The estimation of uniaxial compressive strength conversion factor of trona and interbeds from point load tests and numerical modeling

NASA Astrophysics Data System (ADS)

Ozturk, H.; Altinpinar, M.

2017-07-01

The point load (PL) test is generally used for estimation of uniaxial compressive strength (UCS) of rocks because of its economic advantages and simplicity in testing. If the PL index of a specimen is known, the UCS can be estimated using conversion factors. Several conversion factors have been proposed by various researchers and they are dependent upon the rock type. In the literature, conversion factors on different sedimentary, igneous and metamorphic rocks can be found, but no study exists on trona. In this study, laboratory UCS and field PL tests were carried out on trona and interbeds of volcano-sedimentary rocks. Based on these tests, PL to UCS conversion factors of trona and interbeds are proposed. The tests were modeled numerically using a distinct element method (DEM) software, particle flow code (PFC), in an attempt to guide researchers having various types of modeling problems (excavation, cavern design, hydraulic fracturing, etc.) of the abovementioned rock types. Average PFC parallel bond contact model micro properties for the trona and interbeds were determined within this study so that future researchers can use them to avoid the rigorous PFC calibration procedure. It was observed that PFC overestimates the tensile strength of the rocks by a factor that ranges from 22 to 106.

Experience and the developing prefrontal cortex

PubMed Central

Kolb, Bryan; Mychasiuk, Richelle; Muhammad, Arif; Li, Yilin; Frost, Douglas O.; Gibb, Robbin

2012-01-01

The prefrontal cortex (PFC) receives input from all other cortical regions and functions to plan and direct motor, cognitive, affective, and social behavior across time. It has a prolonged development, which allows the acquisition of complex cognitive abilities through experience but makes it susceptible to factors that can lead to abnormal functioning, which is often manifested in neuropsychiatric disorders. When the PFC is exposed to different environmental events during development, such as sensory stimuli, stress, drugs, hormones, and social experiences (including both parental and peer interactions), the developing PFC may develop in different ways. The goal of the current review is to illustrate how the circuitry of the developing PFC can be sculpted by a wide range of pre- and postnatal factors. We begin with an overview of prefrontal functioning and development, and we conclude with a consideration of how early experiences influence prefrontal development and behavior. PMID:23045653

Impaired reward processing in the human prefrontal cortex distinguishes between persistent and remittent attention deficit hyperactivity disorder.

PubMed

Wetterling, Friedrich; McCarthy, Hazel; Tozzi, Leonardo; Skokauskas, Norbert; O'Doherty, John P; Mulligan, Aisling; Meaney, James; Fagan, Andrew J; Gill, Michael; Frodl, Thomas

2015-11-01

Symptoms of attention deficit hyperactivity disorder (ADHD) in children often persist into adulthood and can lead to severe antisocial behavior. However, to-date it remains unclear whether neuro-functional abnormalities cause ADHD, which in turn can then provide a marker of persistent ADHD. Using event-related functional magnetic resonance imaging (fMRI), we measured blood oxygenation level dependent (BOLD) signal changes in subjects during a reversal learning task in which choice of the correct stimulus led to a probabilistically determined 'monetary' reward or punishment. Participants were diagnosed with ADHD during their childhood (N=32) and were paired with age, gender, and education matched healthy controls (N=32). Reassessment of the ADHD group as adults resulted in a split between either persistent (persisters, N=17) or remitted ADHDs (remitters, N=15). All three groups showed significantly decreased activation in the medial prefrontal cortex (PFC) and the left striatum during punished correct responses, however only remitters and controls presented significant psycho-physiological interaction between these fronto-striatal reward and outcome valence networks. Comparing persisters to remitters and controls showed significantly inverted responses to punishment (P<0.05, family-wise error corrected) in left PFC region. Interestingly, the decreased activation shown after punishment was located in different areas of the PFC for remitters compared with controls, suggesting that remitters might have learned compensation strategies to overcome their ADHD symptoms. Thus, fMRI helps understanding the neuro-functional basis of ADHD related behavior differences and differentiates between persistent and remittent ADHD. © 2015 Wiley Periodicals, Inc.

Distinct Regions within Medial Prefrontal Cortex Process Pain and Cognition

PubMed Central

Jahn, Andrew; Nee, Derek Evan; Alexander, William H.

2016-01-01

Neuroimaging studies of the medial prefrontal cortex (mPFC) suggest that the dorsal anterior cingulate cortex (dACC) region is responsive to a wide variety of stimuli and psychological states, such as pain, cognitive control, and prediction error (PE). In contrast, a recent meta-analysis argues that the dACC is selective for pain, whereas the supplementary motor area (SMA) and pre-SMA are specifically associated with higher-level cognitive processes (Lieberman and Eisenberger, 2015). To empirically test this claim, we manipulated effects of pain, conflict, and PE in a single experiment using human subjects. We observed a robust dorsal-ventral dissociation within the mPFC with cognitive effects of PE and conflict overlapping dorsally and pain localized more ventrally. Classification of subjects based on the presence or absence of a paracingulate sulcus showed that PE effects extended across the dorsal area of the dACC and into the pre-SMA. These results begin to resolve recent controversies by showing the following: (1) the mPFC includes dissociable regions for pain and cognitive processing; and (2) meta-analyses are correct in localizing cognitive effects to the dACC, although these effects extend to the pre-SMA as well. These results both provide evidence distinguishing between different theories of mPFC function and highlight the importance of taking individual anatomical variability into account when conducting empirical studies of the mPFC. SIGNIFICANCE STATEMENT Decades of neuroimaging research have shown the mPFC to represent a wide variety of stimulus processing and cognitive states. However, recently it has been argued whether distinct regions of the mPFC separately process pain and cognitive phenomena. To address this controversy, this study directly compared pain and cognitive processes within subjects. We found a double dissociation within the mPFC with pain localized ventral to the cingulate sulcus and cognitive effects localized more dorsally within the dACC and spreading into the pre-supplementary motor area. This provides empirical evidence to help resolve the current debate about the functional architecture of the mPFC. PMID:27807031

The feasibility study of hot cell decontamination by the PFC spray method

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

Hui-Jun Won; Chong-Hun Jung; Jei-Kwon Moon

2008-01-15

The characteristics of per-fluorocarbon compounds (PFC) are colorless, non-toxic, easily vaporized and nonflammable. Also, some of them are liquids of a high density, low surface tension, low latent heat and low specific heat. These particular chemical and physical properties of fluoro-organic compounds permit their use in very different fields such as electronics, medicine, tribology, nuclear and material science. The Sonatol process was developed under a contract with the DOE. The Sonatol process uses an ultrasonic agitation in a PFC solution that contains a fluorinated surfactant to remove radioactive particles from surfaces. Filtering the suspended particles allows the solutions to bemore » reused indefinitely. They applied the Sonatol process to the decontamination of a heterogeneous legacy Pu-238 waste that exhibited an excessive hydrogen gas generation, which prevents a transportation of such a waste to a Waste Isolation Pilot Plant. Korea Atomic Energy Research Institute (KAERI) is developing dry decontamination technologies applicable to a decontamination of a highly radioactive area loosely contaminated with radioactive particles. This contamination has occurred as a result of an examination of a post-irradiated material or the development of the DUPIC process. The dry decontamination technologies developed are the carbon dioxide pellet spray method and the PFC spray method. As a part of the project, PFC ultrasonic decontamination technology was developed in 2004. The PFC spray decontamination method which is based on the test results of the PFC ultrasonic method has been under development since 2005. The developed PFC spray decontamination equipment consists of four modules (spray, collection, filtration and distillation). Vacuum cup of the collection module gathers the contaminated PFC solution, then the solution is moved to the filtration module and it is recycled. After a multiple recycling of the spent PFC solution, it is purified in the distillation module. A performance test on each module was executed and the results have been reported. A combined test of the four modules, however, has not been performed as yet. The main objective of the present study is to demonstrate the feasibility of the full PFC spray decontamination process. Decontamination of the inside of the IMEF hot cell by the PFC spray method was also performed. PFC spray decontamination process was demonstrated by using a surrogate wall contaminated with Eu{sub 2}O{sub 3} powder. The spray pressure was 41 kgf/cm{sup 2}, the orifice diameter was 0.2 mm and the spray velocity was 0.2 L/min. And, the decontaminated area was 100 cm{sup 2}. From previous test results, we found that the decontamination factor of the PFC spray method was in the range from 9.6 to 62.4. When the decontamination efficiency of Co-60 was high, then the decontamination efficiency of Cs-137 was also high. As the surface roughness of the specimen increased, the PFC spray decontamination efficiency decreased. Inferring from the previous results, the surface of the surrogate wall was cleaned by the PFC spray method. The vacuum cup of the collection module operated well and gathered more than 99 % of the PFC solution. Also, filtration and distillation modules operated well. All the filtered PFC solution flowed to the storage chamber where some of the PFC solution was distilled. The coolant of the distillation module was a dry ice. And, the recycled solution was transferred to the spray module by a high pressure pump. To evaluate the PFC spray decontamination efficiency, a smear device was fabricated and operated by a manipulator. Before and after decontamination, a smear test was performed. The tested area was 100 cm{sup 2} and the radioactivity was estimated indirectly by measuring the radioactivity of the filter paper. The average decontamination factor was in the range between 10 and 15. One application time was 2 minutes. The sprayed PFC solution was collected by the vacuum cup and it was stored in the collection equipment. After the termination of the decontamination test, the flexible hose was cut near a toboggan. The collection equipment that contained the spent PFC solution, vacuum cup, spray nozzle and the flexible hose was stored in a radioactive waste storage tank. A feasibility study for the PFC spray decontamination method for an application to a hot cell surface was performed. The decontamination equipment that consisted of four modules operated well in the hot cell. The collection module gathered the sprayed PFC solution. The solution was purified in the filtration or distillation modules. The main characteristic of the distillation module is the use of dry ice as a coolant. The decontamination factor of IMEF hot cell was in the range from 10 to 15. It was difficult to measure the radioactivity accurately at a given time. We, however, concluded that the PFC spray decontamination method is a promising technology. It generated a small amount of secondary waste and used a non-toxic and non-conducting material. Decontamination work was performed with a little loss of the main decontamination agent. Based on the test results, we are developing an improved PFC spray decontamination process.« less

Motivational effects on the processing of delayed intentions in the anterior prefrontal cortex.

PubMed

Bruening, Jovita; Ludwig, Vera U; Paschke, Lena M; Walter, Henrik; Stelzel, Christine

2018-05-15

Delaying intentions bears the risk of interference from distracting activities during the delay interval. Motivation can increase intention retrieval success but little is known about the underlying brain mechanisms. Here, we investigated whether motivational incentives (monetary reward) modulate the processing of delayed intentions in the anterior prefrontal cortex (aPFC), known to be crucial for intention processing. Using a mixed blocked and event-related functional Magnetic Resonance Imaging design, we specifically tested whether reward affects intention processing in the aPFC in a transient or in a sustained manner and whether this is related to individual differences in retrieval success. We found a generalized effect of reward on both correct intention retrieval and ongoing task performance. Fronto-parietal regions including bilateral lateral aPFC showed sustained activity increases in rewarded compared to non-rewarded blocks as well as transient reward-related activity during the storage phase. Additionally, individual differences in reward-related performance benefits were related to the degree of transient signal increases in right lateral aPFC, specifically during intention encoding. This suggests that the ability to integrate motivational relevance into the encoding of future intentions is crucial for successful intention retrieval in addition to general increases in processing effort. Bilateral aPFC is central to these motivation-cognition interactions. Copyright © 2018 Elsevier Inc. All rights reserved.

A neuropsychological test of belief and doubt: damage to ventromedial prefrontal cortex increases credulity for misleading advertising.

PubMed

Asp, Erik; Manzel, Kenneth; Koestner, Bryan; Cole, Catherine A; Denburg, Natalie L; Tranel, Daniel

2012-01-01

We have proposed the False Tagging Theory (FTT) as a neurobiological model of belief and doubt processes. The theory posits that the prefrontal cortex is critical for normative doubt toward properly comprehended ideas or cognitions. Such doubt is important for advantageous decisions, for example in the financial and consumer purchasing realms. Here, using a neuropsychological approach, we put the FTT to an empirical test, hypothesizing that focal damage to the ventromedial prefrontal cortex (vmPFC) would cause a "doubt deficit" that would result in higher credulity and purchase intention for consumer products featured in misleading advertisements. We presented 8 consumer ads to 18 patients with focal brain damage to the vmPFC, 21 patients with focal brain damage outside the prefrontal cortex, and 10 demographically similar healthy comparison participants. Patients with vmPFC damage were (1) more credulous to misleading ads; and (2) showed the highest intention to purchase the products in the misleading advertisements, relative to patients with brain damage outside the prefrontal cortex and healthy comparison participants. The pattern of findings was obtained even for ads in which the misleading bent was "corrected" by a disclaimer. The evidence is consistent with our proposal that damage to the vmPFC disrupts a "false tagging mechanism" which normally produces doubt and skepticism for cognitive representations. We suggest that the disruption increases credulity for misleading information, even when the misleading information is corrected for by a disclaimer. This mechanism could help explain poor financial decision-making when persons with ventromedial prefrontal dysfunction (e.g., caused by neurological injury or aging) are exposed to persuasive information.

The role of the frontal cortex in memory: an investigation of the Von Restorff effect

PubMed Central

Elhalal, Anat; Davelaar, Eddy J.; Usher, Marius

2014-01-01

Evidence from neuropsychology and neuroimaging indicate that the pre-frontal cortex (PFC) plays an important role in human memory. Although frontal patients are able to form new memories, these memories appear qualitatively different from those of controls by lacking distinctiveness. Neuroimaging studies of memory indicate activation in the PFC under deep encoding conditions, and under conditions of semantic elaboration. Based on these results, we hypothesize that the PFC enhances memory by extracting differences and commonalities in the studied material. To test this hypothesis, we carried out an experimental investigation to test the relationship between the PFC-dependent factors and semantic factors associated with common and specific features of words. These experiments were performed using Free-Recall of word lists with healthy adults, exploiting the correlation between PFC function and fluid intelligence. As predicted, a correlation was found between fluid intelligence and the Von-Restorff effect (better memory for semantic isolates, e.g., isolate “cat” within category members of “fruit”). Moreover, memory for the semantic isolate was found to depend on the isolate's serial position. The isolate item tends to be recalled first, in comparison to non-isolates, suggesting that the process interacts with short term memory. These results are captured within a computational model of free recall, which includes a PFC mechanism that is sensitive to both commonality and distinctiveness, sustaining a trade-off between the two. PMID:25018721

Validity aspects of the patient feedback questionnaire on consultation skills (PFC), a promising learning instrument in medical education.

PubMed

Reinders, Marcel E; Blankenstein, Annette H; Knol, Dirk L; de Vet, Henrica C W; van Marwijk, Harm W J

2009-08-01

A focus on the communicator competency is considered to be an important requirement to help physicians to acquire consultation skills. A feedback questionnaire, in which patients assess consultation skills might be a useful learning tool. An existing questionnaire on patient perception of patient-centeredness (PPPC) was adapted to cover the 'communicator' items in the competency profile. We assessed the face and content validity, the construct validity and the internal consistency of this new patient feedback on consultation skills (PFC) questionnaire. We assessed the face validity of the PFC by interviewing patients and general practice trainees (GPTs) during the developmental process. The content validity was determined by experts (n=10). First-year GPTs (23) collected 222 PFCs, from which the data were used to assess the construct validity (factor analysis), internal consistency, response rates and ceiling effects. The PFC adequately covers the corresponding 'communicator' competency (face and content validity). Factor analysis showed a one-dimensional construct. The internal consistency was high (Cronbach's alpha 0.89). For the single items, the response rate varied from 89.2% to 100%; the maximum score (ceiling effect) varied from 45.5% to 89.2%. The PFC appears to be a valid, internally consistent instrument. The PFC may be a valuable learning tool with which GPTs, other physicians and medical students can acquire feedback from patients regarding their consultation skills.

Sorption of Perfluorochemicals to Matrices Relevant to Sites Impacted by Aqueous Film-Forming Foam

NASA Astrophysics Data System (ADS)

Sepulvado, J.; Higgins, C.

2011-12-01

Perfluorochemicals are a class of emerging contaminants consisting of fluorinated surfactants that are chemically and thermally stable and which contain a fluorocarbon tail that is both hydro- and oleophobic. Because of these unique properties, PFCs have a wide variety of uses including food paper packaging products, stain repellants, nonstick coatings, and aqueous film-forming foams (AFFF). At fire-training facilities, repeated application of AFFF is used to extinguish hydrocarbon fuel fires ignited for training purposes. The presence of perfluochemicals (PFCs) in groundwater as a result of repeated AFFF application at these facilities has been documented. Due to factors such as the recent push towards regulation of PFCs in drinking water, concerns have arisen about the fate of these compounds in the subsurface. Groundwater plumes containing PFC subclasses such as perfluorocarboxylic acids (PFCAs), perfluoroalkylsulfonates (PFAS), and fluorotelomer sulfonates (FtSs) in the μg/L to mg/L range have been detected. These plumes also may contain co-contaminants such as hydrocarbon fuel components and chlorinated solvents, some of which may exist as nonaqueous phase liquids (NAPL). This study examined the sorption of PFCs to soil and aquifer material across the concentration range applicable to AFFF-impacted sites (μg/L - mg/L) and looked at the impact of co-contaminants, including NAPL, on PFC sorption. PFC sorption was variable and indicated that similar to previous work on PFC sorption to sediment, subsurface PFC transport will depend on factors such as the sorbent organic carbon content, PFC subclass, solution chemistry, and PFC chain length.

Hope, coping skills, and the prefrontal cortex in alcohol use disorder recovery.

PubMed

Bradshaw, Spencer D; Shumway, Sterling T; Dsauza, Cynthia M; Morris, Neli; Hayes, Nicholas D

2017-09-01

Alcohol use disorders adversely affect individual and societal health. These disorders are a chronic brain disease, and protective factors against relapse should be studied. Prefrontal cortex (PFC) dysfunction is evident in alcohol use disorders, and research that explores recovery of the PFC in alcohol use disorders is needed, specifically in regard to how psychological and behavioral factors can augment medicalized treatments and protect against relapse. For example, hope or a belief that recovery is possible is an important cognitive construct-thought to precede behavioral action-that has been associated with relapse. In this study, associations between healthy coping skills and hope (psychological/behavioral factors) and PFC regional activation in response to alcohol cue exposure were examined. It was also examined whether such associations were unique to alcohol cues. Forty-two participants, 32 males and nine females in recovery from an alcohol use disorder (AUD), were administered a subjective hope and coping in recovery measure. They also viewed alcohol, positive, negative, and neutral cues during functional near-infrared spectroscopy (fNIR) PFC assessment. Levels of healthy coping skills positively correlated with activation in the right dorsomedial prefrontal cortex (DMPFC) in response to alcohol cues. This finding was unique to alcohol cues. The association between coping skills and activation of the right DMPFC in response to alcohol cues may reflect greater action restraint and top-down PFC control processing that may protect against relapse.

Developing PFC representations using reinforcement learning

PubMed Central

Reynolds, Jeremy R.; O'Reilly, Randall C.

2009-01-01

From both functional and biological considerations, it is widely believed that action production, planning, and goal-oriented behaviors supported by the frontal cortex are organized hierarchically (Fuster, 1990, Koechlin, Ody, & Kouneiher, 2003, & Miller, Galanter, & Pribram, 1960) However, the nature of the different levels of the hierarchy remains unclear, and little attention has been paid to the origins of such a hierarchy. We address these issues through biologically-inspired computational models that develop representations through reinforcement learning. We explore several different factors in these models that might plausibly give rise to a hierarchical organization of representations within the PFC, including an initial connectivity hierarchy within PFC, a hierarchical set of connections between PFC and subcortical structures controlling it, and differential synaptic plasticity schedules. Simulation results indicate that architectural constraints contribute to the segregation of different types of representations, and that this segregation facilitates learning. These findings are consistent with the idea that there is a functional hierarchy in PFC, as captured in our earlier computational models of PFC function and a growing body of empirical data. PMID:19591977

Power Factor Controller

NASA Technical Reports Server (NTRS)

1997-01-01

Frank Nola invented the Power Factor Controller (PFC) at Marshall Space Flight Center more than a decade ago. Nola came up with a way to curb power wastage in AC induction motors. The PFC matches voltage with the motor's actual need by continuously sensing shifts between voltage and current. When it senses a light load it cuts the voltage to the minimum needed. Potential energy savings range from 8 to 65 percent.

Abnormal causal attribution leads to advantageous economic decision-making: A neuropsychological approach

PubMed Central

Koscik, Timothy R.; Tranel, Daniel

2013-01-01

People tend to assume that outcomes are caused by dispositional factors, e.g., a person’s constitution or personality, even when the actual cause is due to situational factors, e.g., luck or coincidence. This is known as the ‘correspondence bias.’ This tendency can lead normal, intelligent persons to make suboptimal decisions. Here, we used a neuropsychological approach to investigate the neural basis of the correspondence bias, by studying economic decision-making in patients with damage to the ventromedial prefrontal cortex (vmPFC). Given the role of the vmPFC in social cognition, we predicted that vmPFC is necessary for the normal correspondence bias. In our experiment, consistent with expectations, healthy (N=46) and brain-damaged (N=30) comparison participants displayed the correspondence bias when investing and invested no differently when given dispositional or situational information. By contrast, vmPFC patients (N=17) displayed a lack of correspondence bias and invested more when given dispositional than situational information. The results support the conclusion that vmPFC is critical for normal social inference and the correspondence bias, and our findings help clarify the important (and potentially disadvantageous) role of social inference in economic decision-making. PMID:23574584

Identification of genes and gene pathways associated with major depressive disorder by integrative brain analysis of rat and human prefrontal cortex transcriptomes

PubMed Central

Malki, K; Pain, O; Tosto, M G; Du Rietz, E; Carboni, L; Schalkwyk, L C

2015-01-01

Despite moderate heritability estimates, progress in uncovering the molecular substrate underpinning major depressive disorder (MDD) has been slow. In this study, we used prefrontal cortex (PFC) gene expression from a genetic rat model of MDD to inform probe set prioritization in PFC in a human post-mortem study to uncover genes and gene pathways associated with MDD. Gene expression differences between Flinders sensitive (FSL) and Flinders resistant (FRL) rat lines were statistically evaluated using the RankProd, non-parametric algorithm. Top ranking probe sets in the rat study were subsequently used to prioritize orthologous selection in a human PFC in a case–control post-mortem study on MDD from the Stanley Brain Consortium. Candidate genes in the human post-mortem study were then tested against a matched control sample using the RankProd method. A total of 1767 probe sets were differentially expressed in the PFC between FSL and FRL rat lines at (q⩽0.001). A total of 898 orthologous probe sets was found on Affymetrix's HG-U95A chip used in the human study. Correcting for the number of multiple, non-independent tests, 20 probe sets were found to be significantly dysregulated between human cases and controls at q⩽0.05. These probe sets tagged the expression profile of 18 human genes (11 upregulated and seven downregulated). Using an integrative rat–human study, a number of convergent genes that may have a role in pathogenesis of MDD were uncovered. Eighty percent of these genes were functionally associated with a key stress response signalling cascade, involving NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells), AP-1 (activator protein 1) and ERK/MAPK, which has been systematically associated with MDD, neuroplasticity and neurogenesis. PMID:25734512

Differential expression of cytoskeletal regulatory factors in the adolescent prefrontal cortex: Implications for cortical development.

PubMed

Shapiro, Lauren P; Parsons, Ryan G; Koleske, Anthony J; Gourley, Shannon L

2017-05-01

The prevalence of depression, anxiety, schizophrenia, and drug and alcohol use disorders peaks during adolescence. Further, up to 50% of "adult" mental health disorders emerge in adolescence. During adolescence, the prefrontal cortex (PFC) undergoes dramatic structural reorganization, in which dendritic spines and synapses are refined, pruned, and stabilized. Understanding the molecular mechanisms that underlie these processes should help to identify factors that influence the development of psychiatric illness. Here we briefly discuss the anatomical connections of the medial and orbital prefrontal cortex (mPFC and OFC, respectively). We then present original findings suggesting that dendritic spines on deep-layer excitatory neurons in the mouse mPFC and OFC prune at different adolescent ages, with later pruning in the OFC. In parallel, we used Western blotting to define levels of several cytoskeletal regulatory proteins during early, mid-, and late adolescence, focusing on tropomyosin-related kinase receptor B (TrkB) and β1-integrin-containing receptors and select signaling partners. We identified regional differences in the levels of several proteins in early and midadolescence that then converged in early adulthood. We also observed age-related differences in TrkB levels, both full-length and truncated isoforms, Rho-kinase 2, and synaptophysin in both PFC subregions. Finally, we identified changes in protein levels in the dorsal and ventral hippocampus that were distinct from those in the PFC. We conclude with a general review of the manner in which TrkB- and β1-integrin-mediated signaling influences neuronal structure in the postnatal brain. Elucidating the role of cytoskeletal regulatory factors throughout adolescence may identify critical mechanisms of PFC development. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Human subthalamic nucleus-medial frontal cortex theta phase coherence is involved in conflict and error related cortical monitoring.

PubMed

Zavala, Baltazar; Tan, Huiling; Ashkan, Keyoumars; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Zaghloul, Kareem; Brown, Peter

2016-08-15

The medial prefrontal cortex (mPFC) is thought to control the shift from automatic to controlled action selection when conflict is present or when mistakes have been recently committed. Growing evidence suggests that this process involves frequency specific communication in the theta (4-8Hz) band between the mPFC and the subthalamic nucleus (STN), which is the main target of deep brain stimulation (DBS) for Parkinson's disease. Key in this hypothesis is the finding that DBS can lead to impulsivity by disrupting the correlation between higher mPFC oscillations and slower reaction times during conflict. In order to test whether theta band coherence between the mPFC and the STN underlies adjustments to conflict and to errors, we simultaneously recorded mPFC and STN electrophysiological activity while DBS patients performed an arrowed flanker task. These recordings revealed higher theta phase coherence between the two sites during the high conflict trials relative to the low conflict trials. These differences were observed soon after conflicting arrows were displayed, but before a response was executed. Furthermore, trials that occurred after an error was committed showed higher phase coherence relative to trials that followed a correct trial, suggesting that mPFC-STN connectivity may also play a role in error related adjustments in behavior. Interestingly, the phase coherence we observed occurred before increases in theta power, implying that the theta phase and power may influence behavior at separate times during cortical monitoring. Finally, we showed that pre-stimulus differences in STN theta power were related to the reaction time on a given trial, which may help adjust behavior based on the probability of observing conflict during a task. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Induction and blockade of adolescent cocaine-induced habits

PubMed Central

DePoy, Lauren M.; Zimmermann, Kelsey S.; Marvar, Paul J.; Gourley, Shannon L.

2017-01-01

Background Cocaine use during adolescence increases vulnerability to drug dependence and decreases the likelihood that individuals will seek treatment as adults. Understanding how early-life cocaine exposure influences decision-making processes in adulthood is thus critically important. Methods Adolescent or adult mice were exposed to subchronic cocaine, then behavioral sensitivity to changes in the predictive relationship between actions and their consequences was tested. Dendritic spines on the principal pyramidal neurons of the orbitofrontal prefrontal cortex (oPFC) were also imaged and enumerated. To determine whether cytoskeletal regulatory systems in the oPFC influenced decision-making strategies, we then inhibited the activity of Abl-family and Rho kinases, as well as NR2B-containing NMDA receptors. We also attempted to block the reinstatement of cocaine seeking in cocaine self-administering mice. Results Adult mice with a history of subchronic cocaine exposure in adolescence engaged habit-based response strategies at the expense of goal-directed decision-making strategies and had fewer dendritic spines in the oPFC. Inhibition of the cytoskeletal regulatory Abl-family kinases in the oPFC recapitulated these neurobehavioral deficiencies, while Rho-kinase inhibition corrected response strategies. Additionally, the NR2B-selective NMDA receptor antagonists ifenprodil and CP-101,606 blocked cocaine-induced habits, and this was dependent on Abl-family signaling in the oPFC. Ifenprodil also mitigated cue-induced reinstatement of cocaine seeking in mice self-administering cocaine. Conclusions We suggest that adolescent cocaine exposure confers a bias towards habit-based behavior in adulthood via long-term cellular structural modifications in the oPFC. Treatments aimed at mitigating the durable consequences of early-life cocaine may benefit from targeting cytoskeletal regulatory systems. PMID:27871669

Molecular mechanisms mediating a deficit in recall of fear extinction in adult mice exposed to cocaine in utero.

PubMed

Kabir, Zeeba D; Katzman, Aaron C; Kosofsky, Barry E

2013-01-01

Prenatal cocaine exposure has been shown to alter cognitive processes of exposed individuals, presumed to be a result of long-lasting molecular alterations in the brain. In adult prenatal cocaine exposed (PCOC) mice we have identified a deficit in recall of fear extinction, a behavior that is dependent on the medial prefrontal cortex (mPFC) and the hippocampus. While we observed no change in the constitutive expression of brain derived neurotrophic factor (BDNF) protein and mRNA in the mPFC and hippocampus of adult PCOC mice, we observed blunted BDNF signaling in the mPFC of adult PCOC mice after fear extinction compared to the control animals. Specifically, during the consolidation phase of the extinction memory, we observed a decrease in BDNF protein and it's phospho-TrkB receptor expression. Interestingly, at this same time point there was a significant increase in total Bdnf mRNA levels in the mPFC of PCOC mice as compared with controls. In the Bdnf gene, we identified decreased constitutive binding of the transcription factors, MeCP2 and P-CREB at the promoters of Bdnf exons I and IV in the mPFC of PCOC mice, that unlike control mice remained unchanged when measured during the behavior. Finally, bilateral infusion of recombinant BDNF protein into the infralimbic subdivision of the mPFC during the consolidation phase of the extinction memory rescued the behavioral deficit in PCOC mice. In conclusion, these findings extend our knowledge of the neurobiologic impact of prenatal cocaine exposure on the mPFC of mice, which may lead to improved clinical recognition and treatment of exposed individuals.

Guanfacine ameliorates hypobaric hypoxia induced spatial working memory deficits.

PubMed

Kauser, H; Sahu, S; Kumar, S; Panjwani, U

2014-01-17

Hypobaric hypoxia (HH) observed at high altitude causes mild cognitive impairment specifically affecting attention and working memory. Adrenergic dysregulation and neuronal damage in prefrontal cortex (PFC) has been implicated in hypoxia induced memory deficits. Optimal stimulation of alpha 2A adrenergic receptor in PFC facilitates the spatial working memory (SWM) under the conditions of adrenergic dysregulation. Therefore the present study was designed to test the efficacy of alpha 2A adrenergic agonist, Guanfacine (GFC), to restore HH induced SWM deficits and PFC neuronal damage. The rats were exposed to chronic HH equivalent to 25,000ft for 7days in an animal decompression chamber and received daily treatment of GFC at a dose of 1mg/kg body weight via the intramuscular route during the period of exposure. The cognitive performance was assessed by Delayed Alternation Task (DAT) using T-Maze and PFC neuronal damage was studied by apoptotic and neurodegenerative markers. Percentage of correct choice decreased significantly while perseverative errors showed a significant increase after 7days HH exposure, GFC significantly ameliorated the SWM deficits and perseveration. There was a marked and significant increase in chromatin condensation, DNA fragmentation, neuronal pyknosis and fluoro Jade positive cells in layer II of the medial PFC in hypoxia exposed group, administration of GFC significantly reduced the magnitude of these changes. Modulation of adrenergic mechanisms by GFC may serve as an effective countermeasure in amelioration of prefrontal deficits and neurodegenerative changes during HH. © 2013.

Blocking Infralimbic Basic Fibroblast Growth Factor (bFGF or FGF2) Facilitates Extinction of Drug Seeking After Cocaine Self-Administration.

PubMed

Hafenbreidel, Madalyn; Twining, Robert C; Rafa Todd, Carolynn; Mueller, Devin

2015-12-01

Drug exposure results in structural and functional changes in brain regions that regulate reward and these changes may underlie the persistence of compulsive drug seeking and relapse. Neurotrophic factors, such as basic fibroblast growth factor (bFGF or FGF2), are necessary for neuronal survival, growth, and differentiation, and may contribute to these drug-induced changes. Following cocaine exposure, bFGF is increased in addiction-related brain regions, including the infralimbic medial prefrontal cortex (IL-mPFC). The IL-mPFC is necessary for extinction, but whether drug-induced overexpression of bFGF in this region affects extinction of drug seeking is unknown. Thus, we determined whether blocking bFGF in IL-mPFC would facilitate extinction following cocaine self-administration. Rats were trained to lever press for intravenous infusions of cocaine before extinction. Blocking bFGF in IL-mPFC before four extinction sessions resulted in facilitated extinction. In contrast, blocking bFGF alone was not sufficient to facilitate extinction, as blocking bFGF and returning rats to their home cage had no effect on subsequent extinction. Furthermore, bFGF protein expression increased in IL-mPFC following cocaine self-administration, an effect reversed by extinction. These results suggest that cocaine-induced overexpression of bFGF inhibits extinction, as blocking bFGF during extinction permits rapid extinction. Therefore, targeted reductions in bFGF during therapeutic interventions could enhance treatment outcomes for addiction.

A hybrid filter to mitigate harmonics caused by nonlinear load and resonance caused by power factor correction capacitor

NASA Astrophysics Data System (ADS)

Adan, N. F.; Soomro, D. M.

2017-01-01

Power factor correction capacitor (PFCC) is commonly installed in industrial applications for power factor correction (PFC). With the expanding use of non-linear equipment such as ASDs, power converters, etc., power factor (PF) improvement has become difficult due to the presence of harmonics. The resulting capacitive impedance of the PFCC may form a resonant circuit with the source inductive reactance at a certain frequency, which is likely to coincide with one of the harmonic frequency of the load. This condition will trigger large oscillatory currents and voltages that may stress the insulation and cause subsequent damage to the PFCC and equipment connected to the power system (PS). Besides, high PF cannot be achieved due to power distortion. This paper presents the design of a three-phase hybrid filter consisting of a single tuned passive filter (STPF) and shunt active power filter (SAPF) to mitigate harmonics and resonance in the PS through simulation using PSCAD/EMTDC software. SAPF was developed using p-q theory. The hybrid filter has resulted in significant improvement on both total harmonic distortion for voltage (THDV) and total demand distortion for current (TDDI) with maximum values of 2.93% and 9.84% respectively which were within the recommended IEEE 519-2014 standard limits. Regarding PF improvement, the combined filters have achieved PF close to desired PF at 0.95 for firing angle, α values up to 40°.

Chronic Gestational Stress Leads to Depressive-Like Behavior and Compromises Medial Prefrontal Cortex Structure and Function during the Postpartum Period

PubMed Central

Leuner, Benedetta; Fredericks, Peter J.; Nealer, Connor; Albin-Brooks, Christopher

2014-01-01

Postpartum depression, which affects approximately 15% of new mothers, is associated with impaired mother-infant interactions and deficits in cognitive function. Exposure to stress during pregnancy is a major risk factor for postpartum depression. However, little is known about the neural consequences of gestational stress. The medial prefrontal cortex (mPFC) is a brain region that has been linked to stress, cognition, maternal care, and mood disorders including postpartum depression. Here we examined the effects of chronic gestational stress on mPFC function and whether these effects might be linked to structural modifications in the mPFC. We found that in postpartum rats, chronic gestational stress resulted in maternal care deficits, increased depressive-like behavior, and impaired performance on an attentional set shifting task that relies on the mPFC. Furthermore, exposure to chronic stress during pregnancy reduced dendritic spine density on mPFC pyramidal neurons and altered spine morphology. Taken together, these findings suggest that pregnancy stress may contribute to postpartum mental illness and its associated symptoms by compromising structural plasticity in the mPFC. PMID:24594708

Power Controller

NASA Technical Reports Server (NTRS)

1983-01-01

The power factor controller (PFC) senses shifts in the relationship between voltage and current, and matches them with a motor's need. This prevents waste as motors do not need a high voltage when they are not operating at full load conditions. PFC is manufactured by Nordic Controls Company, among others, and has proved extremely cost effective.

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

Correlation of within-individual fluctuation of depressed mood with prefrontal cortex activity during verbal working memory task: optical topography study

NASA Astrophysics Data System (ADS)

Sato, Hiroki; Aoki, Ryuta; Katura, Takusige; Matsuda, Ryoichi; Koizumi, Hideaki

2011-12-01

Previous studies showed that interindividual variations in mood state are associated with prefrontal cortex (PFC) activity. In this study, we focused on the depressed-mood state under natural circumstances and examined the relationship between within-individual changes over time in this mood state and PFC activity. We used optical topography (OT), a functional imaging technique based on near-infrared spectroscopy, to measure PFC activity for each participant in three experimental sessions repeated at 2-week intervals. In each session, the participants completed a self-report questionnaire of mood state and underwent OT measurement while performing verbal and spatial working memory (WM) tasks. The results showed that changes in the depressed-mood score between successive sessions were negatively correlated with those in the left PFC activation for the verbal WM task (ρ = -0.56, p < 0.05). In contrast, the PFC activation for the spatial WM task did not co-vary with participants' mood changes. We thus demonstrated that PFC activity during a verbal WM task varies depending on the participant's depressed mood state, independent of trait factors. This suggests that using optical topography to measure PFC activity during a verbal WM task can be used as a potential state marker for an individual's depressed mood state.

Developing PFC representations using reinforcement learning.

PubMed

Reynolds, Jeremy R; O'Reilly, Randall C

2009-12-01

From both functional and biological considerations, it is widely believed that action production, planning, and goal-oriented behaviors supported by the frontal cortex are organized hierarchically [Fuster (1991); Koechlin, E., Ody, C., & Kouneiher, F. (2003). Neuroscience: The architecture of cognitive control in the human prefrontal cortex. Science, 424, 1181-1184; Miller, G. A., Galanter, E., & Pribram, K. H. (1960). Plans and the structure of behavior. New York: Holt]. However, the nature of the different levels of the hierarchy remains unclear, and little attention has been paid to the origins of such a hierarchy. We address these issues through biologically-inspired computational models that develop representations through reinforcement learning. We explore several different factors in these models that might plausibly give rise to a hierarchical organization of representations within the PFC, including an initial connectivity hierarchy within PFC, a hierarchical set of connections between PFC and subcortical structures controlling it, and differential synaptic plasticity schedules. Simulation results indicate that architectural constraints contribute to the segregation of different types of representations, and that this segregation facilitates learning. These findings are consistent with the idea that there is a functional hierarchy in PFC, as captured in our earlier computational models of PFC function and a growing body of empirical data.

Selective post-training time window for memory consolidation interference of cannabidiol into the prefrontal cortex: Reduced dopaminergic modulation and immediate gene expression in limbic circuits.

PubMed

Rossignoli, Matheus Teixeira; Lopes-Aguiar, Cleiton; Ruggiero, Rafael Naime; Do Val da Silva, Raquel Araujo; Bueno-Junior, Lezio Soares; Kandratavicius, Ludmyla; Peixoto-Santos, José Eduardo; Crippa, José Alexandre; Cecilio Hallak, Jaime Eduardo; Zuardi, Antonio Waldo; Szawka, Raphael Escorsim; Anselmo-Franci, Janete; Leite, João Pereira; Romcy-Pereira, Rodrigo Neves

2017-05-14

The prefrontal cortex (PFC), amygdala and hippocampus display a coordinated activity during acquisition of associative fear memories. Evidence indicates that PFC engagement in aversive memory formation does not progress linearly as previously thought. Instead, it seems to be recruited at specific time windows after memory acquisition, which has implications for the treatment of post-traumatic stress disorders. Cannabidiol (CBD), the major non-psychotomimetic phytocannabinoid of the Cannabis sativa plant, is known to modulate contextual fear memory acquisition in rodents. However, it is still not clear how CBD interferes with PFC-dependent processes during post-training memory consolidation. Here, we tested whether intra-PFC infusions of CBD immediately after or 5h following contextual fear conditioning was able to interfere with memory consolidation. Neurochemical and cellular correlates of the CBD treatment were evaluated by the quantification of extracellular levels of dopamine (DA), serotonin, and their metabolites in the PFC and by measuring the cellular expression of activity-dependent transcription factors in cortical and limbic regions. Our results indicate that bilateral intra-PFC CBD infusion impaired contextual fear memory consolidation when applied 5h after conditioning, but had no effect when applied immediately after it. This effect was associated with a reduction in DA turnover in the PFC following retrieval 5days after training. We also observed that post-conditioning infusion of CBD reduced c-fos and zif-268 protein expression in the hippocampus, PFC, and thalamus. Our findings support that CBD interferes with contextual fear memory consolidation by reducing PFC influence on cortico-limbic circuits. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Motor Controller

NASA Technical Reports Server (NTRS)

1988-01-01

M.H. Marks Enterprises' Power Factor Controller (PFC) matches voltage with motor's actual need. Plugged into a motor, PFC continuously determines motor load by sensing shifts between voltage and current flow. When it senses a light load, it cuts voltage to the minimum needed. It offers potential energy savings ranging from eight percent up to 65 percent depending on the application. Myles Marks started out with the notion of writing an article for Popular Electronics magazine at the same time offering to furnish kits to readers interested in assembling PFC's. Within two weeks from publication he had orders for 500 kits and orders are still coming three years later.

Synaptic Impairment in Layer 1 of the Prefrontal Cortex Induced by Repeated Stress During Adolescence is Reversed in Adulthood

PubMed Central

Negrón-Oyarzo, Ignacio; Dagnino-Subiabre, Alexies; Muñoz Carvajal, Pablo

2015-01-01

Chronic stress is a risk factor for the development of psychiatric disorders, some of which involve dysfunction of the prefrontal cortex (PFC). There is a higher prevalence of these chronic stress-related psychiatric disorders during adolescence, when the PFC has not yet fully matured. In the present work we studied the effect of repeated stress during adolescence on synaptic function in the PFC in adolescence and adulthood. To this end, adolescent Sprague-Dawley rats were subjected to seven consecutive days of restraint stress. Afterward, both synaptic transmission and short- and long-term synaptic plasticity were evaluated in layer 1 of medial-PFC (mPFC) slices from adolescent and adult rats. We found that repeated stress significantly reduced the amplitude of evoked field excitatory post-synaptic potential (fEPSP) in the mPFC. Isolation of excitatory transmission reveled that lower-amplitude fEPSPs were associated with a reduction in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated transmission. We also found that repeated stress significantly decreased long-term depression (LTD). Interestingly, AMPA/kainate receptor-mediated transmission and LTD were recovered in adult animals that experienced a three-week stress-free recovery period. The data indicates that the changes in synaptic transmission and plasticity in the mPFC induced by repeated stress during adolescence are reversed in adulthood after a stress-free period. PMID:26617490

Synaptic Impairment in Layer 1 of the Prefrontal Cortex Induced by Repeated Stress During Adolescence is Reversed in Adulthood.

PubMed

Negrón-Oyarzo, Ignacio; Dagnino-Subiabre, Alexies; Muñoz Carvajal, Pablo

2015-01-01

Chronic stress is a risk factor for the development of psychiatric disorders, some of which involve dysfunction of the prefrontal cortex (PFC). There is a higher prevalence of these chronic stress-related psychiatric disorders during adolescence, when the PFC has not yet fully matured. In the present work we studied the effect of repeated stress during adolescence on synaptic function in the PFC in adolescence and adulthood. To this end, adolescent Sprague-Dawley rats were subjected to seven consecutive days of restraint stress. Afterward, both synaptic transmission and short- and long-term synaptic plasticity were evaluated in layer 1 of medial-PFC (mPFC) slices from adolescent and adult rats. We found that repeated stress significantly reduced the amplitude of evoked field excitatory post-synaptic potential (fEPSP) in the mPFC. Isolation of excitatory transmission reveled that lower-amplitude fEPSPs were associated with a reduction in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated transmission. We also found that repeated stress significantly decreased long-term depression (LTD). Interestingly, AMPA/kainate receptor-mediated transmission and LTD were recovered in adult animals that experienced a three-week stress-free recovery period. The data indicates that the changes in synaptic transmission and plasticity in the mPFC induced by repeated stress during adolescence are reversed in adulthood after a stress-free period.

Effects of ketamine administration on mTOR and reticulum stress signaling pathways in the brain after the infusion of rapamycin into prefrontal cortex.

PubMed

Abelaira, Helena M; Réus, Gislaine Z; Ignácio, Zuleide M; Dos Santos, Maria Augusta B; de Moura, Airam B; Matos, Danyela; Demo, Júlia P; da Silva, Júlia B I; Michels, Monique; Abatti, Mariane; Sonai, Beatriz; Dal Pizzol, Felipe; Carvalho, André F; Quevedo, João

2017-04-01

Recent studies show that activation of the mTOR signaling pathway is required for the rapid antidepressant actions of glutamate N-methyl-D-aspartate (NMDA) receptor antagonists. A relationship between mTOR kinase and the endoplasmic reticulum (ER) stress pathway, also known as the unfolded protein response (UPR) has been shown. We evaluate the effects of ketamine administration on the mTOR signaling pathway and proteins of UPR in the prefrontal cortex (PFC), hippocampus, amygdala and nucleus accumbens, after the inhibiton of mTOR signaling in the PFC. Male adult Wistar rats received pharmacological mTOR inhibitor, rapamycin (0.2 nmol), or vehicle into the PFC and then a single dose of ketamine (15 mg/kg, i.p.). The immunocontent of mTOR, eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), eukaryotic elongation factor 2 kinase (eEF2K) homologous protein (CHOP), PKR-like ER kinase (PERK) and inositol-requiring enzyme 1 (IRE1) - alpha were determined in the brain. The mTOR levels were reduced in the rapamycin group treated with saline and ketamine in the PFC; p4EBP1 levels were reduced in the rapamycin group treated with ketamine in the PFC and nucleus accumbens; the levels of peEF2K were increased in the PFC in the vehicle group treated with ketamine and reduced in the rapamycin group treated with ketamine. The PERK and IRE1-alpha levels were decreased in the PFC in the rapamycin group treated with ketamine. Our results suggest that mTOR signaling inhibition by rapamycin could be involved, at least in part, with the mechanism of action of ketamine; and the ketamine antidepressant on ER stress pathway could be also mediated by mTOR signaling pathway in certain brain structures. Copyright © 2016 Elsevier Ltd. All rights reserved.

Liver graft preservation using perfluorocarbon improves the outcomes of simulated donation after cardiac death liver transplantation in rats.

PubMed

Okumura, Shinya; Uemura, Tadahiro; Zhao, Xiangdong; Masano, Yuki; Tsuruyama, Tatsuaki; Fujimoto, Yasuhiro; Iida, Taku; Yagi, Shintaro; Bezinover, Dmitri; Spiess, Bruce; Kaido, Toshimi; Uemoto, Shinji

2017-09-01

The outcomes of liver transplantation (LT) from donation after cardiac death (DCD) donors remain poor due to severe warm ischemia injury. Perfluorocarbon (PFC) is a novel compound with high oxygen carrying capacity. In the present study, a rat model simulating DCD LT was used, and the impact of improved graft oxygenation provided by PFC addition on liver ischemia/reperfusion injury (IRI) and survival after DCD LT was investigated. Orthotopic liver transplants were performed in male Lewis rats, using DCD liver grafts preserved with cold University of Wisconsin (UW) solution in the control group and preserved with cold oxygenated UW solution with addition of 20% PFC in the PFC group. For experiment I, in a 30-minute donor warm ischemia model, postoperative graft injury was analyzed at 3 and 6 hours after transplantation. For experiment II, in a 50-minute donor warm ischemia model, the postoperative survival was assessed. For experiment I, the levels of serum aspartate aminotransferase, alanine aminotransferase, hyaluronic acid, malondialdehyde, and several inflammatory cytokines were significantly lower in the PFC group. The hepatic expression levels of tumor necrosis factor α and interleukin 6 were significantly lower, and the expression level of heme oxygenase 1 was significantly higher in the PFC group. Histological analysis showed significantly less necrosis and apoptosis in the PFC group. Sinusoidal endothelial cells and microvilli of the bile canaliculi were well preserved in the PFC group. For experiment II, the postoperative survival rate was significantly improved in the PFC group. In conclusion, graft preservation with PFC attenuated liver IRI and improved postoperative survival. This graft preservation protocol might be a new therapeutic option to improve the outcomes of DCD LT. Liver Transplantation 23 1171-1185 2017 AASLD. © 2017 by the American Association for the Study of Liver Diseases.

Neonatal isolation augments social dominance by altering actin dynamics in the medial prefrontal cortex.

PubMed

Tada, Hirobumi; Miyazaki, Tomoyuki; Takemoto, Kiwamu; Takase, Kenkichi; Jitsuki, Susumu; Nakajima, Waki; Koide, Mayu; Yamamoto, Naoko; Komiya, Kasane; Suyama, Kumiko; Sano, Akane; Taguchi, Akiko; Takahashi, Takuya

2016-10-25

Social separation early in life can lead to the development of impaired interpersonal relationships and profound social disorders. However, the underlying cellular and molecular mechanisms involved are largely unknown. Here, we found that isolation of neonatal rats induced glucocorticoid-dependent social dominance over nonisolated control rats in juveniles from the same litter. Furthermore, neonatal isolation inactivated the actin-depolymerizing factor (ADF)/cofilin in the juvenile medial prefrontal cortex (mPFC). Isolation-induced inactivation of ADF/cofilin increased stable actin fractions at dendritic spines in the juvenile mPFC, decreasing glutamate synaptic AMPA receptors. Expression of constitutively active ADF/cofilin in the mPFC rescued the effect of isolation on social dominance. Thus, neonatal isolation affects spines in the mPFC by reducing actin dynamics, leading to altered social behavior later in life.

Neonatal isolation augments social dominance by altering actin dynamics in the medial prefrontal cortex

PubMed Central

Tada, Hirobumi; Miyazaki, Tomoyuki; Takemoto, Kiwamu; Takase, Kenkichi; Jitsuki, Susumu; Nakajima, Waki; Koide, Mayu; Yamamoto, Naoko; Komiya, Kasane; Suyama, Kumiko; Sano, Akane; Taguchi, Akiko; Takahashi, Takuya

2016-01-01

Social separation early in life can lead to the development of impaired interpersonal relationships and profound social disorders. However, the underlying cellular and molecular mechanisms involved are largely unknown. Here, we found that isolation of neonatal rats induced glucocorticoid-dependent social dominance over nonisolated control rats in juveniles from the same litter. Furthermore, neonatal isolation inactivated the actin-depolymerizing factor (ADF)/cofilin in the juvenile medial prefrontal cortex (mPFC). Isolation-induced inactivation of ADF/cofilin increased stable actin fractions at dendritic spines in the juvenile mPFC, decreasing glutamate synaptic AMPA receptors. Expression of constitutively active ADF/cofilin in the mPFC rescued the effect of isolation on social dominance. Thus, neonatal isolation affects spines in the mPFC by reducing actin dynamics, leading to altered social behavior later in life. PMID:27791080

Prefrontal Cortex and Drug Abuse Vulnerability: Translation to Prevention and Treatment Interventions

PubMed Central

Perry, Jennifer L.; Joseph, Jane E.; Jiang, Yang; Zimmerman, Rick S.; Kelly, Thomas H.; Darna, Mahesh; Huettl, Peter; Dwoskin, Linda P.; Bardo, Michael T.

2010-01-01

Vulnerability to drug abuse is related to both reward seeking and impulsivity, two constructs thought to have a biological basis in the prefrontal cortex (PFC). This review addresses similarities and differences in neuroanatomy, neurochemistry and behavior associated with PFC function in rodents and primates. Emphasis is placed on monoamine and amino acid neurotransmitter systems located in anatomically distinct subregions: medial prefrontal cortex (mPFC); lateral prefrontal cortex (lPFC); anterior cingulate cortex (ACC); and orbitofrontal cortex (OFC). While there are complex interconnections and overlapping functions among these regions, each is thought to be involved in various functions related to health-related risk behaviors and drug abuse vulnerability. Among the various functions implicated, evidence suggests that mPFC is involved in reward processing, attention and drug reinstatement; lPFC is involved in decision-making, behavioral inhibition and attentional gating; ACC is involved in attention, emotional processing and self-monitoring; and OFC is involved in behavioral inhibition, signaling of expected outcomes and reward/punishment sensitivity. Individual differences factors (e.g., age and sex) influence functioning of these regions, which, in turn, impacts drug abuse vulnerability. Implications for the development of drug abuse prevention and treatment strategies aimed at engaging PFC inhibitory processes that may reduce risk-related behaviors are discussed, including the design of effective public service announcements, cognitive exercises, physical activity, direct current stimulation, feedback control training and pharmacotherapies. A major challenge in drug abuse prevention and treatment rests with improving intervention strategies aimed at strengthening PFC inhibitory systems among at-risk individuals. PMID:20837060

Chronic social isolation suppresses proplastic response and promotes proapoptotic signalling in prefrontal cortex of Wistar rats.

PubMed

Djordjevic, Ana; Adzic, Miroslav; Djordjevic, Jelena; Radojcic, Marija B

2010-08-15

Successful adaptation to stress involves synergized actions of glucocorticoids and catecholamines at several levels of the CNS, including the prefrontal cortex (PFC). Inside the PFC, hormonal signals trigger concerted actions of transcriptional factors, such as glucocorticoid receptor (GR) and nuclear factor kappa B (NFkappaB), culminating in a balanced, proadaptive expression of their common genes, such as proplastic NCAM and/or apoptotic Bax and Bcl-2. In the present study, we hypothesized that chronic stress may compromise the balance between GR and NFkappaB signals and lead to an altered/maladaptive expression of their cognate genes in the PFC. Our results obtained with Wistar rats exposed to chronic social isolation indicated alterations of the GR relative to the NFkappaB, in favor of the GR, in both the cytoplasmic and the nuclear compartments of the PFC. Although these alterations did not affect the induction of proplastic NCAM gene, they decreased the NCAM sialylation necessary for plastic response and caused marked relocation of the mitochondrial membrane antiapoptotic Bcl-2 protein to its cytoplasmic form. Moreover, the compromised PSA-NCAM plastic response found under chronic stress was sustained after exposure of animals to the subsequent acute stress, whereas the proapoptotic signals were further emphasized. It is concluded that chronic social isolation of Wistar animals leads to a maladaptive response of the PFC, considering the diminishment of its plastic potential and potentiating of apoptosis. Such conditions in the PFC are likely to compromise its ability to interact with other CNS structures, such as the hippocampus, which is necessary for successful adaptation to stress. (c) 2010 Wiley-Liss, Inc.

Differential expression of cytoskeletal regulatory factors in the adolescent prefrontal cortex: Implications for cortical development

PubMed Central

Shapiro, Lauren P.; Parsons, Ryan G.; Koleske, Anthony J.; Gourley, Shannon L.

2016-01-01

The prevalence of depression, anxiety, schizophrenia, and drug and alcohol use disorders peaks during adolescence. Further, up to 50% of “adult” mental health disorders emerge in adolescence. During adolescence, the prefrontal cortex undergoes dramatic structural reorganization, in which dendritic spines and synapses are refined, pruned, and stabilized. Understanding the molecular mechanisms that underlie these processes should help to identify factors that influence the development of psychiatric illness. Here we briefly discuss the anatomical connections of the medial and orbital prefrontal cortex (mPFC and OFC, respectively). We then present original findings suggesting that dendritic spines on deep-layer excitatory neurons in the mouse mPFC and OFC prune at different adolescent ages, with later pruning in the OFC. In parallel, we used western blotting to define levels of several cytoskeletal regulatory proteins during early, mid-, and late adolescence, focusing on tropomyosin-related kinase receptor B (TrkB) and β1-integrin-containing receptors and select signaling partners. We identified regional differences in the levels of several proteins in early and mid-adolescence that then converged in early adulthood. We also observed age-related differences in TrkB levels, both full-length and truncated isoforms, Rho-kinase 2 (ROCK2), and synaptophysin in both PFC subregions. Finally, we identified changes in protein levels in the dorsal and ventral hippocampus that were distinct from those in the PFC. We conclude with a general review of the manner in which TrkB- and β1-integrin-mediated signaling influences neuronal structure in the postnatal brain. Elucidating the role of cytoskeletal regulatory factors throughout adolescence may identify critical mechanisms of PFC development. PMID:27735056

Reelin-Haploinsufficiency Disrupts the Developmental Trajectory of the E/I Balance in the Prefrontal Cortex

PubMed Central

Bouamrane, Lamine; Scheyer, Andrew F.; Lassalle, Olivier; Iafrati, Jillian; Thomazeau, Aurore; Chavis, Pascale

2017-01-01

The reelin gene is a strong candidate in the etiology of several psychiatric disorders such as schizophrenia, major depression, bipolar disorders, and autism spectrum disorders. Most of these diseases are accompanied by cognitive and executive-function deficits associated with prefrontal dysfunctions. Mammalian prefrontal cortex (PFC) development is characterized by a protracted postnatal maturation constituting a period of enhanced vulnerability to psychiatric insults. The identification of the molecular components underlying this prolonged postnatal development is necessary to understand the synaptic properties of defective circuits participating in these psychiatric disorders. We have recently shown that reelin plays a key role in the maturation of glutamatergic functions in the postnatal PFC, but no data are available regarding the GABAergic circuits. Here, we undertook a cross-sectional analysis of GABAergic function in deep layer pyramidal neurons of the medial PFC of wild-type and haploinsufficient heterozygous reeler mice. Using electrophysiological approaches, we showed that decreased reelin levels impair the maturation of GABAergic synaptic transmission without affecting the inhibitory nature of GABA. This phenotype consequently impacted the developmental sequence of the synaptic excitation/inhibition (E/I) balance. These data indicate that reelin is necessary for the correct maturation and refinement of GABAergic synaptic circuits in the postnatal PFC and therefore provide a mechanism for altered E/I balance of prefrontal circuits associated with psychiatric disorders. PMID:28127276

Helper signals in the plaque-forming cell response to protein-bound haptens.

PubMed

Roehm, N W; Marrack, P; Kappler, J W

1983-08-01

We have demonstrated the ability of a series of murine T cell hybridomas to deliver an antigen-specific, B cell I-region-restricted helper signal in the generation of specific PFC responses to protein-bound haptens. With some hybridomas the elicitation of optimal PFC responses required the addition of nonspecific factors provided by culture supernatants of concanavalin A-stimulated (Con A SN) spleen cells. Using hapten-primed B cells depleted of both T cells and macrophages (Mphi) we have now demonstrated a requirement for three nonspecific factor preparations to substitute for spleen Con A SN in the elicitation of optimal PFC responses. The first preparation was the interleukin 1 containing culture supernatant of the Mphi tumor cell line P388D1, the second the interleukin 2 (IL-2) and B cell growth factor containing Con A SN of the T cell hybridoma FS6-14.13, and the third, the gamma interferon containing Con A SN of the T cell hybridoma FS7-20.6.18. The P388D1 and FS6-14.13 factor preparations were most effective when added at the initiation of culture, while the FS7-20.6.18 factor preparation was most effective when added at 24 h of culture. The activity of FS6-14.13 Con A SN was depleted by incubation with the IL-2-dependent T cell line HT-2. The activity of FS7-20.6.18 Con A SN was abrogated by incubation at pH 2. The results suggest that the generation of PFC responses to protein-bound haptens require at least three nonspecific factors in addition to an antigen/Ia specific helper signal.

SiC MOSFET Based Single Phase Active Boost Rectifier with Power Factor Correction for Wireless Power Transfer Applications

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

Onar, Omer C; Tang, Lixin; Chinthavali, Madhu Sudhan

2014-01-01

Wireless Power Transfer (WPT) technology is a novel research area in the charging technology that bridges the utility and the automotive industries. There are various solutions that are currently being evaluated by several research teams to find the most efficient way to manage the power flow from the grid to the vehicle energy storage system. There are different control parameters that can be utilized to compensate for the change in the impedance due to variable parameters such as battery state-of-charge, coupling factor, and coil misalignment. This paper presents the implementation of an active front-end rectifier on the grid side formore » power factor control and voltage boost capability for load power regulation. The proposed SiC MOSFET based single phase active front end rectifier with PFC resulted in >97% efficiency at 137mm air-gap and >95% efficiency at 160mm air-gap.« less

Oscillatory Activity in the Medial Prefrontal Cortex and Nucleus Accumbens Correlates with Impulsivity and Reward Outcome

PubMed Central

Rich, P. Dylan; Nevado-Holgado, Alejo J.; Fernando, Anushka B. P.; Van Dijck, Gert; Holzhammer, Tobias; Paul, Oliver; Ruther, Patrick; Paulsen, Ole; Robbins, Trevor W.; Dalley, Jeffrey W.

2014-01-01

Actions expressed prematurely without regard for their consequences are considered impulsive. Such behaviour is governed by a network of brain regions including the prefrontal cortex (PFC) and nucleus accumbens (NAcb) and is prevalent in disorders including attention deficit hyperactivity disorder (ADHD) and drug addiction. However, little is known of the relationship between neural activity in these regions and specific forms of impulsive behaviour. In the present study we investigated local field potential (LFP) oscillations in distinct sub-regions of the PFC and NAcb on a 5-choice serial reaction time task (5-CSRTT), which measures sustained, spatially-divided visual attention and action restraint. The main findings show that power in gamma frequency (50–60 Hz) LFP oscillations transiently increases in the PFC and NAcb during both the anticipation of a cue signalling the spatial location of a nose-poke response and again following correct responses. Gamma oscillations were coupled to low-frequency delta oscillations in both regions; this coupling strengthened specifically when an error response was made. Theta (7–9 Hz) LFP power in the PFC and NAcb increased during the waiting period and was also related to response outcome. Additionally, both gamma and theta power were significantly affected by upcoming premature responses as rats waited for the visual cue to respond. In a subgroup of rats showing persistently high levels of impulsivity we found that impulsivity was associated with increased error signals following a nose-poke response, as well as reduced signals of previous trial outcome during the waiting period. Collectively, these in-vivo neurophysiological findings further implicate the PFC and NAcb in anticipatory impulsive responses and provide evidence that abnormalities in the encoding of rewarding outcomes may underlie trait-like impulsive behaviour. PMID:25333512

History of winning remodels thalamo-PFC circuit to reinforce social dominance.

PubMed

Zhou, Tingting; Zhu, Hong; Fan, Zhengxiao; Wang, Fei; Chen, Yang; Liang, Hexing; Yang, Zhongfei; Zhang, Lu; Lin, Longnian; Zhan, Yang; Wang, Zheng; Hu, Hailan

2017-07-14

Mental strength and history of winning play an important role in the determination of social dominance. However, the neural circuits mediating these intrinsic and extrinsic factors have remained unclear. Working in mice, we identified a dorsomedial prefrontal cortex (dmPFC) neural population showing "effort"-related firing during moment-to-moment competition in the dominance tube test. Activation or inhibition of the dmPFC induces instant winning or losing, respectively. In vivo optogenetic-based long-term potentiation and depression experiments establish that the mediodorsal thalamic input to the dmPFC mediates long-lasting changes in the social dominance status that are affected by history of winning. The same neural circuit also underlies transfer of dominance between different social contests. These results provide a framework for understanding the circuit basis of adaptive and pathological social behaviors. Copyright © 2017, American Association for the Advancement of Science.

Early Adolescent MK-801 Exposure Impairs the Maturation of Ventral Hippocampal Control of Basolateral Amygdala Drive in the Adult Prefrontal Cortex

PubMed Central

Thomases, Daniel R.; Cass, Daryn K.; Meyer, Jacqueline D.; Caballero, Adriana

2014-01-01

The adolescent susceptibility to the onset of psychiatric disorders is only beginning to be understood when factoring in the development of the prefrontal cortex (PFC). The functional maturation of the PFC is dependent upon proper integration of glutamatergic inputs from the ventral hippocampus (vHipp) and the basolateral amygdala (BLA). Here we assessed how transient NMDAR blockade during adolescence alters the functional interaction of vHipp–BLA inputs in regulating PFC plasticity. Local field potential recordings were used to determine changes in long-term depression (LTD) and long-term potentiation (LTP) of PFC responses resulting from vHipp and BLA high-frequency stimulation in adult rats that received repeated injections of saline or the NMDAR antagonist MK-801 from postnatal day 35 (P35) to P40. We found that early adolescent MK-801 exposure elicited an age- and input-specific dysregulation of vHipp–PFC plasticity, characterized by a shift from LTD to LTP without altering the BLA-induced LTP. Data also showed that the vHipp normally resets the LTP state of BLA transmission; however, this inhibitory regulation is absent following early adolescent MK-801 treatment. This deficit was reminiscent of PFC responses seen in drug-naive juveniles. Notably, local prefrontal upregulation of GABAAα1 function completely restored vHipp functionality and its regulation of BLA plasticity in MK-801-treated rats. Thus, NMDAR signaling is critical for the periadolescent acquisition of a GABA-dependent hippocampal control of PFC plasticity, which enables the inhibitory control of the prefrontal output by the vHipp. A dysregulation of this pathway can alter PFC processing of other converging afferents such as those from the BLA. PMID:24990926

Benefit from NASA

NASA Image and Video Library

1997-01-01

Frank Nola invented the Power Factor Controller (PFC) at Marshall Space Flight Center more than a decade ago. Nola came up with a way to curb power wastage in AC induction motors. The PFC matches voltage with the motor's actual need by continuously sensing shifts between voltage and current. When it senses a light load it cuts the voltage to the minimum needed. Potential energy savings range from 8 to 65 percent.

Decreased expression of Freud-1/CC2D1A, a transcriptional repressor of the 5-HT1A receptor, in the prefrontal cortex of subjects with major depression.

PubMed

Szewczyk, Bernadeta; Albert, Paul R; Rogaeva, Anastasia; Fitzgibbon, Heidi; May, Warren L; Rajkowska, Grazyna; Miguel-Hidalgo, Jose J; Stockmeier, Craig A; Woolverton, William L; Kyle, Patrick B; Wang, Zhixia; Austin, Mark C

2010-09-01

Serotonin1A (5-HT(1A)) receptors are reported altered in the brain of subjects with major depressive disorder (MDD). Recent studies have identified transcriptional regulators of the 5-HT(1A) receptor and have documented gender-specific alterations in 5-HT(1A) transcription factor and 5-HT(1A) receptors in female MDD subjects. The 5' repressor element under dual repression binding protein-1 (Freud-1) is a calcium-regulated repressor that negatively regulates the 5-HT(1A) receptor gene. This study documented the cellular expression of Freud-1 in the human prefrontal cortex (PFC) and quantified Freud-1 protein in the PFC of MDD and control subjects as well as in the PFC of rhesus monkeys chronically treated with fluoxetine. Freud-1 immunoreactivity was present in neurons and glia and was co-localized with 5-HT(1A) receptors. Freud-1 protein level was significantly decreased in the PFC of male MDD subjects (37%, p=0.02) relative to gender-matched control subjects. Freud-1 protein was also reduced in the PFC of female MDD subjects (36%, p=0.18) but was not statistically significant. When the data was combined across genders and analysed by age, the decrease in Freud-1 protein level was greater in the younger MDD subjects (48%, p=0.01) relative to age-matched controls as opposed to older depressed subjects. Similarly, 5-HT(1A) receptor protein was significantly reduced in the PFC of the younger MDD subjects (48%, p=0.01) relative to age-matched controls. Adult male rhesus monkeys administered fluoxetine daily for 39 wk revealed no significant change in cortical Freud-1 or 5-HT(1A) receptor proteins compared to vehicle-treated control monkeys. Reduced protein expression of Freud-1 in MDD subjects may reflect dysregulation of this transcription factor, which may contribute to the altered regulation of 5-HT(1A) receptors observed in subjects with MDD. These data may also suggest that reductions in Freud-1 protein expression in the PFC may be associated with early onset of MDD.

The manufacture of blood plasma products in Scotland: a brief history.

PubMed

Foster, Peter R

2016-02-01

A number of essential clinical products are derived from human blood plasma, including immunoglobulin products for the treatment of infections and disorders of immunity; albumin for protein and fluid replacement and coagulation factors for the treatment of haemophilia and other disorders of haemostasis. For many years, these protein pharmaceuticals were manufactured by the Scottish National Blood Transfusion Service (SNBTS) at its Scottish Protein Fractionation Centre (PFC) in Edinburgh, a contribution which ended with the closure of the PFC in 2008. The origins and development of plasma fractionation in Scotland are summarised in this article, as well as issues which contributed to the closure of the PFC. © The Author(s) 2015.

Altered amygdala-prefrontal connectivity during emotion perception in schizophrenia.

PubMed

Bjorkquist, Olivia A; Olsen, Emily K; Nelson, Brady D; Herbener, Ellen S

2016-08-01

Individuals with schizophrenia evidence impaired emotional functioning. Abnormal amygdala activity has been identified as an etiological factor underlying affective impairment in this population, but the exact nature remains unclear. The current study utilized psychophysiological interaction analyses to examine functional connectivity between the amygdala and medial prefrontal cortex (mPFC) during an emotion perception task. Participants with schizophrenia (SZ) and healthy controls (HC) viewed and rated positive, negative, and neutral images while undergoing functional neuroimaging. Results revealed a significant group difference in right amygdala-mPFC connectivity during perception of negative versus neutral images. Specifically, HC participants demonstrated positive functional coupling between the amygdala and mPFC, consistent with co-active processing of salient information. In contrast, SZ participants evidenced negative functional coupling, consistent with top-down inhibition of the amygdala by the mPFC. A significant positive correlation between connectivity strength during negative image perception and clinician-rated social functioning was also observed in SZ participants, such that weaker right amygdala-mPFC coupling during negative compared to neutral image perception was associated with poorer social functioning. Overall, results suggest that emotional dysfunction and associated deficits in functional outcome in schizophrenia may relate to abnormal interactions between the amygdala and mPFC during perception of emotional stimuli. This study adds to the growing literature on abnormal functional connections in schizophrenia and supports the functional disconnection hypothesis of schizophrenia. Copyright © 2016 Elsevier B.V. All rights reserved.

Elevated stress is associated with prefrontal cortex dysfunction during a verbal memory task in women with HIV

PubMed Central

Rubin, Leah H.; Wu, Minjie; Sundermann, Erin E.; Meyer, Vanessa J.; Smith, Rachael; Weber, Kathleen M.; Cohen, Mardge H.; Little, Deborah M.; Maki, Pauline M.

2016-01-01

HIV-infected women may be particularly vulnerable to verbal learning and memory deficits. One factor contributing to these deficits is high perceived stress, which is associated with prefrontal cortical (PFC) atrophy and memory outcomes sensitive to PFC function, including retrieval and semantic clustering. We examined the association between stress and PFC activation during a verbal memory task in 36 HIV-infected women from the Chicago Consortium of the Women’s Interagency HIV Study (WIHS) to better understand the role of the PFC in this stress-related impairment. Participants completed standardized measures of verbal learning and memory and stress (Perceived Stress Scale-10). We used functional magnetic resonance imaging to assess brain function while participants completed encoding and recognition phases of a verbal memory task. HIV-infected women with higher stress (scores in top tertile) performed worse on all verbal memory outcomes including strategic encoding (p’s<0.05) compared to HIV-infected women with lower stress (scores in lower two tertiles). Patterns of brain activation during recognition (but not encoding) differed between women with higher versus lower stress. During recognition, women with higher stress demonstrated greater deactivation in medial PFC and posterior cingulate cortex compared to women with lower stress (p’s<0.05). Greater deactivation in medial PFC marginally related to less efficient strategic retrieval (p=0.06). Similar results were found in analyses focusing on PTSD symptoms. Results suggest that stress might alter the function of the medial PFC in HIV-infected women resulting in less efficient strategic retrieval and deficits in verbal memory. PMID:27094924

Elevated stress is associated with prefrontal cortex dysfunction during a verbal memory task in women with HIV.

PubMed

Rubin, Leah H; Wu, Minjie; Sundermann, Erin E; Meyer, Vanessa J; Smith, Rachael; Weber, Kathleen M; Cohen, Mardge H; Little, Deborah M; Maki, Pauline M

2016-12-01

HIV-infected women may be particularly vulnerable to verbal learning and memory deficits. One factor contributing to these deficits is high perceived stress, which is associated with prefrontal cortical (PFC) atrophy and memory outcomes sensitive to PFC function, including retrieval and semantic clustering. We examined the association between stress and PFC activation during a verbal memory task in 36 HIV-infected women from the Chicago Consortium of the Women's Interagency HIV Study (WIHS) to better understand the role of the PFC in this stress-related impairment. Participants completed standardized measures of verbal learning and memory and stress (perceived stress scale-10). We used functional magnetic resonance imaging to assess brain function while participants completed encoding and recognition phases of a verbal memory task. HIV-infected women with higher stress (scores in top tertile) performed worse on all verbal memory outcomes including strategic encoding (p < 0.05) compared to HIV-infected women with lower stress (scores in lower two tertiles). Patterns of brain activation during recognition (but not encoding) differed between women with higher vs. lower stress. During recognition, women with higher stress demonstrated greater deactivation in medial PFC and posterior cingulate cortex compared to women with lower stress (p < 0.05). Greater deactivation in medial PFC marginally related to less efficient strategic retrieval (p = 0.06). Similar results were found in analyses focusing on PTSD symptoms. Results suggest that stress might alter the function of the medial PFC in HIV-infected women resulting in less efficient strategic retrieval and deficits in verbal memory.

Aniracetam enhances cortical dopamine and serotonin release via cholinergic and glutamatergic mechanisms in SHRSP.

PubMed

Shirane, M; Nakamura, K

2001-10-19

Aniracetam, a cognition enhancer, has been recently found to preferentially increase extracellular levels of dopamine (DA) and serotonin (5-HT) in the prefrontal cortex (PFC), basolateral amygdala and dorsal hippocampus of the mesocorticolimbic system in stroke-prone spontaneously hypertensive rats. In the present study, we aimed to identify actually active substances among aniracetam and its major metabolites and to clarify the mode of action in DA and 5-HT release in the PFC. Local perfusion of mecamylamine, a nicotinic acetylcholine (nACh) and N-methyl-D-aspartate (NMDA) receptor antagonist, into the ventral tegmental area (VTA) and dorsal raphe nucleus (DRN) completely blocked DA and 5-HT release, respectively, in the PFC elicited by orally administered aniracetam. The effects of aniracetam were mimicked by local perfusion of N-anisoyl-gamma-aminobutyric acid [corrected] (N-anisoyl-GABA), one of the major metabolites of aniracetam, into the VTA and DRN. The cortical DA release induced by N-anisoyl-GABA applied to the VTA was also completely abolished by co-perfusion of mecamylamine. Additionally, when p-anisic acid, another metabolite of aniracetam, and N-anisoyl-GABA were locally perfused into the PFC, they induced DA and 5-HT release in the same region, respectively. These results indicate that aniracetam enhances DA and 5-HT release by mainly mediating the action of N-anisoyl-GABA that targets not only somatodendritic nACh and NMDA receptors but also presynaptic nACh receptors.

Age-related changes in overcoming proactive interference in associative memory: The role of PFC-mediated executive control processes at retrieval.

PubMed

Dulas, Michael R; Duarte, Audrey

2016-05-15

Behavioral evidence has shown age-related impairments in overcoming proactive interference in memory, but it is unclear what underlies this deficit. Imaging studies in the young suggest overcoming interference may require several executive control processes supported by the ventrolateral prefrontal cortex (VLPFC) and dorsolateral PFC (DLPFC). The present functional magnetic resonance imaging (fMRI) study investigated whether age-related changes in dissociable executive control processes underlie deficits in overcoming proactive interference in associative memory during retrieval. Participants were tasked with remembering which associate (face or scene) objects were paired with most recently during study, under conditions of high or low proactive interference. Behavioral results demonstrated that, as interference increased, memory performance decreased similarly across groups, with slight associative memory deficits in older adults. Imaging results demonstrated that, across groups, left mid-VLPFC showed increasing activity with increasing interference, though activity did not distinguish correct from incorrect associative memory responses, suggesting this region may not directly serve in successful resolution of proactive interference, per se. Under conditions of high interference, older adults showed reduced associative memory accuracy effects in the DLPFC and anterior PFC. These results suggest that age-related PFC dysfunction may not be ubiquitous. Executive processes supported by ventral regions that detect mnemonic interference may be less affected than processes supported by dorsal and anterior regions that directly resolve interference. Copyright © 2016 Elsevier Inc. All rights reserved.

The frontal cortex and the criminal justice system.

PubMed

Sapolsky, Robert M

2004-11-29

In recent decades, the general trend in the criminal justice system in the USA has been to narrow the range of insanity defences available, with an increasing dependence solely on the M'Naghten rule. This states that innocence by reason of insanity requires that the perpetrator could not understand the nature of their criminal act, or did not know that the act was wrong, by reason of a mental illness. In this essay, I question the appropriateness of this, in light of contemporary neuroscience. Specifically, I focus on the role of the prefrontal cortex (PFC) in cognition, emotional regulation, control of impulsive behaviour and moral reasoning. I review the consequences of PFC damage on these endpoints, the capacity for factors such as alcohol and stress to transiently impair PFC function, and the remarkably late development of the PFC (in which full myelination may not occur until early adulthood). I also consider how individual variation in PFC function and anatomy, within the normative range, covaries with some of these endpoints. This literature is reviewed because of its relevance to issues of criminal insanity; specifically, damage can produce an individual capable of differentiating right from wrong but who, nonetheless, is organically incapable of appropriately regulating their behaviour.

Classical nucleation theory in the phase-field crystal model

NASA Astrophysics Data System (ADS)

Jreidini, Paul; Kocher, Gabriel; Provatas, Nikolas

2018-04-01

A full understanding of polycrystalline materials requires studying the process of nucleation, a thermally activated phase transition that typically occurs at atomistic scales. The numerical modeling of this process is problematic for traditional numerical techniques: commonly used phase-field methods' resolution does not extend to the atomic scales at which nucleation takes places, while atomistic methods such as molecular dynamics are incapable of scaling to the mesoscale regime where late-stage growth and structure formation takes place following earlier nucleation. Consequently, it is of interest to examine nucleation in the more recently proposed phase-field crystal (PFC) model, which attempts to bridge the atomic and mesoscale regimes in microstructure simulations. In this work, we numerically calculate homogeneous liquid-to-solid nucleation rates and incubation times in the simplest version of the PFC model, for various parameter choices. We show that the model naturally exhibits qualitative agreement with the predictions of classical nucleation theory (CNT) despite a lack of some explicit atomistic features presumed in CNT. We also examine the early appearance of lattice structure in nucleating grains, finding disagreement with some basic assumptions of CNT. We then argue that a quantitatively correct nucleation theory for the PFC model would require extending CNT to a multivariable theory.

Neural activation patterns of successful episodic encoding: Reorganization during childhood, maintenance in old age.

PubMed

Shing, Yee Lee; Brehmer, Yvonne; Heekeren, Hauke R; Bäckman, Lars; Lindenberger, Ulman

2016-08-01

The two-component framework of episodic memory (EM) development posits that the contributions of medial temporal lobe (MTL) and prefrontal cortex (PFC) to successful encoding differ across the lifespan. To test the framework's hypotheses, we compared subsequent memory effects (SME) of 10-12 year-old children, younger adults, and older adults using functional magnetic resonance imaging (fMRI). Memory was probed by cued recall, and SME were defined as regional activation differences during encoding between subsequently correctly recalled versus omitted items. In MTL areas, children's SME did not differ in magnitude from those of younger and older adults. In contrast, children's SME in PFC were weaker than the corresponding SME in younger and older adults, in line with the hypothesis that PFC contributes less to successful encoding in childhood. Differences in SME between younger and older adults were negligible. The present results suggest that, among individuals with high memory functioning, the neural circuitry contributing to successful episodic encoding is reorganized from middle childhood to adulthood. Successful episodic encoding in later adulthood, however, is characterized by the ability to maintain the activation patterns that emerged in young adulthood. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Classical nucleation theory in the phase-field crystal model.

PubMed

Jreidini, Paul; Kocher, Gabriel; Provatas, Nikolas

2018-04-01

A full understanding of polycrystalline materials requires studying the process of nucleation, a thermally activated phase transition that typically occurs at atomistic scales. The numerical modeling of this process is problematic for traditional numerical techniques: commonly used phase-field methods' resolution does not extend to the atomic scales at which nucleation takes places, while atomistic methods such as molecular dynamics are incapable of scaling to the mesoscale regime where late-stage growth and structure formation takes place following earlier nucleation. Consequently, it is of interest to examine nucleation in the more recently proposed phase-field crystal (PFC) model, which attempts to bridge the atomic and mesoscale regimes in microstructure simulations. In this work, we numerically calculate homogeneous liquid-to-solid nucleation rates and incubation times in the simplest version of the PFC model, for various parameter choices. We show that the model naturally exhibits qualitative agreement with the predictions of classical nucleation theory (CNT) despite a lack of some explicit atomistic features presumed in CNT. We also examine the early appearance of lattice structure in nucleating grains, finding disagreement with some basic assumptions of CNT. We then argue that a quantitatively correct nucleation theory for the PFC model would require extending CNT to a multivariable theory.

Stress-induced alterations in 5-HT1A receptor transcriptional modulators NUDR and Freud-1.

PubMed

Szewczyk, Bernadeta; Kotarska, Katarzyna; Daigle, Mireille; Misztak, Paulina; Sowa-Kucma, Magdalena; Rafalo, Anna; Curzytek, Katarzyna; Kubera, Marta; Basta-Kaim, Agnieszka; Nowak, Gabriel; Albert, Paul R

2014-11-01

The effect of stress on the mRNA and protein level of the 5-HT1A receptor and two of its key transcriptional modulators, NUDR and Freud-1, was examined in the prefrontal cortex (PFC) and hippocampus (Hp) using rodent models: olfactory bulbectomy (OB) and prenatal stress (PS) in male and female rats; chronic mild stress in male rats (CMS) and pregnancy stress. In PFC, CMS induced the most widespread changes, with significant reduction in both mRNA and protein levels of NUDR, 5-HT1A receptor and in Freud-1 mRNA; while in Hp 5-HT1A receptor and Freud-1 protein levels were also decreased. In male, but not female OB rats PFC Freud-1 and 5-HT1A receptor protein levels were reduced, while in Hp 5-HT1A receptor, Freud-1 and NUDR mRNA's but not protein were reduced. In PS rats PFC 5-HT1A receptor protein was reduced more in females than males; while in Hp Freud-1 protein was increased in females. In pregnancy stress, PFC NUDR, Freud-1 and 5-HT1A protein receptor levels were reduced, and in HP 5-HT1A receptor protein levels were also reduced; in HP only NUDR and Freud-1 mRNA levels were reduced. Overall, CMS and stress during pregnancy produced the most salient changes in 5-HT1A receptor and transcription factor expression, suggesting a primary role for altered transcription factor expression in chronic regulation of 5-HT1A receptor expression. By contrast, OB (in males) and PS (in females) produced gender-specific reductions in PFC 5-HT1A receptor protein levels, suggesting a role for post-transcriptional regulation. These and previous data suggest that chronic stress might be a key regulator of NUDR/Freud-1 gene expression.

Stress-induced alterations in 5-HT1A receptor transcriptional modulators NUDR and Freud-1

PubMed Central

Szewczyk, Bernadeta; Kotarska, Katarzyna; Daigle, Mireille; Misztak, Paulina; Sowa-Kucma, Magdalena; Rafalo, Anna; Curzytek, Katarzyna; Kubera, Marta; Basta-Kaim, Agnieszka; Nowak, Gabriel; Albert, Paul R

2015-01-01

The effect of stress on the mRNA and protein level of the 5-HT1A receptor and two of its key transcriptional modulators, NUDR and Freud-1, was examined in the prefrontal cortex (PFC) and hippocampus (Hp) using rodent models: olfactory bulbectomy (OB) and prenatal stress (PS) in male and female rats; chronic mild stress in male rats (CMS) and pregnancy stress. In PFC, CMS induced the most widespread changes, with significant reduction in both mRNA and protein levels of NUDR, 5-HT1A receptor and in Freud-1 mRNA; while in Hp 5-HT1A receptor and Freud-1 protein levels were also decreased. In male, but not female OB rats PFC Freud-1 and 5-HT1A receptor protein levels were reduced, while in Hp 5-HT1A receptor, Freud-1 and NUDR mRNA’s but not protein were reduced. In PS rats PFC 5-HT1A receptor protein was reduced more in females than males; while in Hp Freud-1 protein was increased in females. In pregnancy stress, PFC NUDR, Freud-1 and 5-HT1A protein receptor levels were reduced, and in HP 5-HT1A receptor protein levels were also reduced; in HP only NUDR and Freud-1 mRNA levels were reduced. Overall, CMS and stress during pregnancy produced the most salient changes in 5-HT1A receptor and transcription factor expression, suggesting a primary role for altered transcription factor expression in chronic regulation of 5-HT1A receptor expression. By contrast, OB (in males) and PS (in females) produced gender-specific reductions in PFC 5-HT1A receptor protein levels, suggesting a role for post-transcriptional regulation. These and previous data suggest that chronic stress might be a key regulator of NUDR/Freud-1 gene expression. PMID:24946016

Alterations in brain-derived neurotrophic factor (BDNF) and its precursor proBDNF in the brain regions of a learned helplessness rat model and the antidepressant effects of a TrkB agonist and antagonist.

PubMed

Shirayama, Yukihiko; Yang, Chun; Zhang, Ji-chun; Ren, Qian; Yao, Wei; Hashimoto, Kenji

2015-12-01

Role of brain-derived neurotrophic factor (BDNF)-TrkB signaling in a learned helplessness (LH) model of depression was investigated. LH rats showed a reduction of BDNF in the medial prefrontal cortex (mPFC), CA3, and dentate gyrus (DG) of the hippocampus, whereas LH rats showed an increase in BDNF in the nucleus accumbens (NAc). Furthermore, levels of proBDNF, a BDNF precursor, were higher in the mPFC, but lower in the NAc, of LH rats. A single bilateral infusion of a TrkB agonist 7,8-DHF, but not a TrkB antagonist ANA-12, into the infralimbic (IL) of mPFC, DG, and CA3, but not the prelimbic (PrL) of mPFC, exerted antidepressant effects in LH rats. In contrast, a single bilateral infusion of ANA-12, but not 7,8-DHF, into the core and shell of NAc exerted antidepressant-like effects in LH rats, with more potent effects observed for the NAc core than for NAc shell. Interestingly, a single administration of 7,8-DHF (10mg/kg, i.p.) significantly improved a decreased phosphorylation of TrkB in the mPFC, CA3, and DG of LH rats. Additionally, ANA-12 (0.5mg/kg, i.p.) significantly improved an increased phosphorylation of TrkB in the NAc of LH rats. In conclusion, these results suggest that LH causes depression-like behavior by altering BDNF in the brain regions, and that proBDNF-BDNF processing and transport may be altered in the mPFC-NAc circuit of LH rats. Therefore, TrkB agonists might exert antidepressant effects by stimulating TrkB in the IL, CA3, and DG, while TrkB antagonists might exert antidepressant effects by blocking TrkB in the NAc. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Hedonic sensitivity to natural rewards is affected by prenatal stress in a sex-dependent manner.

PubMed

Reynaert, Marie-Line; Marrocco, Jordan; Mairesse, Jérôme; Lionetto, Luana; Simmaco, Maurizio; Deruyter, Lucie; Allorge, Delphine; Moles, Anna; Pittaluga, Anna; Maccari, Stefania; Morley-Fletcher, Sara; Van Camp, Gilles; Nicoletti, Ferdinando

2016-11-01

Palatable food is a strong activator of the reward circuitry and may cause addictive behavior leading to eating disorders. How early life events and sex interact in shaping hedonic sensitivity to palatable food is largely unknown. We used prenatally restraint stressed (PRS) rats, which show abnormalities in the reward system and anxious/depressive-like behavior. Some of the hallmarks of PRS rats are known to be sex-dependent. We report that PRS enhanced and reduced milk chocolate-induced conditioned place preference in males and females, respectively. Male PRS rats also show increases in plasma dihydrotestosterone (DHT) levels and dopamine (DA) levels in the nucleus accumbens (NAc), and reductions in 5-hydroxytryptamine (5-HT) levels in the NAc and prefrontal cortex (PFC). In male rats, systemic treatment with the DHT-lowering drug finasteride reduced both milk chocolate preference and NAc DA levels. Female PRS rats showed lower plasma estradiol (E 2 ) levels and lower DA levels in the NAc, and 5-HT levels in the NAc and PFC. E 2 supplementation reversed the reduction in milk chocolate preference and PFC 5-HT levels. In the hypothalamus, PRS increased ERα and ERβ estrogen receptor and CARTP (cocaine-and-amphetamine receptor transcript peptide) mRNA levels in males, and 5-HT 2 C receptor mRNA levels in females. Changes were corrected by treatments with finasteride and E 2 , respectively. These new findings show that early life stress has a profound impact on hedonic sensitivity to high-palatable food via long-lasting changes in gonadal hormones. This paves the way to the development of hormonal strategies aimed at correcting abnormalities in the response to natural rewards. © 2015 Society for the Study of Addiction.

What Is the Evidence for Inter-laminar Integration in a Prefrontal Cortical Minicolumn?

PubMed

Opris, Ioan; Chang, Stephano; Noga, Brian R

2017-01-01

The objective of this perspective article is to examine columnar inter-laminar integration during the executive control of behavior. The integration hypothesis posits that perceptual and behavioral signals are integrated within the prefrontal cortical inter-laminar microcircuits. Inter-laminar minicolumnar activity previously recorded from the dorsolateral prefrontal cortex (dlPFC) of nonhuman primates, trained in a visual delay match-to-sample (DMS) task, was re-assessed from an integrative perspective. Biomorphic multielectrode arrays (MEAs) played a unique role in the in vivo recording of columnar cell firing in the dlPFC layers 2/3 and 5/6. Several integrative aspects stem from these experiments: 1. Functional integration of perceptual and behavioral signals across cortical layers during executive control. The integrative effect of dlPFC minicolumns was shown by: (i) increased correlated firing on correct vs. error trials; (ii) decreased correlated firing when the number of non-matching images increased; and (iii) similar spatial firing preference across cortical-striatal cells during spatial-trials, and less on object-trials. 2. Causal relations to integration of cognitive signals by the minicolumnar turbo-engines. The inter-laminar integration between the perceptual and executive circuits was facilitated by stimulating the infra-granular layers with firing patterns obtained from supra-granular layers that enhanced spatial preference of percent correct performance on spatial trials. 3. Integration across hierarchical levels of the brain. The integration of intention signals (visual spatial, direction) with movement preparation (timing, velocity) in striatum and with the motor command and posture in midbrain is also discussed. These findings provide evidence for inter-laminar integration of executive control signals within brain's prefrontal cortical microcircuits.

The Neural Correlates of Mindful Awareness: A Possible Buffering Effect on Anxiety-Related Reduction in Subgenual Anterior Cingulate Cortex Activity

PubMed Central

Hakamata, Yuko; Iwase, Mikio; Kato, Takashi; Senda, Kohei; Inada, Toshiya

2013-01-01

Background Human personality consists of two fundamental elements character and temperament. Character allays automatic and preconceptual emotional responses determined by temperament. However, the neurobiological basis of character and its interplay with temperament remain elusive. Here, we examined character-temperament interplay and explored the neural basis of character, with a particular focus on the subgenual anterior cingulate cortex extending to a ventromedial portion of the prefrontal cortex (sgACC/vmPFC). Methods Resting brain glucose metabolism (GM) was measured using [18F] fluorodeoxyglucose positron emission tomography in 140 healthy adults. Personality traits were assessed using the Temperament and Character Inventory. Regions of interest (ROI) analysis and whole-brain analysis were performed to examine a combination effect of temperament and character on the sgACC/vmPFC and to explore the neural correlates of character, respectively. Results Harm avoidance (HA), a temperament trait (i.e., depressive, anxious, vulnerable), showed a significant negative impact on the sgACC/vmPFC GM, whereas self-transcendence (ST), a character trait (i.e., intuitive, judicious, spiritual), exhibited a significant positive effect on GM in the same region (HA β = −0.248, p = 0.003; ST: β = 0.250, p = 0.003). In addition, when coupled with strong ST, individuals with strong HA maintained the sgACC/vmPFC GM level comparable to the level of those with low scores on both HA and ST. Furthermore, exploratory whole-brain analysis revealed a significant positive relationship between ST and sgACC/vmPFC GM (peak voxel at x = −8, y = 32, z = −8, k = 423, Z = 4.41, corrected p FDR = 0.030). Conclusion The current findings indicate that the sgACC/vmPFC might play a critical role in mindful awareness to something beyond as well as in emotional regulation. Developing a sense of mindfulness may temper exaggerated emotional responses in individuals with a risk for or having anxiety and depressive disorders. PMID:24130715

The neural correlates of mindful awareness: a possible buffering effect on anxiety-related reduction in subgenual anterior cingulate cortex activity.

PubMed

Hakamata, Yuko; Iwase, Mikio; Kato, Takashi; Senda, Kohei; Inada, Toshiya

2013-01-01

Human personality consists of two fundamental elements character and temperament. Character allays automatic and preconceptual emotional responses determined by temperament. However, the neurobiological basis of character and its interplay with temperament remain elusive. Here, we examined character-temperament interplay and explored the neural basis of character, with a particular focus on the subgenual anterior cingulate cortex extending to a ventromedial portion of the prefrontal cortex (sgACC/vmPFC). Resting brain glucose metabolism (GM) was measured using [(18)F] fluorodeoxyglucose positron emission tomography in 140 healthy adults. Personality traits were assessed using the Temperament and Character Inventory. Regions of interest (ROI) analysis and whole-brain analysis were performed to examine a combination effect of temperament and character on the sgACC/vmPFC and to explore the neural correlates of character, respectively. Harm avoidance (HA), a temperament trait (i.e., depressive, anxious, vulnerable), showed a significant negative impact on the sgACC/vmPFC GM, whereas self-transcendence (ST), a character trait (i.e., intuitive, judicious, spiritual), exhibited a significant positive effect on GM in the same region (HA β = -0.248, p = 0.003; ST: β = 0.250, p = 0.003). In addition, when coupled with strong ST, individuals with strong HA maintained the sgACC/vmPFC GM level comparable to the level of those with low scores on both HA and ST. Furthermore, exploratory whole-brain analysis revealed a significant positive relationship between ST and sgACC/vmPFC GM (peak voxel at x = -8, y = 32, z = -8, k = 423, Z = 4.41, corrected p (FDR) = 0.030). The current findings indicate that the sgACC/vmPFC might play a critical role in mindful awareness to something beyond as well as in emotional regulation. Developing a sense of mindfulness may temper exaggerated emotional responses in individuals with a risk for or having anxiety and depressive disorders.

Visualizing Hyperactivation in Neurodegeneration Based on Prefrontal Oxygenation: A Comparative Study of Mild Alzheimer's Disease, Mild Cognitive Impairment, and Healthy Controls

PubMed Central

Yap, Kah Hui; Ung, Wei Chun; Ebenezer, Esther G. M.; Nordin, Nadira; Chin, Pui See; Sugathan, Sandheep; Chan, Sook Ching; Yip, Hung Loong; Kiguchi, Masashi; Tang, Tong Boon

2017-01-01

Background: Cognitive performance is relatively well preserved during early cognitive impairment owing to compensatory mechanisms. Methods: We explored functional near-infrared spectroscopy (fNIRS) alongside a semantic verbal fluency task (SVFT) to investigate any compensation exhibited by the prefrontal cortex (PFC) in Mild Cognitive Impairment (MCI) and mild Alzheimer's disease (AD). In addition, a group of healthy controls (HC) was studied. A total of 61 volunteers (31 HC, 12 patients with MCI and 18 patients with mild AD) took part in the present study. Results: Although not statistically significant, MCI exhibited a greater mean activation of both the right and left PFC, followed by HC and mild AD. Analysis showed that in the left PFC, the time taken for HC to achieve the activation level was shorter than MCI and mild AD (p = 0.0047 and 0.0498, respectively); in the right PFC, mild AD took a longer time to achieve the activation level than HC and MCI (p = 0.0469 and 0.0335, respectively); in the right PFC, HC, and MCI demonstrated a steeper slope compared to mild AD (p = 0.0432 and 0. 0107, respectively). The results were, however, not significant when corrected by the Bonferroni-Holm method. There was also found to be a moderately positive correlation (R = 0.5886) between the oxygenation levels in the left PFC and a clinical measure [Mini-Mental State Examination (MMSE) score] in MCI subjects uniquely. Discussion: The hyperactivation in MCI coupled with a better SVFT performance may suggest neural compensation, although it is not known to what degree hyperactivation manifests as a potential indicator of compensatory mechanisms. However, hypoactivation plus a poorer SVFT performance in mild AD might indicate an inability to compensate due to the degree of structural impairment. Conclusion: Consistent with the scaffolding theory of aging and cognition, the task-elicited hyperactivation in MCI might reflect the presence of compensatory mechanisms and hypoactivation in mild AD could reflect an inability to compensate. Future studies will investigate the fNIRS parameters with a larger sample size, and their validity as prognostic biomarkers of neurodegeneration. PMID:28919856

Investigating the influence of PFC transection and nicotine on dynamics of AMPA and NMDA receptors of VTA dopaminergic neurons.

PubMed

Chen, Ting; Zhang, Die; Dragomir, Andrei; Kobayashi, Kunikazu; Akay, Yasemin; Akay, Metin

2011-10-21

All drugs of abuse, including nicotine, activate the mesocorticolimbic system that plays critical roles in nicotine reward and reinforcement development and triggers glutamatergic synaptic plasticity on the dopamine (DA) neurons in the ventral tegmental area (VTA). The addictive behavior and firing pattern of the VTA DA neurons are thought to be controlled by the glutamatergic synaptic input from prefrontal cortex (PFC). Interrupted functional input from PFC to VTA was shown to decrease the effects of the drug on the addiction process. Nicotine treatment could enhance the AMPA/NMDA ratio in VTA DA neurons, which is thought as a common addiction mechanism. In this study, we investigate whether or not the lack of glutamate transmission from PFC to VTA could make any change in the effects of nicotine. We used the traditional AMPA/NMDA peak ratio, AMPA/NMDA area ratio, and KL (Kullback-Leibler) divergence analysis method for the present study. Our results using AMPA/NMDA peak ratio showed insignificant difference between PFC intact and transected and treated with saline. However, using AMPA/NMDA area ratio and KL divergence method, we observed a significant difference when PFC is interrupted with saline treatment. One possible reason for the significant effect that the PFC transection has on the synaptic responses (as indicated by the AMPA/NMDA area ratio and KL divergence) may be the loss of glutamatergic inputs. The glutamatergic input is one of the most important factors that contribute to the peak ratio level. Our results suggested that even within one hour after a single nicotine injection, the peak ratio of AMPA/NMDA on VTA DA neurons could be enhanced.

Neural correlates of obstacle negotiation in older adults: An fNIRS study.

PubMed

Chen, Michelle; Pillemer, Sarah; England, Sarah; Izzetoglu, Meltem; Mahoney, Jeannette R; Holtzer, Roee

2017-10-01

Older adults are less efficient at avoiding obstacles compared to young adults, especially under attention-demanding conditions. Using functional near-infrared-spectroscopy (fNIRS), recent studies implicated the prefrontal cortex (PFC) in cognitive control of locomotion, notably under dual-task walking conditions. The neural substrates underlying Obstacle Negotiation (ON), however, have not been established. The current study determined the role of the PFC in ON during walking in seniors. Non-demented older adults (n=90; mean age=78.1±5.5years; %female=51) underwent fNIRS acquisition to assess changes in hemodynamic activity in the PFC during normal-walk [NW] and walk-while-talk [WWT] conditions with and without obstacles. Obstacles were presented as red elliptical shapes using advanced laser technology, which resemble potholes. Linear mixed effects models were used to determine differences in oxygenated hemoglobin (HbO 2 ) levels among the four task conditions. The presence of slow gait, a risk factor for dementia and falls, served as a predictor hypothesized to moderate the effect of obstacles on PFC HbO 2 levels. PFC HbO 2 levels were significantly higher in WWT compared to NW (p<0.001) irrespective of ON. Slow gait moderated the effect of obstacles on HbO 2 levels across task conditions. Specifically, compared to participants with normal gait, PFC HbO 2 levels were significantly increased in ON-NW relative to NW (p=0.017) and ON-WWT relative to WWT (p<0.001) among individuals with slow gait. Consistent with Compensatory Reallocation, ON required greater PFC involvement among individuals with mobility limitations. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

Disruption of Prefrontal Cortex Large Scale Neuronal Activity by Different Classes of Psychotomimetic Drugs

PubMed Central

Wood, Jesse; Kim, Yunbok; Moghaddam, Bita

2012-01-01

In the absence of overt cellular pathology but profound perceptual disorganization and cognitive deficits, schizophrenia is increasingly considered a disorder of neural coordination. Thus, different causal factors can similarly interrupt the dynamic function of neuronal ensembles and networks, in particular in the prefrontal cortex (PFC), leading to behavioral disorganization. The importance of establishing preclinical biomarkers for this aberrant function has prompted investigations into the nature of psychotomimetic drug effects on PFC neuronal activity. The drugs used in this context include serotonergic hallucinogens, amphetamine, and NMDA receptor antagonists. A prominent line of thinking is that these drugs create psychotomimetic states by similarly disinhibiting the activity of PFC pyramidal neurons. In the present study we did not find evidence in support of this mechanism in PFC subregions of freely moving rats. Whereas the NMDA receptor antagonist MK801 increased PFC population activity, the serotonergic hallucinogen DOI dose-dependently decreased population activity. Amphetamine did not strongly affect this measure. Despite different effects on the direction of change in activity, all three drugs caused similar net disruptions of population activity and modulated gamma oscillations. We also observed reduced correlations between spikerate and LFP power selectively in the gamma band suggesting that these drugs disconnect spike-discharge from PFC gamma oscillators. Gamma band oscillations support cognitive functions affected in schizophrenia. These findings provide insight into mechanisms that may lead to cortical processing deficits in schizophrenia and provide a novel electrophysiological approach for phenotypic characterization of animal models of this disease. PMID:22378875

Effects of the mode of re-socialization after juvenile social isolation on medial prefrontal cortex myelination and function.

PubMed

Makinodan, Manabu; Ikawa, Daisuke; Yamamuro, Kazuhiko; Yamashita, Yasunori; Toritsuka, Michihiro; Kimoto, Sohei; Yamauchi, Takahira; Okumura, Kazuki; Komori, Takashi; Fukami, Shin-Ichi; Yoshino, Hiroki; Kanba, Shigenobu; Wanaka, Akio; Kishimoto, Toshifumi

2017-07-14

Social isolation is an important factor in the development of psychiatric disorders. It is necessary to develop an effective psychological treatment, such as cognitive rehabilitation, for children who have already suffered from social isolation, such as neglect and social rejection. We used socially isolated mice to validate whether elaborate re-socialization after juvenile social isolation can restore hypomyelination in the medial prefrontal cortex (mPFC) and the attendant functions manifested in socially isolated mice. While mice who underwent re-socialization with socially isolated mice after juvenile social isolation (Re-IS mice) demonstrated less mPFC activity during exposure to a strange mouse, as well as thinner myelin in the mPFC than controls, mice who underwent re-socialization with socially housed mice after juvenile social isolation (Re-SH mice) caught up with the controls in terms of most mPFC functions, as well as myelination. Moreover, social interaction of Re-IS mice was reduced as compared to controls, but Re-SH mice showed an amount of social interaction comparable to that of controls. These results suggest that the mode of re-socialization after juvenile social isolation has significant effects on myelination in the mPFC and the attendant functions in mice, indicating the importance of appropriate psychosocial intervention after social isolation.

Origin and control of instability in SCR/triac three-phase motor controllers

NASA Technical Reports Server (NTRS)

Dearth, J. J.

1982-01-01

The energy savings and reactive power reduction functions initiated by the power factor controller (PFC) are discussed. A three-phase PFC with soft start is examined analytically and experimentally to determine how well it controls the open loop instability and other possible modes of instability. The detailed mechanism of the open loop instability is determined and shown to impose design constraints on the closed loop system. The design is shown to meet those constraints.

Alterations in Resting-State Functional Connectivity Link Mindfulness Meditation With Reduced Interleukin-6: A Randomized Controlled Trial.

PubMed

Creswell, J David; Taren, Adrienne A; Lindsay, Emily K; Greco, Carol M; Gianaros, Peter J; Fairgrieve, April; Marsland, Anna L; Brown, Kirk Warren; Way, Baldwin M; Rosen, Rhonda K; Ferris, Jennifer L

2016-07-01

Mindfulness meditation training interventions have been shown to improve markers of health, but the underlying neurobiological mechanisms are not known. Building on initial cross-sectional research showing that mindfulness meditation may increase default mode network (DMN) resting-state functional connectivity (rsFC) with regions important in top-down executive control (dorsolateral prefrontal cortex [dlPFC]), here we test whether mindfulness meditation training increases DMN-dlPFC rsFC and whether these rsFC alterations prospectively explain improvements in interleukin (IL)-6 in a randomized controlled trial. Stressed job-seeking unemployed community adults (n = 35) were randomized to either a 3-day intensive residential mindfulness meditation or relaxation training program. Participants completed a 5-minute resting-state scan before and after the intervention program. Participants also provided blood samples at preintervention and at 4-month follow-up, which were assayed for circulating IL-6, a biomarker of systemic inflammation. We tested for alterations in DMN rsFC using a posterior cingulate cortex seed-based analysis and found that mindfulness meditation training, and not relaxation training, increased posterior cingulate cortex rsFC with left dlPFC (p < .05, corrected). These pretraining to posttraining alterations in posterior cingulate cortex-dlPFC rsFC statistically mediated mindfulness meditation training improvements in IL-6 at 4-month follow-up. Specifically, these alterations in rsFC statistically explained 30% of the overall mindfulness meditation training effects on IL-6 at follow-up. These findings provide the first evidence that mindfulness meditation training functionally couples the DMN with a region known to be important in top-down executive control at rest (left dlPFC), which, in turn, is associated with improvements in a marker of inflammatory disease risk. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Measurements of evaporated perfluorocarbon during partial liquid ventilation by a zeolite absorber.

PubMed

Proquitté, Hans; Rüdiger, Mario; Wauer, Roland R; Schmalisch, Gerd

2004-01-01

During partial liquid ventilation (PLV) the knowledge of the quantity of exhaled perfluorocarbon (PFC) allows a continuous substitution of the PFC loss to achieve a constant PFC level in the lungs. The aim of our in vitro study was to determine the PFC loss in the mixed expired gas by an absorber and to investigate the effect of the evaporated PFC on ventilatory measurements. To simulate the PFC loss during PLV, a heated flask was rinsed with a constant airflow of 4 L min(-1) and PFC was infused by different speeds (5, 10, 20 mL h(-1)). An absorber filled with PFC selective zeolites was connected with the flask to measure the PFC in the gas. The evaporated PFC volume and the PFC concentration were determined from the weight gain of the absorber measured by an electronic scale. The PFC-dependent volume error of the CO2SMO plus neonatal pneumotachograph was measured by manual movements of a syringe with volumes of 10 and 28 mL with a rate of 30 min(-1). Under steady state conditions there was a strong correlation (r2 = 0.999) between the infusion speed of PFC and the calculated PFC flow rate. The PFC flow rate was slightly underestimated by 4.3% (p < 0.01). However, this bias was independent from PFC infusion rate. The evaporated PFC volume was precisely measured with errors < 1%. The volume error of the CO2SMO-Plus pneumotachograph increased with increasing PFC content for both tidal volumes (p < 0.01). However for PFC flow rates up to 20 mL/h the error of the measured tidal volumes was < 5%. PFC selective zeolites can be used to quantify accurately the evaporated PFC volume during PLV. With increasing PFC concentrations in the exhaled air the measurement errors of ventilatory parameters have to be taken into account.

Extinction of an instrumental response: a cognitive behavioral assay in Fmr1 knockout mice.

PubMed

Sidorov, M S; Krueger, D D; Taylor, M; Gisin, E; Osterweil, E K; Bear, M F

2014-06-01

Fragile X (FX) is the most common genetic cause of intellectual disability and autism. Previous studies have shown that partial inhibition of metabotropic glutamate receptor signaling is sufficient to correct behavioral phenotypes in a mouse model of FX, including audiogenic seizures, open-field hyperactivity and social behavior. These phenotypes model well the epilepsy (15%), hyperactivity (20%) and autism (30%) that are comorbid with FX in human patients. Identifying reliable and robust mouse phenotypes to model cognitive impairments is critical considering the 90% comorbidity of FX and intellectual disability. Recent work characterized a five-choice visuospatial discrimination assay testing cognitive flexibility, in which FX model mice show impairments associated with decreases in synaptic proteins in prefrontal cortex (PFC). In this study, we sought to determine whether instrumental extinction, another process requiring PFC, is altered in FX model mice, and whether downregulation of metabotropic glutamate receptor signaling pathways is sufficient to correct both visuospatial discrimination and extinction phenotypes. We report that instrumental extinction is consistently exaggerated in FX model mice. However, neither the extinction phenotype nor the visuospatial discrimination phenotype is corrected by approaches targeting metabotropic glutamate receptor signaling. This work describes a novel behavioral extinction assay to model impaired cognition in mouse models of neurodevelopmental disorders, provides evidence that extinction is exaggerated in the FX mouse model and suggests possible limitations of metabotropic glutamate receptor-based pharmacotherapy. © 2014 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

The effect of future time perspective on procrastination: the role of parahippocampal gyrus and ventromedial prefrontal cortex.

PubMed

Liu, Peiwei; Feng, Tingyong

2018-05-09

Procrastination is an almost universal affliction, which occurs across culture and brings serious consequences across multiple fields, such as finance, health and education. Previous research has showed procrastination can be influenced by future time perspective (FTP). However, little is known about the neural basis underlying the impact of FTP on procrastination. To address this question, we used voxel-based morphometry (VBM) based on brain structure. In line with previous findings, the behavioral result indicated that FTP inventory scores were significantly negatively correlated with procrastination inventory scores (r = -0.63, n = 160). The whole-brain VBM results showed that FTP scores were significantly negatively correlated with the grey matter (GM) volumes of the parahippocampal gyrus (paraPHC) and ventromedial prefrontal cortex (vmPFC) after the multiple comparisons correction. Furthermore, mediation analyses revealed that the effect of GM volumes of the paraPHC and vmPFC on procrastination was mediated by FTP. These results suggested that paraPHC and vmPFC, the critical brain regions about episodic future thinking, could be the neural basis responsible for the impact of FTP on procrastination. The present study extends our knowledge on procrastination, and provides a novel perspective to understand the relationship between FTP and procrastination.

A Perfusion MRI Study of Emotional Valence and Arousal in Parkinson's Disease

PubMed Central

Limsoontarakul, Sunsern; Campbell, Meghan C.; Black, Kevin J.

2011-01-01

Background. Brain regions subserving emotion have mostly been studied using functional magnetic resonance imaging (fMRI) during emotion provocation procedures in healthy participants. Objective. To identify neuroanatomical regions associated with spontaneous changes in emotional state over time. Methods. Self-rated emotional valence and arousal scores, and regional cerebral blood flow (rCBF) measured by perfusion MRI, were measured 4 or 8 times spanning at least 2 weeks in each of 21 subjects with Parkinson's disease (PD). A random-effects SPM analysis, corrected for multiple comparisons, identified significant clusters of contiguous voxels in which rCBF varied with valence or arousal. Results. Emotional valence correlated positively with rCBF in several brain regions, including medial globus pallidus, orbital prefrontal cortex (PFC), and white matter near putamen, thalamus, insula, and medial PFC. Valence correlated negatively with rCBF in striatum, subgenual cingulate cortex, ventrolateral PFC, and precuneus—posterior cingulate cortex (PCC). Arousal correlated positively with rCBF in clusters including claustrum-thalamus-ventral striatum and inferior parietal lobule and correlated negatively in clusters including posterior insula—mediodorsal thalamus and midbrain. Conclusion. This study demonstrates that the temporal stability of perfusion MRI allows within-subject investigations of spontaneous fluctuations in mental state, such as mood, over relatively long-time intervals. PMID:21969917

Role of activity-dependent BDNF expression in hippocampal–prefrontal cortical regulation of behavioral perseverance

PubMed Central

Sakata, Kazuko; Martinowich, Keri; Woo, Newton H.; Schloesser, Robert J.; Jimenez, Dennisse V.; Ji, Yuanyuan; Shen, Liya; Lu, Bai

2013-01-01

Activity-dependent gene transcription, including that of the brain-derived neurotrophic factor (Bdnf) gene, has been implicated in various cognitive functions. We previously demonstrated that mutant mice with selective disruption of activity-dependent BDNF expression (BDNF-KIV mice) exhibit deficits in GABA-mediated inhibition in the prefrontal cortex (PFC). Here, we show that disruption of activity-dependent BDNF expression impairs BDNF-dependent late-phase long-term potentiation (L-LTP) in CA1, a site of hippocampal output to the PFC. Interestingly, early-phase LTP and conventional L-LTP induced by strong tetanic stimulation were completely normal in BDNF-KIV mice. In parallel, attenuation of activity-dependent BDNF expression significantly impairs spatial memory reversal and contextual memory extinction, two executive functions that require intact hippocampal–PFC circuitry. In contrast, spatial and contextual memory per se were not affected. Thus, activity-dependent BDNF expression in the hippocampus and PFC may contribute to cognitive and behavioral flexibility. These results suggest distinct roles for different forms of L-LTP and provide a link between activity-dependent BDNF expression and behavioral perseverance, a hallmark of several psychiatric disorders. PMID:23980178

Estrogen Receptor β Agonist Attenuates Endoplasmic Reticulum Stress-Induced Changes in Social Behavior and Brain Connectivity in Mice.

PubMed

Crider, Amanda; Nelson, Tyler; Davis, Talisha; Fagan, Kiley; Vaibhav, Kumar; Luo, Matthew; Kamalasanan, Sunay; Terry, Alvin V; Pillai, Anilkumar

2018-02-12

Impaired social interaction is a key feature of several major psychiatric disorders including depression, autism, and schizophrenia. While, anatomically, the prefrontal cortex (PFC) is known as a key regulator of social behavior, little is known about the cellular mechanisms that underlie impairments of social interaction. One etiological mechanism implicated in the pathophysiology of the aforementioned psychiatric disorders is cellular stress and consequent adaptive responses in the endoplasmic reticulum (ER) that can result from a variety of environmental and physical factors. The ER is an organelle that serves essential roles in protein modification, folding, and maturation of proteins; however, the specific role of ER stress in altered social behavior is unknown. In this study, treatment with tunicamycin, an ER stress inducer, enhanced the phosphorylation level of inositol-requiring ER-to-nucleus signal kinase 1 (IRE1) and increased X-box-binding protein 1 (XBP1) mRNA splicing activity in the mouse PFC, whereas inhibition of IRE1/XBP1 pathway in PFC by a viral particle approach attenuated social behavioral deficits caused by tunicamycin treatment. Reduced estrogen receptor beta (ERβ) protein levels were found in the PFC of male mice following tunicamycin treatment. Pretreatment with an ERβ specific agonist, ERB-041 significantly attenuated tunicamycin-induced deficits in social behavior, and activation of IRE1/XBP1 pathway in mouse PFC. Moreover, ERB-041 inhibited tunicamycin-induced increases in functional connectivity between PFC and hippocampus in male mice. Together, these results show that ERβ agonist attenuates ER stress-induced deficits in social behavior through the IRE-1/XBP1 pathway.

Stunted PFC activity during neuromuscular control under stress with obesity.

PubMed

Mehta, Ranjana K

2016-02-01

Obesity is an established risk factor for impaired cognition, which is primarily regulated by the prefrontal cortex (PFC). However, very little is known about the neural pathways that underlie obesity-related declines in neuromuscular control, particularly under stress. The purpose of this study was to determine the role of the PFC on neuromuscular control during handgrip exertions under stress with obesity. Twenty non-obese and obese young adults performed submaximal handgrip exertions in the absence and presence of a concurrent stressful task. Primary dependent measures included oxygenated hemoglobin (HbO2: a measure of PFC activity) and force fluctuations (an indicator of neuromuscular control). Higher HbO2 levels in the PFC were observed in the non-obese compared to the obese group (P = 0.009). In addition, higher HbO2 levels were observed in the stress compared to the control condition in the non-obese group; however, this trend was reversed in the obese group (P = 0.043). In general, force fluctuations increased by 26% in the stress when compared to the control condition (P = 0.001) and obesity was associated with 39% greater force fluctuation (P = 0.024). Finally, while not significant, obesity-related decrements in force fluctuations were magnified under stress (P = 0.063). The current study provides the first evidence that neuromuscular decrements with obesity were associated with impaired PFC activity and this relationship was augmented in stress conditions. These findings are important because they provide new information on obesity-specific changes in brain function associated with neuromuscular control since the knowledge previously focused largely on obesity-specific changes in peripheral muscle capacity.

GABA content within the ventromedial prefrontal cortex is related to trait anxiety.

PubMed

Delli Pizzi, Stefano; Padulo, Caterina; Brancucci, Alfredo; Bubbico, Giovanna; Edden, Richard A; Ferretti, Antonio; Franciotti, Raffaella; Manippa, Valerio; Marzoli, Daniele; Onofrj, Marco; Sepede, Gianna; Tartaro, Armando; Tommasi, Luca; Puglisi-Allegra, Stefano; Bonanni, Laura

2016-05-01

The ventromedial prefrontal cortex (vmPFC) plays a key role in emotion processing and regulation. vmPFC dysfunction may lead to disinhibition of amygdala causing high anxiety levels. γ-Aminobutyric acid (GABA) inter-neurons within vmPFC shape the information flow to amygdala. Thus, we hypothesize that GABA content within vmPFC could be relevant to trait anxiety. Forty-three healthy volunteers aged between 20 and 88 years were assessed for trait anxiety with the Subscale-2 of the State-Trait-Anxiety Inventory (STAI-Y2) and were studied with proton magnetic resonance spectroscopy to investigate GABA and Glx (glutamate+glutamine) contents within vmPFC. Total creatine (tCr) was used as internal reference. Partial correlations assessed the association between metabolite levels and STAI-Y2 scores, removing the effect of possible nuisance factors including age, educational level, volumes of gray matter and white matter within magnetic resonance spectroscopy voxel. We observed a positive relationship between GABA/tCr and STAI-Y2 scores. No significant relationships were found between Glx/tCr and STAI-Y2 and between tCr/water and STAI-Y2. No differences were found between males and females as regards to age, STAI-Y2, GABA/tCr, Glx/tCr, tCr/water, gray matter and white matter volumes. We suggest a close relationship between GABA content within vmPFC and trait anxiety providing new insights in the physiology of emotional brain. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Breathing gas perfluorocarbon measurements using an absorber filled with zeolites.

PubMed

Proquitté, H; Rüdiger, M; Wauer, R R; Schmalisch, G

2003-11-01

Perfluorocarbon (PFC) has been widely used in the treatment of respiratory diseases; however, PFC content of the breathing gases remains unknown. Therefore, we developed an absorber using PFC selective zeolites for PFC measurement in gases and investigated its accuracy. To generate a breathing gas with different PFC contents a heated flask was rinsed with a constant air flow of 4 litre x min(-1) and 1, 5, 10, and 20 ml of PFC were infused over 20 min using an infusor. The absorber was placed on an electronic scale and the total PFC volume was calculated from the weight gain. Steady-state increase in weight was achieved 3.5 min after stopping the infusion. The calculated PFC volume was slightly underestimated but the measuring error did not exceed -1% for PFC less than 1 ml. The measurement error decreased with increasing PFC volume. This zeolite absorber is an accurate method to quantitatively determine PFC in breathing gases and can be used as a reference method to validate other PFC sensors.

Transport of Nitric Oxide by Perfluorocarbon Emulsion

PubMed Central

Ortiz, Daniel; Briceño, Juan C.; Cabrales, Pedro

2014-01-01

Perfluorocarbon (PFC) emulsions can transport and release various gases based on concentration gradients. The objective of this study was to determine the possibility of carrying and delivering exogenous nitric oxide (NO) into the circulation by simply loading PFC emulsion with NO prior infusion. PFC was equilibrated with room air (PFC) or 300 ppm NO (PFC-NO) at atmospheric pressure. Isotonic saline solution was used as a volume control (Saline). PFC and PFC-NO were infused at a dose of 3.5 mL/kg in the hamster window chamber model. Blood chemistry, and systemic and microvascular hemodynamic response were measured. Infusion of PFC preloaded with NO reduced blood pressure, induced microvascular vasodilation and increased capillary perfusion; although these changes lasted less than 30 min post infusion. On the other hand, infusion of PFC (without NO) produced vasoconstriction; however, the vasoconstriction was followed by vasodilatation at 30 min post infusion. Plasma nitrite and nitrate increased 15 min after infusion of NO preloaded PFC compared to PFC, 60 min after infusion nitrite and nitrate were not different, and 90 min after infusion plasma S-nitrosothiols increased in both groups. Infusion of NO preloaded PFC resulted in acute vascular relaxation, where as infusion of PFC (without NO) produced vasoconstriction, potentially due to NO sequestration by the PFC micelles. The late effects of PFC infusion are due to NO redistribution and plasma S-nitrosothiols. Gas solubility in PFC can provide a tool to modulate plasma vasoactive NO forms availability and improve microcirculatory function and promote increased blood flow. PMID:23966236

Permanent-File-Validation Utility Computer Program

NASA Technical Reports Server (NTRS)

Derry, Stephen D.

1988-01-01

Errors in files detected and corrected during operation. Permanent File Validation (PFVAL) utility computer program provides CDC CYBER NOS sites with mechanism to verify integrity of permanent file base. Locates and identifies permanent file errors in Mass Storage Table (MST) and Track Reservation Table (TRT), in permanent file catalog entries (PFC's) in permit sectors, and in disk sector linkage. All detected errors written to listing file and system and job day files. Program operates by reading system tables , catalog track, permit sectors, and disk linkage bytes to vaidate expected and actual file linkages. Used extensively to identify and locate errors in permanent files and enable online correction, reducing computer-system downtime.

The postnatal 5-HT1A receptor regulates adult anxiety and depression differently via multiple molecules.

PubMed

Ishikawa, Chihiro; Shiga, Takashi

2017-08-01

Serotonin (5-HT) and the 5-HT 1A receptor during development are known to modulate anxiety and depression in later life. However, the brain mechanisms linking the postnatal 5-HT system and adult behavior remain unknown. Here, we examined the effects of pharmacological 5-HT 1A receptor activation during the postnatal period on anxiety and depression-like behavior in adult BALB/c male mice. To elucidate the underlying mechanisms, we measured mRNA expression of the 5-HT 1A receptor, brain-derived neurotrophic factor (BDNF), GABA A receptor subunits, and AMPA receptor subunits in the medial prefrontal cortex (mPFC), amygdala, and hippocampus. Treatment with the selective 5-HT reuptake inhibitor (fluoxetine) and 5-HT 1A receptor agonist (8-OH-DPAT) during the postnatal period decreased anxiety-like behavior in adulthood, whereas only 8-OH-DPAT treatment increased depression-like behavior. Concomitantly with the behavioral effects, postnatal treatment with fluoxetine and 8-OH-DPAT decreased the mRNA expression of the GABA A receptor α3 subunit in the mPFC and ventral hippocampus in adulthood, while 8-OH-DPAT, but not fluoxetine, decreased the mRNA expression of the 5-HT 1A receptor and BDNF in the mPFC and the GABA A receptor α2 subunit in the mPFC and ventral hippocampus. On the basis of the correlative changes between behavior and mRNA expression, these results suggest that the GABA A receptor α3 subunit in the mPFC and ventral hippocampus may regulate anxiety-like behavior. In contrast, depression-like behavior may be regulated by the 5-HT 1A receptor and BDNF in the mPFC and by the GABA A receptor α2 subunit in the mPFC and ventral hippocampus. In summary, activation of the 5-HT 1A receptor during the postnatal period may reduce anxiety levels, but increase depression levels during adulthood via different multiple molecules in the mPFC and ventral hippocampus. Copyright © 2017 Elsevier Inc. 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

Specializations for reward-guided decision-making in the primate ventral prefrontal cortex.

PubMed

Murray, Elisabeth A; Rudebeck, Peter H

2018-05-23

The estimated values of choices, and therefore decision-making based on those values, are influenced by both the chance that the chosen items or goods can be obtained (availability) and their current worth (desirability) as well as by the ability to link the estimated values to choices (a process sometimes called credit assignment). In primates, the prefrontal cortex (PFC) has been thought to contribute to each of these processes; however, causal relationships between particular subdivisions of the PFC and specific functions have been difficult to establish. Recent lesion-based research studies have defined the roles of two different parts of the primate PFC - the orbitofrontal cortex (OFC) and the ventral lateral frontal cortex (VLFC) - and their subdivisions in evaluating each of these factors and in mediating credit assignment during reward-based decision-making.

14 CFR 158.49 - Handling of PFC's.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Handling of PFC's. 158.49 Section 158.49... PASSENGER FACILITY CHARGES (PFC'S) Collection, Handling, and Remittance of PFC's § 158.49 Handling of PFC's... amount of PFC revenue in the covered air carrier's account at the time the bankruptcy petition is filed...

14 CFR 158.49 - Handling of PFC's.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Handling of PFC's. 158.49 Section 158.49... PASSENGER FACILITY CHARGES (PFC'S) Collection, Handling, and Remittance of PFC's § 158.49 Handling of PFC's... amount of PFC revenue in the covered air carrier's account at the time the bankruptcy petition is filed...

14 CFR 158.49 - Handling of PFC's.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Handling of PFC's. 158.49 Section 158.49... PASSENGER FACILITY CHARGES (PFC'S) Collection, Handling, and Remittance of PFC's § 158.49 Handling of PFC's... amount of PFC revenue in the covered air carrier's account at the time the bankruptcy petition is filed...

14 CFR 158.49 - Handling of PFC's.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Handling of PFC's. 158.49 Section 158.49... PASSENGER FACILITY CHARGES (PFC'S) Collection, Handling, and Remittance of PFC's § 158.49 Handling of PFC's... amount of PFC revenue in the covered air carrier's account at the time the bankruptcy petition is filed...

14 CFR 158.49 - Handling of PFC's.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Handling of PFC's. 158.49 Section 158.49... PASSENGER FACILITY CHARGES (PFC'S) Collection, Handling, and Remittance of PFC's § 158.49 Handling of PFC's... amount of PFC revenue in the covered air carrier's account at the time the bankruptcy petition is filed...

Systemic inflammation and resting state connectivity of the default mode network.

PubMed

Marsland, Anna L; Kuan, Dora C-H; Sheu, Lei K; Krajina, Katarina; Kraynak, Thomas E; Manuck, Stephen B; Gianaros, Peter J

2017-05-01

The default mode network (DMN) encompasses brain systems that exhibit coherent neural activity at rest. DMN brain systems have been implicated in diverse social, cognitive, and affective processes, as well as risk for forms of dementia and psychiatric disorders that associate with systemic inflammation. Areas of the anterior cingulate cortex (ACC) and surrounding medial prefrontal cortex (mPFC) within the DMN have been implicated specifically in regulating autonomic and neuroendocrine processes that relate to systemic inflammation via bidirectional signaling mechanisms. However, it is still unclear whether indicators of inflammation relate directly to coherent resting state activity of the ACC, mPFC, or other areas within the DMN. Accordingly, we tested whether plasma interleukin (IL)-6, an indicator of systemic inflammation, covaried with resting-state functional connectivity of the DMN among 98 adults aged 30-54 (39% male; 81% Caucasian). Independent component analyses were applied to resting state fMRI data to generate DMN connectivity maps. Voxel-wise regression analyses were then used to test for associations between IL-6 and DMN connectivity across individuals, controlling for age, sex, body mass index, and fMRI signal motion. Within the DMN, IL-6 covaried positively with connectivity of the sub-genual ACC and negatively with a region of the dorsal medial PFC at corrected statistical thresholds. These novel findings offer evidence for a unique association between a marker of systemic inflammation (IL-6) and ACC and mPFC functional connectivity within the DMN, a network that may be important for linking aspects of immune function to psychological and behavioral states in health and disease. Copyright © 2017 Elsevier Inc. All rights reserved.

A Neuropsychological Test of Belief and Doubt: Damage to Ventromedial Prefrontal Cortex Increases Credulity for Misleading Advertising

PubMed Central

Asp, Erik; Manzel, Kenneth; Koestner, Bryan; Cole, Catherine A.; Denburg, Natalie L.; Tranel, Daniel

2012-01-01

We have proposed the False Tagging Theory (FTT) as a neurobiological model of belief and doubt processes. The theory posits that the prefrontal cortex is critical for normative doubt toward properly comprehended ideas or cognitions. Such doubt is important for advantageous decisions, for example in the financial and consumer purchasing realms. Here, using a neuropsychological approach, we put the FTT to an empirical test, hypothesizing that focal damage to the ventromedial prefrontal cortex (vmPFC) would cause a “doubt deficit” that would result in higher credulity and purchase intention for consumer products featured in misleading advertisements. We presented 8 consumer ads to 18 patients with focal brain damage to the vmPFC, 21 patients with focal brain damage outside the prefrontal cortex, and 10 demographically similar healthy comparison participants. Patients with vmPFC damage were (1) more credulous to misleading ads; and (2) showed the highest intention to purchase the products in the misleading advertisements, relative to patients with brain damage outside the prefrontal cortex and healthy comparison participants. The pattern of findings was obtained even for ads in which the misleading bent was “corrected” by a disclaimer. The evidence is consistent with our proposal that damage to the vmPFC disrupts a “false tagging mechanism” which normally produces doubt and skepticism for cognitive representations. We suggest that the disruption increases credulity for misleading information, even when the misleading information is corrected for by a disclaimer. This mechanism could help explain poor financial decision-making when persons with ventromedial prefrontal dysfunction (e.g., caused by neurological injury or aging) are exposed to persuasive information. PMID:22787439

Sex differences in neural responses to stress and alcohol context cues.

PubMed

Seo, Dongju; Jia, Zhiru; Lacadie, Cheryl M; Tsou, Kristen A; Bergquist, Keri; Sinha, Rajita

2011-11-01

Stress and alcohol context cues are each associated with alcohol-related behaviors, yet neural responses underlying these processes remain unclear. This study investigated the neural correlates of stress and alcohol context cue experiences and examined sex differences in these responses. Using functional magnetic resonance imaging, brain responses were examined while 43 right-handed, socially drinking, healthy individuals (23 females) engaged in brief guided imagery of personalized stress, alcohol-cue, and neutral-relaxing scenarios. Stress and alcohol-cue exposure increased activity in the cortico-limbic-striatal circuit (P < 0.01, corrected), encompassing the medial prefrontal cortex (mPFC), orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), left anterior insula, striatum, and visuomotor regions (parietal and occipital lobe, and cerebellum). Activity in the left dorsal striatum increased during stress, while bilateral ventral striatum activity was evident during alcohol-cue exposure. Men displayed greater stress-related activations in the mPFC, rostral ACC, posterior insula, amygdala, and hippocampus than women, whereas women showed greater alcohol-cue-related activity in the superior and middle frontal gyrus (SFG/MFG) than men. Stress-induced anxiety was positively associated with activity in emotion-modulation regions, including the medial OFC, ventromedial PFC, left superior-mPFC, and rostral ACC in men, but in women with activation in the SFG/MFG, regions involved in cognitive processing. Alcohol craving was significantly associated with the striatum (encompassing dorsal, and ventral) in men, supporting its involvement in alcohol "urge" in healthy men. These results indicate sex differences in neural processing of stress and alcohol-cue experiences and have implications for sex-specific vulnerabilities to stress- and alcohol-related psychiatric disorders. Copyright © 2010 Wiley-Liss, Inc.

A clinical and radiostereometric study of the cemented PFC-sigma prosthesis: a 5-year study of 29 cases with a fixed bearing.

PubMed

von Schewelov, Thord; Besjakov, Jack; Sanzén, Lennart; Carlsson, Ake

2009-07-01

The press-fit condylar (PFC) cruciate-retaining total knee prosthesis is well documented in the literature. In 1997, a modification of the femoral component was introduced, and the prosthesis was renamed PFC-Sigma. The alteration may influence the migratory and rotational pattern of the tibial component and thus long-time survival rate. In this radiostereometric analysis, we found that the micromotion of the PFC-Sigma prosthesis differs slightly from the original PFC design, an advantage of the PFC-Sigma prosthesis. The median maximum total point motion at 5 years was 0.64 mm for the PFC-Sigma design and 0.79 mm for the previous version of PFC (P = .9). However, the PFC-Sigma rotated less around the transverse (x) axis than did the PFC (medians, 0.22 mm and 0.48 mm, respectively; P = .04). From the radiostereometric, radiographic, and clinical data, we conclude that the PFC-Sigma knee prosthesis can be used with confidence.

14 CFR 158.13 - Use of PFC revenue.

Code of Federal Regulations, 2012 CFR

2012-01-01

... PASSENGER FACILITY CHARGES (PFC'S) General § 158.13 Use of PFC revenue. PFC revenue, including any interest... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Use of PFC revenue. 158.13 Section 158.13... costs of approved projects at any airport the public agency controls. (a) Total cost. PFC revenue may be...

14 CFR 158.13 - Use of PFC revenue.

Code of Federal Regulations, 2013 CFR

2013-01-01

... PASSENGER FACILITY CHARGES (PFC'S) General § 158.13 Use of PFC revenue. PFC revenue, including any interest... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Use of PFC revenue. 158.13 Section 158.13... costs of approved projects at any airport the public agency controls. (a) Total cost. PFC revenue may be...

14 CFR 158.13 - Use of PFC revenue.

Code of Federal Regulations, 2014 CFR

2014-01-01

... PASSENGER FACILITY CHARGES (PFC'S) General § 158.13 Use of PFC revenue. PFC revenue, including any interest... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Use of PFC revenue. 158.13 Section 158.13... costs of approved projects at any airport the public agency controls. (a) Total cost. PFC revenue may be...

Cognitive regulation during decision making shifts behavioral control between ventromedial and dorsolateral prefrontal value systems.

PubMed

Hutcherson, Cendri A; Plassmann, Hilke; Gross, James J; Rangel, Antonio

2012-09-26

Cognitive regulation is often used to influence behavioral outcomes. However, the computational and neurobiological mechanisms by which it affects behavior remain unknown. We studied this issue using an fMRI task in which human participants used cognitive regulation to upregulate and downregulate their cravings for foods at the time of choice. We found that activity in both ventromedial prefrontal cortex (vmPFC) and dorsolateral prefrontal cortex (dlPFC) correlated with value. We also found evidence that two distinct regulatory mechanisms were at work: value modulation, which operates by changing the values assigned to foods in vmPFC and dlPFC at the time of choice, and behavioral control modulation, which operates by changing the relative influence of the vmPFC and dlPFC value signals on the action selection process used to make choices. In particular, during downregulation, activation decreased in the value-sensitive region of dlPFC (indicating value modulation) but not in vmPFC, and the relative contribution of the two value signals to behavior shifted toward the dlPFC (indicating behavioral control modulation). The opposite pattern was observed during upregulation: activation increased in vmPFC but not dlPFC, and the relative contribution to behavior shifted toward the vmPFC. Finally, ventrolateral PFC and posterior parietal cortex were more active during both upregulation and downregulation, and were functionally connected with vmPFC and dlPFC during cognitive regulation, which suggests that they help to implement the changes to the decision-making circuitry generated by cognitive regulation.

Cognitive Regulation during Decision Making Shifts Behavioral Control between Ventromedial and Dorsolateral Prefrontal Value Systems

PubMed Central

Plassmann, Hilke; Gross, James J.; Rangel, Antonio

2012-01-01

Cognitive regulation is often used to influence behavioral outcomes. However, the computational and neurobiological mechanisms by which it affects behavior remain unknown. We studied this issue using an fMRI task in which human participants used cognitive regulation to upregulate and downregulate their cravings for foods at the time of choice. We found that activity in both ventromedial prefrontal cortex (vmPFC) and dorsolateral prefrontal cortex (dlPFC) correlated with value. We also found evidence that two distinct regulatory mechanisms were at work: value modulation, which operates by changing the values assigned to foods in vmPFC and dlPFC at the time of choice, and behavioral control modulation, which operates by changing the relative influence of the vmPFC and dlPFC value signals on the action selection process used to make choices. In particular, during downregulation, activation decreased in the value-sensitive region of dlPFC (indicating value modulation) but not in vmPFC, and the relative contribution of the two value signals to behavior shifted toward the dlPFC (indicating behavioral control modulation). The opposite pattern was observed during upregulation: activation increased in vmPFC but not dlPFC, and the relative contribution to behavior shifted toward the vmPFC. Finally, ventrolateral PFC and posterior parietal cortex were more active during both upregulation and downregulation, and were functionally connected with vmPFC and dlPFC during cognitive regulation, which suggests that they help to implement the changes to the decision-making circuitry generated by cognitive regulation. PMID:23015444

Flocculation of Turbid Water Using Polyferric-Based Composite Coagulant

NASA Astrophysics Data System (ADS)

Tan, K. H.; Lai, S. H.

2017-06-01

The flocculation of turbid water using polyferric chloride-polydimethyldiallylammonium chloride (PFC-PDMDAAC) has been studied. Effect of preparation parameters basicity ratio (B ratio) of PFC and PDMDAAC/PFC ratio and operating parameters pH and dosage were investigated. PFC-PDMDAAC displayed maximum turbidity removal of 94.8% at 4.0mg/L when B=0.5 and PDMDAAC/PFC ratio = 7%. The best turbidity removal efficiencies by PFC-PDMDAAC were 84.7% at pH 7.5. These results reveal that PFC-PDMDAAC is efficient for flocculation of turbid water.

Prefrontal cortical BDNF: A regulatory key in cocaine- and food-reinforced behaviors

PubMed Central

Pitts, Elizabeth G.; Taylor, Jane R.; Gourley, Shannon L.

2016-01-01

Brain-derived neurotrophic factor (BDNF) affects synaptic plasticity and neural structure and plays key roles in learning and memory processes. Recent evidence also points to important, yet complex, roles for BDNF in rodent models of cocaine abuse and addiction. Here we examine the role of prefrontal cortical (PFC) BDNF in reward-related decision making and behavioral sensitivity to, and responding for, cocaine. We focus on BDNF within the medial and orbital PFC, its regulation by cocaine during early postnatal development and in adulthood, and how BDNF in turn influences responding for drug reinforcement, including in reinstatement models. When relevant, we draw comparisons and contrasts with experiments using natural (food) reinforcers. We also summarize findings supporting, or refuting, the possibility that BDNF in the medial and orbital PFC regulate the development and maintenance of stimulus-response habits. Further investigation could assist in the development of novel treatment approaches for cocaine use disorders. PMID:26923993

Bidirectional Frontoparietal Oscillatory Systems Support Working Memory.

PubMed

Johnson, Elizabeth L; Dewar, Callum D; Solbakk, Anne-Kristin; Endestad, Tor; Meling, Torstein R; Knight, Robert T

2017-06-19

The ability to represent and select information in working memory provides the neurobiological infrastructure for human cognition. For 80 years, dominant views of working memory have focused on the key role of prefrontal cortex (PFC) [1-8]. However, more recent work has implicated posterior cortical regions [9-12], suggesting that PFC engagement during working memory is dependent on the degree of executive demand. We provide evidence from neurological patients with discrete PFC damage that challenges the dominant models attributing working memory to PFC-dependent systems. We show that neural oscillations, which provide a mechanism for PFC to communicate with posterior cortical regions [13], independently subserve communications both to and from PFC-uncovering parallel oscillatory mechanisms for working memory. Fourteen PFC patients and 20 healthy, age-matched controls performed a working memory task where they encoded, maintained, and actively processed information about pairs of common shapes. In controls, the electroencephalogram (EEG) exhibited oscillatory activity in the low-theta range over PFC and directional connectivity from PFC to parieto-occipital regions commensurate with executive processing demands. Concurrent alpha-beta oscillations were observed over parieto-occipital regions, with directional connectivity from parieto-occipital regions to PFC, regardless of processing demands. Accuracy, PFC low-theta activity, and PFC → parieto-occipital connectivity were attenuated in patients, revealing a PFC-independent, alpha-beta system. The PFC patients still demonstrated task proficiency, which indicates that the posterior alpha-beta system provides sufficient resources for working memory. Taken together, our findings reveal neurologically dissociable PFC and parieto-occipital systems and suggest that parallel, bidirectional oscillatory systems form the basis of working memory. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Npas4 deficiency and prenatal stress interact to affect social recognition in mice.

PubMed

Heslin, K; Coutellier, L

2018-06-01

Neurodevelopmental disorders such as autism spectrum disorders and schizophrenia have an expansive array of reported genetic and environmental contributing factors. However, none of these factors alone can account for a substantial proportion of cases of either disorder. Instead, many gene-by-environment interactions are responsible for neurodevelopmental disturbances that lead to these disorders. The current experiment used heterozygous knock-out mice to examine a potential interaction between 2 factors commonly linked to neurodevelopmental disorders and cognitive deficit: imbalanced excitatory/inhibitory signaling in the cortex and prenatal stress (PNS) exposure. Both of these factors have been linked to disrupt GABAergic signaling in the prefrontal cortex (PFC), a common feature of neurodevelopmental disorders. The neuronal PAS domain protein 4 (Npas4) gene is instrumental in regulation of the excitatory/inhibitory balance in the cortex and hippocampus in response to activation. Npas4 heterozygous and wild-type male and female mice were exposed to either PNS or standard gestation, then evaluated during adulthood in social and anxiety behavioral measures. The combination of PNS and Npas4 deficiency in male mice impaired social recognition. This behavioral deficit was associated with decreased parvalbumin and cFos protein expression in the infralimbic region of the PFC following social stimulation in Npas4 heterozygous males. In contrast, females displayed fewer behavioral effects and molecular changes in PFC in response to PNS and decreased Npas4. © 2017 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Direct comparison of prefrontal cortex regions engaged by working and long-term memory tasks.

PubMed

Braver, T S; Barch, D M; Kelley, W M; Buckner, R L; Cohen, N J; Miezin, F M; Snyder, A Z; Ollinger, J M; Akbudak, E; Conturo, T E; Petersen, S E

2001-07-01

Neuroimaging studies have suggested the involvement of ventrolateral, dorsolateral, and frontopolar prefrontal cortex (PFC) regions in both working (WM) and long-term memory (LTM). The current study used functional magnetic resonance imaging (fMRI) to directly compare whether these PFC regions show selective activation associated with one memory domain. In a within-subjects design, subjects performed the n-back WM task (two-back condition) as well as LTM encoding (intentional memorization) and retrieval (yes-no recognition) tasks. Additionally, each task was performed with two different types of stimulus materials (familiar words, unfamiliar faces) in order to determine the influence of material-type vs task-type. A bilateral region of dorsolateral PFC (DL-PFC; BA 46/9) was found to be selectively activated during the two-back condition, consistent with a hypothesized role for this region in active maintenance and/or manipulation of information in WM. Left frontopolar PFC (FP-PFC) was also found to be selectively engaged during the two-back. Although FP-PFC activity has been previously associated with retrieval from LTM, no frontopolar regions were found to be selectively engaged by retrieval. Finally, lateralized ventrolateral PFC (VL-PFC) regions were found to be selectively engaged by material-type, but uninfluenced by task-type. These results highlight the importance of examining PFC activity across multiple memory domains, both for functionally differentiating PFC regions (e.g., task-selectivity vs material-selectivity in DL-PFC and VL-PFC) and for testing the applicability of memory domain-specific theories (e.g., FP-PFC in LTM retrieval).

The relationships between sixteen perfluorinated compound concentrations in blood serum and food, and other parameters, in the general population of South Korea with proportionate stratified sampling method.

PubMed

Kim, Hee-Young; Kim, Seung-Kyu; Kang, Dong-Mug; Hwang, Yong-Sik; Oh, Jeong-Eun

2014-02-01

Serum samples were collected from volunteers of various ages and both genders using a proportionate stratified sampling method, to assess the exposure of the general population in Busan, South Korea to perfluorinated compounds (PFCs). 16 PFCs were investigated in serum samples from 306 adults (124 males and 182 females) and one day composite diet samples (breakfast, lunch, and dinner) from 20 of the serum donors, to investigate the relationship between food and serum PFC concentrations. Perfluorooctanoic acid and perfluorooctanesulfonic acid were the dominant PFCs in the serum samples, with mean concentrations of 8.4 and 13 ng/mL, respectively. Perfluorotridecanoic acid was the dominant PFC in the composite food samples, ranging from

Economic decision-making in psychopathy: a comparison with ventromedial prefrontal lesion patients.

PubMed

Koenigs, Michael; Kruepke, Michael; Newman, Joseph P

2010-06-01

Psychopathy, which is characterized by a constellation of antisocial behavioral traits, may be subdivided on the basis of etiology: "primary" (low-anxious) psychopathy is viewed as a direct consequence of some core intrinsic deficit, whereas "secondary" (high-anxious) psychopathy is viewed as an indirect consequence of environmental factors or other psychopathology. Theories on the neurobiology of psychopathy have targeted dysfunction within ventromedial prefrontal cortex (vmPFC) as a putative mechanism, yet the relationship between vmPFC function and psychopathy subtype has not been fully explored. In this study, we administered two laboratory decision-making tasks (the Ultimatum Game and the Dictator Game) to a group of prisoners (n=47) to determine whether the different subtypes of psychopathy (primary vs. secondary) are associated with characteristic patterns of economic decision-making, and furthermore, whether either subtype exhibits similar performance to patients with vmPFC lesions. Comparing primary psychopaths (n=6) to secondary psychopaths (n=6) and non-psychopaths (n=22), we found that primary psychopathy was associated with significantly lower acceptance rates of unfair Ultimatum offers and lower offer amounts in the Dictator Game. Moreover, primary psychopaths were quantitatively similar to vmPFC lesion patients in their response patterns. These results support the purported connection between psychopathy and vmPFC dysfunction, bolster the distinction between primary and secondary psychopathy, and demonstrate the utility of laboratory economic decision-making tests in differentiating clinical subgroups. Copyright 2010 Elsevier Ltd. All rights reserved.

Selective representation of task-relevant objects and locations in the monkey prefrontal cortex.

PubMed

Everling, Stefan; Tinsley, Chris J; Gaffan, David; Duncan, John

2006-04-01

In the monkey prefrontal cortex (PFC), task context exerts a strong influence on neural activity. We examined different aspects of task context in a temporal search task. On each trial, the monkey (Macaca mulatta) watched a stream of pictures presented to left or right of fixation. The task was to hold fixation until seeing a particular target, and then to make an immediate saccade to it. Sometimes (unilateral task), the attended pictures appeared alone, with a cue at trial onset indicating whether they would be presented to left or right. Sometimes (bilateral task), the attended picture stream (cued side) was accompanied by an irrelevant stream on the opposite side. In two macaques, we recorded responses from a total of 161 cells in the lateral PFC. Many cells (75/161) showed visual responses. Object-selective responses were strongly shaped by task relevance - with stronger responses to targets than to nontargets, failure to discriminate one nontarget from another, and filtering out of information from an irrelevant stimulus stream. Location selectivity occurred rather independently of object selectivity, and independently in visual responses and delay periods between one stimulus and the next. On error trials, PFC activity followed the correct rules of the task, rather than the incorrect overt behaviour. Together, these results suggest a highly programmable system, with responses strongly determined by the rules and requirements of the task performed.

A digital prediction algorithm for a single-phase boost PFC

NASA Astrophysics Data System (ADS)

Qing, Wang; Ning, Chen; Weifeng, Sun; Shengli, Lu; Longxing, Shi

2012-12-01

A novel digital control algorithm for digital control power factor correction is presented, which is called the prediction algorithm and has a feature of a higher PF (power factor) with lower total harmonic distortion, and a faster dynamic response with the change of the input voltage or load current. For a certain system, based on the current system state parameters, the prediction algorithm can estimate the track of the output voltage and the inductor current at the next switching cycle and get a set of optimized control sequences to perfectly track the trajectory of input voltage. The proposed prediction algorithm is verified at different conditions, and computer simulation and experimental results under multi-situations confirm the effectiveness of the prediction algorithm. Under the circumstances that the input voltage is in the range of 90-265 V and the load current in the range of 20%-100%, the PF value is larger than 0.998. The startup and the recovery times respectively are about 0.1 s and 0.02 s without overshoot. The experimental results also verify the validity of the proposed method.

14 CFR 158.43 - Public agency notification to collect PFC's.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Public agency notification to collect PFC's... TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Collection, Handling, and Remittance of PFC's § 158.43 Public agency notification to collect PFC's. (a) Following approval of an application...

14 CFR 158.69 - Recordkeeping and auditing: Collecting carriers.

Code of Federal Regulations, 2013 CFR

2013-01-01

... TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Reporting, Recordkeeping and Audits § 158... than 50,000 PFC's annually shall provide for an audit at least annually of its PFC account. (1) The... maintain for each public agency for which they collect a PFC an accounting record of PFC revenue collected...

14 CFR 158.43 - Public agency notification to collect PFC's.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Public agency notification to collect PFC's... TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Collection, Handling, and Remittance of PFC's § 158.43 Public agency notification to collect PFC's. (a) Following approval of an application...

14 CFR 158.30 - PFC Authorization at Non-Hub Airports.

Code of Federal Regulations, 2013 CFR

2013-01-01

... (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Application and Approval § 158.30 PFC Authorization... public agency's notice of intent about its PFC program, the FAA will issue a written acknowledgment of... its entirety, the public agency may implement its PFC program. The public agency's implementation must...

14 CFR 158.43 - Public agency notification to collect PFC's.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Public agency notification to collect PFC's... TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Collection, Handling, and Remittance of PFC's § 158.43 Public agency notification to collect PFC's. (a) Following approval of an application...

14 CFR 158.51 - Remittance of PFC's.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Remittance of PFC's. 158.51 Section 158.51... PASSENGER FACILITY CHARGES (PFC'S) Collection, Handling, and Remittance of PFC's § 158.51 Remittance of PFC's. Passenger facility charges collected by carriers shall be remitted to the public agency on a...

14 CFR 158.30 - PFC Authorization at Non-Hub Airports.

Code of Federal Regulations, 2014 CFR

2014-01-01

... (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Application and Approval § 158.30 PFC Authorization... public agency's notice of intent about its PFC program, the FAA will issue a written acknowledgment of... its entirety, the public agency may implement its PFC program. The public agency's implementation must...

14 CFR 158.30 - PFC Authorization at Non-Hub Airports.

Code of Federal Regulations, 2010 CFR

2010-01-01

... (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Application and Approval § 158.30 PFC Authorization... public agency's notice of intent about its PFC program, the FAA will issue a written acknowledgment of... its entirety, the public agency may implement its PFC program. The public agency's implementation must...

14 CFR 158.43 - Public agency notification to collect PFC's.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Public agency notification to collect PFC's... TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Collection, Handling, and Remittance of PFC's § 158.43 Public agency notification to collect PFC's. (a) Following approval of an application...

14 CFR 158.51 - Remittance of PFC's.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Remittance of PFC's. 158.51 Section 158.51... PASSENGER FACILITY CHARGES (PFC'S) Collection, Handling, and Remittance of PFC's § 158.51 Remittance of PFC's. Passenger facility charges collected by carriers shall be remitted to the public agency on a...

14 CFR 158.51 - Remittance of PFC's.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Remittance of PFC's. 158.51 Section 158.51... PASSENGER FACILITY CHARGES (PFC'S) Collection, Handling, and Remittance of PFC's § 158.51 Remittance of PFC's. Passenger facility charges collected by carriers shall be remitted to the public agency on a...

14 CFR 158.43 - Public agency notification to collect PFC's.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Public agency notification to collect PFC's... TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Collection, Handling, and Remittance of PFC's § 158.43 Public agency notification to collect PFC's. (a) Following approval of an application...

14 CFR 158.51 - Remittance of PFC's.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Remittance of PFC's. 158.51 Section 158.51... PASSENGER FACILITY CHARGES (PFC'S) Collection, Handling, and Remittance of PFC's § 158.51 Remittance of PFC's. Passenger facility charges collected by carriers shall be remitted to the public agency on a...

14 CFR 158.30 - PFC Authorization at Non-Hub Airports.

Code of Federal Regulations, 2012 CFR

2012-01-01

... (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Application and Approval § 158.30 PFC Authorization... public agency's notice of intent about its PFC program, the FAA will issue a written acknowledgment of... its entirety, the public agency may implement its PFC program. The public agency's implementation must...

14 CFR 158.51 - Remittance of PFC's.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Remittance of PFC's. 158.51 Section 158.51... PASSENGER FACILITY CHARGES (PFC'S) Collection, Handling, and Remittance of PFC's § 158.51 Remittance of PFC's. Passenger facility charges collected by carriers shall be remitted to the public agency on a...

14 CFR 158.30 - PFC Authorization at Non-Hub Airports.

Code of Federal Regulations, 2011 CFR

2011-01-01

... (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Application and Approval § 158.30 PFC Authorization... public agency's notice of intent about its PFC program, the FAA will issue a written acknowledgment of... its entirety, the public agency may implement its PFC program. The public agency's implementation must...

14 CFR 158.69 - Recordkeeping and auditing: Collecting carriers.

Code of Federal Regulations, 2014 CFR

2014-01-01

... TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Reporting, Recordkeeping and Audits § 158... than 50,000 PFC's annually shall provide for an audit at least annually of its PFC account. (1) The... maintain for each public agency for which they collect a PFC an accounting record of PFC revenue collected...

PFC Decontamination of a Metal Surface and the Recycling of a Spent PFC Solution

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

Jung, C.H.; Won, H.J.; Oh, W.Z.

2006-07-01

PFC (per-fluorocarbon) ultrasonic decontamination behavior of loosely contaminated metal specimens such as a plate, pipe, welding and a crevice specimen in a mixed solution of PFC and an anionic surfactant was investigated. Perfluoroheptane (C{sub 7}F{sub 16}) was used as a PFC ultrasonic media. The contaminants were completely removed for almost all of the tested specimens except for the longest pipe length specimen. For the 6-cm long specimen, 98.5 % of the contaminants were removed. For the recycling of the PFC solution, a distillation test for the spent PFC solution was also performed. The results show that 97.5 % of themore » PFC was recycled without a loss of the decontamination efficiency. (authors)« less

Coordinated Excitation and Inhibition of Prefrontal Ensembles During Awake Hippocampal Sharp-Wave Ripple Events

PubMed Central

Jadhav, Shantanu P.; Rothschild, Gideon; Roumis, Demetris K.; Frank, Loren M.

2016-01-01

SUMMARY Interactions between the hippocampus and prefrontal cortex (PFC) are critical for learning and memory. Hippocampal activity during awake sharp wave ripple (SWR) events is important for spatial learning, and hippocampal SWR activity often represents past or potential future experiences. Whether or how this reactivation engages the PFC, and how reactivation might interact with ongoing patterns of PFC activity remains unclear. We recorded hippocampal CA1 and PFC activity in animals learning spatial tasks and found that many PFC cells showed spiking modulation during SWRs. Unlike in CA1, SWR-related activity in PFC comprised both excitation and inhibition of distinct populations. Within individual SWRs, excitation activated PFC cells with representations related to the concurrently reactivated hippocampal representation, while inhibition suppressed PFC cells with unrelated representations. Thus, awake SWRs mark times of strong coordination between hippocampus and PFC that reflects structured reactivation of representations related to ongoing experience. PMID:26971950

GABA content within medial prefrontal cortex predicts the variability of fronto-limbic effective connectivity

PubMed Central

Pizzi, Stefano Delli; Chiacchieretta, Piero; Mantini, Dante; Bubbico, Giovanna; Edden, Richard A.; Onofrj, Marco; Ferretti, Antonio

2017-01-01

The amygdala-medial prefrontal cortex (mPFC) circuit plays a key role in social behavior. The amygdala and mPFC are bidirectionally connected, functionally and anatomically, via the uncinate fasciculus. Recent evidence suggests that GABA-ergic neurotransmission within the mPFC could be central to the regulation of amygdala activity related to emotions and anxiety processing. However, the functional and neurochemical interactions within amygdala-mPFC circuits are unclear. In the current study, multimodal magnetic resonance imaging techniques were combined to investigate effective connectivity within the amygdala-mPFC network and its relationship with mPFC neurotransmission in 22 healthy subjects aged between 41 and 88 years. Effective connectivity in the amygdala-mPFC circuit was assessed on resting-state functional magnetic resonance imaging data using spectral dynamic causal modelling. State and trait anxiety were also assessed. The mPFC was shown to be the target of incoming outputs from the amygdalae and the source of exciting inputs to the limbic system. The amygdalae were reciprocally connected by excitatory projections. About half of the variance relating to the strength of top–down endogenous connection between right amygdala and mPFC was explained by mPFC GABA levels. State anxiety was correlated with the strength of the endogenous connections between right amygdala and mPFC. We suggest that mPFC GABA content predicts variability in the effective connectivity within the mPFC-amygdala circuit, providing new insights on emotional physiology and the underlying functional and neurochemical interactions. PMID:28386778

14 CFR 158.7 - Exclusivity of authority.

Code of Federal Regulations, 2011 CFR

2011-01-01

...) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) General § 158.7 Exclusivity of authority. (a) A State... imposition or collection of a PFC or the use of PFC revenue. (b) No contract or agreement between an air... impose a PFC or use the PFC revenue in accordance with this part. [Doc. No. 26385, 56 FR 24278, May 29...

14 CFR 158.39 - Use of excess PFC revenue.

Code of Federal Regulations, 2014 CFR

2014-01-01

...) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Application and Approval § 158.39 Use of excess PFC revenue. (a) If the PFC revenue remitted to the public agency, plus interest earned thereon, exceeds the allowable... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Use of excess PFC revenue. 158.39 Section...

14 CFR 158.39 - Use of excess PFC revenue.

Code of Federal Regulations, 2010 CFR

2010-01-01

...) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Application and Approval § 158.39 Use of excess PFC revenue. (a) If the PFC revenue remitted to the public agency, plus interest earned thereon, exceeds the allowable... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Use of excess PFC revenue. 158.39 Section...

14 CFR 158.37 - Amendment of approved PFC.

Code of Federal Regulations, 2013 CFR

2013-01-01

...) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Application and Approval § 158.37 Amendment of approved PFC. (a)(1) A public agency may amend the FAA's decision with respect to an approved PFC to: (i) Increase or... approved. (2) A public agency may not amend the FAA's decision with respect to an approved PFC to add...

14 CFR 158.37 - Amendment of approved PFC.

Code of Federal Regulations, 2011 CFR

2011-01-01

...) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Application and Approval § 158.37 Amendment of approved PFC. (a)(1) A public agency may amend the FAA's decision with respect to an approved PFC to: (i) Increase or... approved. (2) A public agency may not amend the FAA's decision with respect to an approved PFC to add...

14 CFR 158.37 - Amendment of approved PFC.

Code of Federal Regulations, 2010 CFR

2010-01-01

...) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Application and Approval § 158.37 Amendment of approved PFC. (a)(1) A public agency may amend the FAA's decision with respect to an approved PFC to: (i) Increase or... approved. (2) A public agency may not amend the FAA's decision with respect to an approved PFC to add...

14 CFR 158.47 - Collection of PFC's on tickets issued outside the U.S.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Collection of PFC's on tickets issued... OF TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Collection, Handling, and Remittance of PFC's § 158.47 Collection of PFC's on tickets issued outside the U.S. (a) For tickets issued...

14 CFR 158.47 - Collection of PFC's on tickets issued outside the U.S.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Collection of PFC's on tickets issued... OF TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Collection, Handling, and Remittance of PFC's § 158.47 Collection of PFC's on tickets issued outside the U.S. (a) For tickets issued...

14 CFR 158.39 - Use of excess PFC revenue.

Code of Federal Regulations, 2011 CFR

2011-01-01

...) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Application and Approval § 158.39 Use of excess PFC revenue. (a) If the PFC revenue remitted to the public agency, plus interest earned thereon, exceeds the allowable... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Use of excess PFC revenue. 158.39 Section...

14 CFR 158.39 - Use of excess PFC revenue.

Code of Federal Regulations, 2013 CFR

2013-01-01

...) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Application and Approval § 158.39 Use of excess PFC revenue. (a) If the PFC revenue remitted to the public agency, plus interest earned thereon, exceeds the allowable... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Use of excess PFC revenue. 158.39 Section...

14 CFR 158.7 - Exclusivity of authority.

Code of Federal Regulations, 2013 CFR

2013-01-01

...) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) General § 158.7 Exclusivity of authority. (a) A State... imposition or collection of a PFC or the use of PFC revenue. (b) No contract or agreement between an air... impose a PFC or use the PFC revenue in accordance with this part. [Doc. No. 26385, 56 FR 24278, May 29...

14 CFR 158.37 - Amendment of approved PFC.

Code of Federal Regulations, 2014 CFR

2014-01-01

...) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Application and Approval § 158.37 Amendment of approved PFC. (a)(1) A public agency may amend the FAA's decision with respect to an approved PFC to: (i) Increase or... approved. (2) A public agency may not amend the FAA's decision with respect to an approved PFC to add...

14 CFR 158.47 - Collection of PFC's on tickets issued outside the U.S.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Collection of PFC's on tickets issued... OF TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Collection, Handling, and Remittance of PFC's § 158.47 Collection of PFC's on tickets issued outside the U.S. (a) For tickets issued...

14 CFR 158.37 - Amendment of approved PFC.

Code of Federal Regulations, 2012 CFR

2012-01-01

...) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Application and Approval § 158.37 Amendment of approved PFC. (a)(1) A public agency may amend the FAA's decision with respect to an approved PFC to: (i) Increase or... approved. (2) A public agency may not amend the FAA's decision with respect to an approved PFC to add...

14 CFR 158.7 - Exclusivity of authority.

Code of Federal Regulations, 2010 CFR

2010-01-01

...) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) General § 158.7 Exclusivity of authority. (a) A State... imposition or collection of a PFC or the use of PFC revenue. (b) No contract or agreement between an air... impose a PFC or use the PFC revenue in accordance with this part. [Doc. No. 26385, 56 FR 24278, May 29...

14 CFR 158.7 - Exclusivity of authority.

Code of Federal Regulations, 2012 CFR

2012-01-01

...) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) General § 158.7 Exclusivity of authority. (a) A State... imposition or collection of a PFC or the use of PFC revenue. (b) No contract or agreement between an air... impose a PFC or use the PFC revenue in accordance with this part. [Doc. No. 26385, 56 FR 24278, May 29...

14 CFR 158.39 - Use of excess PFC revenue.

Code of Federal Regulations, 2012 CFR

2012-01-01

...) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Application and Approval § 158.39 Use of excess PFC revenue. (a) If the PFC revenue remitted to the public agency, plus interest earned thereon, exceeds the allowable... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Use of excess PFC revenue. 158.39 Section...

14 CFR 158.47 - Collection of PFC's on tickets issued outside the U.S.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Collection of PFC's on tickets issued... OF TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Collection, Handling, and Remittance of PFC's § 158.47 Collection of PFC's on tickets issued outside the U.S. (a) For tickets issued...

14 CFR 158.7 - Exclusivity of authority.

Code of Federal Regulations, 2014 CFR

2014-01-01

...) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) General § 158.7 Exclusivity of authority. (a) A State... imposition or collection of a PFC or the use of PFC revenue. (b) No contract or agreement between an air... impose a PFC or use the PFC revenue in accordance with this part. [Doc. No. 26385, 56 FR 24278, May 29...

Protection of tokamak plasma facing components by a capillary porous system with lithium

NASA Astrophysics Data System (ADS)

Lyublinski, I.; Vertkov, A.; Mirnov, S.; Lazarev, V.

2015-08-01

Development of plasma facing material (PFM) based on the Capillary-Porous System (CPS) with lithium and activity on realization of lithium application strategy are addressed to meet the challenges under the creation of steady-state tokamak fusion reactor and fusion neutron source. Presented overview of experimental study of lithium CPS in plasma devices demonstrates the progress in protection of tokamak plasma facing components (PFC) from damage, stabilization and self-renewal of liquid lithium surface, elimination of plasma pollution and lithium accumulation in tokamak chamber. The possibility of PFC protection from the high power load related to cooling of the tokamak boundary plasma by radiation of non-fully stripped lithium ions supported by experimental results. This approach demonstrated in scheme of closed loops of Li circulation in the tokamak vacuum chamber and realized in a series of design of tokamak in-vessel elements.

Hippocampal-prefrontal theta-gamma coupling during performance of a spatial working memory task.

PubMed

Tamura, Makoto; Spellman, Timothy J; Rosen, Andrew M; Gogos, Joseph A; Gordon, Joshua A

2017-12-19

Cross-frequency coupling supports the organization of brain rhythms and is present during a range of cognitive functions. However, little is known about whether and how long-range cross-frequency coupling across distant brain regions subserves working memory. Here we report that theta-slow gamma coupling between the hippocampus and medial prefrontal cortex (mPFC) is augmented in a genetic mouse model of cognitive dysfunction. This increased cross-frequency coupling is observed specifically when the mice successfully perform a spatial working memory task. In wild-type mice, increasing task difficulty by introducing a long delay or by optogenetically interfering with encoding, also increases theta-gamma coupling during correct trials. Finally, epochs of high hippocampal theta-prefrontal slow gamma coupling are associated with increased synchronization of neurons within the mPFC. These findings suggest that enhancement of theta-slow gamma coupling reflects a compensatory mechanism to maintain spatial working memory performance in the setting of increased difficulty.

Distinguishing the roles of dorsolateral and anterior PFC in visual metacognition.

PubMed

Shekhar, Medha; Rahnev, Dobromir

2018-05-02

Visual metacognition depends on regions within the prefrontal cortex. Two areas in particular have been repeatedly implicated: the dorsolateral prefrontal cortex (DLPFC) and the anterior prefrontal cortex (aPFC). However, it is still unclear what the function of each of these areas is and how they differ from each other. To establish the specific roles of DLPFC and aPFC in metacognition, we employed online transcranial magnetic stimulation (TMS) to causally interfere with their functioning during confidence generation. Human subjects from both sexes performed a perceptual decision-making task and provided confidence ratings. We found a clear dissociation between the two areas: DLPFC TMS lowered confidence ratings, whereas aPFC TMS increased metacognitive ability but only for the second half of the experimental blocks. These results support a functional architecture where DLPFC reads out the strength of the sensory evidence and relays it to aPFC, which makes the confidence judgement by potentially incorporating additional, non-perceptual information. Indeed, simulations from a model that incorporates these putative DLPFC and aPFC functions reproduced our behavioral results. These findings establish DLPFC and aPFC as distinct nodes in a metacognitive network and suggest specific contributions from each of these regions to confidence generation. SIGNIFICANCE STATEMENT The prefrontal cortex (PFC) is known to be critical for metacognition. Two of its sub-regions - dorsolateral PFC (DLPFC) and anterior PFC (aPFC) - have specifically been implicated in confidence generation. However, it is unclear if these regions have distinct functions related to the underlying metacognitive computation. Using a causal intervention with transcranial magnetic stimulation (TMS), we demonstrate that DLPFC and aPFC have dissociable contributions: targeting DLPFC decreased average confidence ratings, while targeting aPFC specifically affected metacognitive scores. Based on these results, we postulated specific functions for DLPFC and aPFC in metacognitive computation and corroborated them using a computational model that reproduced our results. Our causal results reveal the existence of a specialized modular organization in PFC for confidence generation. Copyright © 2018 the authors.

14 CFR 158.45 - Collection of PFC's on tickets issued in the U.S.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Collection of PFC's on tickets issued in... TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Collection, Handling, and Remittance of PFC's § 158.45 Collection of PFC's on tickets issued in the U.S. (a) On and after the charge effective...

14 CFR 158.45 - Collection of PFC's on tickets issued in the U.S.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Collection of PFC's on tickets issued in... TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Collection, Handling, and Remittance of PFC's § 158.45 Collection of PFC's on tickets issued in the U.S. (a) On and after the charge effective...

14 CFR 158.5 - Authority to impose PFC's.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Authority to impose PFC's. 158.5 Section...) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) General § 158.5 Authority to impose PFC's. Subject to the... service airport to impose a PFC of $1, $2, $3, $4, or $4.50 on passengers enplaned at such an airport. No...

14 CFR 158.45 - Collection of PFC's on tickets issued in the U.S.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Collection of PFC's on tickets issued in... TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Collection, Handling, and Remittance of PFC's § 158.45 Collection of PFC's on tickets issued in the U.S. (a) On and after the charge effective...

14 CFR 158.5 - Authority to impose PFC's.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Authority to impose PFC's. 158.5 Section...) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) General § 158.5 Authority to impose PFC's. Subject to the... service airport to impose a PFC of $1, $2, $3, $4, or $4.50 on passengers enplaned at such an airport. No...

14 CFR 158.5 - Authority to impose PFC's.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Authority to impose PFC's. 158.5 Section...) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) General § 158.5 Authority to impose PFC's. Subject to the... service airport to impose a PFC of $1, $2, $3, $4, or $4.50 on passengers enplaned at such an airport. No...

14 CFR 158.45 - Collection of PFC's on tickets issued in the U.S.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Collection of PFC's on tickets issued in... TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Collection, Handling, and Remittance of PFC's § 158.45 Collection of PFC's on tickets issued in the U.S. (a) On and after the charge effective...

14 CFR 158.45 - Collection of PFC's on tickets issued in the U.S.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Collection of PFC's on tickets issued in... TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Collection, Handling, and Remittance of PFC's § 158.45 Collection of PFC's on tickets issued in the U.S. (a) On and after the charge effective...

14 CFR 158.5 - Authority to impose PFC's.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Authority to impose PFC's. 158.5 Section...) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) General § 158.5 Authority to impose PFC's. Subject to the... service airport to impose a PFC of $1, $2, $3, $4, or $4.50 on passengers enplaned at such an airport. No...

14 CFR 158.5 - Authority to impose PFC's.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Authority to impose PFC's. 158.5 Section...) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) General § 158.5 Authority to impose PFC's. Subject to the... service airport to impose a PFC of $1, $2, $3, $4, or $4.50 on passengers enplaned at such an airport. No...

Neural Correlates of Direct Access Trading in a Real Stock Market: An fMRI Investigation.

PubMed

Raggetti, GianMario; Ceravolo, Maria G; Fattobene, Lucrezia; Di Dio, Cinzia

2017-01-01

Background: While financial decision making has been barely explored, no study has previously investigated the neural correlates of individual decisions made by professional traders involved in real stock market negotiations, using their own financial resources. Aim: We sought to detect how different brain areas are modulated by factors like age, expertise, psychological profile (speculative risk seeking or aversion) and, eventually, size and type (Buy/Sell) of stock negotiations, made through Direct Access Trading (DAT) platforms. Subjects and methods: Twenty male traders underwent fMRI while negotiating in the Italian stock market using their own preferred trading platform. Results: At least 20 decision events were collected during each fMRI session. Risk averse traders performed a lower number of financial transactions with respect to risk seekers, with a lower average economic value, but with a higher rate of filled proposals. Activations were observed in cortical and subcortical areas traditionally involved in decision processes, including the ventrolateral and dorsolateral prefrontal cortex (vlPFC, dlPFC), the posterior parietal cortex (PPC), the nucleus accumbens (NAcc), and dorsal striatum. Regression analysis indicated an important role of age in modulating activation of left NAcc, while traders' expertise was negatively related to activation of vlPFC. High value transactions were associated with a stronger activation of the right PPC when subjects' buy rather than sell. The success of the trading activity, based on a large number of filled transactions, was related with higher activation of vlPFC and dlPFC. Independent of chronological and professional age, traders differed in their attitude to DAT, with distinct brain activity profiles being detectable during fMRI sessions. Those subjects who described themselves as very self-confident, showed a lower or absent activation of both the caudate nucleus and the dlPFC, while more reflexive traders showed greater activation of areas involved in strategic decision making. Discussion: The neural correlates in DAT are similar to those observed in other decision making contexts. Trading is handled as a well-learned automatic behavior by expert traders; for those who mostly rely on heuristics, cognitive effort decreases, and transaction speed increases, but decision efficiency lowers following a poor involvement of the dlPFC.

Medial Prefrontal Cortex Reduces Memory Interference by Modifying Hippocampal Encoding

PubMed Central

Guise, Kevin G.; Shapiro, Matthew L.

2017-01-01

Summary The prefrontal cortex (PFC) is crucial for accurate memory performance when prior knowledge interferes with new learning, but the mechanisms that minimize proactive interference are unknown. To investigate these, we assessed the influence of medial PFC (mPFC) activity on spatial learning and hippocampal coding in a plus maze task that requires both structures. mPFC inactivation did not impair spatial learning or retrieval per se, but impaired the ability to follow changing spatial rules. mPFC and CA1 ensembles recorded simultaneously predicted goal choices and tracked changing rules; inactivating mPFC attenuated CA1 prospective coding. mPFC activity modified CA1 codes during learning, which in turn predicted how quickly rats adapted to subsequent rule changes. The results suggest that task rules signaled by the mPFC become incorporated into hippocampal representations and support prospective coding. By this mechanism, mPFC activity prevents interference by “teaching” the hippocampus to retrieve distinct representations of similar circumstances. PMID:28343868

INCREASES IN FUNCTIONAL CONNECTIVITY BETWEEN PREFRONTAL CORTEX AND STRIATUM DURING CATEGORY LEARNING

PubMed Central

Antzoulatos, Evan G.; Miller, Earl K.

2014-01-01

SUMMARY Functional connectivity between the prefrontal cortex (PFC) and striatum (STR) is thought critical for cognition, and has been linked to conditions like autism and schizophrenia. We recorded from multiple electrodes in PFC and STR while monkeys acquired new categories. Category learning was accompanied by an increase in beta-band synchronization of LFPs between, but not within, the PFC and STR. After learning, different pairs of PFC-STR electrodes showed stronger synchrony for one or the other category, suggesting category-specific functional circuits. This category-specific synchrony was also seen between PFC spikes and STR LFPs, but not the reverse, reflecting the direct monosynaptic connections from the PFC to STR. However, causal connectivity analyses suggested that the polysynaptic connections from STR to the PFC exerted a stronger overall influence. This supports models positing that the basal ganglia “train” the PFC. Category learning may depend on the formation of functional circuits between the PFC and STR. PMID:24930701

Increased antidepressant sensitivity after prefrontal cortex glucocorticoid receptor gene deletion in mice.

PubMed

Hussain, Rifat J; Jacobson, Lauren

2015-01-01

Our laboratory has previously shown that antidepressants regulate glucocorticoid receptor (GR) expression in the prefrontal cortex (PFC). To determine if PFC GR are involved in antidepressant effects on behavior or hypothalamic-pituitary-adrenocortical (HPA) axis activity, we treated floxed GR male mice with saline or 15 or 30 mg/kg/d imipramine after PFC injection of adeno-associated virus 2/9 vectors transducing expression of Cre recombinase, to knock-down GR (PFC-GRKD), or green fluorescent protein (PFC-GFP), to serve as a control. The pattern of virally transduced GR deletion, common to all imipramine treatment groups, included the infralimbic, prelimbic, and medial anterior cingulate cortex at its largest extent, but was confined to the prelimbic and anterior cingulate cortex at its smallest extent. PFC GR knock-down increased behavioral sensitivity to imipramine, with imipramine-treated PFC-GRKD but not PFC-GFP mice exhibiting significant decreases in depression-like immobility during forced swim. PFC GR deletion did not alter general locomotor activity. The 30 mg/kg dose of imipramine increased plasma corticosterone levels immediately after a 5-min forced swim, but PFC GR knock-down had no significant effect on plasma corticosterone under these experimental conditions. We conclude that PFC GR knock-down, likely limited to the medial prelimbic and anterior cingulate cortices, can increase behavioral sensitivity to antidepressants. These findings indicate a novel role for PFC GR in influencing antidepressant response. Copyright © 2014 Elsevier Inc. All rights reserved.

14 CFR 158.17 - Project eligibility at PFC levels of $4 or $4.50.

Code of Federal Regulations, 2013 CFR

2013-01-01

... TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) General § 158.17 Project eligibility at PFC levels of $4 or $4.50. (a) A project for any airport is eligible for PFC funding at levels of $4... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Project eligibility at PFC levels of $4 or...

14 CFR 158.17 - Project eligibility at PFC levels of $4 or $4.50.

Code of Federal Regulations, 2014 CFR

2014-01-01

... TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) General § 158.17 Project eligibility at PFC levels of $4 or $4.50. (a) A project for any airport is eligible for PFC funding at levels of $4... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Project eligibility at PFC levels of $4 or...

14 CFR 158.17 - Project eligibility at PFC levels of $4 or $4.50.

Code of Federal Regulations, 2011 CFR

2011-01-01

... TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) General § 158.17 Project eligibility at PFC levels of $4 or $4.50. (a) A project for any airport is eligible for PFC funding at levels of $4... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Project eligibility at PFC levels of $4 or...

14 CFR 158.17 - Project eligibility at PFC levels of $4 or $4.50.

Code of Federal Regulations, 2012 CFR

2012-01-01

... TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) General § 158.17 Project eligibility at PFC levels of $4 or $4.50. (a) A project for any airport is eligible for PFC funding at levels of $4... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Project eligibility at PFC levels of $4 or...

14 CFR 158.17 - Project eligibility at PFC levels of $4 or $4.50.

Code of Federal Regulations, 2010 CFR

2010-01-01

... TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) General § 158.17 Project eligibility at PFC levels of $4 or $4.50. (a) A project for any airport is eligible for PFC funding at levels of $4... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Project eligibility at PFC levels of $4 or...

Complexity of VTA DA neural activities in response to PFC transection in nicotine treated rats.

PubMed

Chen, Ting Y; Zhang, Die; Dragomir, Andrei; Akay, Yasemin M; Akay, Metin

2011-02-27

The dopaminergic (DA) neurons in the ventral tegmental area (VTA) are widely implicated in the addiction and natural reward circuitry of the brain. These neurons project to several areas of the brain, including prefrontal cortex (PFC), nucleus accubens (NAc) and amygdala. The functional coupling between PFC and VTA has been demonstrated, but little is known about how PFC mediates nicotinic modulation in VTA DA neurons. The objectives of this study were to investigate the effect of acute nicotine exposure on the VTA DA neuronal firing and to understand how the disruption of communication from PFC affects the firing patterns of VTA DA neurons. Extracellular single-unit recordings were performed on Sprague-Dawley rats and nicotine was administered after stable recording was established as baseline. In order to test how input from PFC affects the VTA DA neuronal firing, bilateral transections were made immediate caudal to PFC to mechanically delete the interaction between VTA and PFC. The complexity of the recorded neural firing was subsequently assessed using a method based on the Lempel-Ziv estimator. The results were compared with those obtained when computing the entropy of neural firing. Exposure to nicotine triggered a significant increase in VTA DA neurons firing complexity when communication between PFC and VTA was present, while transection obliterated the effect of nicotine. Similar results were obtained when entropy values were estimated. Our findings suggest that PFC plays a vital role in mediating VTA activity. We speculate that increased firing complexity with acute nicotine administration in PFC intact subjects is due to the close functional coupling between PFC and VTA. This hypothesis is supported by the fact that deletion of PFC results in minor alterations of VTA DA neural firing when nicotine is acutely administered.

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.

A spiking neural integrator model of the adaptive control of action by the medial prefrontal cortex.

PubMed

Bekolay, Trevor; Laubach, Mark; Eliasmith, Chris

2014-01-29

Subjects performing simple reaction-time tasks can improve reaction times by learning the expected timing of action-imperative stimuli and preparing movements in advance. Success or failure on the previous trial is often an important factor for determining whether a subject will attempt to time the stimulus or wait for it to occur before initiating action. The medial prefrontal cortex (mPFC) has been implicated in enabling the top-down control of action depending on the outcome of the previous trial. Analysis of spike activity from the rat mPFC suggests that neural integration is a key mechanism for adaptive control in precisely timed tasks. We show through simulation that a spiking neural network consisting of coupled neural integrators captures the neural dynamics of the experimentally recorded mPFC. Errors lead to deviations in the normal dynamics of the system, a process that could enable learning from past mistakes. We expand on this coupled integrator network to construct a spiking neural network that performs a reaction-time task by following either a cue-response or timing strategy, and show that it performs the task with similar reaction times as experimental subjects while maintaining the same spiking dynamics as the experimentally recorded mPFC.

Neurobiological correlates of distinct post-traumatic stress disorder symptom profiles during threat anticipation in combat veterans.

PubMed

Grupe, D W; Wielgosz, J; Davidson, R J; Nitschke, J B

2016-07-01

Previous research in post-traumatic stress disorder (PTSD) has identified disrupted ventromedial prefrontal cortex (vmPFC) function in those with v. without PTSD. It is unclear whether this brain region is uniformly affected in all individuals with PTSD, or whether vmPFC dysfunction is related to individual differences in discrete features of this heterogeneous disorder. In a sample of 51 male veterans of Operation Enduring Freedom/Operation Iraqi Freedom, we collected functional magnetic resonance imaging data during a novel threat anticipation task with crossed factors of threat condition and temporal unpredictability. Voxelwise regression analyses related anticipatory brain activation to individual differences in overall PTSD symptom severity, as well as individual differences in discrete symptom subscales (re-experiencing, emotional numbing/avoidance, and hyperarousal). The vmPFC showed greater anticipatory responses for safety relative to threat, driven primarily by deactivation during threat anticipation. During unpredictable threat anticipation, increased PTSD symptoms were associated with relatively greater activation for threat v. However, simultaneous regression on individual symptom subscales demonstrated that this effect was driven specifically by individual differences in hyperarousal symptoms. Furthermore, this analysis revealed an additional, anatomically distinct region of the vmPFC in which re-experiencing symptoms were associated with greater activation during threat anticipation. Increased anticipatory responses to unpredictable threat in distinct vmPFC subregions were uniquely associated with elevated hyperarousal and re-experiencing symptoms in combat veterans. These results underscore the disruptive impact of uncertainty for veterans, and suggest that investigating individual differences in discrete aspects of PTSD may advance our understanding of underlying neurobiological mechanisms.

Prevention of alcohol-heightened aggression by CRF-R1 antagonists in mice: critical role for DRN-PFC serotonin pathway.

PubMed

Quadros, Isabel M; Hwa, Lara S; Shimamoto, Akiko; Carlson, Julia; DeBold, Joseph F; Miczek, Klaus A

2014-11-01

Alcohol can escalate aggressive behavior in a significant subgroup of rodents, humans, and nonhuman primates. The present study investigated whether blockade of corticotropin-releasing factor receptor type 1 (CRF-R1) could prevent the emergence of alcohol-heightened aggression in mice. The serotonin (5-HT) pathway from the dorsal raphe nucleus (DRN) to the medial prefrontal cortex (mPFC) by CRF-R1 was investigated as a possible target for the prevention of alcohol-heightened aggressive behavior. Male CFW mice that reliably exhibited aggressive behaviors after consuming 1 g/kg of alcohol received systemic or intra-DRN administration of CRF-R1 antagonists, CP-154,526 or MTIP, before a confrontation with a male conspecific. Blockade of DRN CRF-R1 receptors with both antagonists significantly reduced only alcohol-heightened aggression, whereas systemic administration reduced both alcohol-heightened and species-typical aggression. Next, a 5-HT1A agonist, 8-OH-DPAT, was coadministered with CP-154,526 into the DRN to temporarily disrupt 5-HT activity. This manipulation abolished the antiaggressive effects of intra-DRN CP-154,526. In the mPFC, in vivo microdialysis revealed that extracellular 5-HT levels were increased in mice that consumed alcohol and were then injected with CP-154,526, both systemically or intra-DRN. Neither alcohol nor CP-154,526 alone affected 5-HT release in the mPFC. The present results suggest the DRN as a critical site for CRF-R1 to modulate alcohol-heightened aggression via action on the serotonergic DRN-PFC pathway.

78 FR 41184 - Notice of Intent To Rule on Passenger Facility Charge (PFC) Application 11-05-C-00-SFO to Impose...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-09

... Facility Charge (PFC) Application 11-05-C-00-SFO to Impose and Use PFC Revenue at San Francisco... the application to impose and use PFC revenue at San Francisco International Airport (SFO), under the... FAA proposes to rule and invites public comment on the application to impose and use PFC revenue at...

Activation of the medial prefrontal cortex by escapable stress is necessary for protection against subsequent inescapable stress-induced potentiation of morphine conditioned place preference.

PubMed

Rozeske, Robert R; Der-Avakian, Andre; Watkins, Linda R; Maier, Steven F

2012-01-01

Stress can be a predisposing factor in the development of psychiatric disorders. However, not all individuals develop psychiatric disorders following a traumatic event. An attempt to understand these individual differences has led to a focus on factors that produce resistance. Interestingly, in rats, an experience with escapable tailshock (ES) before inescapable tailshock (IS) prevents the typical anxiety-like behavioral outcomes of IS. This type of resistance has been termed 'behavioral immunization', and it depends on activation of the medial prefrontal cortex (mPFC) during ES. However, one outcome of IS that is not anxiety-related is potentiation of morphine conditioned place preference (CPP). The present experiments investigated whether prior ES would block IS-induced potentiation of morphine CPP. Rats received either ES, IS or homecage control treatment on day 1 and then either IS or homecage control treatment on day 2. Twenty-four hours following day 2, rats underwent morphine conditioning, and CPP was subsequently assessed. In a second experiment, rats received ES 3, 14 or 56 days prior to IS to determine the duration of behavioral immunization. In a final experiment, rats were microinjected with the GABA(A) agonist muscimol (50 ng/0.5 μL) or saline in the mPFC before day 1 of stress. Prior ES blocked IS-induced potentiation of morphine CPP. This immunizing effect of ES lasted for at least 56 days. Additionally, intra-mPFC muscimol during ES prevented behavioral immunization. These results suggest that prior experience with ES activates the mPFC and produces long-lasting neural alterations that block subsequent IS-induced potentiation of morphine CPP. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Biological and cognitive underpinnings of religious fundamentalism.

PubMed

Zhong, Wanting; Cristofori, Irene; Bulbulia, Joseph; Krueger, Frank; Grafman, Jordan

2017-06-01

Beliefs profoundly affect people's lives, but their cognitive and neural pathways are poorly understood. Although previous research has identified the ventromedial prefrontal cortex (vmPFC) as critical to representing religious beliefs, the means by which vmPFC enables religious belief is uncertain. We hypothesized that the vmPFC represents diverse religious beliefs and that a vmPFC lesion would be associated with religious fundamentalism, or the narrowing of religious beliefs. To test this prediction, we assessed religious adherence with a widely-used religious fundamentalism scale in a large sample of 119 patients with penetrating traumatic brain injury (pTBI). If the vmPFC is crucial to modulating diverse personal religious beliefs, we predicted that pTBI patients with lesions to the vmPFC would exhibit greater fundamentalism, and that this would be modulated by cognitive flexibility and trait openness. Instead, we found that participants with dorsolateral prefrontal cortex (dlPFC) lesions have fundamentalist beliefs similar to patients with vmPFC lesions and that the effect of a dlPFC lesion on fundamentalism was significantly mediated by decreased cognitive flexibility and openness. These findings indicate that cognitive flexibility and openness are necessary for flexible and adaptive religious commitment, and that such diversity of religious thought is dependent on dlPFC functionality. Copyright © 2017 Elsevier Ltd. All rights reserved.

Early-Course Unmedicated Schizophrenia Patients Exhibit Elevated Prefrontal Connectivity Associated with Longitudinal Change

PubMed Central

Anticevic, Alan; Hu, Xinyu; Xiao, Yuan; Hu, Junmei; Li, Fei; Bi, Feng; Cole, Michael W.; Savic, Aleksandar; Yang, Genevieve J.; Repovs, Grega; Murray, John D.; Wang, Xiao-Jing; Huang, Xiaoqi; Lui, Su; Krystal, John H.

2015-01-01

Strong evidence implicates prefrontal cortex (PFC) as a major source of functional impairment in severe mental illness such as schizophrenia. Numerous schizophrenia studies report deficits in PFC structure, activation, and functional connectivity in patients with chronic illness, suggesting that deficient PFC functional connectivity occurs in this disorder. However, the PFC functional connectivity patterns during illness onset and its longitudinal progression remain uncharacterized. Emerging evidence suggests that early-course schizophrenia involves increased PFC glutamate, which might elevate PFC functional connectivity. To test this hypothesis, we examined 129 non-medicated, human subjects diagnosed with early-course schizophrenia and 106 matched healthy human subjects using both whole-brain data-driven and hypothesis-driven PFC analyses of resting-state fMRI. We identified increased PFC connectivity in early-course patients, predictive of symptoms and diagnostic classification, but less evidence for “hypoconnectivity.” At the whole-brain level, we observed “hyperconnectivity” around areas centered on the default system, with modest overlap with PFC-specific effects. The PFC hyperconnectivity normalized for a subset of the sample followed longitudinally (n = 25), which also predicted immediate symptom improvement. Biologically informed computational modeling implicates altered overall connection strength in schizophrenia. The initial hyperconnectivity, which may decrease longitudinally, could have prognostic and therapeutic implications. PMID:25568120

Theta synchronizes the activity of medial prefrontal neurons during learning

PubMed Central

Paz, Rony; Bauer, Elizabeth P.; Paré, Denis

2008-01-01

Memory consolidation is thought to involve the gradual transfer of transient hippocampal-dependent traces to distributed neocortical sites via the rhinal cortices. Recently, medial prefrontal (mPFC) neurons were shown to facilitate this process when their activity becomes synchronized. However, the mechanisms underlying this enhanced synchrony remain unclear. Because the hippocampus projects to the mPFC, we tested whether theta oscillations contribute to synchronize mPFC neurons during learning. Thus, we obtained field (LFP) and unit recordings from multiple mPFC sites during the acquisition of a trace-conditioning task, where a visual conditioned stimulus (CS) predicted reward delivery. In quiet waking, the activity of mPFC neurons was modulated by theta oscillations. During conditioning, CS presentation caused an increase in mPFC theta power that augmented as the CS gained predictive value for reward delivery. This increased theta power coincided with a transient theta phase locking at distributed mPFC sites, an effect that was also manifest in the timing of mPFC unit activity. Overall, these results show that theta oscillations contribute to synchronize neuronal activity at distributed mPFC sites, suggesting that the hippocampus, by generating a stronger theta source during learning, can synchronize mPFC activity, in turn facilitating rhinal transfer of its activity to the neocortex. PMID:18612069

Early-course unmedicated schizophrenia patients exhibit elevated prefrontal connectivity associated with longitudinal change.

PubMed

Anticevic, Alan; Hu, Xinyu; Xiao, Yuan; Hu, Junmei; Li, Fei; Bi, Feng; Cole, Michael W; Savic, Aleksandar; Yang, Genevieve J; Repovs, Grega; Murray, John D; Wang, Xiao-Jing; Huang, Xiaoqi; Lui, Su; Krystal, John H; Gong, Qiyong

2015-01-07

Strong evidence implicates prefrontal cortex (PFC) as a major source of functional impairment in severe mental illness such as schizophrenia. Numerous schizophrenia studies report deficits in PFC structure, activation, and functional connectivity in patients with chronic illness, suggesting that deficient PFC functional connectivity occurs in this disorder. However, the PFC functional connectivity patterns during illness onset and its longitudinal progression remain uncharacterized. Emerging evidence suggests that early-course schizophrenia involves increased PFC glutamate, which might elevate PFC functional connectivity. To test this hypothesis, we examined 129 non-medicated, human subjects diagnosed with early-course schizophrenia and 106 matched healthy human subjects using both whole-brain data-driven and hypothesis-driven PFC analyses of resting-state fMRI. We identified increased PFC connectivity in early-course patients, predictive of symptoms and diagnostic classification, but less evidence for "hypoconnectivity." At the whole-brain level, we observed "hyperconnectivity" around areas centered on the default system, with modest overlap with PFC-specific effects. The PFC hyperconnectivity normalized for a subset of the sample followed longitudinally (n = 25), which also predicted immediate symptom improvement. Biologically informed computational modeling implicates altered overall connection strength in schizophrenia. The initial hyperconnectivity, which may decrease longitudinally, could have prognostic and therapeutic implications. Copyright © 2015 the authors 0270-6474/15/350267-20$15.00/0.

Biological and cognitive underpinnings of religious fundamentalism

PubMed Central

Zhong, Wanting; Cristofori, Irene; Bulbulia, Joseph; Krueger, Frank; Grafman, Jordan

2017-01-01

Beliefs profoundly affect people's lives, but their cognitive and neural pathways are poorly understood. Although previous research has identified the ventromedial prefrontal cortex (vmPFC) as critical to representing religious beliefs, the means by which vmPFC enables religious belief is uncertain. We hypothesized that the vmPFC represents diverse religious beliefs and that a vmPFC lesion would be associated with religious fundamentalism, or the narrowing ofreligious beliefs. To test this prediction, we assessed religious adherence with a widely-used religious fundamentalism scale in a large sample of 119 patients with penetrating traumatic brain injury (pTBI). If the vmPFC is crucial to modulating diverse personal religious beliefs, we predicted that pTBI patients with lesions to the vmPFC would exhibit greater fundamentalism, and that this would be modulated by cognitive flexibility and trait openness. Instead, we found that participants with dorsolateral prefrontal cortex (dlPFC) lesions have fundamentalist beliefs similar to patients with vmPFC lesions and that the effect of a dlPFC lesion on fundamentalism was significantly mediated by decreased cognitive flexibility and openness. These findings indicate that cognitive flexibility and openness are necessary for flexible and adaptive religious commitment, and that such diversity of religious thought is dependent on dlPFC functionality. PMID:28392301

Endobronchial perfluorocarbon reduces inflammatory activity before and after lung transplantation in an animal experimental model.

PubMed

Forgiarini Junior, Luiz Alberto; Holand, Arthur Rodrigo Ronconi; Forgiarini, Luiz Felipe; da Rosa, Darlan Pase; Marroni, Norma Anair Possa; Cardoso, Paulo Francisco Guerreiro; Andrade, Cristiano Feijó

2013-01-01

The aim of this study was to evaluate the use of liquid perfluorocarbon (PFC) as an adjuvant substance for lung preservation and assess its role in pulmonary protection after transplantation. Seventy-two rat lungs were flushed with low-potassium dextran (LPD) solution and randomized into three main groups: control with LPD alone and experimental with 3 (PFC3) and 7 mL/kg (PFC7) of endobronchial PFC instilled just after harvest. Each group was divided into four subgroups according to preservation time (3, 6, 12, and 24 hours). Afterwards, we performed lung transplantation using rat lungs preserved for 12 hours with LPD alone or with 7 mL/kg of endobronchial PFC. There was a significant increase in oxidative stress in the control group at 6 h of cold ischemic time compared with the PFC3 and PFC7 groups. The apoptotic activity and NF-κB expression were significantly higher in the control group compared with the PFC groups at 3, 12, and 24 h of cold preservation. After transplantation, the NF-κB, iNOS, and nitrotyrosine expression as well as caspase 3 activity were significantly lower in the PFC groups. The use of endobronchial PFC as an adjuvant to the current preservation strategy improved graft viability.

Power Controller

NASA Technical Reports Server (NTRS)

1982-01-01

The device called the Power Factor Controller (PFC) offers exceptional energy conservation potential by virtue of its ability to sense shifts in the relationship between voltage and current flow, and to match them with the motor's need. Originating from the solar heating/cooling program, the PFC senses a light load, it cuts the voltage level to the minimum needed which in turn reduces current flow and heat loss. Laboratory tests showed that the PFC could reduce power used by six to eight percent under normal motor loads, and as much as 65 percent when the motor was idling. Over 150 companies have been granted NASA licenses for commercial use of this technology. One system that utilizes this technology is the Vectrol Energy System, (VES) produced by Vectrol, Inc. a subsidiary of Westinghouse. The VES is being used at Woodward & Lothrop, on their escalators. Energy use is regulated according to how many people are on the escalator at any time. It is estimated that the energy savings are between 30 to 40 percent.

Dopamine and serotonin interactions in the prefrontal cortex: insights on antipsychotic drugs and their mechanism of action.

PubMed

Di Pietro, N C; Seamans, J K

2007-12-01

Diminished activity within the prefrontal cortex (PFC) has been associated with many of the cognitive deficits that are observed in schizophrenia. It has been hypothesized that antipsychotic drugs (APDs) used to treat schizophrenia restore normal activity by antagonizing the dopamine (DA) D2 receptor, which is also known to modulate key ionic currents in the PFC. However, the hypothesis that an under-active cortical DA system is responsible for schizophrenic symptoms has been challenged by evidence that newer atypical APDs are weak antagonists at the D2 receptor but potent antagonists at the serotonin (5-HT) 2A receptor . This review examines how DA and 5-HT modulate cortical activity and how they may interact in ways that are relevant to schizophrenia. It is concluded that although D2 receptor antagonism remains a critical factor in restoring impaired cortical activity, effects on 5-HT receptors may act in a synergistic manner on NMDA and GABA currents to potentiate antipsychotic actions in the PFC.

Converging models of schizophrenia - Network alterations of prefrontal cortex underlying cognitive impairments

PubMed Central

Sakurai, Takeshi; Gamo, Nao J; Hikida, Takatoshi; Kim, Sun-Hong; Murai, Toshiya; Tomoda, Toshifumi; Sawa, Akira

2015-01-01

The prefrontal cortex (PFC) and its connections with other brain areas are crucial for cognitive function. Cognitive impairments are one of the core symptoms associated with schizophrenia, and manifest even before the onset of the disorder. Altered neural networks involving PFC contribute to cognitive impairments in schizophrenia. Both genetic and environmental risk factors affect the development of the local circuitry within PFC as well as development of broader brain networks, and make the system vulnerable to further insults during adolescence, leading to the onset of the disorder in young adulthood. Since spared cognitive functions correlate with functional outcome and prognosis, a better understanding of the mechanisms underlying cognitive impairments will have important implications for novel therapeutics for schizophrenia focusing on cognitive functions. Multidisciplinary approaches, from basic neuroscience to clinical studies, are required to link molecules, circuitry, networks, and behavioral phenotypes. Close interactions among such fields by sharing a common language on connectomes, behavioral readouts, and other concepts are crucial for this goal. PMID:26408506

Reduced intrasubject variability with reinforcement in boys, but not girls, with ADHD: Associations with prefrontal anatomy

PubMed Central

Rosch, Keri S.; Dirlikov, Benjamin; Mostofsky, Stewart H.

2015-01-01

This study examined the impact of motivational contingencies (reinforcement and punishment) on Go/No-Go (GNG) task performance in girls and boys with ADHD relative to typically developing (TD) children and associations with prefrontal anatomy. Children ages 8–12 with ADHD (n=107, 36 girls) and TD controls (n=95, 34 girls) completed a standard and a motivational GNG task and associations with prefrontal cortex (PFC) surface area were examined. Intrasubject variability (ISV) was lower during the motivational compared to the standard GNG among TD girls and boys, and boys with ADHD, but not among girls with ADHD. A greater reduction in ISV was associated with greater PFC surface area among children with ADHD. This novel demonstration of improvement in ISV with motivational contingencies for boys, but not girls, with ADHD and associations with PFC anatomy informs our understanding of sex differences and motivational factors contributing to ISV in children with ADHD. PMID:26141238

HEMORHEOLOGICAL IMPLICATIONS OF PERFLUOROCARBON BASED OXYGEN CARRIER INTERACTION WITH COLLOID PLASMA EXPANDERS AND BLOOD

PubMed Central

Vásquez, Diana M.; Ortiz, Daniel; Alvarez, Oscar A.; Briceño, Juan C.; Cabrales, Pedro

2013-01-01

Perfluorocarbon (PFC) emulsion based oxygen carriers lack colloid osmotic pressure (COP) and must be administered with colloid-based plasma expanders (PEs). Although PFC emulsions have been widely studied, there is limited information about PFC emulsion interaction with PEs and blood. Their interaction forms aggregates due to electrostatic and rheological phenomena, and change blood rheology and blood flow. This study analyzes the effects of the interaction between PFC emulsions with blood in the presence of clinically-used PEs. The rheological behavior of the mixtures was analyzed in parallel with in vivo analysis of blood flow in microvessels using intravital microscopy when administered in a clinically relevant scenario. The interaction between the PFC emulsion and PE with blood produced PFC droplets and red blood cell (RBCs) aggregation, and increased blood viscosity. The PFC droplets formed aggregates when mixed with PEs containing electrolytes, and the aggregation increased with the electrolyte concentration. Mixtures of PFC with PEs that produced PFC aggregates also induced RCBs aggregation when mixed with blood, increasing blood viscosity at low shear rates. The more viscous suspension at low shear rates produced a blunted blood flow velocity profile in vivo relative to non-aggregating mixtures of PFC and PEs. For the PEs evaluated, albumin produced minimal to undetectable aggregation. PFC and PEs interaction with blood can affect sections of the microcirculation with low shear rate (e.g. arterioles, venules, and pulmonary circulation) because aggregates could cause capillary occlusion, decrease perfusion, pulmonary emboli, or focal ischemia. PMID:23606592

Activation of beta- and alpha-2-adrenoceptors in the basolateral amygdala has opposing effects on hippocampal-prefrontal long-term potentiation.

PubMed

Lim, Ee Peng; Dawe, Gavin S; Jay, Thérèse M

2017-01-01

Noradrenaline (NA), released by the locus coeruleus (LC), plays a key role in mediating the effects of stress on memory functions. The LC provides diffuse projections to many forebrain nuclei including the hippocampus, the prefrontal cortex (PFC), and the basolateral amygdala (BLA). These three structures are intricately interlinked. The hippocampal-prefrontal (H-PFC) pathway is involved in various cognitive functions. The first aim of this study was to examine the role of BLA in H-PFC plasticity by infusion of drugs to activate and inactivate the BLA and studying the effects on H-PFC long-term potentiation (LTP) in the rat in vivo. Activation of the BLA with glutamate impaired, while inactivation with muscimol augmented, H-PFC LTP. This study also aimed to demonstrate how directly applying noradrenaline and other noradrenergic agents in the BLA can affect H-PFC LTP. Noradrenaline at 1μg/0.2μl enhanced H-PFC LTP. Stimulating alpha-2-adrenoceptors in the BLA with clonidine enhanced LTP while blocking alpha-2 adrenoceptors with idazoxan impaired it. Propranolol, a non-selective beta antagonist, enhanced H-PFC LTP while isoprenaline, a non-selective beta agonist, decreased H-PFC LTP. These results suggest that the BLA regulates H-PFC plasticity negatively and also provide a mechanism by which noradrenaline in the BLA can affect H-PFC plasticity via alpha-2 and beta adrenoceptors. Copyright © 2016 Elsevier Inc. All rights reserved.

Late onset deficits in synaptic plasticity in the valproic acid rat model of autism.

PubMed

Martin, Henry G S; Manzoni, Olivier J

2014-01-01

Valproic acid (VPA) is a frequently used drug in the treatment of epilepsy, bipolar disorders and migraines; however it is also a potent teratogen. Prenatal exposure increases the risk of childhood malformations and can result in cognitive deficits. In rodents in utero exposure to VPA also causes neurodevelopmental abnormalities and is an important model of autism. In early postnatal life VPA exposed rat pups show changes in medial prefrontal cortex (mPFC) physiology and synaptic connectivity. Specifically, principal neurons show decreased excitability but increased local connectivity, coupled with an increase in long-term potentiation (LTP) due to an up-regulation of NMDA receptor (NMDAR) expression. However recent evidence suggests compensatory homeostatic mechanisms lead to normalization of synaptic NMDARs during later postnatal development. Here we have extended study of mPFC synaptic physiology into adulthood to better understand the longitudinal consequences of early developmental abnormalities in VPA exposed rats. Surprisingly in contrast to early postnatal life and adolescence, we find that adult VPA exposed rats show reduced synaptic function. Both NMDAR mediated currents and LTP are lower in adult VPA rats, although spontaneous activity and endocannabinoid dependent long-term depression are normal. We conclude that rather than correcting, synaptic abnormalities persist into adulthood in VPA exposed rats, although a quite different synaptic phenotype is present. This switch from hyper to hypo function in mPFC may be linked to some of the neurodevelopmental defects found in prenatal VPA exposure and autism spectrum disorders in general.

Neural activation to emotional faces in adolescents with autism spectrum disorders.

PubMed

Weng, Shih-Jen; Carrasco, Melisa; Swartz, Johnna R; Wiggins, Jillian Lee; Kurapati, Nikhil; Liberzon, Israel; Risi, Susan; Lord, Catherine; Monk, Christopher S

2011-03-01

Autism spectrum disorders (ASD) involve a core deficit in social functioning and impairments in the ability to recognize face emotions. In an emotional faces task designed to constrain group differences in attention, the present study used functional MRI to characterize activation in the amygdala, ventral prefrontal cortex (vPFC), and striatum, three structures involved in socio-emotional processing in adolescents with ASD. Twenty-two adolescents with ASD and 20 healthy adolescents viewed facial expressions (happy, fearful, sad and neutral) that were briefly presented (250 ms) during functional MRI acquisition. To monitor attention, subjects pressed a button to identify the gender of each face. The ASD group showed greater activation to the faces relative to the control group in the amygdala, vPFC and striatum. Follow-up analyses indicated that the ASD relative to control group showed greater activation in the amygdala, vPFC and striatum (p < .05 small volume corrected), particularly to sad faces. Moreover, in the ASD group, there was a negative correlation between developmental variables (age and pubertal status) and mean activation from the whole bilateral amygdala; younger adolescents showed greater activation than older adolescents. There were no group differences in accuracy or reaction time in the gender identification task. When group differences in attention to facial expressions were limited, adolescents with ASD showed greater activation in structures involved in socio-emotional processing. © 2010 The Authors. Journal of Child Psychology and Psychiatry © 2010 Association for Child and Adolescent Mental Health.

Cannabinoid modulation of prefrontal-limbic activation during fear extinction learning and recall in humans

PubMed Central

Rabinak, Christine A.; Angstadt, Mike; Lyons, Maryssa; Mori, Shoko; Milad, Mohammed R.; Liberzon, Israel; Phan, K. Luan

2013-01-01

Pre-extinction administration of ∆9-tetrahydrocannibinol (THC) facilitates recall of extinction in healthy humans, and evidence from animal studies suggest that this likely involves via enhancement of the cannabinoid system within the ventromedial prefrontal cortex (vmPFC) and hippocampus (HIPP), brain structures critical to fear extinction. However, the effect of cannabinoids on the underlying neural circuitry of extinction memory recall in humans has not been demonstrated. We conducted a functional magnetic resonance imaging (fMRI) study using a randomized, double-blind, placebo-controlled, between-subjects design (N=14/group) coupled with a standard Pavlovian fear extinction paradigm and an acute pharmacological challenge with oral dronabinol (synthetic THC) in healthy adult volunteers. We examined the effects of THC on vmPFC and HIPP activation when tested for recall of extinction learning 24 hours after extinction learning. Compared to subjects who received placebo, participants who received THC showed increased vmPFC and HIPP activation to a previously extinguished conditioned stimulus (CS+E) during extinction memory recall. This study provides the first evidence that pre-extinction administration of THC modulates prefrontal-limbic circuits during fear extinction in humans and prompts future investigation to test if cannabinoid agonists can rescue or correct the impaired behavioral and neural function during extinction recall in patients with PTSD. Ultimately, the cannabinoid system may serve as a promising target for innovative intervention strategies (e.g. pharmacological enhancement of exposure-based therapy) in PTSD and other fear learning-related disorders. PMID:24055595

DISC1 gene and affective psychopathology: a combined structural and functional MRI study.

PubMed

Opmeer, Esther M; van Tol, Marie-José; Kortekaas, Rudie; van der Wee, Nic J A; Woudstra, Saskia; van Buchem, Mark A; Penninx, Brenda W; Veltman, Dick J; Aleman, André

2015-02-01

The gene Disrupted-In-Schizophrenia-1 (DISC1) has been indicated as a determinant of psychopathology, including affective disorders, and shown to influence prefrontal cortex (PFC) and hippocampus functioning, regions of major interest for affective disorders. We aimed to investigate whether DISC1 differentially modulates brain function during executive and memory processing, and morphology in regions relevant for depression and anxiety disorders (affective disorders). 128 participants, with (n = 103) and without (controls; n = 25) affective disorders underwent genotyping for Ser704Cys (with Cys-allele considered as risk-allele) and structural and functional (f) Magnetic Resonance Imaging (MRI) during visuospatial planning and emotional episodic memory tasks. For both voxel-based morphometry and fMRI analyses, we investigated the effect of genotype in controls and explored genotypeXdiagnosis interactions. Results are reported at p < 0.05 FWE small volume corrected. In controls, Cys-carriers showed smaller bilateral (para)hippocampal volumes compared with Ser-homozygotes, and lower activation in the anterior cingulate cortex (ACC) and dorsolateral PFC during visuospatial planning. In anxiety patients, Cys-carriers showed larger (para)hippocampal volumes and more ACC activation during visuospatial planning. In depressive patients, no effect of genotype was observed and overall, no effect of genotype on episodic memory processing was detected. We demonstrated that Ser704Cys-genotype influences (para)hippocampal structure and functioning the dorsal PFC during executive planning, most prominently in unaffected controls. Results suggest that presence of psychopathology moderates Ser704Cys effects. Copyright © 2014 Elsevier Ltd. All rights reserved.

Mechanisms of rule acquisition and rule following in inductive reasoning.

PubMed

Crescentini, Cristiano; Seyed-Allaei, Shima; De Pisapia, Nicola; Jovicich, Jorge; Amati, Daniele; Shallice, Tim

2011-05-25

Despite the recent interest in the neuroanatomy of inductive reasoning processes, the regional specificity within prefrontal cortex (PFC) for the different mechanisms involved in induction tasks remains to be determined. In this study, we used fMRI to investigate the contribution of PFC regions to rule acquisition (rule search and rule discovery) and rule following. Twenty-six healthy young adult participants were presented with a series of images of cards, each consisting of a set of circles numbered in sequence with one colored blue. Participants had to predict the position of the blue circle on the next card. The rules that had to be acquired pertained to the relationship among succeeding stimuli. Responses given by subjects were categorized in a series of phases either tapping rule acquisition (responses given up to and including rule discovery) or rule following (correct responses after rule acquisition). Mid-dorsolateral PFC (mid-DLPFC) was active during rule search and remained active until successful rule acquisition. By contrast, rule following was associated with activation in temporal, motor, and medial/anterior prefrontal cortex. Moreover, frontopolar cortex (FPC) was active throughout the rule acquisition and rule following phases before a rule became familiar. We attributed activation in mid-DLPFC to hypothesis generation and in FPC to integration of multiple separate inferences. The present study provides evidence that brain activation during inductive reasoning involves a complex network of frontal processes and that different subregions respond during rule acquisition and rule following phases.

40 CFR 98.306 - Data reporting requirements.

Code of Federal Regulations, 2013 CFR

2013-07-01

...) Pounds of SF6 and PFC returned to facility after off-site recycling. (i) Pounds of SF6 and PFC in bulk...) Pounds of SF6 and PFC sent off-site for recycling. (l) Pounds of SF6 and PFC sent off-site for...

40 CFR 98.306 - Data reporting requirements.

Code of Federal Regulations, 2014 CFR

2014-07-01

...) Pounds of SF6 and PFC returned to facility after off-site recycling. (i) Pounds of SF6 and PFC in bulk...) Pounds of SF6 and PFC sent off-site for recycling. (l) Pounds of SF6 and PFC sent off-site for...

40 CFR 98.306 - Data reporting requirements.

Code of Federal Regulations, 2012 CFR

2012-07-01

...) Pounds of SF6 and PFC returned to facility after off-site recycling. (i) Pounds of SF6 and PFC in bulk...) Pounds of SF6 and PFC sent off-site for recycling. (l) Pounds of SF6 and PFC sent off-site for...

40 CFR 98.306 - Data reporting requirements.

Code of Federal Regulations, 2011 CFR

2011-07-01

...) Pounds of SF6 and PFC returned to facility after off-site recycling. (i) Pounds of SF6 and PFC in bulk...) Pounds of SF6 and PFC sent off-site for recycling. (l) Pounds of SF6 and PFC sent off-site for...

Lesion of medial prefrontal dopamine terminals abolishes habituation of accumbens shell dopamine responsiveness to taste stimuli.

PubMed

Bimpisidis, Zisis; De Luca, Maria Antonietta; Pisanu, Augusta; Di Chiara, Gaetano

2013-02-01

Taste stimuli increase extracellular dopamine (DA) in the nucleus accumbens (NAc) and in the medial prefrontal cortex (mPFC). This effect shows single-trial habituation in NAc shell but not in core or in mPFC. Morphine sensitization abolishes habituation of DA responsiveness in NAc shell but induces it in mPFC. These observations support the hypothesis of an inhibitory influence of mPFC DA on NAc DA. To test this hypothesis, we used in vivo microdialysis to investigate the effect of mPFC 6-hydroxy-dopamine (6-OHDA) lesions on the NAc DA responsiveness to taste stimuli. 6-OHDA was infused bilaterally in the mPFC of rats implanted with guide cannulae. After 1 week, rats were implanted with an intraoral catheter, microdialysis probes were inserted into the guide cannulae, and dialysate DA was monitored in NAc shell/core after intraoral chocolate. 6-OHDA infusion reduced tissue DA in the mPFC by 75%. Tyrosine hydroxylase immunohistochemistry showed that lesions were confined to the mPFC. mPFC 6-OHDA lesion did not affect the NAc shell DA responsiveness to chocolate in naive rats but abolished habituation in rats pre-exposed to the taste. In the NAc core, mPFC lesion potentiated, delayed and prolonged the stimulatory DA response to taste but failed to affect DA in pre-exposed rats. Behavioural taste reactions and motor activity were not affected. The results indicate a top-down control of NAc DA by mPFC and a reciprocal relationship between DA transmission in these two areas. Moreover, habituation of DA responsiveness in the NAc shell is dependent upon an intact DA input to the mPFC. © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

The effect of the perfluorocarbon emulsion Oxycyte on platelet count and function in the treatment of decompression sickness in a swine model.

PubMed

Cronin, William A; Senese, Angela L; Arnaud, Francoise G; Regis, David P; Auker, Charles R; Mahon, Richard T

2016-09-01

Decompression from elevated ambient pressure is associated with platelet activation and decreased platelet counts. Standard treatment for decompression sickness (DCS) is hyperbaric oxygen therapy. Intravenous perfluorocarbon (PFC) emulsion is a nonrecompressive therapy being examined that improves mortality in animal models of DCS. However, PFC emulsions are associated with a decreased platelet count. We used a swine model of DCS to study the effect of PFC therapy on platelet count, function, and hemostasis. Castrated male swine (n = 50) were fitted with a vascular port, recovered, randomized, and compressed to 180 feet of sea water (fsw) for 31 min followed by decompression at 30 fsw/min. Animals were observed for DCS, administered 100% oxygen, and treated with either emulsified PFC Oxycyte (DCS-PFC) or isotonic saline (DCS-NS). Controls underwent the same procedures, but were not compressed (Sham-PFC and Sham-NS). Measurements of platelet count, thromboelastometry, and coagulation were obtained 1 h before compression and 1, 24, 48, 96, 168 and 192 h after treatment. No significant changes in normalized platelet counts were observed. Prothrombin time was elevated in DCS-PFC from 48 to 192 h compared with DCS-NS, and from 96 to 192 h compared with Sham-PFC. Normalized activated partial thromboplastin time was also elevated in DCS-PFC from 168 to 192 h compared with Sham-PFC. No bleeding events were noted. DCS treated with PFC (Oxycyte) does not impact platelet numbers, whole blood clotting by thromboelastometry, or clinical bleeding. Late changes in prothrombin time and activated partial thromboplastin time associated with PFC use in both DCS therapy and controls warrant further investigation.

Neural Correlates of Hostile Jokes: Cognitive and Motivational Processes in Humor Appreciation.

PubMed

Chan, Yu-Chen; Liao, Yi-Jun; Tu, Cheng-Hao; Chen, Hsueh-Chih

2016-01-01

Hostile jokes (HJs) provide aggressive catharsis and a feeling of superiority. Behavioral research has found that HJs are perceived as funnier than non-hostile jokes (NJs). The purpose of the present study was to identify the neural correlates of the interaction between type and humor by comparing HJs, NJs, and their corresponding hostile sentences (HSs) and non-hostile sentences (NSs). HJs primarily showed activation in the dorsomedial prefrontal cortex (dmPFC) and midbrain compared with the corresponding hostile baseline. Conversely, NJs primarily revealed activation in the ventromedial PFC (vmPFC), amygdala, midbrain, ventral anterior cingulate cortex, and nucleus accumbens (NAcc) compared with the corresponding non-hostile baseline. These results support the critical role of the medial PFC (mPFC) for the neural correlates of social cognition and socio-emotional processing in response to different types of jokes. Moreover, the processing of HJs showed increased activation in the dmPFC, which suggested cognitive operations of social motivation, whereas the processing of NJs displayed increased activation in the vmPFC, which suggested social-affective engagement. HJs versus NJs primarily showed increased activation in the dmPFC and midbrain, whereas NJs versus HJs primarily displayed greater activation in the amygdala and midbrain. The psychophysiological interaction (PPI) analysis demonstrated functional coupling of the dmPFC-dlPFC and midbrain-dmPFC for HJs and functional coupling of the vmPFC-midbrain and amygdala-midbrain-NAcc for NJs. Surprisingly, HJs were not perceived as funnier than NJs. Future studies could further investigate the neural correlates of potentially important traits of high-hostility tendencies in humor appreciation based on the psychoanalytic and superiority theories of humor.

Essential role of GluD1 in dendritic spine development and GluN2B to GluN2A NMDAR subunit switch in the cortex and hippocampus reveals ability of GluN2B inhibition in correcting hyperconnectivity.

PubMed

Gupta, Subhash C; Yadav, Roopali; Pavuluri, Ratnamala; Morley, Barbara J; Stairs, Dustin J; Dravid, Shashank M

2015-06-01

The glutamate delta-1 (GluD1) receptor is highly expressed in the forebrain. We have previously shown that loss of GluD1 leads to social and cognitive deficits in mice, however, its role in synaptic development and neurotransmission remains poorly understood. Here we report that GluD1 is enriched in the medial prefrontal cortex (mPFC) and GluD1 knockout mice exhibit a higher dendritic spine number, greater excitatory neurotransmission as well as higher number of synapses in mPFC. In addition abnormalities in the LIMK1-cofilin signaling, which regulates spine dynamics, and a lower ratio of GluN2A/GluN2B expression was observed in the mPFC in GluD1 knockout mice. Analysis of the GluD1 knockout CA1 hippocampus similarly indicated the presence of higher spine number and synapses and altered LIMK1-cofilin signaling. We found that systemic administration of an N-methyl-d-aspartate (NMDA) receptor partial agonist d-cycloserine (DCS) at a high-dose, but not at a low-dose, and a GluN2B-selective inhibitor Ro-25-6981 partially normalized the abnormalities in LIMK1-cofilin signaling and reduced excess spine number in mPFC and hippocampus. The molecular effects of high-dose DCS and GluN2B inhibitor correlated with their ability to reduce the higher stereotyped behavior and depression-like behavior in GluD1 knockout mice. Together these findings demonstrate a critical requirement for GluD1 in normal spine development in the cortex and hippocampus. Moreover, these results identify inhibition of GluN2B-containing receptors as a mechanism for reducing excess dendritic spines and stereotyped behavior which may have therapeutic value in certain neurodevelopmental disorders such as autism. Copyright © 2015 Elsevier Ltd. All rights reserved.

14 CFR 158.53 - Collection compensation.

Code of Federal Regulations, 2014 CFR

2014-01-01

...) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Collection, Handling, and Remittance of PFC's § 158.53 Collection compensation. (a) As compensation for collecting, handling, and remitting the PFC revenue, the collecting air carrier is entitled to: (1) $0.11 of each PFC collected. (2) Any interest or other investment...

14 CFR 158.53 - Collection compensation.

Code of Federal Regulations, 2013 CFR

2013-01-01

...) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Collection, Handling, and Remittance of PFC's § 158.53 Collection compensation. (a) As compensation for collecting, handling, and remitting the PFC revenue, the collecting air carrier is entitled to: (1) $0.11 of each PFC collected. (2) Any interest or other investment...

14 CFR 158.53 - Collection compensation.

Code of Federal Regulations, 2011 CFR

2011-01-01

...) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Collection, Handling, and Remittance of PFC's § 158.53 Collection compensation. (a) As compensation for collecting, handling, and remitting the PFC revenue, the collecting air carrier is entitled to: (1) $0.11 of each PFC collected. (2) Any interest or other investment...

14 CFR 158.53 - Collection compensation.

Code of Federal Regulations, 2012 CFR

2012-01-01

...) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Collection, Handling, and Remittance of PFC's § 158.53 Collection compensation. (a) As compensation for collecting, handling, and remitting the PFC revenue, the collecting air carrier is entitled to: (1) $0.11 of each PFC collected. (2) Any interest or other investment...

The neural bases for devaluing radical political statements revealed by penetrating traumatic brain injury

PubMed Central

Cristofori, Irene; Viola, Vanda; Chau, Aileen; Zhong, Wanting; Krueger, Frank; Zamboni, Giovanna; Grafman, Jordan

2015-01-01

Given the determinant role of ventromedial prefrontal cortex (vmPFC) in valuation, we examined whether vmPFC lesions also modulate how people scale political beliefs. Patients with penetrating traumatic brain injury (pTBI; N = 102) and healthy controls (HCs; N = 31) were tested on the political belief task, where they rated 75 statements expressing political opinions concerned with welfare, economy, political involvement, civil rights, war and security. Each statement was rated for level of agreement and scaled along three dimensions: radicalism, individualism and conservatism. Voxel-based lesion-symptom mapping (VLSM) analysis showed that diminished scores for the radicalism dimension (i.e. statements were rated as less radical than the norms) were associated with lesions in bilateral vmPFC. After dividing the pTBI patients into three groups, according to lesion location (i.e. vmPFC, dorsolateral prefrontal cortex [dlPFC] and parietal cortex), we found that the vmPFC, but not the dlPFC, group had reduced radicalism scores compared with parietal and HC groups. These findings highlight the crucial role of the vmPFC in appropriately valuing political behaviors and may explain certain inappropriate social judgments observed in patients with vmPFC lesions. PMID:25656509

Role of medial prefrontal cortex serotonin 2A receptors in the control of retrieval of recognition memory in rats.

PubMed

Bekinschtein, Pedro; Renner, Maria Constanza; Gonzalez, Maria Carolina; Weisstaub, Noelia

2013-10-02

Often, retrieval cues are not uniquely related to one specific memory, which could lead to memory interference. Controlling interference is particularly important during episodic memory retrieval or when remembering specific events in a spatiotemporal context. Despite a clear involvement of prefrontal cortex (PFC) in episodic memory in human studies, information regarding the mechanisms and neurotransmitter systems in PFC involved in memory is scarce. Although the serotoninergic system has been linked to PFC functionality and modulation, its role in memory processing is poorly understood. We hypothesized that the serotoninergic system in PFC, in particular the 5-HT2A receptor (5-HT2AR) could have a role in the control of memory retrieval. In this work we used different versions of the object recognition task in rats to study the role of the serotoninergic modulation in the medial PFC (mPFC) in memory retrieval. We found that blockade of 5-HT2AR in mPFC affects retrieval of an object in context memory in a spontaneous novelty preference task, while sparing single-item recognition memory. We also determined that 5-HT2ARs in mPFC are required for hippocampal-mPFC interaction during retrieval of this type of memory, suggesting that the mPFC controls the expression of memory traces stored in the hippocampus biasing retrieval to the most relevant one.

Functional and neurochemical interactions within the amygdala-medial prefrontal cortex circuit and their relevance to emotional processing

PubMed Central

Pizzi, Stefano Delli; Chiacchiaretta, Piero; Mantini, Dante; Bubbico, Giovanna; Ferretti, Antonio; Edden, Richard A.; Di Giulio, Camillo; Onofrj, Marco

2017-01-01

The amygdala–medial prefrontal cortex (mPFC) circuit plays a key role in emotional processing. GABA-ergic inhibition within the mPFC has been suggested to play a role in the shaping of amygdala activity. However, the functional and neurochemical interactions within the amygdala–mPFC circuits and their relevance to emotional processing remain unclear. To investigate this circuit, we obtained resting-state functional magnetic resonance imaging (rs-fMRI) and proton MR spectroscopy in 21 healthy subjects to assess the potential relationship between GABA levels within mPFC and the amygdala–mPFC functional connectivity. Trait anxiety was assessed using the State-Trait Anxiety Inventory (STAI-Y2). Partial correlations were used to measure the relationships among the functional connectivity outcomes, mPFC GABA levels and STAI-Y2 scores. Age, educational level and amount of the gray and white matters within 1H-MRS volume of interest were included as nuisance variables. The rs-fMRI signals of the amygdala and the vmPFC were significantly anti-correlated. This negative functional coupling between the two regions was inversely correlated with the GABA+/tCr level within the mPFC and the STAI-Y2 scores. We suggest a close relationship between mPFC GABA levels and functional interactions within the amygdala-vmPFC circuit, providing new insights in the physiology of emotion. PMID:27566606

Functional and neurochemical interactions within the amygdala-medial prefrontal cortex circuit and their relevance to emotional processing.

PubMed

Delli Pizzi, Stefano; Chiacchiaretta, Piero; Mantini, Dante; Bubbico, Giovanna; Ferretti, Antonio; Edden, Richard A; Di Giulio, Camillo; Onofrj, Marco; Bonanni, Laura

2017-04-01

The amygdala-medial prefrontal cortex (mPFC) circuit plays a key role in emotional processing. GABA-ergic inhibition within the mPFC has been suggested to play a role in the shaping of amygdala activity. However, the functional and neurochemical interactions within the amygdala-mPFC circuits and their relevance to emotional processing remain unclear. To investigate this circuit, we obtained resting-state functional magnetic resonance imaging (rs-fMRI) and proton MR spectroscopy in 21 healthy subjects to assess the potential relationship between GABA levels within mPFC and the amygdala-mPFC functional connectivity. Trait anxiety was assessed using the State-Trait Anxiety Inventory (STAI-Y2). Partial correlations were used to measure the relationships among the functional connectivity outcomes, mPFC GABA levels and STAI-Y2 scores. Age, educational level and amount of the gray and white matters within 1 H-MRS volume of interest were included as nuisance variables. The rs-fMRI signals of the amygdala and the vmPFC were significantly anti-correlated. This negative functional coupling between the two regions was inversely correlated with the GABA+/tCr level within the mPFC and the STAI-Y2 scores. We suggest a close relationship between mPFC GABA levels and functional interactions within the amygdala-vmPFC circuit, providing new insights in the physiology of emotion.

Relationship between the prefrontal function and the severity of the emotional symptoms during a verbal fluency task in patients with major depressive disorder: a multi-channel NIRS study.

PubMed

Liu, Xiaomin; Sun, Gaoxiang; Zhang, Xiaoqian; Xu, Bo; Shen, Chenyu; Shi, Lujie; Ma, Xiangyun; Ren, Xiajin; Feng, Kun; Liu, Pozi

2014-10-03

Multi-channel near-infrared spectroscopy (NIRS) is a noninvasive and low-cost functional neuroimaging technique in psychiatric research, and it has been wildly used for detecting the spatiotemporal characteristics of brain activity. In order to evaluate the clinical value of NIRS data in the assistant diagnosis of major depressive disorder (MDD), prefrontal cortex (PFC) hemoglobin concentration exchange of 30 MDD patients combined with anxious and obsessive-compulsive symptom was detected by NIRS under voice fluency task (VFT), then the relationship between the severity of depressive, anxious and obsessive-compulsive symptom assessed by Hamilton Rating Scale for Depression (HAMD), Hamilton Anxiety Rating Scale (HAMA) and Yale-Brown Obsessive Compulsive Scale (Y-BOCS) with NIRS data in PFC was analyzed. Hypoactivation in lateral and lower PFC of MDD patients was confirmed in this study. Furthermore, Spearman correlation found that oxy-hemoglobin concentration ([oxy-Hb]) exchange in right-lateral PFC was associated with the severity of anxiety, while bilateral PFC and antero-medial PFC were associated with severity of depression. Meanwhile, no statistical correlation was observed on the severity of obsessive-compulsive symptom. The results prompted that MDD patients with anxiety and obsession-compulsion symptom showed a PFC hypoactivation state in NIRS. Furthermore, the function of right-lateral PFC was associated with anxiety symptom, while bilateral PFC and antero-medial PFC were associated with depression symptom. Different from depression and anxiety, obsession-compulsion may have a different biological character in PFC function. Copyright © 2014 Elsevier Inc. All rights reserved.

A fully Bayesian before-after analysis of permeable friction course (PFC) pavement wet weather safety.

PubMed

Buddhavarapu, Prasad; Smit, Andre F; Prozzi, Jorge A

2015-07-01

Permeable friction course (PFC), a porous hot-mix asphalt, is typically applied to improve wet weather safety on high-speed roadways in Texas. In order to warrant expensive PFC construction, a statistical evaluation of its safety benefits is essential. Generally, the literature on the effectiveness of porous mixes in reducing wet-weather crashes is limited and often inconclusive. In this study, the safety effectiveness of PFC was evaluated using a fully Bayesian before-after safety analysis. First, two groups of road segments overlaid with PFC and non-PFC material were identified across Texas; the non-PFC or reference road segments selected were similar to their PFC counterparts in terms of site specific features. Second, a negative binomial data generating process was assumed to model the underlying distribution of crash counts of PFC and reference road segments to perform Bayesian inference on the safety effectiveness. A data-augmentation based computationally efficient algorithm was employed for a fully Bayesian estimation. The statistical analysis shows that PFC is not effective in reducing wet weather crashes. It should be noted that the findings of this study are in agreement with the existing literature, although these studies were not based on a fully Bayesian statistical analysis. Our study suggests that the safety effectiveness of PFC road surfaces, or any other safety infrastructure, largely relies on its interrelationship with the road user. The results suggest that the safety infrastructure must be properly used to reap the benefits of the substantial investments. Copyright © 2015 Elsevier Ltd. All rights reserved.

A perfluorochemical loss/restoration (L/R) system for tidal liquid ventilation.

PubMed

Libros, R; Philips, C M; Wolfson, M R; Shaffer, T H

2000-01-01

Tidal liquid ventilation is the transport of dissolved respiratory gases via volume exchange of perfluorochemical (PFC) liquid to and from the PFC-filled lung. All gas-liquid surface tension is eliminated, increasing compliance and providing lung protection due to lower inflation pressures. Tidal liquid ventilation is achieved by cycling fluid from a reservoir to and from the lung by a ventilator. Current approaches are microprocessor-based with feedback control. During inspiration, warmed oxygenated PFC liquid is pumped from a fluid reservoir/gas exchanger into the lung. PFC fluid is conserved by condensing (60-80% efficiency) vapor in the expired gas. A feedback-control system was developed to automatically replace PFC lost due to condenser inefficiency. This loss/restoration (L/R) system consists of a PFC-vapor thermal detector (+/- 2.5%), pneumatics, amplifiers, a gas flow detector (+/- 1%), a PFC pump (+/- 5%), and a controller. Gravimetric studies of perflubron loss from a flask due to evaporation were compared with experimental L/R results and found to be within +/- 1.4%. In addition, when L/R studies were conducted with a previously reported liquid ventilation system over a four-hour period, the L/R system maintained system perflubron volume to within +/- 1% of prime volume and 11.5% of replacement volume, and the difference between experimental PFC loss and that of the L/R system was 1.8 mL/hr. These studies suggest that the PFC L/R system may have significant economic (appropriate dosing for PFC loss) as well as physiologic (maintenance of PFC inventory in the lungs and liquid ventilator) impact on liquid ventilation procedures.

Protein Kinase A Deregulation in the Medial Prefrontal Cortex Impairs Working Memory in Murine Oligophrenin-1 Deficiency.

PubMed

Zhang, Chun-Lei; Aime, Mattia; Laheranne, Emilie; Houbaert, Xander; El Oussini, Hajer; Martin, Christelle; Lepleux, Marilyn; Normand, Elisabeth; Chelly, Jamel; Herzog, Etienne; Billuart, Pierre; Humeau, Yann

2017-11-15

Classical and systems genetics have identified wide networks of genes associated with cognitive and neurodevelopmental diseases. In parallel to deciphering the role of each of these genes in neuronal or synaptic function, evaluating the response of neuronal and molecular networks to gene loss of function could reveal some pathophysiological mechanisms potentially accessible to nongenetic therapies. Loss of function of the Rho-GAP oligophrenin-1 is associated with cognitive impairments in both human and mouse. Upregulation of both PKA and ROCK has been reported in Ophn1 -/ y mice, but it remains unclear whether kinase hyperactivity contributes to the behavioral phenotypes. In this study, we thoroughly characterized a prominent perseveration phenotype displayed by Ophn1 -deficient mice using a Y-maze spatial working memory (SWM) test. We report that Ophn1 deficiency in the mouse generated severe cognitive impairments, characterized by both a high occurrence of perseverative behaviors and a lack of deliberation during the SWM test. In vivo and in vitro pharmacological experiments suggest that PKA dysregulation in the mPFC underlies cognitive dysfunction in Ophn1 -deficient mice, as assessed using a delayed spatial alternation task results. Functionally, mPFC neuronal networks appeared to be affected in a PKA-dependent manner, whereas hippocampal-PFC projections involved in SWM were not affected in Ophn1 -/y mice. Thus, we propose that discrete gene mutations in intellectual disability might generate "secondary" pathophysiological mechanisms, which are prone to become pharmacological targets for curative strategies in adult patients. SIGNIFICANCE STATEMENT Here we report that Ophn1 deficiency generates severe impairments in performance at spatial working memory tests, characterized by a high occurrence of perseverative behaviors and a lack of decision making. This cognitive deficit is consecutive to PKA deregulation in the mPFC that prevents Ophn1 KO mice to exploit a correctly acquired rule. Functionally, mPFC neuronal networks appear to be affected in a PKA-dependent manner, whereas behaviorally important hippocampal projections were preserved by the mutation. Thus, we propose that discrete gene mutations in intellectual disability can generate "secondary" pathophysiological mechanisms prone to become pharmacological targets for curative strategies in adults. Copyright © 2017 the authors 0270-6474/17/3711114-13$15.00/0.

14 CFR 158.13 - Use of PFC revenue.

Code of Federal Regulations, 2010 CFR

2010-01-01

... costs of approved projects at any airport the public agency controls. (a) Total cost. PFC revenue may be... costs. Public agencies may use PFC revenue to pay for allowable administrative support costs. Public... debt service and financing costs. (1) Public agencies may use PFC revenue to pay debt service and...

75 FR 18255 - Passenger Facility Charge Database System for Air Carrier Reporting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-09

... Facility Charge Database System for Air Carrier Reporting AGENCY: Federal Aviation Administration (FAA... the Passenger Facility Charge (PFC) database system to report PFC quarterly report information. In... developed a national PFC database system in order to more easily track the PFC program on a nationwide basis...

14 CFR 158.85 - Termination of authority to impose PFC's.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Termination of authority to impose PFC's... TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Termination § 158.85 Termination of authority to impose PFC's. (a) The FAA begins proceedings to terminate the public agency's authority to...

14 CFR 158.24 - Notice and opportunity for public comment.

Code of Federal Regulations, 2010 CFR

2010-01-01

... TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Application and Approval § 158.24 Notice... project(s) the public agency is considering for funding by PFC's; (ii) A brief justification for each project the public agency is considering for funding by PFC's; (iii) The PFC level for each project; (iv...

14 CFR 158.85 - Termination of authority to impose PFC's.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Termination of authority to impose PFC's... TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Termination § 158.85 Termination of authority to impose PFC's. (a) The FAA begins proceedings to terminate the public agency's authority to...

14 CFR 158.85 - Termination of authority to impose PFC's.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Termination of authority to impose PFC's... TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Termination § 158.85 Termination of authority to impose PFC's. (a) The FAA begins proceedings to terminate the public agency's authority to...

14 CFR 158.24 - Notice and opportunity for public comment.

Code of Federal Regulations, 2014 CFR

2014-01-01

... TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Application and Approval § 158.24 Notice... project(s) the public agency is considering for funding by PFC's; (ii) A brief justification for each project the public agency is considering for funding by PFC's; (iii) The PFC level for each project; (iv...

14 CFR 158.85 - Termination of authority to impose PFC's.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Termination of authority to impose PFC's... TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Termination § 158.85 Termination of authority to impose PFC's. (a) The FAA begins proceedings to terminate the public agency's authority to...

14 CFR 158.23 - Consultation with air carriers and foreign air carriers.

Code of Federal Regulations, 2012 CFR

2012-01-01

... OF TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Application and Approval... notice before filing a request to amend the FAA's decision with respect to an approved PFC as discussed... funding by PFC's; (2) The PFC level for each project, the proposed charge effective date, the estimated...

14 CFR 158.24 - Notice and opportunity for public comment.

Code of Federal Regulations, 2013 CFR

2013-01-01

... TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Application and Approval § 158.24 Notice... project(s) the public agency is considering for funding by PFC's; (ii) A brief justification for each project the public agency is considering for funding by PFC's; (iii) The PFC level for each project; (iv...

14 CFR 158.24 - Notice and opportunity for public comment.

Code of Federal Regulations, 2011 CFR

2011-01-01

... TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Application and Approval § 158.24 Notice... project(s) the public agency is considering for funding by PFC's; (ii) A brief justification for each project the public agency is considering for funding by PFC's; (iii) The PFC level for each project; (iv...

14 CFR 158.23 - Consultation with air carriers and foreign air carriers.

Code of Federal Regulations, 2010 CFR

2010-01-01

... OF TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Application and Approval... notice before filing a request to amend the FAA's decision with respect to an approved PFC as discussed... funding by PFC's; (2) The PFC level for each project, the proposed charge effective date, the estimated...

14 CFR 158.85 - Termination of authority to impose PFC's.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Termination of authority to impose PFC's... TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Termination § 158.85 Termination of authority to impose PFC's. (a) The FAA begins proceedings to terminate the public agency's authority to...

77 FR 44307 - Notice of Passenger Facility Charge (PFC) Approvals and Disapprovals

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-27

... Required to Collect PFC's: Air taxi/ commercial operators filing FAA Form 1800-31. Determination: Approved... Air Carriers Not Required to Collect PFC's: Nonscheduled/ on-demand air carriers filing FAA Form 1800... Carriers Not Required to Collect PFC's: None. Brief Description of Projects Approved for Collection and Use...

14 CFR 158.24 - Notice and opportunity for public comment.

Code of Federal Regulations, 2012 CFR

2012-01-01

... TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Application and Approval § 158.24 Notice... project(s) the public agency is considering for funding by PFC's; (ii) A brief justification for each project the public agency is considering for funding by PFC's; (iii) The PFC level for each project; (iv...

14 CFR 158.23 - Consultation with air carriers and foreign air carriers.

Code of Federal Regulations, 2011 CFR

2011-01-01

... OF TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Application and Approval... notice before filing a request to amend the FAA's decision with respect to an approved PFC as discussed... funding by PFC's; (2) The PFC level for each project, the proposed charge effective date, the estimated...

14 CFR 158.23 - Consultation with air carriers and foreign air carriers.

Code of Federal Regulations, 2014 CFR

2014-01-01

... OF TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Application and Approval... notice before filing a request to amend the FAA's decision with respect to an approved PFC as discussed... funding by PFC's; (2) The PFC level for each project, the proposed charge effective date, the estimated...

14 CFR 158.23 - Consultation with air carriers and foreign air carriers.

Code of Federal Regulations, 2013 CFR

2013-01-01

... OF TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Application and Approval... notice before filing a request to amend the FAA's decision with respect to an approved PFC as discussed... funding by PFC's; (2) The PFC level for each project, the proposed charge effective date, the estimated...

Cannabis use in early psychosis is associated with reduced glutamate levels in the prefrontal cortex.

PubMed

Rigucci, Silvia; Xin, Lijing; Klauser, Paul; Baumann, Philipp S; Alameda, Luis; Cleusix, Martine; Jenni, Raoul; Ferrari, Carina; Pompili, Maurizio; Gruetter, Rolf; Do, Kim Q; Conus, Philippe

2018-01-01

Recent studies have shown that cannabis may disrupt glutamate (Glu) signaling depressing Glu tone in frequent users. Current evidence have also consistently reported lower Glu-levels in various brain regions, particularly in the medial prefrontal cortex (mPFC) of chronic schizophrenia patients, while findings in early psychosis (EP) are not conclusive. Since cannabis may alter Glu synaptic plasticity and its use is a known risk factor for psychosis, studies focusing on Glu signaling in EP with or without a concomitant cannabis-usage seem crucial. We investigate the effect of cannabis use on prefrontal Glu-levels in EP users vs. both EP non-users and healthy controls (HC). Magnetic resonance spectroscopy was used to measure [Glu mPFC ] of 35 EP subjects (18 of whom were cannabis users) and 33 HC. For correlative analysis, neuropsychological performances were scored by the MATRICS-consensus cognitive battery. [Glu mPFC ] was lower in EP users comparing to both HC and EP non-users (p < 0.001 and p = 0.01, respectively), while no differences were observed between EP non-users and HC. A greater [Glu mPFC ]-decline with age was observed in EP users (r = -.46; p = 0.04), but not in EP non-users or HC. Among neuropsychological outcomes, working memory was the only domain that differentiates patients depending on their cannabis use, with users having poorer performances. Cannabis use is associated with reduced prefrontal [Glu mPFC ] and with a stronger Glu-levels decline with age. Glutamatergic abnormalities might influence the cognitive impairment observed in users and have some relevance for the progression of the disease.

Lower glutamic acid decarboxylase 65kD mRNA and protein levels in the prefrontal cortex in schizoaffective disorder but not schizophrenia

PubMed Central

Glausier, JR; Kimoto, S; Fish, KN; Lewis, DA

2014-01-01

Background Altered GABA signaling in the prefrontal cortex (PFC) has been associated with cognitive dysfunction in schizophrenia and schizoaffective disorder. PFC levels of the GABA-synthesizing enzyme glutamic acid decarboxylase 67kD (GAD67) has been consistently reported to be lower in these disorders, but the status of the second GABA-synthesizing enzyme, GAD65, remains unclear. Methods GAD65 mRNA levels were quantified in PFC area 9 by quantitative polymerase chain reaction from 62 subjects with schizophrenia or schizoaffective disorder and 62 matched healthy comparison subjects. GAD65 relative protein levels were quantified in a subset of subject pairs by confocal immunofluorescence microscopy. Results Mean GAD65 mRNA levels were 13.6% lower in schizoaffective disorder subjects, but did not differ in schizophrenia subjects, relative to their matched healthy comparison subjects. In the subjects with schizoaffective disorder, mean GAD65 protein levels were 19.4% lower and were correlated with GAD65 mRNA levels. Lower GAD65 mRNA and protein measures within schizoaffective disorder subjects was not attributable to factors commonly comorbid with the diagnosis. Conclusions In concert with previous studies, these findings suggest that schizoaffective disorder is associated with lower levels of both GAD65 and GAD67 mRNA and protein in the PFC, whereas subjects with schizophrenia have lower mean levels of only GAD67 mRNA and protein. Because cognitive function is generally better preserved in subjects with schizoaffective disorder relative to subjects with schizophrenia, these findings may support an interpretation that GAD65 down-regulation provides a homeostatic response complementary to GAD67 down-regulation expression that serves to reduce inhibition in the face of lower PFC network activity. PMID:24993056

Chronic administration of resveratrol prevents morphological changes in prefrontal cortex and hippocampus of aged rats.

PubMed

Monserrat Hernández-Hernández, Elizabeth; Serrano-García, Carolina; Antonio Vázquez-Roque, Rubén; Díaz, Alfonso; Monroy, Elibeth; Rodríguez-Moreno, Antonio; Florán, Benjamin; Flores, Gonzalo

2016-05-01

Resveratrol may induce its neuroprotective effects by reducing oxidative damage and chronic inflammation apart from improving vascular function and activating longevity genes, it also has the ability to promote the activity of neurotrophic factors. Morphological changes in dendrites of the pyramidal neurons of the prefrontal cortex (PFC) and hippocampus have been reported in the brain of aging humans, or in humans with neurodegenerative diseases such as Alzheimer's disease. These changes are reflected particularly in the decrement of both the dendritic tree and spine density. Here we evaluated the effect of resveratrol on the dendrites of pyramidal neurons of the PFC (Layers 3 and 5), CA1- and CA3-dorsal hippocampus (DH) as well as CA1-ventral hippocampus, dentate gyrus (DG), and medium spiny neurons of the nucleus accumbens of aged rats. 18-month-old rats were administered resveratrol (20 mg/kg, orally) daily for 60 days. Dendritic morphology was studied by the Golgi-Cox stain procedure, followed by Sholl analysis on 20-month-old rats. In all resveratrol-treated rats, a significant increase in dendritic length and spine density in pyramidal neurons of the PFC, CA1, and CA3 of DH was observed. Interestingly, the enhancement in dendritic length was close to the soma in pyramidal neurons of the PFC, whereas in neurons of the DH and DG, the increase in dendritic length was further from the soma. Our results suggest that resveratrol induces modifications of dendritic morphology in the PFC, DH, and DG. These changes may explain the therapeutic effect of resveratrol in aging and in Alzheimer's disease. © 2016 Wiley Periodicals, Inc.

Perturbations in reward-related decision-making induced by reduced prefrontal cortical GABA transmission: Relevance for psychiatric disorders.

PubMed

Piantadosi, Patrick T; Khayambashi, Shahin; Schluter, Magdalen G; Kutarna, Agnes; Floresco, Stan B

2016-02-01

The prefrontal cortex (PFC) is critical for higher-order cognitive functions, including decision-making. In psychiatric conditions such as schizophrenia, prefrontal dysfunction co-occurs with pronounced alterations in decision-making ability. These alterations include a diminished ability to utilize probabilistic reinforcement in guiding future choice, and a reduced willingness to expend effort to receive reward. Among the neurochemical abnormalities observed in the PFC of individuals with schizophrenia are alterations in the production and function of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). To probe how PFC GABA hypofunction may contribute to alterations in cost/benefit decision-making, we assessed the effects GABAA-receptor antagonist bicuculline (BIC; 50 ng in 0.5 μl saline/hemisphere) infusion in the medial PFC of rats during performance on a series of well-validated cost/benefit decision-making tasks. Intra-PFC BIC reduced risky choice and reward sensitivity during probabilistic discounting and decreased the preference for larger rewards associated with a greater effort cost, similar to the behavioral sequelae observed in schizophrenia. Additional experiments revealed that these treatments did not alter instrumental responding on a progressive ratio schedule, nor did they impair the ability to discriminate between reward and no reward. However, BIC induced a subtle but consistent impairment in preference for larger vs. smaller rewards of equal cost. BIC infusion also increased decision latencies and impaired the ability to "stay on task" as indexed by reduced rates of instrumental responding. Collectively, these results implicate prefrontal GABAergic dysfunction as a key contributing factor to abnormal decision-making observed in schizophrenia and other neuropsychiatric conditions with similar neurobiological and behavioral alterations. Copyright © 2015 Elsevier Ltd. All rights reserved.

Power-Factor Controllers: How Safe?

NASA Technical Reports Server (NTRS)

Long, K.; Christian, W.; Kovacik, J.; Grazyk, T.

1985-01-01

Potential safety problems with power-factor controllers (PFC's) evaluated. Based on study of PFCs in use with appliances, report recommends measures to prevent consumers from misapplying these energy saving devices. Device used on such appliances as refrigerators, sewing machines, pumps, hair dryers, and food processors. When misused, they fail to save energy and may cause damage.

Neural Correlates of Direct Access Trading in a Real Stock Market: An fMRI Investigation

PubMed Central

Raggetti, GianMario; Ceravolo, Maria G.; Fattobene, Lucrezia; Di Dio, Cinzia

2017-01-01

Background: While financial decision making has been barely explored, no study has previously investigated the neural correlates of individual decisions made by professional traders involved in real stock market negotiations, using their own financial resources. Aim: We sought to detect how different brain areas are modulated by factors like age, expertise, psychological profile (speculative risk seeking or aversion) and, eventually, size and type (Buy/Sell) of stock negotiations, made through Direct Access Trading (DAT) platforms. Subjects and methods: Twenty male traders underwent fMRI while negotiating in the Italian stock market using their own preferred trading platform. Results: At least 20 decision events were collected during each fMRI session. Risk averse traders performed a lower number of financial transactions with respect to risk seekers, with a lower average economic value, but with a higher rate of filled proposals. Activations were observed in cortical and subcortical areas traditionally involved in decision processes, including the ventrolateral and dorsolateral prefrontal cortex (vlPFC, dlPFC), the posterior parietal cortex (PPC), the nucleus accumbens (NAcc), and dorsal striatum. Regression analysis indicated an important role of age in modulating activation of left NAcc, while traders' expertise was negatively related to activation of vlPFC. High value transactions were associated with a stronger activation of the right PPC when subjects' buy rather than sell. The success of the trading activity, based on a large number of filled transactions, was related with higher activation of vlPFC and dlPFC. Independent of chronological and professional age, traders differed in their attitude to DAT, with distinct brain activity profiles being detectable during fMRI sessions. Those subjects who described themselves as very self-confident, showed a lower or absent activation of both the caudate nucleus and the dlPFC, while more reflexive traders showed greater activation of areas involved in strategic decision making. Discussion: The neural correlates in DAT are similar to those observed in other decision making contexts. Trading is handled as a well-learned automatic behavior by expert traders; for those who mostly rely on heuristics, cognitive effort decreases, and transaction speed increases, but decision efficiency lowers following a poor involvement of the dlPFC. PMID:29033782

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

The prefrontal cortex: a target for antipsychotic drugs.

PubMed

Artigas, F

2010-01-01

At therapeutic doses, classical antipsychotic drugs occupy a large proportion of subcortical dopamine D2 receptors, whereas atypical antipsychotics preferentially occupy cortical 5-HT(2) receptors. However, the exact cellular and network basis of their therapeutic action is not fully understood. To review the mechanism of action of antipsychotic drugs with a particular emphasis on their action in the prefrontal cortex (PFC). The PFC controls a large number of higher brain functions altered in schizophrenia. Histological studies indicate the presence of a large proportion of PFC neurons expressing monoaminergic receptors sensitive to the action of atypical- and to a lesser extentclassical antipsychotic drugs. Functional studies also indicate that both drug families act at PFC level. Atypical antipsychotic drugs likely exert their therapeutic activity by a preferential action on PFC neurons, thus modulating the PFC output to basal ganglia circuits. Classical antipsychotics also interact with these PFC targets in addition to blocking massively striatal D2 receptors.

Vagus nerve stimulation reduces cocaine seeking and alters plasticity in the extinction network.

PubMed

Childs, Jessica E; DeLeon, Jaime; Nickel, Emily; Kroener, Sven

2017-01-01

Drugs of abuse cause changes in the prefrontal cortex (PFC) and associated regions that impair inhibitory control over drug-seeking. Breaking the contingencies between drug-associated cues and the delivery of the reward during extinction learning reduces rates of relapse. Here we used vagus nerve stimulation (VNS) to induce targeted synaptic plasticity to facilitate extinction of appetitive behaviors and to reduce relapse. Rats self-administered cocaine and were given VNS during extinction. Relapse to drug-seeking was assessed in a cued reinstatement session. We used immunohistochemistry to measure changes in the expression of the phosphorylated transcription factor cAMP response-element binding protein (pCREB) in the PFC and the basolateral amygdala (BLA), which regulate cue learning and extinction. In vivo recordings of evoked field potentials measured drug- and VNS-induced changes in metaplasticity in the pathway from the PFC to the BLA. VNS-treated rats showed improved rates of extinction and reduced reinstatement. Following reinstatement, pCREB levels were reduced in the IL and BLA of VNS-treated rats. Evoked responses in the BLA were greatly reduced in VNS-treated rats, and these rats were also resistant to the induction of LTD. Taken together, these results show that VNS facilitates extinction and reduces reinstatement. Changes in the pathway between the PFC and the amygdala may contribute to these beneficial effects. © 2016 Childs et al.; Published by Cold Spring Harbor Laboratory Press.

Individual differences in impulsive action and dopamine transporter function in rat orbitofrontal cortex.

PubMed

Yates, J R; Darna, M; Beckmann, J S; Dwoskin, L P; Bardo, M T

2016-01-28

Impulsivity, which can be subdivided into impulsive action and impulsive choice, is implicated as a factor underlying drug abuse vulnerability. Although previous research has shown that dopamine (DA) systems in prefrontal cortex are involved in impulsivity and substance abuse, it is not known if inherent variation in DA transporter (DAT) function contributes to impulsivity. The current study determined if individual differences in either impulsive action or impulsive choice are related to DAT function in orbitofrontal (OFC) and/or medial prefrontal cortex (mPFC). Rats were first tested both for impulsive action in a cued go/no-go task and for impulsive choice in a delay-discounting task. Following behavioral evaluation, in vitro [(3)H]DA uptake assays were performed in OFC and mPFC isolated from individual rats. Vmax in OFC, but not mPFC, was correlated with performance in the cued go/no-go task, with decreased OFC DAT function being associated with high impulsive action. In contrast, Vmax in OFC and mPFC was not correlated with performance in the delay-discounting task. The current results demonstrate that impulsive behavior in cued go/no-go performance is associated with decreased DAT function in OFC, suggesting that hyperdopaminergic tone in this prefrontal subregion mediates, at least in part, increased impulsive action. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Vagus nerve stimulation reduces cocaine seeking and alters plasticity in the extinction network

PubMed Central

Childs, Jessica E.; DeLeon, Jaime; Nickel, Emily

2017-01-01

Drugs of abuse cause changes in the prefrontal cortex (PFC) and associated regions that impair inhibitory control over drug-seeking. Breaking the contingencies between drug-associated cues and the delivery of the reward during extinction learning reduces rates of relapse. Here we used vagus nerve stimulation (VNS) to induce targeted synaptic plasticity to facilitate extinction of appetitive behaviors and to reduce relapse. Rats self-administered cocaine and were given VNS during extinction. Relapse to drug-seeking was assessed in a cued reinstatement session. We used immunohistochemistry to measure changes in the expression of the phosphorylated transcription factor cAMP response-element binding protein (pCREB) in the PFC and the basolateral amygdala (BLA), which regulate cue learning and extinction. In vivo recordings of evoked field potentials measured drug- and VNS-induced changes in metaplasticity in the pathway from the PFC to the BLA. VNS-treated rats showed improved rates of extinction and reduced reinstatement. Following reinstatement, pCREB levels were reduced in the IL and BLA of VNS-treated rats. Evoked responses in the BLA were greatly reduced in VNS-treated rats, and these rats were also resistant to the induction of LTD. Taken together, these results show that VNS facilitates extinction and reduces reinstatement. Changes in the pathway between the PFC and the amygdala may contribute to these beneficial effects. PMID:27980074

Putting race in context: social class modulates processing of race in the ventromedial prefrontal cortex and amygdala

PubMed Central

Hitlin, Steven; Magnotta, Vincent; Tranel, Daniel

2017-01-01

Abstract A growing body of literature demonstrates that racial group membership can influence neural responses, e.g. when individuals perceive or interact with persons of another race. However, little attention has been paid to social class, a factor that interacts with racial inequalities in American society. We extend previous literature on race-related neural activity by focusing on how the human brain responds to racial out-groups cast in positively valued social class positions vs less valued ones. We predicted that the ventromedial prefrontal cortex (vmPFC) and the amygdala would have functionally dissociable roles, with the vmPFC playing a more significant role within socially valued in-groups (i.e. the middle-class) and the amygdala having a more crucial role for socially ambivalent and threatening categories (i.e. upper and lower class). We tested these predictions with two complementary studies: (i) a neuropsychological experiment with patients with the vmPFC or amygdala lesions, contrasted with brain damaged and normal comparison participants, and (ii) a functional magnetic resonance imaging experiment with 15 healthy adults. Our findings suggest that two distinct mechanisms underlie class-based racial evaluations, one engaging the vmPFC for positively identified in-group class and another recruiting the amygdala for the class groups that are marginalized or perceived as potential threats. PMID:28398590

Putting race in context: social class modulates processing of race in the ventromedial prefrontal cortex and amygdala.

PubMed

Firat, Rengin B; Hitlin, Steven; Magnotta, Vincent; Tranel, Daniel

2017-08-01

A growing body of literature demonstrates that racial group membership can influence neural responses, e.g. when individuals perceive or interact with persons of another race. However, little attention has been paid to social class, a factor that interacts with racial inequalities in American society. We extend previous literature on race-related neural activity by focusing on how the human brain responds to racial out-groups cast in positively valued social class positions vs less valued ones. We predicted that the ventromedial prefrontal cortex (vmPFC) and the amygdala would have functionally dissociable roles, with the vmPFC playing a more significant role within socially valued in-groups (i.e. the middle-class) and the amygdala having a more crucial role for socially ambivalent and threatening categories (i.e. upper and lower class). We tested these predictions with two complementary studies: (i) a neuropsychological experiment with patients with the vmPFC or amygdala lesions, contrasted with brain damaged and normal comparison participants, and (ii) a functional magnetic resonance imaging experiment with 15 healthy adults. Our findings suggest that two distinct mechanisms underlie class-based racial evaluations, one engaging the vmPFC for positively identified in-group class and another recruiting the amygdala for the class groups that are marginalized or perceived as potential threats. © The Author (2017). Published by Oxford University Press.

14 CFR 158.33 - Duration of authority to impose a PFC before project implementation.

Code of Federal Regulations, 2011 CFR

2011-01-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Application and Approval § 158.33 Duration of authority to impose a PFC before project implementation. (a) A... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Duration of authority to impose a PFC...

14 CFR 158.31 - Duration of authority to impose a PFC after project implementation.

Code of Federal Regulations, 2014 CFR

2014-01-01

..., DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Application and Approval....S.C. 47524 and 47526, and the authority to collect the PFC is terminated under that statute's... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Duration of authority to impose a PFC after...

14 CFR 158.31 - Duration of authority to impose a PFC after project implementation.

Code of Federal Regulations, 2011 CFR

2011-01-01

..., DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Application and Approval....S.C. 47524 and 47526, and the authority to collect the PFC is terminated under that statute's... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Duration of authority to impose a PFC after...

14 CFR 158.35 - Extension of time to submit application to use PFC revenue.

Code of Federal Regulations, 2010 CFR

2010-01-01

... use PFC revenue. 158.35 Section 158.35 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Application and Approval § 158.35 Extension of time to submit application to use PFC revenue. (a) A public agency may request an...

14 CFR 158.31 - Duration of authority to impose a PFC after project implementation.

Code of Federal Regulations, 2012 CFR

2012-01-01

..., DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Application and Approval....S.C. 47524 and 47526, and the authority to collect the PFC is terminated under that statute's... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Duration of authority to impose a PFC after...

14 CFR 158.31 - Duration of authority to impose a PFC after project implementation.

Code of Federal Regulations, 2013 CFR

2013-01-01

..., DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Application and Approval....S.C. 47524 and 47526, and the authority to collect the PFC is terminated under that statute's... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Duration of authority to impose a PFC after...

14 CFR 158.35 - Extension of time to submit application to use PFC revenue.

Code of Federal Regulations, 2013 CFR

2013-01-01

... use PFC revenue. 158.35 Section 158.35 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Application and Approval § 158.35 Extension of time to submit application to use PFC revenue. (a) A public agency may request an...

14 CFR 158.33 - Duration of authority to impose a PFC before project implementation.

Code of Federal Regulations, 2010 CFR

2010-01-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Application and Approval § 158.33 Duration of authority to impose a PFC before project implementation. (a) A... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Duration of authority to impose a PFC...

14 CFR 158.35 - Extension of time to submit application to use PFC revenue.

Code of Federal Regulations, 2011 CFR

2011-01-01

... use PFC revenue. 158.35 Section 158.35 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Application and Approval § 158.35 Extension of time to submit application to use PFC revenue. (a) A public agency may request an...

14 CFR 158.33 - Duration of authority to impose a PFC before project implementation.

Code of Federal Regulations, 2014 CFR

2014-01-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Application and Approval § 158.33 Duration of authority to impose a PFC before project implementation. (a) A... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Duration of authority to impose a PFC...

14 CFR 158.35 - Extension of time to submit application to use PFC revenue.

Code of Federal Regulations, 2014 CFR

2014-01-01

... use PFC revenue. 158.35 Section 158.35 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Application and Approval § 158.35 Extension of time to submit application to use PFC revenue. (a) A public agency may request an...

14 CFR 158.33 - Duration of authority to impose a PFC before project implementation.

Code of Federal Regulations, 2013 CFR

2013-01-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Application and Approval § 158.33 Duration of authority to impose a PFC before project implementation. (a) A... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Duration of authority to impose a PFC...

14 CFR 158.33 - Duration of authority to impose a PFC before project implementation.

Code of Federal Regulations, 2012 CFR

2012-01-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Application and Approval § 158.33 Duration of authority to impose a PFC before project implementation. (a) A... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Duration of authority to impose a PFC...

14 CFR 158.31 - Duration of authority to impose a PFC after project implementation.

Code of Federal Regulations, 2010 CFR

2010-01-01

..., DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Application and Approval....S.C. 47524 and 47526, and the authority to collect the PFC is terminated under that statute's... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Duration of authority to impose a PFC after...

14 CFR 158.35 - Extension of time to submit application to use PFC revenue.

Code of Federal Regulations, 2012 CFR

2012-01-01

... use PFC revenue. 158.35 Section 158.35 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Application and Approval § 158.35 Extension of time to submit application to use PFC revenue. (a) A public agency may request an...

A Pilot Study of Tissue Factor-Tissue Factor Pathway Inhibitor Axis and Other Selected Coagulation Parameters in Broiler Chickens Administered in Ovo with Selected Prebiotics*.

PubMed

Buzala, Mateusz; Ponczek, Michal Blazej; Slomka, Artur; Roslewska, Aleksandra; Janicki, Bogdan; Zekanowska, Ewa; Bednarczyk, Marek

The tissue factor (TF) - tissue factor pathway inhibitor (TFPI) axis plays a major role in hemostasis. Disorders of the coagulation system are commonly diagnosed with the help of screening tests such as prothrombin time (PT), activated partial thromboplastin time (aPTT), and plasma fibrinogen concentration (PFC). However, the effect of prebiotics on the hemostasis system has not been characterized in poultry yet. This study was designed to determine the effect of in ovo administration ofprebiotics on blood coagulation parameters of broiler chickens depending on their age. The study was conducted with 180 broiler chick embryos, the air cells of which were injected on day 12 of incubation with prebiotics (experimental groups: Bi2tos, DiNovoo and RFO) or physiological saline solution (control group). At 1, 21 and 42 days of rearing, blood was sampled from 15 broiler chickens from each group. An enzyme immunoassay was performed to determine plasma TF and TFPI levels, and PT, aPTT and PFC were determined in the chicken blood. We demonstrated that: 1) total TF levels increased with age in the experimental groups, 2) prebiotics had no significant effect on TF levels between the groups at a particular age, 3) total TFPI levels differed between both the type of in ovo injected substance and the broiler chicken age, 4) in the control group, PT and aPTT were found to increase with age whilst fibrinogen concentration decreased. The main conclusion from this pilot study is that total TF and TFPI levels change with age, however no clear patterns regarding TFPI were detected yet. The levels of PT, aPTT and PFC varied with the prebiotics administered in ovo as well as with the age of broiler chickens.

Ventromedial prefrontal cortex encodes emotional value.

PubMed

Winecoff, Amy; Clithero, John A; Carter, R McKell; Bergman, Sara R; Wang, Lihong; Huettel, Scott A

2013-07-03

The ventromedial prefrontal cortex (vmPFC) plays a critical role in processing appetitive stimuli. Recent investigations have shown that reward value signals in the vmPFC can be altered by emotion regulation processes; however, to what extent the processing of positive emotion relies on neural regions implicated in reward processing is unclear. Here, we investigated the effects of emotion regulation on the valuation of emotionally evocative images. Two independent experimental samples of human participants performed a cognitive reappraisal task while undergoing fMRI. The experience of positive emotions activated the vmPFC, whereas the regulation of positive emotions led to relative decreases in vmPFC activation. During the experience of positive emotions, vmPFC activation tracked participants' own subjective ratings of the valence of stimuli. Furthermore, vmPFC activation also tracked normative valence ratings of the stimuli when participants were asked to experience their emotions, but not when asked to regulate them. A separate analysis of the predictive power of vmPFC on behavior indicated that even after accounting for normative stimulus ratings and condition, increased signal in the vmPFC was associated with more positive valence ratings. These results suggest that the vmPFC encodes a domain-general value signal that tracks the value of not only external rewards, but also emotional stimuli.

The neural bases for devaluing radical political statements revealed by penetrating traumatic brain injury.

PubMed

Cristofori, Irene; Viola, Vanda; Chau, Aileen; Zhong, Wanting; Krueger, Frank; Zamboni, Giovanna; Grafman, Jordan

2015-08-01

Given the determinant role of ventromedial prefrontal cortex (vmPFC) in valuation, we examined whether vmPFC lesions also modulate how people scale political beliefs. Patients with penetrating traumatic brain injury (pTBI; N = 102) and healthy controls (HCs; N = 31) were tested on the political belief task, where they rated 75 statements expressing political opinions concerned with welfare, economy, political involvement, civil rights, war and security. Each statement was rated for level of agreement and scaled along three dimensions: radicalism, individualism and conservatism. Voxel-based lesion-symptom mapping (VLSM) analysis showed that diminished scores for the radicalism dimension (i.e. statements were rated as less radical than the norms) were associated with lesions in bilateral vmPFC. After dividing the pTBI patients into three groups, according to lesion location (i.e. vmPFC, dorsolateral prefrontal cortex [dlPFC] and parietal cortex), we found that the vmPFC, but not the dlPFC, group had reduced radicalism scores compared with parietal and HC groups. These findings highlight the crucial role of the vmPFC in appropriately valuing political behaviors and may explain certain inappropriate social judgments observed in patients with vmPFC lesions. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Comparing and Contrasting the Cognitive Effects of Hippocampal and Ventromedial Prefrontal Cortex Damage: A Review of Human Lesion Studies.

PubMed

McCormick, Cornelia; Ciaramelli, Elisa; De Luca, Flavia; Maguire, Eleanor A

2018-03-15

The hippocampus and ventromedial prefrontal cortex (vmPFC) are closely connected brain regions whose functions are still debated. In order to offer a fresh perspective on understanding the contributions of these two brain regions to cognition, in this review we considered cognitive tasks that usually elicit deficits in hippocampal-damaged patients (e.g., autobiographical memory retrieval), and examined the performance of vmPFC-lesioned patients on these tasks. We then took cognitive tasks where performance is typically compromised following vmPFC damage (e.g., decision making), and looked at how these are affected by hippocampal lesions. Three salient motifs emerged. First, there are surprising gaps in our knowledge about how hippocampal and vmPFC patients perform on tasks typically associated with the other group. Second, while hippocampal or vmPFC damage seems to adversely affect performance on so-called hippocampal tasks, the performance of hippocampal and vmPFC patients clearly diverges on classic vmPFC tasks. Third, although performance appears analogous on hippocampal tasks, on closer inspection, there are significant disparities between hippocampal and vmPFC patients. Based on these findings, we suggest a tentative hierarchical model to explain the functions of the hippocampus and vmPFC. We propose that the vmPFC initiates the construction of mental scenes by coordinating the curation of relevant elements from neocortical areas, which are then funneled into the hippocampus to build a scene. The vmPFC then engages in iterative re-initiation via feedback loops with neocortex and hippocampus to facilitate the flow and integration of the multiple scenes that comprise the coherent unfolding of an extended mental event. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

The Function and Organization of Lateral Prefrontal Cortex: A Test of Competing Hypotheses

PubMed Central

Reynolds, Jeremy R.; O'Reilly, Randall C.; Cohen, Jonathan D.; Braver, Todd S.

2012-01-01

The present experiment tested three hypotheses regarding the function and organization of lateral prefrontal cortex (PFC). The first account (the information cascade hypothesis) suggests that the anterior-posterior organization of lateral PFC is based on the timing with which cue stimuli reduce uncertainty in the action selection process. The second account (the levels-of-abstraction hypothesis) suggests that the anterior-posterior organization of lateral PFC is based on the degree of abstraction of the task goals. The current study began by investigating these two hypotheses, and identified several areas of lateral PFC that were predicted to be active by both the information cascade and levels-of-abstraction accounts. However, the pattern of activation across experimental conditions was inconsistent with both theoretical accounts. Specifically, an anterior area of mid-dorsolateral PFC exhibited sensitivity to experimental conditions that, according to both accounts, should have selectively engaged only posterior areas of PFC. We therefore investigated a third possible account (the adaptive context maintenance hypothesis) that postulates that both posterior and anterior regions of PFC are reliably engaged in task conditions requiring active maintenance of contextual information, with the temporal dynamics of activity in these regions flexibly tracking the duration of maintenance demands. Activity patterns in lateral PFC were consistent with this third hypothesis: regions across lateral PFC exhibited transient activation when contextual information had to be updated and maintained in a trial-by-trial manner, but sustained activation when contextual information had to be maintained over a series of trials. These findings prompt a reconceptualization of current views regarding the anterior-posterior organization of lateral PFC, but do support other findings regarding the active maintenance role of lateral PFC in sequential working memory paradigms. PMID:22355309

Endogenous Opioid Signaling in the Medial Prefrontal Cortex is Required for the Expression of Hunger-Induced Impulsive Action.

PubMed

Selleck, Ryan A; Lake, Curtis; Estrada, Viridiana; Riederer, Justin; Andrzejewski, Matthew; Sadeghian, Ken; Baldo, Brian A

2015-09-01

Opioid transmission and dysregulated prefrontal cortex (PFC) activity have both been implicated in the inhibitory-control deficits associated with addiction and binge-type eating disorders. What remains unknown, however, is whether endogenous opioid transmission within the PFC modulates inhibitory control. Here, we compared intra-PFC opioid manipulations with a monoamine manipulation (d-amphetamine), in two sucrose-reinforced tasks: progressive ratio (PR), which assays the motivational value of an incentive, and differential reinforcement of low response rates (DRLs), a test of inhibitory control. Intra-PFC methylnaloxonium (M-NX, a limited diffusion opioid antagonist) was given to rats in a 'low-drive' condition (2-h food deprivation), and also after a motivational shift to a 'high-drive' condition (18-h food deprivation). Intra-PFC DAMGO (D-[Ala2,N-MePhe4, Gly-ol]-enkephalin; a μ-opioid agonist) and d-amphetamine were also tested in both tasks, under the low-drive condition. Intra-PFC M-NX nearly eliminated impulsive action in DRL engendered by hunger, at a dose (1 μg) that significantly affected neither hunger-induced PR enhancement nor hyperactivity. At a higher dose (3 μg), M-NX eliminated impulsive action and returned PR breakpoint to low-drive levels. Conversely, intra-PFC DAMGO engendered 'high-drive-like' effects: enhancement of PR and impairment of DRL performance. Intra-PFC d-amphetamine failed to produce effects in either task. These results establish that endogenous PFC opioid transmission is both necessary and sufficient for the expression of impulsive action in a high-arousal, high-drive appetitive state, and that PFC-based opioid systems enact functionally unique effects on food impulsivity and motivation relative to PFC-based monoamine systems. Opioid antagonists may represent effective treatments for a range of psychiatric disorders with impulsivity features.

Endoscopic treatment of large pancreatic fluid collections (PFC) using self-expanding metallic stents (SEMS) - a two-center experience.

PubMed

Chaves, Dalton Marques; Mönkemüller, Klaus; Carneiro, Fred; Medrado, Bruno; Dos Santos, Marcos; Wodak, Stephanie; Reimão, Sílvia; Sakai, Paulo; de Moura, Eduardo

2014-12-01

Background/study aim: During the last several years, endoscopic ultrasound (EUS)-guided pancreatic fluid collections' (PFC) drainage has evolved into the preferred drainage technique. Recently, self-expanding metallic stents (SEMS) have been used as an alternative to double pigtail stents, with the advantage of providing a larger diameter fistula, thereby decreasing the risk of early obstruction and also allowing for direct endoscopic exploration of the cavity. The aim of this study was to evaluate the technical and clinical success, safety, and outcome of patients undergoing EUS-guided drainage of complex PFC using SEMS. The study was conducted at two tertiary hospitals from January 2010 to January 2013. All patients with PFC referred for endoscopic drainage were enrolled in a prospective database. The inclusion criteria were: (1) patients with pseudocysts or walled-off necrosis based on the revised Atlanta classification; (2) symptomatic patients with thick PFC; (3) PFC that persisted more than 6 weeks; and (4) large PFC diameter (≥ 9 cm). The exclusion criteria consisted of coagulation disorders, PFC bleeding or infection, and failure-to-inform written consent. A total of 16 patients (9 females, 7 males; mean age 52.6, range 20 - 82) underwent EUS drainage with SEMS. There were 14 cases of pseudocysts and 2 cases of walled-off necrosis. The etiologies of the PFC were mainly gallstones (8 of 16 patients, 50 %) and alcohol (5 of 16 patients, 31 %). Technical success was achieved in 100 % of the cases. All patients had a complete resolution of the PFC. Transmural EUS-guided drainage of complex PFC using SEMS is feasible, appears safe, and is efficacious. However, the exchange of the UC (uncovered)-SEMS for plastic stents is mandatory within 1 week. Future prospective studies, preferably multicenter studies, comparing SEMS versus traditional plastic stents for the drainage of PFC are warranted.

Negative urgency and ventromedial prefrontal cortex responses to alcohol cues: FMRI evidence of emotion-based impulsivity.

PubMed

Cyders, Melissa A; Dzemidzic, Mario; Eiler, William J; Coskunpinar, Ayca; Karyadi, Kenny; Kareken, David A

2014-02-01

Recent research has highlighted the role of emotion-based impulsivity (negative and positive urgency personality traits) for alcohol use and abuse, but has yet to examine how these personality traits interact with the brain's motivational systems. Using functional magnetic resonance imaging (fMRI), we tested whether urgency traits and mood induction affected medial prefrontal responses to alcohol odors (AcO). Twenty-seven social drinkers (mean age = 25.2, 14 males) had 6 fMRI scans while viewing negative, neutral, or positive mood images (3 mood conditions) during intermittent exposure to AcO and appetitive control (AppCo) aromas. Voxel-wise analyses (p < 0.001) confirmed [AcO > AppCo] activation throughout medial prefrontal cortex (mPFC) and ventromedial PFC (vmPFC) regions. Extracted from a priori mPFC and vmPFC regions and analyzed in Odor (AcO, AppCo) × Mood factorial models, AcO activation was greater than AppCo in left vmPFC (p < 0.001), left mPFC (p = 0.002), and right vmPFC (p = 0.01) regions. Mood did not interact significantly with activation, but the covariate of trait negative urgency accounted for significant variance in left vmPFC (p = 0.01) and right vmPFC (p = 0.01) [AcO > AppCo] activation. Negative urgency also mediated the relationship between vmPFC activation and both (i) subjective craving and (ii) problematic drinking. The trait of negative urgency is associated with neural responses to alcohol cues in the vmPFC, a region involved in reward value and emotion-guided decision-making. This suggests that negative urgency might alter subjective craving and brain regions involved in coding reward value. Copyright © 2013 by the Research Society on Alcoholism.

Ex vivo dissection of optogenetically activated mPFC and hippocampal inputs to neurons in the basolateral amygdala: implications for fear and emotional memory

PubMed Central

Hübner, Cora; Bosch, Daniel; Gall, Andrea; Lüthi, Andreas; Ehrlich, Ingrid

2014-01-01

Many lines of evidence suggest that a reciprocally interconnected network comprising the amygdala, ventral hippocampus (vHC), and medial prefrontal cortex (mPFC) participates in different aspects of the acquisition and extinction of conditioned fear responses and fear behavior. This could at least in part be mediated by direct connections from mPFC or vHC to amygdala to control amygdala activity and output. However, currently the interactions between mPFC and vHC afferents and their specific targets in the amygdala are still poorly understood. Here, we use an ex-vivo optogenetic approach to dissect synaptic properties of inputs from mPFC and vHC to defined neuronal populations in the basal amygdala (BA), the area that we identify as a major target of these projections. We find that BA principal neurons (PNs) and local BA interneurons (INs) receive monosynaptic excitatory inputs from mPFC and vHC. In addition, both these inputs also recruit GABAergic feedforward inhibition in a substantial fraction of PNs, in some neurons this also comprises a slow GABAB-component. Amongst the innervated PNs we identify neurons that project back to subregions of the mPFC, indicating a loop between neurons in mPFC and BA, and a pathway from vHC to mPFC via BA. Interestingly, mPFC inputs also recruit feedforward inhibition in a fraction of INs, suggesting that these inputs can activate dis-inhibitory circuits in the BA. A general feature of both mPFC and vHC inputs to local INs is that excitatory inputs display faster rise and decay kinetics than in PNs, which would enable temporally precise signaling. However, mPFC and vHC inputs to both PNs and INs differ in their presynaptic release properties, in that vHC inputs are more depressing. In summary, our data describe novel wiring, and features of synaptic connections from mPFC and vHC to amygdala that could help to interpret functions of these interconnected brain areas at the network level. PMID:24634648

Sad mood induction has an opposite effect on amygdala response to emotional stimuli in euthymic patients with bipolar disorder and healthy controls

PubMed Central

Horacek, Jiri; Mikolas, Pavol; Tintera, Jaroslav; Novak, Tomas; Palenicek, Tomas; Brunovsky, Martin; Höschl, Cyril; Alda, Martin

2015-01-01

Background Aberrant amygdala reactivity to affective stimuli represents a candidate factor predisposing patients with bipolar disorder (BD) to relapse, but it is unclear to what extent amygdala reactivity is state-dependent. We evaluated the modulatory influence of mood on amygdala reactivity and functional connectivity in patients with remitted BD and healthy controls. Methods Amygdala response to sad versus neutral faces was investigated using fMRI during periods of normal and sad mood induced by autobiographical scripts. We assessed the functional connectivity of the amygdala to characterize the influence of mood state on the network responsible for the amygdala response. Results We included 20 patients with remitted BD and 20 controls in our study. The sad and normal mood exerted opposite effects on the amygdala response to emotional faces in patients compared with controls (F1,38 = 5.85, p = 0.020). Sad mood amplified the amygdala response to sad facial stimuli in controls but attenuated the amygdala response in patients. The groups differed in functional connectivity between the amygdala and the inferior prefrontal gyrus (p ≤ 0.05, family-wise error–corrected) of ventrolateral prefrontal cortex (vlPFC) corresponding to Brodmann area 47. The sad mood challenge increased connectivity during the period of processing sad faces in patients but decreased connectivity in controls. Limitations Limitations to our study included long-term medication use in the patient group and the fact that we mapped only depressive (not manic) reactivity. Conclusion Our results support the role of the amygdala–vlPFC as the system of dysfunctional contextual affective processing in patients with BD. Opposite amygdala reactivity unmasked by the mood challenge paradigm could represent a trait marker of altered mood regulation in patients with BD. PMID:25703646

A new efficient method for synaptic vesicle quantification reveals differences between medial prefrontal cortex perforated and nonperforated synapses.

PubMed

Nava, Nicoletta; Chen, Fenghua; Wegener, Gregers; Popoli, Maurizio; Nyengaard, Jens Randel

2014-02-01

Communication between neurons is mediated by the release of neurotransmitter-containing vesicles from presynaptic terminals. Quantitative characterization of synaptic vesicles can be highly valuable for understanding mechanisms underlying synaptic function and plasticity. We performed a quantitative ultrastructural analysis of cortical excitatory synapses by mean of a new, efficient method, as an alternative to three-dimensional (3D) reconstruction. Based on a hierarchical sampling strategy and unequivocal identification of the region of interest, serial sections from excitatory synapses of medial prefrontal cortex (mPFC) of six Sprague-Dawley rats were acquired with a transmission electron microscope. Unbiased estimates of total 3D volume of synaptic terminals were obtained through the Cavalieri estimator, and adequate correction factors for vesicle profile number estimation were applied for final vesicle quantification. Our analysis was based on 79 excitatory synapses, nonperforated (NPSs) and perforated (PSs) subtypes. We found that total number of docked and reserve-pool vesicles in PSs significantly exceeded that in NPSs (by, respectively, 77% and 78%). These differences were found to be related to changes in size between the two subtypes (active zone area by 86%; bouton volume by 105%) rather than to postsynaptic density shape. Positive significant correlations were found between number of docked and reserve-pool vesicles, active zone area and docked vesicles, and bouton volume and reserve pool vesicles. Our method confirmed the large size of mPFC PSs and a linear correlation between presynaptic features of typical hippocampal synapses. Moreover, a greater number of docked vesicles in PSs may promote a high synaptic strength of these synapses. Copyright © 2013 Wiley Periodicals, Inc.

Sad mood induction has an opposite effect on amygdala response to emotional stimuli in euthymic patients with bipolar disorder and healthy controls.

PubMed

Horacek, Jiri; Mikolas, Pavol; Tintera, Jaroslav; Novak, Tomas; Palenicek, Tomas; Brunovsky, Martin; Höschl, Cyril; Alda, Martin

2014-12-16

Aberrant amygdala reactivity to affective stimuli represents a candidate factor predisposing patients with bipolar disorder (BD) to relapse, but it is unclear to what extent amygdala reactivity is state-dependent. We evaluated the modulatory influence of mood on amygdala reactivity and functional connectivity in patients with remitted BD and healthy controls. Amygdala response to sad versus neutral faces was investigated using fMRI during periods of normal and sad mood induced by autobiographical scripts. We assessed the functional connectivity of the amygdala to characterize the influence of mood state on the network responsible for the amygdala response. We included 20 patients with remitted BD and 20 controls in our study. The sad and normal mood exerted opposite effects on the amygdala response to emotional faces in patients compared with controls ( F 1,38 = 5.85, p = 0.020). Sad mood amplified the amygdala response to sad facial stimuli in controls but attenuated the amygdala response in patients. The groups differed in functional connectivity between the amygdala and the inferior prefrontal gyrus ( p ≤ 0.05, family-wise error-corrected) of ventrolateral prefrontal cortex (vlPFC) corresponding to Brodmann area 47. The sad mood challenge increased connectivity during the period of processing sad faces in patients but decreased connectivity in controls. Limitations to our study included long-term medication use in the patient group and the fact that we mapped only depressive (not manic) reactivity. Our results support the role of the amygdala-vlPFC as the system of dysfunctional contextual affective processing in patients with BD. Opposite amygdala reactivity unmasked by the mood challenge paradigm could represent a trait marker of altered mood regulation in patients with BD.

Sad mood induction has an opposite effect on amygdala response to emotional stimuli in euthymic patients with bipolar disorder and healthy controls.

PubMed

Horacek, Jiri; Mikolas, Pavol; Tintera, Jaroslav; Novak, Tomas; Palenicek, Tomas; Brunovsky, Martin; Höschl, Cyril; Alda, Martin

2015-03-01

Aberrant amygdala reactivity to affective stimuli represents a candidate factor predisposing patients with bipolar disorder (BD) to relapse, but it is unclear to what extent amygdala reactivity is state-dependent. We evaluated the modulatory influence of mood on amygdala reactivity and functional connectivity in patients with remitted BD and healthy controls. Amygdala response to sad versus neutral faces was investigated using fMRI during periods of normal and sad mood induced by autobiographical scripts. We assessed the functional connectivity of the amygdala to characterize the influence of mood state on the network responsible for the amygdala response. We included 20 patients with remitted BD and 20 controls in our study. The sad and normal mood exerted opposite effects on the amygdala response to emotional faces in patients compared with controls (F1,38 = 5.85, p = 0.020). Sad mood amplified the amygdala response to sad facial stimuli in controls but attenuated the amygdala response in patients. The groups differed in functional connectivity between the amygdala and the inferior prefrontal gyrus (p ≤ 0.05, family-wise error-corrected) of ventrolateral prefrontal cortex (vlPFC) corresponding to Brodmann area 47. The sad mood challenge increased connectivity during the period of processing sad faces in patients but decreased connectivity in controls. Limitations to our study included long-term medication use in the patient group and the fact that we mapped only depressive (not manic) reactivity. Our results support the role of the amygdala-vlPFC as the system of dysfunctional contextual affective processing in patients with BD. Opposite amygdala reactivity unmasked by the mood challenge paradigm could represent a trait marker of altered mood regulation in patients with BD.

14 CFR 158.41 - General.

Code of Federal Regulations, 2014 CFR

2014-01-01

... FACILITY CHARGES (PFC'S) Collection, Handling, and Remittance of PFC's § 158.41 General. This subpart contains the requirements for notification, collection, handling and remittance of PFC's. ...

14 CFR 158.41 - General.

Code of Federal Regulations, 2013 CFR

2013-01-01

... FACILITY CHARGES (PFC'S) Collection, Handling, and Remittance of PFC's § 158.41 General. This subpart contains the requirements for notification, collection, handling and remittance of PFC's. ...

14 CFR 158.41 - General.

Code of Federal Regulations, 2012 CFR

2012-01-01

... FACILITY CHARGES (PFC'S) Collection, Handling, and Remittance of PFC's § 158.41 General. This subpart contains the requirements for notification, collection, handling and remittance of PFC's. ...

14 CFR 158.41 - General.

Code of Federal Regulations, 2011 CFR

2011-01-01

... FACILITY CHARGES (PFC'S) Collection, Handling, and Remittance of PFC's § 158.41 General. This subpart contains the requirements for notification, collection, handling and remittance of PFC's. ...

14 CFR 158.41 - General.

Code of Federal Regulations, 2010 CFR

2010-01-01

... FACILITY CHARGES (PFC'S) Collection, Handling, and Remittance of PFC's § 158.41 General. This subpart contains the requirements for notification, collection, handling and remittance of PFC's. ...

14 CFR 158.9 - Limitations.

Code of Federal Regulations, 2010 CFR

2010-01-01

... PASSENGER FACILITY CHARGES (PFC'S) General § 158.9 Limitations. (a) No public agency may impose a PFC on any... Department of Transportation for which PFC's may not be imposed under this section; (3) Who is a nonrevenue... a point or points in the U.S. to collect a PFC from a passenger. [Doc. No. 26385, 56 FR 24278, May...

14 CFR 158.9 - Limitations.

Code of Federal Regulations, 2012 CFR

2012-01-01

... PASSENGER FACILITY CHARGES (PFC'S) General § 158.9 Limitations. (a) No public agency may impose a PFC on any... Department of Transportation for which PFC's may not be imposed under this section; (3) Who is a nonrevenue... a point or points in the U.S. to collect a PFC from a passenger. [Doc. No. 26385, 56 FR 24278, May...

14 CFR 158.9 - Limitations.

Code of Federal Regulations, 2013 CFR

2013-01-01

... PASSENGER FACILITY CHARGES (PFC'S) General § 158.9 Limitations. (a) No public agency may impose a PFC on any... Department of Transportation for which PFC's may not be imposed under this section; (3) Who is a nonrevenue... a point or points in the U.S. to collect a PFC from a passenger. [Doc. No. 26385, 56 FR 24278, May...

14 CFR 158.9 - Limitations.

Code of Federal Regulations, 2011 CFR

2011-01-01

... PASSENGER FACILITY CHARGES (PFC'S) General § 158.9 Limitations. (a) No public agency may impose a PFC on any... Department of Transportation for which PFC's may not be imposed under this section; (3) Who is a nonrevenue... a point or points in the U.S. to collect a PFC from a passenger. [Doc. No. 26385, 56 FR 24278, May...

14 CFR 158.9 - Limitations.

Code of Federal Regulations, 2014 CFR

2014-01-01

... PASSENGER FACILITY CHARGES (PFC'S) General § 158.9 Limitations. (a) No public agency may impose a PFC on any... Department of Transportation for which PFC's may not be imposed under this section; (3) Who is a nonrevenue... a point or points in the U.S. to collect a PFC from a passenger. [Doc. No. 26385, 56 FR 24278, May...

Contributions of primate prefrontal cortex and medial temporal lobe to temporal-order memory.

PubMed

Naya, Yuji; Chen, He; Yang, Cen; Suzuki, Wendy A

2017-12-19

Neuropsychological and neurophysiological studies have emphasized the role of the prefrontal cortex (PFC) in maintaining information about the temporal order of events or items for upcoming actions. However, the medial temporal lobe (MTL) has also been considered critical to bind individual events or items to their temporal context in episodic memory. Here we characterize the contributions of these brain areas by comparing single-unit activity in the dorsal and ventral regions of macaque lateral PFC (d-PFC and v-PFC) with activity in MTL areas including the hippocampus (HPC), entorhinal cortex, and perirhinal cortex (PRC) as well as in area TE during the encoding phase of a temporal-order memory task. The v-PFC cells signaled specific items at particular time periods of the task. By contrast, MTL cortical cells signaled specific items across multiple time periods and discriminated the items between time periods by modulating their firing rates. Analysis of the temporal dynamics of these signals showed that the conjunctive signal of item and temporal-order information in PRC developed earlier than that seen in v-PFC. During the delay interval between the two cue stimuli, while v-PFC provided prominent stimulus-selective delay activity, MTL areas did not. Both regions of PFC and HPC exhibited an incremental timing signal that appeared to represent the continuous passage of time during the encoding phase. However, the incremental timing signal in HPC was more prominent than that observed in PFC. These results suggest that PFC and MTL contribute to the encoding of the integration of item and timing information in distinct ways.

Mediodorsal Thalamic Neurons Mirror the Activity of Medial Prefrontal Neurons Responding to Movement and Reinforcement during a Dynamic DNMTP Task

PubMed Central

Miller, Rikki L.A.

2017-01-01

Abstract The mediodorsal nucleus (MD) interacts with medial prefrontal cortex (mPFC) to support learning and adaptive decision-making. MD receives driver (layer 5) and modulatory (layer 6) projections from PFC and is the main source of driver thalamic projections to middle cortical layers of PFC. Little is known about the activity of MD neurons and their influence on PFC during decision-making. We recorded MD neurons in rats performing a dynamic delayed nonmatching to position (dDNMTP) task and compared results to a previous study of mPFC with the same task (Onos et al., 2016). Criterion event-related responses were observed for 22% (254/1179) of neurons recorded in MD, 237 (93%) of which exhibited activity consistent with mPFC response types. More MD than mPFC neurons exhibited responses related to movement (45% vs. 29%) and reinforcement (51% vs. 27%). MD had few responses related to lever presses, and none related to preparation or memory delay, which constituted 43% of event-related activity in mPFC. Comparison of averaged normalized population activity and population response times confirmed the broad similarity of common response types in MD and mPFC and revealed differences in the onset and offset of some response types. Our results show that MD represents information about actions and outcomes essential for decision-making during dDNMTP, consistent with evidence from lesion studies that MD supports reward-based learning and action-selection. These findings support the hypothesis that MD reinforces task-relevant neural activity in PFC that gives rise to adaptive behavior. PMID:29034318

Mediodorsal Thalamic Neurons Mirror the Activity of Medial Prefrontal Neurons Responding to Movement and Reinforcement during a Dynamic DNMTP Task.

PubMed

Miller, Rikki L A; Francoeur, Miranda J; Gibson, Brett M; Mair, Robert G

2017-01-01

The mediodorsal nucleus (MD) interacts with medial prefrontal cortex (mPFC) to support learning and adaptive decision-making. MD receives driver (layer 5) and modulatory (layer 6) projections from PFC and is the main source of driver thalamic projections to middle cortical layers of PFC. Little is known about the activity of MD neurons and their influence on PFC during decision-making. We recorded MD neurons in rats performing a dynamic delayed nonmatching to position (dDNMTP) task and compared results to a previous study of mPFC with the same task (Onos et al., 2016). Criterion event-related responses were observed for 22% (254/1179) of neurons recorded in MD, 237 (93%) of which exhibited activity consistent with mPFC response types. More MD than mPFC neurons exhibited responses related to movement (45% vs. 29%) and reinforcement (51% vs. 27%). MD had few responses related to lever presses, and none related to preparation or memory delay, which constituted 43% of event-related activity in mPFC. Comparison of averaged normalized population activity and population response times confirmed the broad similarity of common response types in MD and mPFC and revealed differences in the onset and offset of some response types. Our results show that MD represents information about actions and outcomes essential for decision-making during dDNMTP, consistent with evidence from lesion studies that MD supports reward-based learning and action-selection. These findings support the hypothesis that MD reinforces task-relevant neural activity in PFC that gives rise to adaptive behavior.

Effect of oxygenated perfluorocarbon on isolated islets during transportation.

PubMed

Terai, Sachio; Tsujimura, Toshiaki; Li, Shiri; Hori, Yuichi; Toyama, Hirochika; Shinzeki, Makoto; Matsumoto, Ippei; Kuroda, Yoshikazu; Ku, Yonson

2010-08-01

Previous studies demonstrated the efficacy of the two-layer method (TLM) using oxygenated perfluorochemicals (PFC) for pancreas preservation. The current study investigated the effect of oxygenated PFC on isolated islets during transportation. Purified rat islets were stored in an airtight conical tube for 24h in RPMI culture medium at 22 degrees C or University of Wisconsin solution (UW) at 4 degrees C, either with or without oxygenated PFC. After storage, the islets were assessed for in vitro viability by static incubation (SI), FDA/PI staining, and energy status (ATP, energy charge, and ADP/ATP ratio) and for in vivo viability by a transplantation study. UW at 4 degrees C and RPMI medium at 22 degrees C maintained islet quality almost equally in both in vitro and in vivo assessments. The ATP levels and energy status in the groups with PFC were significantly lower than those without PFC. The groups with PFC showed a significantly higher ADP/ATP ratio than those without PFC. In the transplantation study, blood glucose levels and AUC in the UW+PFC group were significantly higher than those in UW group. UW at 4 degrees C and RPMI medium at 22 degrees C maintained islet quality equally under the conditions for islet transportation. The addition of oxygenated PFC, while advantageous for pancreas preservation, is not useful for islet transportation. Copyright 2010 Elsevier Inc. All rights reserved.

Investigating the role of the ventromedial prefrontal cortex in the assessment of brands.

PubMed

Santos, José Paulo; Seixas, Daniela; Brandão, Sofia; Moutinho, Luiz

2011-01-01

The ventromedial prefrontal cortex (vmPFC) is believed to be important in everyday preference judgments, processing emotions during decision-making. However, there is still controversy in the literature regarding the participation of the vmPFC. To further elucidate the contribution of the vmPFC in brand preference, we designed a functional magnetic resonance imaging (fMRI) study where 18 subjects assessed positive, indifferent, and fictitious brands. Also, both the period during and after the decision process were analyzed, hoping to unravel temporally the role of the vmPFC, using modeled and model-free fMRI analysis. Considering together the period before and after decision-making, there was activation of the vmPFC when comparing positive with indifferent or fictitious brands. However, when the decision-making period was separated from the moment after the response, and especially for positive brands, the vmPFC was more active after the choice than during the decision process itself, challenging some of the existing literature. The results of the present study support the notion that the vmPFC may be unimportant in the decision stage of brand preference, questioning theories that postulate that the vmPFC is in the origin of such a choice. Further studies are needed to investigate in detail why the vmPFC seems to be involved in brand preference only after the decision process.

Investigating the Role of the Ventromedial Prefrontal Cortex in the Assessment of Brands

PubMed Central

Santos, José Paulo; Seixas, Daniela; Brandão, Sofia; Moutinho, Luiz

2011-01-01

The ventromedial prefrontal cortex (vmPFC) is believed to be important in everyday preference judgments, processing emotions during decision-making. However, there is still controversy in the literature regarding the participation of the vmPFC. To further elucidate the contribution of the vmPFC in brand preference, we designed a functional magnetic resonance imaging (fMRI) study where 18 subjects assessed positive, indifferent, and fictitious brands. Also, both the period during and after the decision process were analyzed, hoping to unravel temporally the role of the vmPFC, using modeled and model-free fMRI analysis. Considering together the period before and after decision-making, there was activation of the vmPFC when comparing positive with indifferent or fictitious brands. However, when the decision-making period was separated from the moment after the response, and especially for positive brands, the vmPFC was more active after the choice than during the decision process itself, challenging some of the existing literature. The results of the present study support the notion that the vmPFC may be unimportant in the decision stage of brand preference, questioning theories that postulate that the vmPFC is in the origin of such a choice. Further studies are needed to investigate in detail why the vmPFC seems to be involved in brand preference only after the decision process. PMID:21687799

14 CFR 158.18 - Use of PFC revenue to pay for debt service for non-eligible projects.

Code of Federal Regulations, 2011 CFR

2011-01-01

..., DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) General § 158.18 Use of PFC revenue to pay for debt service for non-eligible projects. (a) The FAA may authorize a public... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Use of PFC revenue to pay for debt service...

14 CFR 158.18 - Use of PFC revenue to pay for debt service for non-eligible projects.

Code of Federal Regulations, 2013 CFR

2013-01-01

..., DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) General § 158.18 Use of PFC revenue to pay for debt service for non-eligible projects. (a) The FAA may authorize a public... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Use of PFC revenue to pay for debt service...

14 CFR 158.18 - Use of PFC revenue to pay for debt service for non-eligible projects.

Code of Federal Regulations, 2010 CFR

2010-01-01

..., DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) General § 158.18 Use of PFC revenue to pay for debt service for non-eligible projects. (a) The FAA may authorize a public... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Use of PFC revenue to pay for debt service...

14 CFR 158.18 - Use of PFC revenue to pay for debt service for non-eligible projects.

Code of Federal Regulations, 2014 CFR

2014-01-01

..., DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) General § 158.18 Use of PFC revenue to pay for debt service for non-eligible projects. (a) The FAA may authorize a public... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Use of PFC revenue to pay for debt service...

14 CFR 158.18 - Use of PFC revenue to pay for debt service for non-eligible projects.

Code of Federal Regulations, 2012 CFR

2012-01-01

..., DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) General § 158.18 Use of PFC revenue to pay for debt service for non-eligible projects. (a) The FAA may authorize a public... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Use of PFC revenue to pay for debt service...

vlPFC-vmPFC-Amygdala Interactions Underlie Age-Related Differences in Cognitive Regulation of Emotion.

PubMed

Silvers, Jennifer A; Insel, Catherine; Powers, Alisa; Franz, Peter; Helion, Chelsea; Martin, Rebecca E; Weber, Jochen; Mischel, Walter; Casey, B J; Ochsner, Kevin N

2017-07-01

Emotion regulation is a critical life skill that develops throughout childhood and adolescence. Despite this development in emotional processes, little is known about how the underlying brain systems develop with age. This study examined emotion regulation in 112 individuals (aged 6-23 years) as they viewed aversive and neutral images using a reappraisal task. On "reappraisal" trials, participants were instructed to view the images as distant, a strategy that has been previously shown to reduce negative affect. On "reactivity" trials, participants were instructed to view the images without regulating emotions to assess baseline emotional responding. During reappraisal, age predicted less negative affect, reduced amygdala responses and inverse coupling between the ventromedial prefrontal cortex (vmPFC) and amygdala. Moreover, left ventrolateral prefrontal (vlPFC) recruitment mediated the relationship between increasing age and diminishing amygdala responses. This negative vlPFC-amygdala association was stronger for individuals with inverse coupling between the amygdala and vmPFC. These data provide evidence that vmPFC-amygdala connectivity facilitates vlPFC-related amygdala modulation across development. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The role of medial prefrontal cortex in memory and decision making.

PubMed

Euston, David R; Gruber, Aaron J; McNaughton, Bruce L

2012-12-20

Some have claimed that the medial prefrontal cortex (mPFC) mediates decision making. Others suggest mPFC is selectively involved in the retrieval of remote long-term memory. Yet others suggests mPFC supports memory and consolidation on time scales ranging from seconds to days. How can all these roles be reconciled? We propose that the function of the mPFC is to learn associations between context, locations, events, and corresponding adaptive responses, particularly emotional responses. Thus, the ubiquitous involvement of mPFC in both memory and decision making may be due to the fact that almost all such tasks entail the ability to recall the best action or emotional response to specific events in a particular place and time. An interaction between multiple memory systems may explain the changing importance of mPFC to different types of memories over time. In particular, mPFC likely relies on the hippocampus to support rapid learning and memory consolidation. Copyright © 2012 Elsevier Inc. All rights reserved.

Massive remobilization of permafrost carbon during post-glacial warming

PubMed Central

Tesi, T.; Muschitiello, F.; Smittenberg, R. H.; Jakobsson, M.; Vonk, J. E.; Hill, P.; Andersson, A.; Kirchner, N.; Noormets, R.; Dudarev, O.; Semiletov, I.; Gustafsson, Ö

2016-01-01

Recent hypotheses, based on atmospheric records and models, suggest that permafrost carbon (PF-C) accumulated during the last glaciation may have been an important source for the atmospheric CO2 rise during post-glacial warming. However, direct physical indications for such PF-C release have so far been absent. Here we use the Laptev Sea (Arctic Ocean) as an archive to investigate PF-C destabilization during the last glacial–interglacial period. Our results show evidence for massive supply of PF-C from Siberian soils as a result of severe active layer deepening in response to the warming. Thawing of PF-C must also have brought about an enhanced organic matter respiration and, thus, these findings suggest that PF-C may indeed have been an important source of CO2 across the extensive permafrost domain. The results challenge current paradigms on the post-glacial CO2 rise and, at the same time, serve as a harbinger for possible consequences of the present-day warming of PF-C soils. PMID:27897191

Capturing the temporal evolution of choice across prefrontal cortex

PubMed Central

Hunt, Laurence T; Behrens, Timothy EJ; Hosokawa, Takayuki; Wallis, Jonathan D; Kennerley, Steven W

2015-01-01

Activity in prefrontal cortex (PFC) has been richly described using economic models of choice. Yet such descriptions fail to capture the dynamics of decision formation. Describing dynamic neural processes has proven challenging due to the problem of indexing the internal state of PFC and its trial-by-trial variation. Using primate neurophysiology and human magnetoencephalography, we here recover a single-trial index of PFC internal states from multiple simultaneously recorded PFC subregions. This index can explain the origins of neural representations of economic variables in PFC. It describes the relationship between neural dynamics and behaviour in both human and monkey PFC, directly bridging between human neuroimaging data and underlying neuronal activity. Moreover, it reveals a functionally dissociable interaction between orbitofrontal cortex, anterior cingulate cortex and dorsolateral PFC in guiding cost-benefit decisions. We cast our observations in terms of a recurrent neural network model of choice, providing formal links to mechanistic dynamical accounts of decision-making. DOI: http://dx.doi.org/10.7554/eLife.11945.001 PMID:26653139

Dynamic frontotemporal systems process space and time in working memory

PubMed Central

Adams, Jenna N.; Solbakk, Anne-Kristin; Endestad, Tor; Larsson, Pål G.; Ivanovic, Jugoslav; Meling, Torstein R.; Lin, Jack J.; Knight, Robert T.

2018-01-01

How do we rapidly process incoming streams of information in working memory, a cognitive mechanism central to human behavior? Dominant views of working memory focus on the prefrontal cortex (PFC), but human hippocampal recordings provide a neurophysiological signature distinct from the PFC. Are these regions independent, or do they interact in the service of working memory? We addressed this core issue in behavior by recording directly from frontotemporal sites in humans performing a visuospatial working memory task that operationalizes the types of identity and spatiotemporal information we encounter every day. Theta band oscillations drove bidirectional interactions between the PFC and medial temporal lobe (MTL; including the hippocampus). MTL theta oscillations directed the PFC preferentially during the processing of spatiotemporal information, while PFC theta oscillations directed the MTL for all types of information being processed in working memory. These findings reveal an MTL theta mechanism for processing space and time and a domain-general PFC theta mechanism, providing evidence that rapid, dynamic MTL–PFC interactions underlie working memory for everyday experiences. PMID:29601574

Activation of Corticostriatal Circuitry Relieves Chronic Neuropathic Pain

PubMed Central

Lee, Michelle; Manders, Toby R.; Eberle, Sarah E.; Su, Chen; D'amour, James; Yang, Runtao; Lin, Hau Yueh; Deisseroth, Karl; Froemke, Robert C.

2015-01-01

Neural circuits that determine the perception and modulation of pain remain poorly understood. The prefrontal cortex (PFC) provides top-down control of sensory and affective processes. While animal and human imaging studies have shown that the PFC is involved in pain regulation, its exact role in pain states remains incompletely understood. A key output target for the PFC is the nucleus accumbens (NAc), an important component of the reward circuitry. Interestingly, recent human imaging studies suggest that the projection from the PFC to the NAc is altered in chronic pain. The function of this corticostriatal projection in pain states, however, is not known. Here we show that optogenetic activation of the PFC produces strong antinociceptive effects in a rat model (spared nerve injury model) of persistent neuropathic pain. PFC activation also reduces the affective symptoms of pain. Furthermore, we show that this pain-relieving function of the PFC is likely mediated by projections to the NAc. Thus, our results support a novel role for corticostriatal circuitry in pain regulation. PMID:25834050

Comparison of Phase Field Crystal and Molecular Dynamics Simulations for a Shrinking Grain

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

Radhakrishnan, Balasubramaniam; Gorti, Sarma B; Nicholson, Don M

2012-01-01

The Phase-Field Crystal (PFC) model represents the atomic density as a continuous function, whose spatial distribution evolves at diffusional, rather than vibrational time scales. PFC provides a tool to study defect interactions at the atomistic level but over longer time scales than in molecular dynamics (MD). We examine the behavior of the PFC model with the goal of relating the PFC parameters to physical parameters of real systems, derived from MD simulations. For this purpose we model the phenomenon of the shrinking of a spherical grain situated in a matrix. By comparing the rate of shrinking of the central grainmore » using MD and PFC we obtain a relationship between PFC and MD time scales for processes driven by grain boundary diffusion. The morphological changes in the central grain including grain shape and grain rotation are also examined in order to assess the accuracy of the PFC in capturing the evolution path predicted by MD.« less

The medial prefrontal and orbitofrontal cortices differentially regulate dopamine system function.

PubMed

Lodge, Daniel J

2011-05-01

The prefrontal cortex (PFC) is essential for top-down control over higher-order executive function. In this study we demonstrate that the medial prefrontal cortex (mPFC) and orbitofrontal cortex (OFC) differentially regulate VTA dopamine neuron activity, and furthermore, the pattern of activity in the PFC drastically alters the dopamine neuron response. Thus, although single-pulse activation of the mPFC either excites or inhibits equivalent numbers of dopamine neurons, activation of the OFC induces a primarily inhibitory response. Moreover, activation of the PFC with a pattern that mimics spontaneous burst firing of pyramidal neurons produces a strikingly different response. Specifically, burst-like activation of the mPFC induces a massive increase in dopamine neuron firing, whereas a similar pattern of OFC activation largely inhibits dopamine activity. Taken together, these data demonstrate that the mPFC and OFC differentially regulate dopamine neuron activity, and that the pattern of cortical activation is critical for determining dopamine system output.

dcc orchestrates the development of the prefrontal cortex during adolescence and is altered in psychiatric patients.

PubMed

Manitt, C; Eng, C; Pokinko, M; Ryan, R T; Torres-Berrío, A; Lopez, J P; Yogendran, S V; Daubaras, M J J; Grant, A; Schmidt, E R E; Tronche, F; Krimpenfort, P; Cooper, H M; Pasterkamp, R J; Kolb, B; Turecki, G; Wong, T P; Nestler, E J; Giros, B; Flores, C

2013-12-17

Adolescence is a period of heightened susceptibility to psychiatric disorders of medial prefrontal cortex (mPFC) dysfunction and cognitive impairment. mPFC dopamine (DA) projections reach maturity only in early adulthood, when their control over cognition becomes fully functional. The mechanisms governing this protracted and unique development are unknown. Here we identify dcc as the first DA neuron gene to regulate mPFC connectivity during adolescence and dissect the mechanisms involved. Reduction or loss of dcc from DA neurons by Cre-lox recombination increased mPFC DA innervation. Underlying this was the presence of ectopic DA fibers that normally innervate non-cortical targets. Altered DA input changed the anatomy and electrophysiology of mPFC circuits, leading to enhanced cognitive flexibility. All phenotypes only emerged in adulthood. Using viral Cre, we demonstrated that dcc organizes mPFC wiring specifically during adolescence. Variations in DCC may determine differential predisposition to mPFC disorders in humans. Indeed, DCC expression is elevated in brains of antidepressant-free subjects who committed suicide.

Massive remobilization of permafrost carbon during post-glacial warming

NASA Astrophysics Data System (ADS)

Tesi, T.; Muschitiello, F.; Smittenberg, R. H.; Jakobsson, M.; Vonk, J. E.; Hill, P.; Andersson, A.; Kirchner, N.; Noormets, R.; Dudarev, O.; Semiletov, I.; Gustafsson, Ö.

2016-11-01

Recent hypotheses, based on atmospheric records and models, suggest that permafrost carbon (PF-C) accumulated during the last glaciation may have been an important source for the atmospheric CO2 rise during post-glacial warming. However, direct physical indications for such PF-C release have so far been absent. Here we use the Laptev Sea (Arctic Ocean) as an archive to investigate PF-C destabilization during the last glacial-interglacial period. Our results show evidence for massive supply of PF-C from Siberian soils as a result of severe active layer deepening in response to the warming. Thawing of PF-C must also have brought about an enhanced organic matter respiration and, thus, these findings suggest that PF-C may indeed have been an important source of CO2 across the extensive permafrost domain. The results challenge current paradigms on the post-glacial CO2 rise and, at the same time, serve as a harbinger for possible consequences of the present-day warming of PF-C soils.

Medial PFC Damage Abolishes the Self-reference Effect

PubMed Central

Philippi, Carissa L.; Duff, Melissa C.; Denburg, Natalie L.; Tranel, Daniel; Rudrauf, David

2012-01-01

Functional neuroimaging studies suggest that the medial PFC (mPFC) is a key component of a large-scale neural system supporting a variety of self-related processes. However, it remains unknown whether the mPFC is critical for such processes. In this study, we used a human lesion approach to examine this question. We administered a standard trait judgment paradigm [Kelley, W. M., Macrae, C. N., Wyland, C. L., Caglar, S., Inati, S., & Heatherton, T. F. Finding the self? An event-related fMRI study. Journal of Cognitive Neuroscience, 14, 785–794, 2002] to patients with focal brain damage to the mPFC. The self-reference effect (SRE), a memory advantage conferred by self-related processing, served as a measure of intact self-processing ability. We found that damage to the mPFC abolished the SRE. The results demonstrate that the mPFC is necessary for the SRE and suggest that this structure is important for self-referential processing and the neural representation of self. PMID:21942762

The Network Architecture of Cortical Processing in Visuo-spatial Reasoning

PubMed Central

Shokri-Kojori, Ehsan; Motes, Michael A.; Rypma, Bart; Krawczyk, Daniel C.

2012-01-01

Reasoning processes have been closely associated with prefrontal cortex (PFC), but specifically emerge from interactions among networks of brain regions. Yet it remains a challenge to integrate these brain-wide interactions in identifying the flow of processing emerging from sensory brain regions to abstract processing regions, particularly within PFC. Functional magnetic resonance imaging data were collected while participants performed a visuo-spatial reasoning task. We found increasing involvement of occipital and parietal regions together with caudal-rostral recruitment of PFC as stimulus dimensions increased. Brain-wide connectivity analysis revealed that interactions between primary visual and parietal regions predominantly influenced activity in frontal lobes. Caudal-to-rostral influences were found within left-PFC. Right-PFC showed evidence of rostral-to-caudal connectivity in addition to relatively independent influences from occipito-parietal cortices. In the context of hierarchical views of PFC organization, our results suggest that a caudal-to-rostral flow of processing may emerge within PFC in reasoning tasks with minimal top-down deductive requirements. PMID:22624092

The network architecture of cortical processing in visuo-spatial reasoning.

PubMed

Shokri-Kojori, Ehsan; Motes, Michael A; Rypma, Bart; Krawczyk, Daniel C

2012-01-01

Reasoning processes have been closely associated with prefrontal cortex (PFC), but specifically emerge from interactions among networks of brain regions. Yet it remains a challenge to integrate these brain-wide interactions in identifying the flow of processing emerging from sensory brain regions to abstract processing regions, particularly within PFC. Functional magnetic resonance imaging data were collected while participants performed a visuo-spatial reasoning task. We found increasing involvement of occipital and parietal regions together with caudal-rostral recruitment of PFC as stimulus dimensions increased. Brain-wide connectivity analysis revealed that interactions between primary visual and parietal regions predominantly influenced activity in frontal lobes. Caudal-to-rostral influences were found within left-PFC. Right-PFC showed evidence of rostral-to-caudal connectivity in addition to relatively independent influences from occipito-parietal cortices. In the context of hierarchical views of PFC organization, our results suggest that a caudal-to-rostral flow of processing may emerge within PFC in reasoning tasks with minimal top-down deductive requirements.

Bardoxolone methyl prevents high-fat diet-induced alterations in prefrontal cortex signalling molecules involved in recognition memory.

PubMed

Camer, Danielle; Yu, Yinghua; Szabo, Alexander; Fernandez, Francesca; Dinh, Chi H L; Huang, Xu-Feng

2015-06-03

High fat (HF) diets are known to induce changes in synaptic plasticity in the forebrain leading to learning and memory impairments. Previous studies of oleanolic acid derivatives have found that these compounds can cross the blood-brain barrier to prevent neuronal cell death. We examined the hypothesis that the oleanolic acid derivative, bardoxolone methyl (BM) would prevent diet-induced cognitive deficits in mice fed a HF diet. C57BL/6J male mice were fed a lab chow (LC) (5% of energy as fat), a HF (40% of energy as fat), or a HF diet supplemented with 10mg/kg/day BM orally for 21weeks. Recognition memory was assessed by performing a novel object recognition test on the treated mice. Downstream brain-derived neurotrophic factor (BDNF) signalling molecules were examined in the prefrontal cortex (PFC) and hippocampus of mice via Western blotting and N-methyl-d-aspartate (NMDA) receptor binding. BM treatment prevented HF diet-induced impairment in recognition memory (p<0.001). In HF diet fed mice, BM administration attenuated alterations in the NMDA receptor binding density in the PFC (p<0.05), however, no changes were seen in the hippocampus (p>0.05). In the PFC and hippocampus of the HF diet fed mice, BM administration improved downstream BDNF signalling as indicated by increased protein levels of BDNF, phosphorylated tropomyosin related kinase B (pTrkB) and phosphorylated protein kinase B (pAkt), and increased phosphorylated AMP-activated protein kinase (pAMPK) (p<0.05). BM administration also prevented the HF diet-induced increase in the protein levels of inflammatory molecules, phosphorylated c-Jun N-terminal kinase (pJNK) in the PFC, and protein tyrosine phosphatase 1B (PTP1B) in both the PFC and hippocampus. In summary, these findings suggest that BM prevents HF diet-induced impairments in recognition memory by improving downstream BDNF signal transduction, increasing pAMPK, and reducing inflammation in the PFC and hippocampus. Copyright © 2015 Elsevier Inc. All rights reserved.

Role of Adrenal Glucocorticoid Signaling in Prefrontal Cortex Gene Expression and Acute Behavioral Responses to Ethanol

PubMed Central

Costin, Blair N.; Wolen, Aaron R.; Fitting, Sylvia; Shelton, Keith L.; Miles, Michael F.

2012-01-01

Background Glucocorticoid hormones modulate acute and chronic behavioral and molecular responses to drugs of abuse including psychostimulants and opioids. There is growing evidence that glucocorticoids might also modulate behavioral responses to ethanol. Acute ethanol activates the HPA axis, causing release of adrenal glucocorticoid hormones. Our prior genomic studies suggest glucocorticoids play a role in regulating gene expression in the prefrontal cortex (PFC) of DBA2/J (D2) mice following acute ethanol administration. However, few studies have analyzed the role of glucocorticoid signaling in behavioral responses to acute ethanol. Such work could be significant, given the predictive value for level of response to acute ethanol in the risk for alcoholism. Methods We studied whether the glucocorticoid receptor (GR) antagonist, RU-486, or adrenalectomy (ADX) altered male D2 mouse behavioral responses to acute (locomotor activation, anxiolysis or loss-of-righting reflex (LORR)) or repeated (sensitization) ethanol treatment. Whole genome microarray analysis and bioinformatics approaches were used to identify PFC candidate genes possibly responsible for altered behavioral responses to ethanol following ADX. Results ADX and RU-486 both impaired acute ethanol (2 g/kg) induced locomotor activation in D2 mice without affecting basal locomotor activity. However, neither ADX nor RU-486 altered initiation of ethanol sensitization (locomotor activation or jump counts), ethanol-induced anxiolysis or LORR. ADX mice showed microarray gene expression changes in PFC that significantly overlapped with acute ethanol-responsive gene sets derived by our prior microarray studies. Q-rtPCR analysis verified that ADX decreased PFC expression of Fkbp5 while significantly increasing Gpr6 expression. In addition, high dose RU-486 pre-treatment blunted ethanol-induced Fkbp5 expression. Conclusions Our studies suggest that ethanol’s activation of adrenal glucocorticoid release and subsequent GR activation may partially modulate ethanol’s acute locomotor activation in male D2 mice. Furthermore, since adrenal glucocorticoid basal tone regulated PFC gene expression, including a significant set of acute ethanol-responsive genes, this suggests that glucocorticoid regulated PFC gene expression may be an important factor modulating acute behavioral responses to ethanol. PMID:22671426

Association of diabetic foot care and amputation rates in Germany.

PubMed

Kröger, Knut; Moysidis, Theodoros; Feghaly, Michel; Schäfer, Erika; Bufe, Alexander

2016-10-01

Podologists are nurses who care for the diabetic foot (orthotics, offloading devices, blisters, calluses, treatment of fungus infection and patient education). In contrast to podiatrists, they are not qualified to perform any surgical treatment or wound care. We analysed whether there is an association between the decrease in major amputations and the number of podologic foot care (PFC) visits prescribed in Germany. Detailed list of all major lower limb amputations (OPS 5-864) performed from 2007 to 2011 was provided by the Federal Statistical Office. Data were separated for the 16 federal states in Germany. Detailed lists of the number of PFC treatments for each of the 5 years were derived from the federal report of the statutory health insurance. The total numbers of hospitalised cases per year having diabetes mellitus documented as an additional diagnosis were used to adjust for the different rates of people with diabetes in each federal state. Within a 5-year time period, population-based major amputations per 100 000 people dropped from 21·7 in 2007 to 17·5 in 2011 (-18·5%); whereas the number of PFC treatments per 1000 insured increased from 22 in 2007 to 60 in 2011 (+172·7%). The total number of major amputations divided by the total number of hospitalised cases with the additional diagnosis of diabetes mellitus (DM) shows an inverse correlation with the number of PFC treatments per 1000 insured (Pearson's correlation factor is -0·52049). The five countries with the highest increase in PFC compared with the five countries with the lowest increase (35·6 versus 15·4 per 1000 insured) will have only small differences in the decrease in major amputation rates in this period (-5·1 versus -3·4 per 100.000). There is a strong association between increasing utilisation PFC and decreasing major amputations in Germany. Further study is required to document the cost-effectiveness of this service. © 2014 The Authors. International Wound Journal © 2014 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Neuropsychopharmacology and Neurogenetic Aspects of Executive Functioning: Should Reward Gene Polymorphisms Constitute a Diagnostic Tool to Identify Individuals at Risk for Impaired Judgment?

PubMed Central

Bowirrat, Abdalla; Chen, Thomas JH; Oscar-Berman, Marlene; Madigan, Margaret; Chen, Amanda LH; Bailey, John A.; Braverman, Eric R.; Kerner, Mallory; Giordano, John; Morse, Siohban; Downs, B. William; Waite, Roger L.; Fornari, Frank; Armaly, Zaher; Blum, Kenneth

2013-01-01

Executive functions are processes that act in harmony to control behaviors necessary for maintaining focus and achieving outcomes. Executive dysfunction in neuropsychiatric disorders is attributed to structural or functional pathology of brain networks involving prefrontal cortex (PFC) and its connections with other brain regions. The PFC receives innervations from different neurons associated with a number of neurotransmitters, especially dopamine (DA). Here we review findings on the contribution of PFC DA to higher-order cognitive and emotional behaviors. We suggest examination of multifactorial interactions of an individual’s genetic history, along with environmental risk factors, can assist in the characterization of executive functioning for that individual. Based upon the results of genetic studies we also propose genetic mapping as a probable diagnostic tool serving as a therapeutic adjunct for augmenting executive functioning capabilities. We conclude that preservation of the neurological underpinnings of executive functions requires the integrity of complex neural systems including the influence of specific genes and associated polymorphisms to provide adequate neurotransmission. PMID:22371275

Ventromedial prefrontal cortex response to concentrated sucrose reflects liking rather than sweet quality coding.

PubMed

Rudenga, Kristin J; Small, Dana M

2013-09-01

The perception of the pleasantness of sweet tastes varies widely across individuals. Here, we exploit these differences to isolate brain response to sweet-taste pleasantness while controlling for intensity, quality, and physiological significance. Thirty subjects participated in functional MRI scanning while consuming individually calibrated weak and strong sucrose solutions. All subjects found the weak sweet taste to be neutral in pleasantness, but half of the subjects found strong sweet taste pleasant (likers), whereas half found strong sweet taste unpleasant (dislikers). Greater response was observed in the ventromedial prefrontal cortex (vmPFC) to the sucrose when it was rated pleasant versus neutral compared with unpleasant versus neutral. This suggests that response in the vmPFC underlies sweet-taste preference, this region is preferentially sensitive to affectively positive tastes, and it is the positive value rather than physiological significance, quality, or intensity that drives responses here. Likers versus dislikers did not differ in their diet, alcohol use, body weight, gender, or taq1A allele status, but likers were more likely to report emotional eating. None of these factors influenced response in the vmPFC.

Layer 2/3 pyramidal cells in the medial prefrontal cortex moderate stress induced depressive behaviors

PubMed Central

Shrestha, Prerana; Mousa, Awni; Heintz, Nathaniel

2015-01-01

Major depressive disorder (MDD) is a prevalent illness that can be precipitated by acute or chronic stress. Studies of patients with Wolfram syndrome and carriers have identified Wfs1 mutations as causative for MDD. The medial prefrontal cortex (mPFC) is known to be involved in depression and behavioral resilience, although the cell types and circuits in the mPFC that moderate depressive behaviors in response to stress have not been determined. Here, we report that deletion of Wfs1 from layer 2/3 pyramidal cells impairs the ability of the mPFC to suppress stress-induced depressive behaviors, and results in hyperactivation of the hypothalamic–pituitary–adrenal axis and altered accumulation of important growth and neurotrophic factors. Our data identify superficial layer 2/3 pyramidal cells as critical for moderation of stress in the context of depressive behaviors and suggest that dysfunction in these cells may contribute to the clinical relationship between stress and depression. DOI: http://dx.doi.org/10.7554/eLife.08752.001 PMID:26371510

Neuropsychopharmacology and neurogenetic aspects of executive functioning: should reward gene polymorphisms constitute a diagnostic tool to identify individuals at risk for impaired judgment?

PubMed

Bowirrat, Abdalla; Chen, Thomas J H; Oscar-Berman, Marlene; Madigan, Margaret; Chen, Amanda Lh; Bailey, John A; Braverman, Eric R; Kerner, Mallory; Giordano, John; Morse, Siobhan; Downs, B William; Waite, Roger L; Fornari, Frank; Armaly, Zaher; Blum, Kenneth

2012-04-01

Executive functions are processes that act in harmony to control behaviors necessary for maintaining focus and achieving outcomes. Executive dysfunction in neuropsychiatric disorders is attributed to structural or functional pathology of brain networks involving prefrontal cortex (PFC) and its connections with other brain regions. The PFC receives innervations from different neurons associated with a number of neurotransmitters, especially dopamine (DA). Here we review findings on the contribution of PFC DA to higher-order cognitive and emotional behaviors. We suggest that examination of multifactorial interactions of an individual's genetic history, along with environmental risk factors, can assist in the characterization of executive functioning for that individual. Based upon the results of genetic studies, we also propose genetic mapping as a probable diagnostic tool serving as a therapeutic adjunct for augmenting executive functioning capabilities. We conclude that preservation of the neurological underpinnings of executive functions requires the integrity of complex neural systems including the influence of specific genes and associated polymorphisms to provide adequate neurotransmission.

Cumulative adversity and smaller gray matter volume in medial prefrontal, anterior cingulate, and insula regions.

PubMed

Ansell, Emily B; Rando, Kenneth; Tuit, Keri; Guarnaccia, Joseph; Sinha, Rajita

2012-07-01

Cumulative adversity and stress are associated with risk of psychiatric disorders. While basic science studies show repeated and chronic stress effects on prefrontal and limbic neurons, human studies examining cumulative stress and effects on brain morphology are rare. Thus, we assessed whether cumulative adversity is associated with differences in gray matter volume, particularly in regions regulating emotion, self-control, and top-down processing in a community sample. One hundred three healthy community participants, aged 18 to 48 and 68% male, completed interview assessment of cumulative adversity and a structural magnetic resonance imaging protocol. Whole-brain voxel-based-morphometry analysis was performed adjusting for age, gender, and total intracranial volume. Cumulative adversity was associated with smaller volume in medial prefrontal cortex (PFC), insular cortex, and subgenual anterior cingulate regions (familywise error corrected, p < .001). Recent stressful life events were associated with smaller volume in two clusters: the medial PFC and the right insula. Life trauma was associated with smaller volume in the medial PFC, anterior cingulate, and subgenual regions. The interaction of greater subjective chronic stress and greater cumulative life events was associated with smaller volume in the orbitofrontal cortex, insula, and anterior and subgenual cingulate regions. Current results demonstrate that increasing cumulative exposure to adverse life events is associated with smaller gray matter volume in key prefrontal and limbic regions involved in stress, emotion and reward regulation, and impulse control. These differences found in community participants may serve to mediate vulnerability to depression, addiction, and other stress-related psychopathology. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Cumulative Adversity and Smaller Gray Matter Volume in Medial Prefrontal, Anterior Cingulate, and Insula Regions

PubMed Central

Ansell, Emily B.; Rando, Kenneth; Tuit, Keri; Guarnaccia, Joseph; Sinha, Rajita

2012-01-01

Background Cumulative adversity and stress are associated with risk of psychiatric disorders. While basic science studies show repeated and chronic stress effects on prefrontal and limbic neurons, human studies examining cumulative stress and effects on brain morphology are rare. Thus, we assessed whether cumulative adversity is associated with differences in gray matter volume, particularly in regions regulating emotion, self-control, and top-down processing in a community sample. Methods One hundred three healthy community participants, aged 18 to 48 and 68% male, completed interview assessment of cumulative adversity and a structural magnetic resonance imaging protocol. Whole-brain voxel-based-morphometry analysis was performed adjusting for age, gender, and total intracranial volume. Results Cumulative adversity was associated with smaller volume in medial prefrontal cortex (PFC), insular cortex, and subgenual anterior cingulate regions (familywise error corrected, p <.001). Recent stressful life events were associated with smaller volume in two clusters: the medial PFC and the right insula. Life trauma was associated with smaller volume in the medial PFC, anterior cingulate, and subgenual regions. The interaction of greater subjective chronic stress and greater cumulative life events was associated with smaller volume in the orbitofrontal cortex, insula, and anterior and subgenual cingulate regions. Conclusions Current results demonstrate that increasing cumulative exposure to adverse life events is associated with smaller gray matter volume in key prefrontal and limbic regions involved in stress, emotion and reward regulation, and impulse control. These differences found in community participants may serve to mediate vulnerability to depression, addiction, and other stress-related psychopathology. PMID:22218286

Toward a new understanding of attention-deficit hyperactivity disorder pathophysiology: an important role for prefrontal cortex dysfunction.

PubMed

Arnsten, Amy F T

2009-01-01

Recent advances in neurobiology have aided our understanding of attention-deficit hyperactivity disorder (ADHD). The higher-order association cortices in the temporal and parietal lobes and prefrontal cortex (PFC) interconnect to mediate aspects of attention. The parietal association cortices are important for orienting attentional resources in time/space, while the temporal association cortices analyse visual features critical for identifying objects/places. These posterior cortices are engaged by the salience of a stimulus (its physical characteristics such as movement and colour). Conversely, the PFC is critical for regulating attention based on relevance (i.e. its meaning). The PFC is important for screening distractions, sustaining attention and shifting/dividing attention in a task-appropriate manner. The PFC is critical for regulating behaviour/emotion, especially for inhibiting inappropriate emotions, impulses and habits. The PFC is needed for allocating/planning to achieve goals and organizing behaviour/thought. These regulatory abilities are often referred to as executive functions. In humans, the right hemisphere of the PFC is important for regulating distractions, inappropriate behaviour and emotional responses. Imaging studies of patients with ADHD indicate that these regions are underactive with weakened connections to other parts of the brain. The PFC regulates attention and behaviour through networks of interconnected pyramidal cells. These networks excite each other to store goals/rules to guide actions and are highly dependent on their neurochemical environment, as small changes in the catecholamines noradrenaline (NA) or dopamine (DA) can have marked effects on PFC function. NA and DA are released in the PFC according to our arousal state; too little (during fatigue or boredom) or too much (during stress) impairs PFC function. Optimal amounts are released when we are alert/interested. The beneficial effects of NA occur at postsynaptic alpha(2A)-receptors on the dendritic spines of PFC pyramidal cells. Stimulation of these receptors initiates a series of chemical events inside the cell. These chemical signals lead to the closing of special ion channels, thus strengthening the connectivity of network inputs to the cell. Conversely, the beneficial effects of moderate amounts of DA occur at D(1) receptors, which act by weakening irrelevant inputs to the cells on another set of spines. Genetic linkage studies of ADHD suggest that these catecholamine pathways may be altered in some families with ADHD, e.g. alterations in the enzyme that synthesizes NA (DA beta-hydroxylase) are associated with weakened PFC abilities. Pharmacological studies in animals indicate catecholamine actions in the PFC are highly relevant to ADHD. Blocking NA alpha(2A)-receptors in the PFC with yohimbine produces a profile similar to ADHD: locomotor hyperactivity, impulsivity and poor working memory. Conversely, drugs that enhance alpha(2)-receptor stimulation improve PFC function. Guanfacine directly stimulates postsynaptic alpha(2A)-receptors in the PFC and improves functioning, while methylphenidate and atomoxetine increase endogenous NA and DA levels and indirectly improve PFC function via alpha(2A)- and D(1) receptor actions. Methylphenidate and atomoxetine have more potent actions in the PFC than in subcortical structures, which may explain why proper administration of stimulant medications does not lead to abuse. Further understanding of the neurobiology of attention and impulse control will allow us to better tailor treatments for specific patient needs.

Repeated microinjections into the medial prefrontal cortex (mPFC) impair extinction of conditioned place preference in mice.

PubMed

Groblewski, Peter A; Cunningham, Christopher L

2012-04-21

The medial prefrontal cortex (mPFC) is important for extinction of many behaviors including conditioned place preference (CPP). We examined the effects of intra-mPFC inactivation (with bupivacaine) on extinction of ethanol-induced CPP in mice. Injections of both bupivacaine and vehicle impaired extinction whereas no-surgery control mice extinguished normally. Consistent with recently reported effects of mPFC lesions, these data suggest that extinction was impaired by excessive mPFC damage induced by repeated intracranial infusions. Copyright © 2012 Elsevier B.V. All rights reserved.

Medial prefrontal cortex involvement in the expression of extinction and ABA renewal of instrumental behavior for a food reinforcer.

PubMed

Eddy, Meghan C; Todd, Travis P; Bouton, Mark E; Green, John T

2016-02-01

Instrumental renewal, the return of extinguished instrumental responding after removal from the extinction context, is an important model of behavioral relapse that is poorly understood at the neural level. In two experiments, we examined the role of the dorsomedial prefrontal cortex (dmPFC) and the ventromedial prefrontal cortex (vmPFC) in extinction and ABA renewal of instrumental responding for a sucrose reinforcer. Previous work, exclusively using drug reinforcers, has suggested that the roles of the dmPFC and vmPFC in expression of extinction and ABA renewal may depend at least in part on the type of drug reinforcer used. The current experiments used a food reinforcer because the behavioral mechanisms underlying the extinction and renewal of instrumental responding are especially well worked out in this paradigm. After instrumental conditioning in context A and extinction in context B, we inactivated dmPFC, vmPFC, or a more ventral medial prefrontal cortex region by infusing baclofen/muscimol (B/M) just prior to testing in both contexts. In rats with inactivated dmPFC, ABA renewal was still present (i.e., responding increased when returned to context A); however responding was lower (less renewal) than controls. Inactivation of vmPFC increased responding in context B (the extinction context) and decreased responding in context A, indicating no renewal in these animals. There was no effect of B/M infusion on rats with cannula placements ventral to the vmPFC. Fluorophore-conjugated muscimol was infused in a subset of rats following test to visualize infusion spread. Imaging suggested that the infusion spread was minimal and mainly constrained to the targeted area. Together, these experiments suggest that there is a region of medial prefrontal cortex encompassing both dmPFC and vmPFC that is important for ABA renewal of extinguished instrumental responding for a food reinforcer. In addition, vmPFC, but not dmPFC, is important for expression of extinction of responding for a food reinforcer. The role of the medial prefrontal cortex in renewal in the original conditioning context may depend in part on control over excitatory context-response or context-(response-outcome) relations that might be learned in acquisition. The role of the vmPFC in expression of extinction may depend on its control over inhibitory context-response or context-(response-outcome) relations that are learned in extinction. Copyright © 2015 Elsevier Inc. All rights reserved.

Local Intratracheal Delivery of Perfluorocarbon Nanoparticles to Lung Cancer Demonstrated with Magnetic Resonance Multimodal Imaging

PubMed Central

Wu, Lina; Wen, Xiaofei; Wang, Xiance; Wang, Chunan; Sun, Xilin; Wang, Kai; Zhang, Huiying; Williams, Todd; Stacy, Allen J.; Chen, Junjie; Schmieder, Anne H.; Lanza, Gregory M.; Shen, Baozhong

2018-01-01

Eighty percent of lung cancers originate as subtle premalignant changes in the airway mucosal epithelial layer of bronchi and alveoli, which evolve and penetrate deeper into the parenchyma. Liquid-ventilation, with perfluorocarbons (PFC) was first demonstrated in rodents in 1966 then subsequently applied as lipid-encapsulated PFC emulsions to improve pulmonary function in neonatal infants suffering with respiratory distress syndrome in 1996. Subsequently, PFC nanoparticles (NP) were extensively studied as intravenous (IV) vascular-constrained nanotechnologies for diagnostic imaging and targeted drug delivery applications. Methods: This proof-of-concept study compared intratumoral localization of fluorescent paramagnetic (M) PFC NP in the Vx2 rabbit model using proton (1H) and fluorine (19F) magnetic resonance (MR) imaging (3T) following intratracheal (IT) or IV administration. MRI results were corroborated by fluorescence microscopy. Results: Dynamic 1H-MR and 19F-MR images (3T) obtained over 72 h demonstrated marked and progressive accumulation of M-PFC NP within primary lung Vx2 tumors during the first 12 h post IT administration. Marked 1H and 19F MR signal persisted for over 72 h. In contradistinction, IV M-PFC NP produced a modest transient signal during the initial 2 h post-injection that was consistent circumferential blood pool tumor enhancement. Fluorescence microscopy of excised tumors corroborated the MR results and revealed enormous intratumor NP deposition on day 3 after IT but not IV treatment. Rhodamine-phospholipid incorporated into the PFC nanoparticle surfactant was distributed widely within the tumor on day 3, which is consistent with a hemifusion-based contact drug delivery mechanism previously reported. Fluorescence microscopy also revealed similar high concentrations of M-PFC NP given IT for metastatic Vx2 lung tumors. Biodistribution studies in mice revealed that M-PFC NP given IV distributed into the reticuloendothelial organs, whereas, the same dosage given IT was basically not detected beyond the lung itself. PFC NP given IT did not impact rabbit behavior or impair respiratory function. PFC NP effects on cells in culture were negligible and when given IV or IT no changes in rabbit hematology nor serum clinical chemistry parameters were measured. Conclusion: IT delivery of PFC NP offered unique opportunity to locally deliver PFC NP in high concentrations into lung cancers with minimal extratumor systemic exposure. PMID:29290827

14 CFR 158.11 - Public agency request not to require collection of PFC's by a class of air carriers or foreign...

Code of Federal Regulations, 2012 CFR

2012-01-01

... collection of PFC's by a class of air carriers or foreign air carriers or for service to isolated communities... TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) General § 158.11 Public agency request not to require collection of PFC's by a class of air carriers or foreign air carriers or for service to...

14 CFR 158.11 - Public agency request not to require collection of PFC's by a class of air carriers or foreign...

Code of Federal Regulations, 2014 CFR

2014-01-01

... collection of PFC's by a class of air carriers or foreign air carriers or for service to isolated communities... TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) General § 158.11 Public agency request not to require collection of PFC's by a class of air carriers or foreign air carriers or for service to...

14 CFR 158.11 - Public agency request not to require collection of PFC's by a class of air carriers or foreign...

Code of Federal Regulations, 2010 CFR

2010-01-01

... collection of PFC's by a class of air carriers or foreign air carriers or for service to isolated communities... TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) General § 158.11 Public agency request not to require collection of PFC's by a class of air carriers or foreign air carriers or for service to...

14 CFR 158.11 - Public agency request not to require collection of PFC's by a class of air carriers or foreign...

Code of Federal Regulations, 2013 CFR

2013-01-01

... collection of PFC's by a class of air carriers or foreign air carriers or for service to isolated communities... TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) General § 158.11 Public agency request not to require collection of PFC's by a class of air carriers or foreign air carriers or for service to...

14 CFR 158.11 - Public agency request not to require collection of PFC's by a class of air carriers or foreign...

Code of Federal Regulations, 2011 CFR

2011-01-01

... collection of PFC's by a class of air carriers or foreign air carriers or for service to isolated communities... TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) General § 158.11 Public agency request not to require collection of PFC's by a class of air carriers or foreign air carriers or for service to...

Prefrontal cortical-specific differences in behavior and synaptic plasticity between adolescent and adult mice.

PubMed

Konstantoudaki, Xanthippi; Chalkiadaki, Kleanthi; Vasileiou, Elisabeth; Kalemaki, Katerina; Karagogeos, Domna; Sidiropoulou, Kyriaki

2018-03-01

Adolescence is a highly vulnerable period for the emergence of major neuropsychological disorders and is characterized by decreased cognitive control and increased risk-taking behavior and novelty-seeking. The prefrontal cortex (PFC) is involved in the cognitive control of impulsive and risky behavior. Although the PFC is known to reach maturation later than other cortical areas, little information is available regarding the functional changes from adolescence to adulthood in PFC, particularly compared with other primary cortical areas. This study aims to understand the development of PFC-mediated, compared with non-PFC-mediated, cognitive functions. Toward this aim, we performed cognitive behavioral tasks in adolescent and adult mice and subsequently investigated synaptic plasticity in two different cortical areas. Our results showed that adolescent mice exhibit impaired performance in PFC-dependent cognitive tasks compared with adult mice, whereas their performance in non-PFC-dependent tasks is similar to that of adults. Furthermore, adolescent mice exhibited decreased long-term potentiation (LTP) within upper-layer synapses of the PFC but not the barrel cortex. Blocking GABA A receptor function significantly augments LTP in both the adolescent and adult PFC. No change in intrinsic excitability of PFC pyramidal neurons was observed between adolescent and adult mice. Finally, increased expression of the NR2A subunit of the N-methyl-d-aspartate receptors is found only in the adult PFC, a change that could underlie the emergence of LTP. In conclusion, our results demonstrate physiological and behavioral changes during adolescence that are specific to the PFC and could underlie the reduced cognitive control in adolescents. NEW & NOTEWORTHY This study reports that adolescent mice exhibit impaired performance in cognitive functions dependent on the prefrontal cortex but not in cognitive functions dependent on other cortical regions. The current results propose reduced synaptic plasticity in the upper layers of the prefrontal cortex as a cellular correlate of this weakened cognitive function. This decreased synaptic plasticity is due to reduced N-methyl-d-aspartate receptor expression but not due to dampened intrinsic excitability or enhanced GABAergic signaling during adolescence.

Silica-coated quantum dots for optical evaluation of perfluorocarbon droplet interactions with cells.

PubMed

Gorelikov, Ivan; Martin, Amanda L; Seo, Minseok; Matsuura, Naomi

2011-12-20

There has been recent interest in developing new, targeted, perfluorocarbon (PFC) droplet-based contrast agents for medical imaging (e.g., magnetic resonance imaging, X-ray/computed tomography, and ultrasound imaging). However, due to the large number of potential PFCs and droplet stabilization strategies available, it is challenging to determine in advance the PFC droplet formulation that will result in the optimal in vivo behavior and imaging performance required for clinical success. We propose that the integration of fluorescent quantum dots (QDs) into new PFC droplet agents can help to rapidly screen new PFC-based candidate agents for biological compatibility early in their development. QD labels can allow the interaction of PFC droplets with single cells to be assessed at high sensitivity and resolution using optical methods in vitro, complementing the deeper depth penetration but lower resolution provided by PFC droplet imaging using in vivo medical imaging systems. In this work, we introduce a simple and robust method to miscibilize silica-coated nanoparticles into hydrophobic and lipophobic PFCs through fluorination of the silica surface via a hydrolysis-condensation reaction with 1H,1H,2H,2H-perfluorodecyltriethoxysilane. Using CdSe/ZnS core/shell QDs, we show that nanoscale, QD-labeled PFC droplets can be easily formed, with similar sizes and surface charges as unlabeled PFC droplets. The QD label can be used to determine the PFC droplet uptake into cells in vitro by fluorescence microscopy and flow cytometry, and can be used to validate the fate of PFC droplets in vivo in small animals via fluorescence microscopy of histological tissue sections. This is demonstrated in macrophage and cancer cells, and in rabbits, respectively. This work reveals the potential of using QD labels for rapid, preclinical, optical assessment of different PFC droplet formulations for their future use in patients. © 2011 American Chemical Society

A boost of confidence: The role of the ventromedial prefrontal cortex in memory, decision-making, and schemas.

PubMed

Hebscher, Melissa; Gilboa, Asaf

2016-09-01

The ventromedial prefrontal cortex (vmPFC) has been implicated in a wide array of functions across multiple domains. In this review, we focus on the vmPFC's involvement in mediating strategic aspects of memory retrieval, memory-related schema functions, and decision-making. We suggest that vmPFC generates a confidence signal that informs decisions and memory-guided behaviour. Confidence is central to these seemingly diverse functions: (1) Strategic retrieval: lesions to the vmPFC impair an early, automatic, and intuitive monitoring process ("feeling of rightness"; FOR) often associated with confabulation (spontaneous reporting of erroneous memories). Critically, confabulators typically demonstrate high levels of confidence in their false memories, suggesting that faulty monitoring following vmPFC damage may lead to indiscriminate confidence signals. (2) Memory schemas: the vmPFC is critically involved in instantiating and maintaining contextually relevant schemas, broadly defined as higher level knowledge structures that encapsulate lower level representational elements. The correspondence between memory retrieval cues and these activated schemas leads to FOR monitoring. Stronger, more elaborate schemas produce stronger FOR and influence confidence in the veracity of memory candidates. (3) Finally, we review evidence on the vmPFC's role in decision-making, extending this role to decision-making during memory retrieval. During non-mnemonic and mnemonic decision-making the vmPFC automatically encodes confidence. Confidence signal in the vmPFC is revealed as a non-linear relationship between a first-order monitoring assessment and second-order action or choice. Attempting to integrate the multiple functions of the vmPFC, we propose a posterior-anterior organizational principle for this region. More posterior vmPFC regions are involved in earlier, automatic, subjective, and contextually sensitive functions, while more anterior regions are involved in controlled actions based on these earlier functions. Confidence signals reflect the non-linear relationship between first-order, posterior-mediated and second-order, anterior-mediated processes and are represented along the entire axis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Atmospheric abundance and global emissions of perfluorocarbons CF4, C2F6 and C3F8 since 1800 inferred from ice core, firn, air archive and in situ measurements

NASA Astrophysics Data System (ADS)

Trudinger, Cathy M.; Fraser, Paul J.; Etheridge, David M.; Sturges, William T.; Vollmer, Martin K.; Rigby, Matt; Martinerie, Patricia; Mühle, Jens; Worton, David R.; Krummel, Paul B.; Steele, L. Paul; Miller, Benjamin R.; Laube, Johannes; Mani, Francis S.; Rayner, Peter J.; Harth, Christina M.; Witrant, Emmanuel; Blunier, Thomas; Schwander, Jakob; O'Doherty, Simon; Battle, Mark

2016-09-01

Perfluorocarbons (PFCs) are very potent and long-lived greenhouse gases in the atmosphere, released predominantly during aluminium production and semiconductor manufacture. They have been targeted for emission controls under the United Nations Framework Convention on Climate Change. Here we present the first continuous records of the atmospheric abundance of CF4 (PFC-14), C2F6 (PFC-116) and C3F8 (PFC-218) from 1800 to 2014. The records are derived from high-precision measurements of PFCs in air extracted from polar firn or ice at six sites (DE08, DE08-2, DSSW20K, EDML, NEEM and South Pole) and air archive tanks and atmospheric air sampled from both hemispheres. We take account of the age characteristics of the firn and ice core air samples and demonstrate excellent consistency between the ice core, firn and atmospheric measurements. We present an inversion for global emissions from 1900 to 2014. We also formulate the inversion to directly infer emission factors for PFC emissions due to aluminium production prior to the 1980s. We show that 19th century atmospheric levels, before significant anthropogenic influence, were stable at 34.1 ± 0.3 ppt for CF4 and below detection limits of 0.002 and 0.01 ppt for C2F6 and C3F8, respectively. We find a significant peak in CF4 and C2F6 emissions around 1940, most likely due to the high demand for aluminium during World War II, for example for construction of aircraft, but these emissions were nevertheless much lower than in recent years. The PFC emission factors for aluminium production in the early 20th century were significantly higher than today but have decreased since then due to improvements and better control of the smelting process. Mitigation efforts have led to decreases in emissions from peaks in 1980 (CF4) or early-to-mid-2000s (C2F6 and C3F8) despite the continued increase in global aluminium production; however, these decreases in emissions appear to have recently halted. We see a temporary reduction of around 15 % in CF4 emissions in 2009, presumably associated with the impact of the global financial crisis on aluminium and semiconductor production.

Occurrence, fate, and fluxes of perfluorochemicals (PFCs) in an urban catchment: Marina Reservoir, Singapore.

PubMed

Nguyen, Viet Tung; Gin, Karina Yew-Hoong; Reinhard, Martin; Liu, Changhui

2012-01-01

A study was carried out to characterize the occurrence, sources and sinks of perfluorochemicals (PFCs) in the Marina Catchment and Reservoir, Singapore. Salinity depth profiles indicated the reservoir was stratified with lower layers consisting of sea water (salinity ranging from 32 to 35 g L(-1)) and a brackish surface layer containing approximately 14-65% seawater. The PFC mixture detected in catchment waters contained perfluoroalkyl carboxylates (PFCAs), particularly perfluorooctanoate (PFOA), perfluorohexanoate (PFHpA), perfluorooctane sulfonate (PFOS) and PFC transformation products. PFC concentrations in storm runoff were generally higher than those in dry weather flow of canals and rivers. PFC concentration profiles measured during storm events indicated 'first flush' behavior, probably because storm water is leaching PFC compounds from non-point sources present in the catchment area. Storm runoff carries high concentrations of suspended solids (SS), which suggests that PFC transport is via SS. In Marina Bay, PFCs are deposited in the sediments along with the SS. In sediments, the total PFC concentration was 4,700 ng kg(-1), approximately 200 times higher than in the bottom water layers. Total perfluoroalkyl sulfonates (PFSAs), particularly PFOS and 6:2 fluoro telomer sulfonate (6:2 FtS) were dominant PFCs in the sediments. PFC sorption by sediments varied with perfluorocarbon chain length, type of functional group and sediment characteristics. A first approximation analysis based on SS transport suggested that the annual PFC input into the reservoir was approximately 35 ± 12 kg y(-1). Contributions of SS, dry weather flow of river/canals, and rainfall were approximately 70, 25 and 5%, respectively. This information will be useful for improving strategies to protect the reservoir from PFC contamination.

The Emulsified PFC Oxycyte® Improved Oxygen Content and Lung Injury Score in a Swine Model of Oleic Acid Lung Injury (OALI).

PubMed

Haque, Ashraful; Scultetus, Anke H; Arnaud, Francoise; Dickson, Leonora J; Chun, Steve; McNamee, George; Auker, Charles R; McCarron, Richard M; Mahon, Richard T

2016-12-01

Perfluorocarbons (PFCs) can transport 50 times more oxygen than human plasma. Their properties may be advantageous in preservation of tissue viability in oxygen-deprived states, such as in acute lung injury. We hypothesized that an intravenous dose of the PFC emulsion Oxycyte ® would improve tissue oxygenation and thereby mitigate the effects of acute lung injury. Intravenous oleic acid (OA) was used to induce lung injury in anesthetized and instrumented Yorkshire swine assigned to three experimental groups: (1) PFC post-OA received Oxycyte ® (5 ml/kg) 45 min after oleic acid-induced lung injury (OALI); (2) PFC pre-OA received Oxycyte ® 45 min before OALI; and (3) Controls which received equivalent dose of normal saline. Animals were observed for 3 h after OALI began, and then euthanized. The median survival times for PFC post-OA, PFC pre-OA, and control were 240, 87.5, and 240 min, respectively (p = 0.001). Mean arterial pressure and mean pulmonary arterial pressure were both higher in the PFC post-OA (p < 0.001 for both parameters). Oxygen content was significantly different between PFC post-OA and the control (p = 0.001). Histopathological grading of lung injury indicated that edema and congestion was significantly less severe in the PFC post-OA compared to control (p = 0.001). The intravenous PFC Oxycyte ® improves blood oxygen content and lung histology when used as a treatment after OALI, while Oxycyte ® used prior to OALI was associated with increased mortality. Further exploration in other injury models is indicated.

Neural Correlates of Hostile Jokes: Cognitive and Motivational Processes in Humor Appreciation

PubMed Central

Chan, Yu-Chen; Liao, Yi-Jun; Tu, Cheng-Hao

2016-01-01

Hostile jokes (HJs) provide aggressive catharsis and a feeling of superiority. Behavioral research has found that HJs are perceived as funnier than non-hostile jokes (NJs). The purpose of the present study was to identify the neural correlates of the interaction between type and humor by comparing HJs, NJs, and their corresponding hostile sentences (HSs) and non-hostile sentences (NSs). HJs primarily showed activation in the dorsomedial prefrontal cortex (dmPFC) and midbrain compared with the corresponding hostile baseline. Conversely, NJs primarily revealed activation in the ventromedial PFC (vmPFC), amygdala, midbrain, ventral anterior cingulate cortex, and nucleus accumbens (NAcc) compared with the corresponding non-hostile baseline. These results support the critical role of the medial PFC (mPFC) for the neural correlates of social cognition and socio-emotional processing in response to different types of jokes. Moreover, the processing of HJs showed increased activation in the dmPFC, which suggested cognitive operations of social motivation, whereas the processing of NJs displayed increased activation in the vmPFC, which suggested social-affective engagement. HJs versus NJs primarily showed increased activation in the dmPFC and midbrain, whereas NJs versus HJs primarily displayed greater activation in the amygdala and midbrain. The psychophysiological interaction (PPI) analysis demonstrated functional coupling of the dmPFC–dlPFC and midbrain–dmPFC for HJs and functional coupling of the vmPFC–midbrain and amygdala–midbrain–NAcc for NJs. Surprisingly, HJs were not perceived as funnier than NJs. Future studies could further investigate the neural correlates of potentially important traits of high-hostility tendencies in humor appreciation based on the psychoanalytic and superiority theories of humor. PMID:27840604

The medial prefrontal cortex is involved in spatial memory retrieval under partial-cue conditions.

PubMed

Jo, Yong Sang; Park, Eun Hye; Kim, Il Hwan; Park, Soon Kwon; Kim, Hyun; Kim, Hyun Taek; Choi, June-Seek

2007-12-05

Brain circuits involved in pattern completion, or retrieval of memory from fragmented cues, were investigated. Using different versions of the Morris water maze, we explored the roles of the CA3 subregion of the hippocampus and the medial prefrontal cortex (mPFC) in spatial memory retrieval under various conditions. In a hidden platform task, both CA3 and mPFC lesions disrupted memory retrieval under partial-cue, but not under full-cue, conditions. For a delayed matching-to-place task, CA3 lesions produced a deficit in both forming and recalling spatial working memory regardless of extramaze cue conditions. In contrast, damage to mPFC impaired memory retrieval only when a fraction of cues was available. To corroborate the lesion study, we examined the expression of the immediate early gene c-fos in mPFC and the hippocampus. After training of spatial reference memory in full-cue conditions for 6 d, the same training procedure in the absence of all cues except one increased the number of Fos-immunoreactive cells in mPFC and CA3. Furthermore, mPFC inactivation with muscimol, a GABA agonist, blocked memory retrieval in the degraded-cue environment. However, mPFC-lesioned animals initially trained in a single-cue environment had no difficulty in retrieving spatial memory when the number of cues was increased, demonstrating that contextual change per se did not impair the behavioral performance of the mPFC-lesioned animals. Together, these findings strongly suggest that pattern completion requires interactions between mPFC and the hippocampus, in which mPFC plays significant roles in retrieving spatial information maintained in the hippocampus for efficient navigation.

The impact of the Val158Met catechol-O-methyltransferase genotype on neural correlates of sad facial affect processing in patients with bipolar disorder and their relatives.

PubMed

Lelli-Chiesa, G; Kempton, M J; Jogia, J; Tatarelli, R; Girardi, P; Powell, J; Collier, D A; Frangou, S

2011-04-01

The Met allele of the catechol-O-methyltransferase (COMT) valine-to-methionine (Val158Met) polymorphism is known to affect dopamine-dependent affective regulation within amygdala-prefrontal cortical (PFC) networks. It is also thought to increase the risk of a number of disorders characterized by affective morbidity including bipolar disorder (BD), major depressive disorder (MDD) and anxiety disorders. The disease risk conferred is small, suggesting that this polymorphism represents a modifier locus. Therefore our aim was to investigate how the COMT Val158Met may contribute to phenotypic variation in clinical diagnosis using sad facial affect processing as a probe for its neural action. We employed functional magnetic resonance imaging to measure activation in the amygdala, ventromedial PFC (vmPFC) and ventrolateral PFC (vlPFC) during sad facial affect processing in family members with BD (n=40), MDD and anxiety disorders (n=22) or no psychiatric diagnosis (n=25) and 50 healthy controls. Irrespective of clinical phenotype, the Val158 allele was associated with greater amygdala activation and the Met158 allele with greater signal change in the vmPFC and vlPFC. Signal changes in the amygdala and vmPFC were not associated with disease expression. However, in the right vlPFC the Met158 allele was associated with greater activation in all family members with affective morbidity compared with relatives without a psychiatric diagnosis and healthy controls. Our results suggest that the COMT Val158Met polymorphism has a pleiotropic effect within the neural networks subserving emotional processing. Furthermore the Met158 allele further reduces cortical efficiency in the vlPFC in individuals with affective morbidity.

Too much of a good thing: blocking noradrenergic facilitation in medial prefrontal cortex prevents the detrimental effects of chronic stress on cognition.

PubMed

Jett, Julianne D; Morilak, David A

2013-03-01

Cognitive impairments associated with dysfunction of the medial prefrontal cortex (mPFC) are prominent in stress-related psychiatric disorders. We have shown that enhancing noradrenergic tone acutely in the rat mPFC facilitated extra-dimensional (ED) set-shifting on the attentional set-shifting test (AST), whereas chronic unpredictable stress (CUS) impaired ED. In this study, we tested the hypothesis that the acute facilitatory effect of norepinephrine (NE) in mPFC becomes detrimental when activated repeatedly during CUS. Using microdialysis, we showed that the release of NE evoked in mPFC by acute stress was unchanged at the end of CUS treatment. Thus, to then determine if repeated elicitation of this NE activity in mPFC during CUS may have contributed to the ED deficit, we infused a cocktail of α(1)-, β(1)-, and β(2)-adrenergic receptor antagonists into the mPFC prior to each CUS session, then tested animals drug free on the AST. Antagonist treatment prevented the CUS-induced ED deficit, suggesting that NE signaling during CUS compromised mPFC function. We confirmed that this was not attributable to sensitization of adrenergic receptor function following chronic antagonist treatment, by administering an additional microinjection into the mPFC immediately prior to ED testing. Acute antagonist treatment did not reverse the beneficial effects of chronic drug treatment during CUS, nor have any effect on baseline ED performance in chronic vehicle controls. Thus, we conclude that blockade of noradrenergic receptors in mPFC protected against the detrimental cognitive effects of CUS, and that repeated elicitation of noradrenergic facilitatory activity is one mechanism by which chronic stress may promote mPFC cognitive dysfunction.

Prefrontal control of cerebellum-dependent associative motor learning.

PubMed

Chen, Hao; Yang, Li; Xu, Yan; Wu, Guang-yan; Yao, Juan; Zhang, Jun; Zhu, Zhi-ru; Hu, Zhi-an; Sui, Jian-feng; Hu, Bo

2014-02-01

Behavioral studies have demonstrated that both medial prefrontal cortex (mPFC) and cerebellum play critical roles in trace eyeblink conditioning. However, little is known regarding the mechanism by which the two brain regions interact. By use of electrical stimulation of the caudal mPFC as a conditioned stimulus, we show evidence that persistent outputs from the mPFC to cerebellum are necessary and sufficient for the acquisition and expression of a trace conditioned response (CR)-like response. Specifically, the persistent outputs of caudal mPFC are relayed to the cerebellum via the rostral part of lateral pontine nuclei. Moreover, interfering with persistent activity by blockade of the muscarinic Ach receptor in the caudal mPFC impairs the expression of learned trace CRs. These results suggest an important way for the caudal mPFC to interact with the cerebellum during associative motor learning.

Fyn-Dependent Gene Networks in Acute Ethanol Sensitivity

PubMed Central

Farris, Sean P.; Miles, Michael F.

2013-01-01

Studies in humans and animal models document that acute behavioral responses to ethanol are predisposing factor for the risk of long-term drinking behavior. Prior microarray data from our laboratory document strain- and brain region-specific variation in gene expression profile responses to acute ethanol that may be underlying regulators of ethanol behavioral phenotypes. The non-receptor tyrosine kinase Fyn has previously been mechanistically implicated in the sedative-hypnotic response to acute ethanol. To further understand how Fyn may modulate ethanol behaviors, we used whole-genome expression profiling. We characterized basal and acute ethanol-evoked (3 g/kg) gene expression patterns in nucleus accumbens (NAC), prefrontal cortex (PFC), and ventral midbrain (VMB) of control and Fyn knockout mice. Bioinformatics analysis identified a set of Fyn-related gene networks differently regulated by acute ethanol across the three brain regions. In particular, our analysis suggested a coordinate basal decrease in myelin-associated gene expression within NAC and PFC as an underlying factor in sensitivity of Fyn null animals to ethanol sedation. An in silico analysis across the BXD recombinant inbred (RI) strains of mice identified a significant correlation between Fyn expression and a previously published ethanol loss-of-righting-reflex (LORR) phenotype. By combining PFC gene expression correlates to Fyn and LORR across multiple genomic datasets, we identified robust Fyn-centric gene networks related to LORR. Our results thus suggest that multiple system-wide changes exist within specific brain regions of Fyn knockout mice, and that distinct Fyn-dependent expression networks within PFC may be important determinates of the LORR due to acute ethanol. These results add to the interpretation of acute ethanol behavioral sensitivity in Fyn kinase null animals, and identify Fyn-centric gene networks influencing variance in ethanol LORR. Such networks may also inform future design of pharmacotherapies for the treatment and prevention of alcohol use disorders. PMID:24312422

Extinction of aversive memories associated with morphine withdrawal requires ERK-mediated epigenetic regulation of brain-derived neurotrophic factor transcription in the rat ventromedial prefrontal cortex.

PubMed

Wang, Wei-Sheng; Kang, Shuo; Liu, Wen-Tao; Li, Mu; Liu, Yao; Yu, Chuan; Chen, Jie; Chi, Zhi-Qiang; He, Ling; Liu, Jing-Gen

2012-10-03

Recent evidence suggests that histone deacetylase (HDAC) inhibitors facilitate extinction of rewarding memory of drug taking. However, little is known about the role of chromatin modification in the extinction of aversive memory of drug withdrawal. In this study, we used conditioned place aversion (CPA), a highly sensitive model for measuring aversive memory of drug withdrawal, to investigate the role of epigenetic regulation of brain-derived neurotrophic factor (BDNF) gene expression in extinction of aversive memory. We found that CPA extinction training induced an increase in recruiting cAMP response element-binding protein (CREB) to and acetylation of histone H3 at the promoters of BDNF exon I transcript and increased BDNF mRNA and protein expression in the ventromedial prefrontal cortex (vmPFC) of acute morphine-dependent rats and that such epigenetic regulation of BDNF gene transcription could be facilitated or diminished by intra-vmPFC infusion of HDAC inhibitor trichostatin A or extracellular signal-regulated kinase (ERK) inhibitor U0126 (1,4-diamino-2,3-dicyano-1,4-bis(methylthio)butadiene) before extinction training. Correspondingly, disruption of the epigenetic regulation of BDNF gene transcription with U0126 or suppression of BDNF signaling with Trk receptor antagonist K252a or BDNF scavenger tyrosine kinase receptor B (TrkB)-Fc blocked extinction of CPA behavior. We also found that extinction training-induced activation of ERK and CREB and extinction of CPA behavior could be potentiated or suppressed by intra-vmPFC infusion of d-cycloserine, a NMDA receptor partial agonist or aminophosphonopentanoic acid, a NMDA receptor antagonist. We conclude that extinction of aversive memory of morphine withdrawal requires epigenetic regulation of BDNF gene transcription in the vmPFC through activation of the ERK-CREB signaling pathway perhaps in a NMDA receptor-dependent manner.

Levels of integration in cognitive control and sequence processing in the prefrontal cortex.

PubMed

Bahlmann, Jörg; Korb, Franziska M; Gratton, Caterina; Friederici, Angela D

2012-01-01

Cognitive control is necessary to flexibly act in changing environments. Sequence processing is needed in language comprehension to build the syntactic structure in sentences. Functional imaging studies suggest that sequence processing engages the left ventrolateral prefrontal cortex (PFC). In contrast, cognitive control processes additionally recruit bilateral rostral lateral PFC regions. The present study aimed to investigate these two types of processes in one experimental paradigm. Sequence processing was manipulated using two different sequencing rules varying in complexity. Cognitive control was varied with different cue-sets that determined the choice of a sequencing rule. Univariate analyses revealed distinct PFC regions for the two types of processing (i.e. sequence processing: left ventrolateral PFC and cognitive control processing: bilateral dorsolateral and rostral PFC). Moreover, in a common brain network (including left lateral PFC and intraparietal sulcus) no interaction between sequence and cognitive control processing was observed. In contrast, a multivariate pattern analysis revealed an interaction of sequence and cognitive control processing, such that voxels in left lateral PFC and parietal cortex showed different tuning functions for tasks involving different sequencing and cognitive control demands. These results suggest that the difference between the process of rule selection (i.e. cognitive control) and the process of rule-based sequencing (i.e. sequence processing) find their neuronal underpinnings in distinct activation patterns in lateral PFC. Moreover, the combination of rule selection and rule sequencing can shape the response of neurons in lateral PFC and parietal cortex.

Levels of Integration in Cognitive Control and Sequence Processing in the Prefrontal Cortex

PubMed Central

Bahlmann, Jörg; Korb, Franziska M.; Gratton, Caterina; Friederici, Angela D.

2012-01-01

Cognitive control is necessary to flexibly act in changing environments. Sequence processing is needed in language comprehension to build the syntactic structure in sentences. Functional imaging studies suggest that sequence processing engages the left ventrolateral prefrontal cortex (PFC). In contrast, cognitive control processes additionally recruit bilateral rostral lateral PFC regions. The present study aimed to investigate these two types of processes in one experimental paradigm. Sequence processing was manipulated using two different sequencing rules varying in complexity. Cognitive control was varied with different cue-sets that determined the choice of a sequencing rule. Univariate analyses revealed distinct PFC regions for the two types of processing (i.e. sequence processing: left ventrolateral PFC and cognitive control processing: bilateral dorsolateral and rostral PFC). Moreover, in a common brain network (including left lateral PFC and intraparietal sulcus) no interaction between sequence and cognitive control processing was observed. In contrast, a multivariate pattern analysis revealed an interaction of sequence and cognitive control processing, such that voxels in left lateral PFC and parietal cortex showed different tuning functions for tasks involving different sequencing and cognitive control demands. These results suggest that the difference between the process of rule selection (i.e. cognitive control) and the process of rule-based sequencing (i.e. sequence processing) find their neuronal underpinnings in distinct activation patterns in lateral PFC. Moreover, the combination of rule selection and rule sequencing can shape the response of neurons in lateral PFC and parietal cortex. PMID:22952762

Temporal kinetics of prefrontal modulation of the extrastriate cortex during visual attention.

PubMed

Yago, Elena; Duarte, Audrey; Wong, Ting; Barceló, Francisco; Knight, Robert T

2004-12-01

Single-unit, event-related potential (ERP), and neuroimaging studies have implicated the prefrontal cortex (PFC) in top-down control of attention and working memory. We conducted an experiment in patients with unilateral PFC damage (n = 8) to assess the temporal kinetics of PFC-extrastriate interactions during visual attention. Subjects alternated attention between the left and the right hemifields in successive runs while they detected target stimuli embedded in streams of repetitive task-irrelevant stimuli (standards). The design enabled us to examine tonic (spatial selection) and phasic (feature selection) PFC-extrastriate interactions. PFC damage impaired performance in the visual field contralateral to lesions, as manifested by both larger reaction times and error rates. Assessment of the extrastriate P1 ERP revealed that the PFC exerts a tonic (spatial selection) excitatory input to the ipsilateral extrastriate cortex as early as 100 msec post stimulus delivery. The PFC exerts a second phasic (feature selection) excitatory extrastriate modulation from 180 to 300 msec, as evidenced by reductions in selection negativity after damage. Finally, reductions of the N2 ERP to target stimuli supports the notion that the PFC exerts a third phasic (target selection) signal necessary for successful template matching during postselection analysis of target features. The results provide electrophysiological evidence of three distinct tonic and phasic PFC inputs to the extrastriate cortex in the initial few hundred milliseconds of stimulus processing. Damage to this network appears to underlie the pervasive deficits in attention observed in patients with prefrontal lesions.

The medial dorsal thalamic nucleus and the medial prefrontal cortex of the rat function together to support associative recognition and recency but not item recognition.

PubMed

Cross, Laura; Brown, Malcolm W; Aggleton, John P; Warburton, E Clea

2012-12-21

In humans recognition memory deficits, a typical feature of diencephalic amnesia, have been tentatively linked to mediodorsal thalamic nucleus (MD) damage. Animal studies have occasionally investigated the role of the MD in single-item recognition, but have not systematically analyzed its involvement in other recognition memory processes. In Experiment 1 rats with bilateral excitotoxic lesions in the MD or the medial prefrontal cortex (mPFC) were tested in tasks that assessed single-item recognition (novel object preference), associative recognition memory (object-in-place), and recency discrimination (recency memory task). Experiment 2 examined the functional importance of the interactions between the MD and mPFC using disconnection techniques. Unilateral excitotoxic lesions were placed in both the MD and the mPFC in either the same (MD + mPFC Ipsi) or opposite hemispheres (MD + mPFC Contra group). Bilateral lesions in the MD or mPFC impaired object-in-place and recency memory tasks, but had no effect on novel object preference. In Experiment 2 the MD + mPFC Contra group was significantly impaired in the object-in-place and recency memory tasks compared with the MD + mPFC Ipsi group, but novel object preference was intact. Thus, connections between the MD and mPFC are critical for recognition memory when the discriminations involve associative or recency information. However, the rodent MD is not necessary for single-item recognition memory.

76 FR 4411 - Notice of Intent To Rule on Application 10-06-C-00-BOS To Impose and Use the Revenue From a...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-25

... requests for clarification in support of Massport's application to impose and use a PFC at Boston-Logan..., 2010, which was the date of Massport's submission of its PFC application for collection and use of PFC... Massport's PFC application under the provisions of the 49 U.S.C. 40117 and 14 CFR part 158. Background: On...

Sevoflurane Induces Coherent Slow-Delta Oscillations in Rats.

PubMed

Guidera, Jennifer A; Taylor, Norman E; Lee, Justin T; Vlasov, Ksenia Y; Pei, JunZhu; Stephen, Emily P; Mayo, J Patrick; Brown, Emery N; Solt, Ken

2017-01-01

Although general anesthetics are routinely administered to surgical patients to induce loss of consciousness, the mechanisms underlying anesthetic-induced unconsciousness are not fully understood. In rats, we characterized changes in the extradural EEG and intracranial local field potentials (LFPs) within the prefrontal cortex (PFC), parietal cortex (PC), and central thalamus (CT) in response to progressively higher doses of the inhaled anesthetic sevoflurane. During induction with a low dose of sevoflurane, beta/low gamma (12-40 Hz) power increased in the frontal EEG and PFC, PC and CT LFPs, and PFC-CT and PFC-PFC LFP beta/low gamma coherence increased. Loss of movement (LOM) coincided with an abrupt decrease in beta/low gamma PFC-CT LFP coherence. Following LOM, cortically coherent slow-delta (0.1-4 Hz) oscillations were observed in the frontal EEG and PFC, PC and CT LFPs. At higher doses of sevoflurane sufficient to induce loss of the righting reflex, coherent slow-delta oscillations were dominant in the frontal EEG and PFC, PC and CT LFPs. Dynamics similar to those observed during induction were observed as animals emerged from sevoflurane anesthesia. We conclude that the rat is a useful animal model for sevoflurane-induced EEG oscillations in humans, and that coherent slow-delta oscillations are a correlate of sevoflurane-induced behavioral arrest and loss of righting in rats.

Predictive Coding in Area V4: Dynamic Shape Discrimination under Partial Occlusion

PubMed Central

Choi, Hannah; Pasupathy, Anitha; Shea-Brown, Eric

2018-01-01

The primate visual system has an exquisite ability to discriminate partially occluded shapes. Recent electrophysiological recordings suggest that response dynamics in intermediate visual cortical area V4, shaped by feedback from prefrontal cortex (PFC), may play a key role. To probe the algorithms that may underlie these findings, we build and test a model of V4 and PFC interactions based on a hierarchical predictive coding framework. We propose that probabilistic inference occurs in two steps. Initially, V4 responses are driven solely by bottom-up sensory input and are thus strongly influenced by the level of occlusion. After a delay, V4 responses combine both feedforward input and feedback signals from the PFC; the latter reflect predictions made by PFC about the visual stimulus underlying V4 activity. We find that this model captures key features of V4 and PFC dynamics observed in experiments. Specifically, PFC responses are strongest for occluded stimuli and delayed responses in V4 are less sensitive to occlusion, supporting our hypothesis that the feedback signals from PFC underlie robust discrimination of occluded shapes. Thus, our study proposes that area V4 and PFC participate in hierarchical inference, with feedback signals encoding top-down predictions about occluded shapes. PMID:29566355

Tyramide Signal Amplification Permits Immunohistochemical Analyses of Androgen Receptors in the Rat Prefrontal Cortex

PubMed Central

Low, Katelyn L.; Ma, Chunqi; Soma, Kiran K.

2017-01-01

Research on neural androgen receptors (ARs) has traditionally focused on brain regions that regulate reproductive and aggressive behaviors, such as the hypothalamus and amygdala. Although many cells in the prefrontal cortex (PFC) also express ARs, the number of ARs per cell appears to be much lower, and thus, AR immunostaining is often hard to detect and quantify in the PFC. Here, we demonstrate that biotin tyramide signal amplification (TSA) dramatically increases AR immunoreactivity in the rat brain, including critical regions of the PFC such as the medial PFC (mPFC) and orbitofrontal cortex (OFC). We show that TSA is useful for AR detection with both chromogenic and immunofluorescent immunohistochemistry. Double-labeling studies reveal that AR+ cells in the PFC and hippocampus are NeuN+ but not GFAP+ and thus primarily neuronal. Finally, in gonadally intact rats, more AR+ cells are present in the mPFC and OFC of males than of females. Future studies can use TSA to further examine AR immunoreactivity across ages, sexes, strains, and different procedures (e.g., fixation methods). In light of emerging evidence for the androgen regulation of executive function and working memory, these results may help understand the distribution and roles of ARs in the PFC. PMID:28438093

Depression of Excitatory Synapses onto Parvalbumin Interneurons in the Medial Prefrontal Cortex in Susceptibility to Stress

PubMed Central

Delevich, Kristen

2015-01-01

In response to extreme stress, individuals either show resilience or succumb to despair. The prefrontal cortex (PFC) is required for coping with stress, and PFC dysfunction has been implicated in stress-related mental disorders, including depression. Nevertheless, the mechanisms by which the PFC participates in stress responses remain unclear. Here, we investigate the role of parvalbumin (PV) interneurons in the medial PFC (mPFC) in shaping behavioral responses to stress induced by the learned helplessness procedure, in which animals are subjected to an unpredictable and inescapable stressor. PV interneurons in the mPFC were probed and manipulated in knock-in mice expressing the Cre recombinase under the endogenous parvalbumin promoter. Notably, we found that excitatory synaptic transmission onto these neurons was decreased in mice showing helplessness, a behavioral state that is thought to resemble features of human depression. Furthermore, selective suppression of PV interneurons in the mPFC using hM4Di, a DREADD (designer receptor exclusively activated by designer drug), promoted helplessness, indicating that activation of these neurons during stress promotes the establishment of resilient behavior. Our results reveal a cellular mechanism of mPFC dysfunction that may contribute to the emergence of maladaptive behavioral responses in the face of adverse life events. PMID:25698754

Oscillatory activity in neocortical networks during tactile discrimination near the limit of spatial acuity.

PubMed

Adhikari, Bhim M; Sathian, K; Epstein, Charles M; Lamichhane, Bidhan; Dhamala, Mukesh

2014-05-01

Oscillatory interactions within functionally specialized but distributed brain regions are believed to be central to perceptual and cognitive functions. Here, using human scalp electroencephalography (EEG) recordings combined with source reconstruction techniques, we study how oscillatory activity functionally organizes different neocortical regions during a tactile discrimination task near the limit of spatial acuity. While undergoing EEG recordings, blindfolded participants felt a linear three-dot array presented electromechanically, under computer control, and reported whether the central dot was offset to the left or right. The average brain response differed significantly for trials with correct and incorrect perceptual responses in the timeframe approximately between 130 and 175ms. During trials with correct responses, source-level peak activity appeared in the left primary somatosensory cortex (SI) at around 45ms, in the right lateral occipital complex (LOC) at 130ms, in the right posterior intraparietal sulcus (pIPS) at 160ms, and finally in the left dorsolateral prefrontal cortex (dlPFC) at 175ms. Spectral interdependency analysis of activity in these nodes showed two distinct distributed networks, a dominantly feedforward network in the beta band (12-30Hz) that included all four nodes and a recurrent network in the gamma band (30-100Hz) that linked SI, pIPS and dlPFC. Measures of network activity in both bands were correlated with the accuracy of task performance. These findings suggest that beta and gamma band oscillatory networks coordinate activity between neocortical regions mediating sensory and cognitive processing to arrive at tactile perceptual decisions. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Unity Power Factor Operated PFC Converter Based Power Supply for Computers

NASA Astrophysics Data System (ADS)

Singh, Shikha; Singh, Bhim; Bhuvaneswari, G.; Bist, Vashist

2017-11-01

Power Supplies (PSs) employed in personal computers pollute the single phase ac mains by drawing distorted current at a substandard Power Factor (PF). The harmonic distortion of the supply current in these personal computers are observed 75% to 90% with the Crest Factor (CF) being very high which escalates losses in the distribution system. To find a tangible solution to these issues, a non-isolated PFC converter is employed at the input of isolated converter that is capable of improving the input power quality apart from regulating the dc voltage at its output. This is given to the isolated stage that yields completely isolated and stiffly regulated multiple output voltages which is the prime requirement of computer PS. The operation of the proposed PS is evaluated under various operating conditions and the results show improved performance depicting nearly unity PF and low input current harmonics. The prototype of this PS is developed in laboratory environment and test results are recorded which corroborate the power quality improvement observed in simulation results under various operating conditions.

Optogenetic dissection of medial prefrontal cortex circuitry

PubMed Central

Riga, Danai; Matos, Mariana R.; Glas, Annet; Smit, August B.; Spijker, Sabine; Van den Oever, Michel C.

2014-01-01

The medial prefrontal cortex (mPFC) is critically involved in numerous cognitive functions, including attention, inhibitory control, habit formation, working memory and long-term memory. Moreover, through its dense interconnectivity with subcortical regions (e.g., thalamus, striatum, amygdala and hippocampus), the mPFC is thought to exert top-down executive control over the processing of aversive and appetitive stimuli. Because the mPFC has been implicated in the processing of a wide range of cognitive and emotional stimuli, it is thought to function as a central hub in the brain circuitry mediating symptoms of psychiatric disorders. New optogenetics technology enables anatomical and functional dissection of mPFC circuitry with unprecedented spatial and temporal resolution. This provides important novel insights in the contribution of specific neuronal subpopulations and their connectivity to mPFC function in health and disease states. In this review, we present the current knowledge obtained with optogenetic methods concerning mPFC function and dysfunction and integrate this with findings from traditional intervention approaches used to investigate the mPFC circuitry in animal models of cognitive processing and psychiatric disorders. PMID:25538574

Optogenetic dissection of medial prefrontal cortex circuitry.

PubMed

Riga, Danai; Matos, Mariana R; Glas, Annet; Smit, August B; Spijker, Sabine; Van den Oever, Michel C

2014-01-01

The medial prefrontal cortex (mPFC) is critically involved in numerous cognitive functions, including attention, inhibitory control, habit formation, working memory and long-term memory. Moreover, through its dense interconnectivity with subcortical regions (e.g., thalamus, striatum, amygdala and hippocampus), the mPFC is thought to exert top-down executive control over the processing of aversive and appetitive stimuli. Because the mPFC has been implicated in the processing of a wide range of cognitive and emotional stimuli, it is thought to function as a central hub in the brain circuitry mediating symptoms of psychiatric disorders. New optogenetics technology enables anatomical and functional dissection of mPFC circuitry with unprecedented spatial and temporal resolution. This provides important novel insights in the contribution of specific neuronal subpopulations and their connectivity to mPFC function in health and disease states. In this review, we present the current knowledge obtained with optogenetic methods concerning mPFC function and dysfunction and integrate this with findings from traditional intervention approaches used to investigate the mPFC circuitry in animal models of cognitive processing and psychiatric disorders.

Chemogenetic inhibition of the medial prefrontal cortex reverses the effects of REM sleep loss on sucrose consumption

PubMed Central

McEown, Kristopher; Takata, Yohko; Cherasse, Yoan; Nagata, Nanae; Aritake, Kosuke; Lazarus, Michael

2016-01-01

Rapid eye movement (REM) sleep loss is associated with increased consumption of weight-promoting foods. The prefrontal cortex (PFC) is thought to mediate reward anticipation. However, the precise role of the PFC in mediating reward responses to highly palatable foods (HPF) after REM sleep deprivation is unclear. We selectively reduced REM sleep in mice over a 25–48 hr period and chemogenetically inhibited the medial PFC (mPFC) by using an altered glutamate-gated and ivermectin-gated chloride channel that facilitated neuronal inhibition through hyperpolarizing infected neurons. HPF consumption was measured while the mPFC was inactivated and REM sleep loss was induced. We found that REM sleep loss increased HPF consumption compared to control animals. However, mPFC inactivation reversed the effect of REM sleep loss on sucrose consumption without affecting fat consumption. Our findings provide, for the first time, a causal link between REM sleep, mPFC function and HPF consumption. DOI: http://dx.doi.org/10.7554/eLife.20269.001 PMID:27919319

Optogenetic stimulation of infralimbic PFC reproduces ketamine's rapid and sustained antidepressant actions.

PubMed

Fuchikami, Manabu; Thomas, Alexandra; Liu, Rongjian; Wohleb, Eric S; Land, Benjamin B; DiLeone, Ralph J; Aghajanian, George K; Duman, Ronald S

2015-06-30

Ketamine produces rapid and sustained antidepressant actions in depressed patients, but the precise cellular mechanisms underlying these effects have not been identified. Here we determined if modulation of neuronal activity in the infralimbic prefrontal cortex (IL-PFC) underlies the antidepressant and anxiolytic actions of ketamine. We found that neuronal inactivation of the IL-PFC completely blocked the antidepressant and anxiolytic effects of systemic ketamine in rodent models and that ketamine microinfusion into IL-PFC reproduced these behavioral actions of systemic ketamine. We also found that optogenetic stimulation of the IL-PFC produced rapid and long-lasting antidepressant and anxiolytic effects and that these effects are associated with increased number and function of spine synapses of layer V pyramidal neurons. The results demonstrate that ketamine infusions or optogenetic stimulation of IL-PFC are sufficient to produce long-lasting antidepressant behavioral and synaptic responses similar to the effects of systemic ketamine administration.

Metabotropic glutamate receptor 3 activation is required for long-term depression in medial prefrontal cortex and fear extinction

PubMed Central

Walker, Adam G.; Wenthur, Cody J.; Xiang, Zixiu; Rook, Jerri M.; Emmitte, Kyle A.; Niswender, Colleen M.; Lindsley, Craig W.; Conn, P. Jeffrey

2015-01-01

Clinical studies have revealed that genetic variations in metabotropic glutamate receptor 3 (mGlu3) affect performance on cognitive tasks dependent upon the prefrontal cortex (PFC) and may be linked to psychiatric conditions such as schizophrenia, bipolar disorder, and addiction. We have performed a series of studies aimed at understanding how mGlu3 influences PFC function and cognitive behaviors. In the present study, we found that activation of mGlu3 can induce long-term depression in the mouse medial PFC (mPFC) in vitro. Furthermore, in vivo administration of a selective mGlu3 negative allosteric modulator impaired learning in the mPFC-dependent fear extinction task. The results of these studies implicate mGlu3 as a major regulator of PFC function and cognition. Additionally, potentiators of mGlu3 may be useful in alleviating prefrontal impairments associated with several CNS disorders. PMID:25583490

Generalisation benefits of output gating in a model of prefrontal cortex

NASA Astrophysics Data System (ADS)

Kriete, Trent; Noelle, David C.

2011-06-01

The prefrontal cortex (PFC) plays a central role in flexible cognitive control, including the suppression of habitual responding in favour of situation-appropriate behaviours that can be quite novel. PFC provides a kind of working memory, maintaining the rules, goals, and/or actions that are to control behaviour in the current context. For flexible control, these PFC representations must be sufficiently componential to support systematic generalisation to novel situations. The anatomical structure of PFC can be seen as implementing a componential 'slot-filler' structure, with different components encoded over isolated pools of neurons. Previous PFC models have highlighted the importance of a dynamic gating mechanism to selectively update individual 'slot' contents. In this article, we present simulation results that suggest that systematic generalisation also requires an 'output gating' mechanism that limits the influence of PFC on more posterior brain areas to reflect a small number of representational components at any one time.

Fear Memory Recall Potentiates Opiate Reward Sensitivity through Dissociable Dopamine D1 versus D4 Receptor-Dependent Memory Mechanisms in the Prefrontal Cortex.

PubMed

Jing Li, Jing; Szkudlarek, Hanna; Renard, Justine; Hudson, Roger; Rushlow, Walter; Laviolette, Steven R

2018-05-09

Disturbances in prefrontal cortical (PFC) dopamine (DA) transmission are well established features of psychiatric disorders involving pathological memory processing, such as post-traumatic stress disorder and opioid addiction. Transmission through PFC DA D4 receptors (D4Rs) has been shown to potentiate the emotional salience of normally nonsalient emotional memories, whereas transmission through PFC DA D1 receptors (D1Rs) has been demonstrated to selectively block recall of reward- or aversion-related associative memories. In the present study, using a combination of fear conditioning and opiate reward conditioning in male rats, we examined the role of PFC D4/D1R signaling during the processing of fear-related memory acquisition and recall and subsequent sensitivity to opiate reward memory formation. We report that PFC D4R activation potentiates the salience of normally subthreshold fear conditioning memory cues and simultaneously potentiates the rewarding effects of systemic or intra-ventral tegmental area (VTA) morphine conditioning cues. In contrast, blocking the recall of salient fear memories with intra-PFC D1R activation, blocks the ability of fear memory recall to potentiate systemic or intra-VTA morphine place preference. These effects were dependent upon dissociable PFC phosphorylation states involving calcium-calmodulin-kinase II or extracellular signal-related kinase 1-2, following intra-PFC D4 or D1R activation, respectively. Together, these findings reveal new insights into how aberrant PFC DAergic transmission and associated downstream molecular signaling pathways may modulate fear-related emotional memory processing and concomitantly increase opioid addiction vulnerability. SIGNIFICANCE STATEMENT Post-traumatic stress disorder is highly comorbid with addiction. In this study, we use a translational model of fear memory conditioning to examine how transmission through dopamine D1 or D4 receptors, in the prefrontal cortex (PFC), may differentially control acquisition or recall of fear memories and how these mechanisms might regulate sensitivity to the rewarding effects of opioids. We demonstrate that PFC D4 activation not only controls the salience of fear memory acquisition, but potentiates the rewarding effects of opioids. In contrast, PFC D1 receptor activation blocks recall of fear memories and prevents potentiation of opioid reward effects. Together, these findings demonstrate novel PFC mechanisms that may account for how emotional memory disturbances might increase the addictive liability of opioid-class drugs. Copyright © 2018 the authors 0270-6474/18/384543-13$15.00/0.

Immediate Repair Bond Strength of Fiber-reinforced Composite after Saliva or Water Contamination.

PubMed

Bijelic-Donova, Jasmina; Flett, Andrew; Lassila, Lippo V J; Vallittu, Pekka K

2018-05-31

This in vitro study aimed to evaluate the shear bond strength (SBS) of particulate filler composite (PFC) to saliva- or water-contaminated fiber-reinforced composite (FRC). One type of FRC substrate with semi-interpenetrating polymer matrix (semi-IPN) (everStick C&B) was used in this investigation. A microhybrid PFC (Filtek Z250) substrate served as control. Freshly cured PFC and FRC substrates were first subjected to different contamination and surface cleaning treatments, then the microhybrid PFC restorative material (Filtek Z250) was built up on the substrates in 2-mm increments and light cured. Uncontaminated and saliva- or water-contaminated substrate surfaces were either left untreated or were cleaned via phosphoric acid etching or water spray accompanied with or without adhesive composite application prior applying the adherent PFC material. SBS was evaluated after thermocycling the specimens (6000 cycles, 5°C and 55°C). Three-way ANOVA showed that both the surface contamination and the surface treatment signficantly affected the bond strength (p < 0.05). Saliva contamination reduced the SBS more than did the water contamination. SBS loss after saliva contamination was 73.7% and 31.3% for PFC and FRC, respectively. After water contamination, SBS loss was 17.2% and 13.3% for PFC and FRC, respectively. The type of surface treatment was significant for PFC (p < 0.05), but not for FRC (p = 0.572). Upon contamination of freshly cured PFC or semi-IPN FRC, surfaces should be re-prepared via phosphoric acid etching, water cleaning, drying, and application of adhesive composite in order to recover optimal bond strength.

Ultrastructural organization of medial prefrontal inputs to the rhinal cortices.

PubMed

Apergis-Schoute, John; Pinto, Aline; Paré, Denis

2006-07-01

Accumulating evidence suggests that the medial prefrontal cortex (mPFC) plays a critical role in the formation, retrieval and long-term storage of hippocampal-dependent memories. Consistent with this, there are direct hippocampal projections to the mPFC. Moreover, the mPFC sends robust projections to the perirhinal and entorhinal cortices, two interconnected cortical fields that funnel information into and out of the hippocampus. However, the significance of the latter projection remains unclear because no data are available regarding the rhinal targets of mPFC axons. This question was examined in the present study using a combination of anterograde tracing with Phaseolus vulgaris leucoagglutinin and pre-embedding gamma-aminobutyric acid (GABA) immunocytochemistry in guinea pigs. Following Phaseolus vulgaris leucoagglutinin injections in the mPFC, anterogradely labeled axons were seen in the perirhinal (mainly superficial layers) and lateral entorhinal (mainly deep layers) cortices. In the electron microscope, the synaptic articulation of anterogradely labeled mPFC axon terminals with perirhinal and entorhinal neurons was found to be nearly identical. In these two rhinal fields, mPFC axon terminals only formed asymmetric synapses, typically with GABA-immunonegative spines ( approximately 70%) but occasionally with dendritic profiles ( approximately 30%), half of which were GABA immunopositive. In the light of earlier observations, these findings indicate that mPFC inputs exert mainly excitatory effects in the rhinal cortices, prevalently on principal neurons. Thus, these results suggest that the mPFC may affect hippocampal-dependent memories by enhancing impulse traffic into and out of the hippocampus at the level of the rhinal cortices.

Electrical stimulation of the rostral medial prefrontal cortex in rabbits inhibits the expression of conditioned eyelid responses but not their acquisition

PubMed Central

Leal-Campanario, Rocío; Fairén, Alfonso; Delgado-García, José M.; Gruart, Agnès

2007-01-01

We have studied the role of rostral medial prefrontal cortex (mPFC) on reflexively evoked blinks and on classically conditioned eyelid responses in alert-behaving rabbits. The rostral mPFC was identified by its afferent projections from the medial half of the thalamic mediodorsal nuclear complex. Classical conditioning consisted of a delay paradigm using a 370-ms tone as the conditioned stimulus (CS) and a 100-ms air puff directed at the left cornea as the unconditioned stimulus (US). The CS coterminated with the US. Electrical train stimulation of the contralateral rostral mPFC produced a significant inhibition of air-puff-evoked blinks. The same train stimulation of the rostral mPFC presented during the CS–US interval for 10 successive conditioning sessions significantly reduced the generation of conditioned responses (CRs) as compared with values reached by control animals. Interestingly, the percentage of CRs almost reached control values when train stimulation of the rostral mPFC was removed from the fifth conditioning session on. The electrical stimulation of the rostral mPFC in well conditioned animals produced a significant decrease in the percentage of CRs. Moreover, the stimulation of the rostral mPFC was also able to modify the kinematics (latency, amplitude, and velocity) of evoked CRs. These results suggest that the rostral mPFC is a potent inhibitor of reflexively evoked and classically conditioned eyeblinks but that activation prevents only the expression of CRs, not their latent acquisition. Functional and behavioral implications of this inhibitory role of the rostral mPFC are discussed. PMID:17592148

Survey of patterns, levels, and trends of perfluorinated compounds in aquatic organisms and bird eggs from representative German ecosystems.

PubMed

Rüdel, Heinz; Müller, Josef; Jürling, Heinrich; Bartel-Steinbach, Martina; Koschorreck, Jan

2011-11-01

Samples from the German Environmental Specimen Bank (ESB) covering particularly the years 1994-1996, 2000-2002, and 2006-2009 were analyzed for perfluorinated compounds (PFC; mainly C4-C13 carboxylic and sulfonic acids) to gain an overview on current PFC levels and patterns in marine, limnetic, and terrestrial biota; to assess their concentrations in different trophic levels; and to investigate whether risk management measures for PFC are successful. Specimens, either standardized annual pooled samples (blue mussels, eelpout liver, bream liver, pigeon eggs) or individual single samples (cormorant eggs, rook eggs), were collected for the German ESB program from representative sampling sites according to documented guidelines. After appropriate extraction, PFC were quantified under ISO/IEC 17025 accreditation by HPLC/MS-MS with isotopically labeled internal standards. Limits of quantification (LOQs) were 0.2-0.5 ng/g. Data are reported on a wet weight basis. In most samples the predominant PFC was perfluorooctane sulfonic acid (PFOS). However, in marine mussels from North and Baltic Seas, PFOS levels were mostly below the LOQ, but low residues of PFOS amide were found which declined in recent years. Livers of eelpout showed maximum concentrations of 15-25 ng/g PFOS in the period 2000-2002 and low amounts of perfluoropentanoate in all years. Beside PFOS (median 48 ng/g) several PFC could be determined in cormorant eggs sampled in 2009 from a Baltic Sea site. For a freshwater ecosystem, current PFC burdens for cormorant eggs were even higher (median 400 ng/g PFOS). Livers of bream from rivers showed concentrations of 130-260 ng/g PFOS, but for bream from a reference lake levels were only about 6 ng/g. In contrast to cormorants, eggs of rook and feral pigeon from terrestrial ecosystems displayed only low PFC burdens (up to 6 ng/g PFOS). Generally, PFC levels were lower in marine than in freshwater biota. PFC burdens were higher in biota from the ESB-North Sea sites than in Baltic Sea organisms. Levels of PFC were quite high especially in top predators of both limnetic and marine ecosystems. Only low PFC levels were detected in eggs of terrestrial birds. A decrease of PFOS levels from maximum values around the year 2000 observed at least in North Sea biota may be a result of a production cease and shifts in marketing pattern.

Chronic restraint stress causes anxiety- and depression-like behaviors, downregulates glucocorticoid receptor expression, and attenuates glutamate release induced by brain-derived neurotrophic factor in the prefrontal cortex.

PubMed

Chiba, Shuichi; Numakawa, Tadahiro; Ninomiya, Midori; Richards, Misty C; Wakabayashi, Chisato; Kunugi, Hiroshi

2012-10-01

Stress and the resulting increase in glucocorticoid levels have been implicated in the pathophysiology of depressive disorders. We investigated the effects of chronic restraint stress (CRS: 6 hours × 28 days) on anxiety- and depression-like behaviors in rats and on the possible changes in glucocorticoid receptor (GR) expression as well as brain-derived neurotrophic factor (BDNF)-dependent neural function in the prefrontal cortex (PFC). We observed significant reductions in body weight gain, food intake and sucrose preference from 1 week after the onset of CRS. In the 5th week of CRS, we conducted open-field (OFT), elevated plus-maze (EPM) and forced swim tests (FST). We observed a decrease in the number of entries into open arms during the EPM (anxiety-like behavior) and increased immobility during the FST (depression-like behavior). When the PFC was removed after CRS and subject to western blot analysis, the GR expression reduced compared with control, while the levels of BDNF and its receptors remained unchanged. Basal glutamate concentrations in PFC acute slice which were measured by high performance liquid chromatography were not influenced by CRS. However, BDNF-induced glutamate release was attenuated after CRS. These results suggest that reduced GR expression and altered BDNF function may be involved in chronic stress-induced anxiety--and depression-like behaviors. Copyright © 2012 Elsevier Inc. All rights reserved.

Lower glutamic acid decarboxylase 65-kDa isoform messenger RNA and protein levels in the prefrontal cortex in schizoaffective disorder but not schizophrenia.

PubMed

Glausier, Jill R; Kimoto, Sohei; Fish, Kenneth N; Lewis, David A

2015-01-15

Altered gamma-aminobutyric acid (GABA) signaling in the prefrontal cortex (PFC) has been associated with cognitive dysfunction in patients with schizophrenia and schizoaffective disorder. Levels of the GABA-synthesizing enzyme glutamic acid decarboxylase 67-kDa isoform (GAD67) in the PFC have been consistently reported to be lower in patients with these disorders, but the status of the second GABA-synthesizing enzyme, glutamic acid decarboxylase 65-kDa isoform (GAD65), remains unclear. GAD65 messenger RNA (mRNA) levels were quantified in PFC area 9 by quantitative polymerase chain reaction from 62 subjects with schizophrenia or schizoaffective disorder and 62 matched healthy comparison subjects. In a subset of subject pairs, GAD65 relative protein levels were quantified by confocal immunofluorescence microscopy. Mean GAD65 mRNA levels were 13.6% lower in subjects with schizoaffective disorder but did not differ in subjects with schizophrenia relative to their matched healthy comparison subjects. In the subjects with schizoaffective disorder, mean GAD65 protein levels were 19.4% lower and were correlated with GAD65 mRNA levels. Lower GAD65 mRNA and protein levels within subjects with schizoaffective disorder were not attributable to factors commonly comorbid with the diagnosis. In concert with previous studies, these findings suggest that schizoaffective disorder is associated with lower levels of both GAD65 and GAD67 mRNA and protein in the PFC, whereas subjects with schizophrenia have lower mean levels of only GAD67 mRNA and protein. Because cognitive function is generally better preserved in patients with schizoaffective disorder relative to patients with schizophrenia, these findings may support an interpretation that GAD65 downregulation provides a homeostatic response complementary to GAD67 downregulation that serves to reduce inhibition in the face of lower PFC network activity. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Effects of prenatal cocaine exposure on social development in mice.

PubMed

Kabir, Zeeba D; Kennedy, Bruce; Katzman, Aaron; Lahvis, Garet P; Kosofsky, Barry E

2014-01-01

Prenatal cocaine exposure (PCE) in humans and animals has been shown to impair social development. Molecules that mediate synaptic plasticity and learning in the medial prefrontal cortex (mPFC), specifically brain-derived neurotrophic factor (BDNF) and its downstream signaling molecule, early growth response protein 1 (egr1), have been shown to affect the regulation of social interactions (SI). In this study we determined the effects of PCE on SI and the corresponding ultrasonic vocalizations (USVs) in developing mice. Furthermore, we studied the PCE-induced changes in the constitutive expression of BDNF, egr1 and their transcriptional regulators in the mPFC as a possible molecular mechanism mediating the altered SI. In prenatal cocaine-exposed (PCOC) mice we identified increased SI and USV production at postnatal day (PD) 25, and increased SI but not USVs at PD35. By PD45 the expression of both social behaviors normalized in PCOC mice. At the molecular level, we found increased BDNF exon IV and egr1 mRNA in the mPFC of PCOC mice at PD30 that normalized by PD45. This was concurrent with increased EGR1 protein in the mPFC of PCOC mice at PD30, suggesting a role of egr1 in the enhanced SI observed in juvenile PCOC mice. Additionally, by measuring the association of acetylation of histone 3 at lysine residues 9 and 14 (acH3K9,14) and MeCP2 at the promoters of BDNF exons I and IV and egr1, our results provide evidence of promoter-specific alterations in the mPFC of PCOC juvenile mice, with increased association of acH3K9,14 only at the BDNF exon IV promoter. These results identify a potential PCE-induced molecular alteration as the underlying neurobiological mechanism mediating the altered social development in juvenile mice. © 2014 S. Karger AG, Basel.

Rescue of impaired sociability and anxiety-like behavior in adult cacna1c-deficient mice by pharmacologically targeting eIF2α

PubMed Central

Kabir, ZD; Che, A; Fischer, DK; Rice, RC; Rizzo, BK; Byrne, M; Glass, MJ; De Marco Garcia, NV; Rajadhyaksha, AM

2018-01-01

CACNA1C, encoding the Cav1.2 subunit of L-type Ca2+ channels, has emerged as one of the most prominent and highly replicable susceptibility genes for several neuropsychiatric disorders. Cav1.2 channels play a crucial role in calcium-mediated processes involved in brain development and neuronal function. Within the CACNA1C gene, disease-associated single-nucleotide polymorphisms have been associated with impaired social and cognitive processing and altered prefrontal cortical (PFC) structure and activity. These findings suggest that aberrant Cav1.2 signaling may contribute to neuropsychiatric-related disease symptoms via impaired PFC function. Here, we show that mice harboring loss of cacna1c in excitatory glutamatergic neurons of the forebrain (fbKO) that we have previously reported to exhibit anxiety-like behavior, displayed a social behavioral deficit and impaired learning and memory. Furthermore, focal knockdown of cacna1c in the adult PFC recapitulated the social deficit and elevated anxiety-like behavior, but not the deficits in learning and memory. Electrophysiological and molecular studies in the PFC of cacna1c fbKO mice revealed higher E/I ratio in layer 5 pyramidal neurons and lower general protein synthesis. This was concurrent with reduced activity of mTORC1 and its downstream mRNA translation initiation factors eIF4B and 4EBP1, as well as elevated phosphorylation of eIF2α, an inhibitor of mRNA translation. Remarkably, systemic treatment with ISRIB, a small molecule inhibitor that suppresses the effects of phosphorylated eIF2α on mRNA translation, was sufficient to reverse the social deficit and elevated anxiety-like behavior in adult cacna1c fbKO mice. ISRIB additionally normalized the lower protein synthesis and higher E/I ratio in the PFC. Thus this study identifies a novel Cav1.2 mechanism in neuropsychiatric-related endophenotypes and a potential future therapeutic target to explore. PMID:28584287

Damage to the ventromedial prefrontal cortex is associated with impairments in both spontaneous and deliberative moral judgments

PubMed Central

Cameron, C. Daryl; Reber, Justin; Spring, Victoria L.; Tranel, Daniel

2018-01-01

Implicit moral evaluations—spontaneous, unintentional judgments about the moral status of actions or persons—are thought to play a pivotal role in moral experience, suggesting a need for research to model these moral evaluations in clinical populations. Prior research reveals that the ventromedial prefrontal cortex (vmPFC) is a critical area underpinning affect and morality, and patients with vmPFC lesions show abnormalities in moral judgment and moral behavior. We use indirect measurement and multinomial modeling to understand differences in implicit moral evaluations among patients with vmPFC lesions. Our model quantifies multiple processes of moral judgment: implicit moral evaluations in response to distracting moral transgressions (Unintentional Judgment), accurate moral judgments about target actions (Intentional Judgment), and a directional tendency to judge actions as morally wrong (Response Bias). Compared to individuals with non-vmPFC brain damage and neurologically healthy comparisons, patients with vmPFC lesions showed a dual deficit in processes of moral judgment. First, patients with vmPFC lesions showed reduced Unintentional Judgment about moral transgressions, but not about non-moral negative affective distracters. Second, patients with vmPFC lesions showed reduced Intentional Judgment about target actions. These findings highlight the utility of a formal modeling approach in moral psychology, revealing a dual deficit in multiple component processes of moral judgment among patients with vmPFC lesions. PMID:29382558

Damage to the ventromedial prefrontal cortex is associated with impairments in both spontaneous and deliberative moral judgments.

PubMed

Cameron, C Daryl; Reber, Justin; Spring, Victoria L; Tranel, Daniel

2018-03-01

Implicit moral evaluations-spontaneous, unintentional judgments about the moral status of actions or persons-are thought to play a pivotal role in moral experience, suggesting a need for research to model these moral evaluations in clinical populations. Prior research reveals that the ventromedial prefrontal cortex (vmPFC) is a critical area underpinning affect and morality, and patients with vmPFC lesions show abnormalities in moral judgment and moral behavior. We use indirect measurement and multinomial modeling to understand differences in implicit moral evaluations among patients with vmPFC lesions. Our model quantifies multiple processes of moral judgment: implicit moral evaluations in response to distracting moral transgressions (Unintentional Judgment), accurate moral judgments about target actions (Intentional Judgment), and a directional tendency to judge actions as morally wrong (Response Bias). Compared to individuals with non-vmPFC brain damage and neurologically healthy comparisons, patients with vmPFC lesions showed a dual deficit in processes of moral judgment. First, patients with vmPFC lesions showed reduced Unintentional Judgment about moral transgressions, but not about non-moral negative affective distracters. Second, patients with vmPFC lesions showed reduced Intentional Judgment about target actions. These findings highlight the utility of a formal modeling approach in moral psychology, revealing a dual deficit in multiple component processes of moral judgment among patients with vmPFC lesions. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effects of chronic REM sleep restriction on D1 receptor and related signal pathways in rat prefrontal cortex.

PubMed

Han, Yan; Wen, Xiaosa; Rong, Fei; Chen, Xinmin; Ouyang, Ruying; Wu, Shuai; Nian, Hua; Ma, Wenling

2015-01-01

The prefrontal cortex (PFC) mediates cognitive function that is sensitive to disruption by sleep loss, and molecular mechanisms regulating neural dysfunction induced by chronic sleep restriction (CSR), particularly in the PFC, have yet to be completely understood. The aim of the present study was to investigate the effect of chronic REM sleep restriction (REM-CSR) on the D1 receptor (D1R) and key molecules in D1R' signal pathways in PFC. We employed the modified multiple platform method to create the REM-CSR rat model. The ultrastructure of PFC was observed by electron microscopy. HPLC was performed to measure the DA level in PFC. The expressions of genes and proteins of related molecules were assayed by real-time PCR and Western blot, respectively. The general state and morphology of PFC in rats were changed by CSR, and DA level and the expression of D1R in PFC were markedly decreased (P < 0.01, P < 0.05); the expression of phosphor-PKAcα was significantly lowered in CSR rats (P < 0.05). The present results suggested that the alteration of neuropathology and D1R expression in PFC may be associated with CSR induced cognitive dysfunction, and the PKA pathway of D1R may play an important role in the impairment of advanced neural function.

Effects of Chronic REM Sleep Restriction on D1 Receptor and Related Signal Pathways in Rat Prefrontal Cortex

PubMed Central

Han, Yan; Wen, Xiaosa; Rong, Fei; Chen, Xinmin; Ouyang, Ruying; Wu, Shuai; Nian, Hua; Ma, Wenling

2015-01-01

The prefrontal cortex (PFC) mediates cognitive function that is sensitive to disruption by sleep loss, and molecular mechanisms regulating neural dysfunction induced by chronic sleep restriction (CSR), particularly in the PFC, have yet to be completely understood. The aim of the present study was to investigate the effect of chronic REM sleep restriction (REM-CSR) on the D1 receptor (D1R) and key molecules in D1R' signal pathways in PFC. We employed the modified multiple platform method to create the REM-CSR rat model. The ultrastructure of PFC was observed by electron microscopy. HPLC was performed to measure the DA level in PFC. The expressions of genes and proteins of related molecules were assayed by real-time PCR and Western blot, respectively. The general state and morphology of PFC in rats were changed by CSR, and DA level and the expression of D1R in PFC were markedly decreased (P < 0.01, P < 0.05); the expression of phosphor-PKAcα was significantly lowered in CSR rats (P < 0.05). The present results suggested that the alteration of neuropathology and D1R expression in PFC may be associated with CSR induced cognitive dysfunction, and the PKA pathway of D1R may play an important role in the impairment of advanced neural function. PMID:25793215

Valence processing of first impressions in the dorsomedial prefrontal cortex: a near-infrared spectroscopy study.

PubMed

Yu, Chi-Lin; Wang, Min-Ying; Hu, Jon-Fan

2016-05-25

Previous studies have suggested that the dorsomedial prefrontal cortex (dmPFC) plays a central role in processing first impressions; however, little is known about how dmPFC processes different valences of first impressions. Moreover, it is still unclear as to whether the dmPFC shows lateralization or only induces different levels of activation when processing positive and negative impressions. To address these questions in the present study, the brain activities for the impression judgments expressed by participants were measured with near-infrared spectroscopy. For each real facial picture, participants were asked to evaluate their first impressions on a scale from 'bad' to 'good' using a keyboard. The results showed that although the right dmPFC has a higher sensitivity in processing impressions, both the hemispheres of dmPFC showed a significant trend where the activation of positive impressions was higher than the negative ones. Accordingly, it is proposed that the dmPFC acts as a single mechanism responsible for delineating the processing of first impressions rather than two lateralized systems. Therefore, a 'positivity dominance hypothesis' is also proposed, which states that dmPFC in both hemispheres have a higher sensitivity and priority for positive impressions than negative ones. The present study provides valuable findings with respect to the role of the dmPFC in the processes of first impression formation.

Anodal transcranial direct current stimulation over right dorsolateral prefrontal cortex alters decision making during approach-avoidance conflict.

PubMed

Chrysikou, Evangelia G; Gorey, Claire; Aupperle, Robin L

2017-03-01

Approach-avoidance conflict (AAC) refers to situations associated with both rewarding and threatening outcomes. The AAC task was developed to measure AAC decision-making. Approach behavior during this task has been linked to self-reported anxiety sensitivity and has elicited anterior cingulate, insula, caudate and right dorsolateral prefrontal cortex (dlPFC) activity, with right lateral PFC tracking the extent of approach behavior. Guided by these results, we used excitatory transcranial direct current stimulation (tDCS) to demonstrate the causal involvement of right dlPFC in AAC decision-making. Participants received anodal tDCS at 1.5mA over either left or right dlPFC or sham stimulation, while performing the AAC task and a control short-term memory task. Analyses of variance (ANOVA) revealed that for individuals with high anxiety sensitivity excitatory right (but not left or sham) dlPFC stimulation elicited measurable decreases in approach behavior during conflict. Excitatory left (but not right or sham) dlPFC simulation improved performance on the control task. These results support a possible asymmetry between the contributions of right and left dlPFC to AAC resolution during emotional decision-making. Increased activity in right dlPFC may contribute to anxiety-related symptoms and, as such, serve as a neurobehavioral target of anxiolytic treatments aiming to decrease avoidance behavior. © The Author (2016). Published by Oxford University Press.

Depression of excitatory synapses onto parvalbumin interneurons in the medial prefrontal cortex in susceptibility to stress.

PubMed

Perova, Zinaida; Delevich, Kristen; Li, Bo

2015-02-18

In response to extreme stress, individuals either show resilience or succumb to despair. The prefrontal cortex (PFC) is required for coping with stress, and PFC dysfunction has been implicated in stress-related mental disorders, including depression. Nevertheless, the mechanisms by which the PFC participates in stress responses remain unclear. Here, we investigate the role of parvalbumin (PV) interneurons in the medial PFC (mPFC) in shaping behavioral responses to stress induced by the learned helplessness procedure, in which animals are subjected to an unpredictable and inescapable stressor. PV interneurons in the mPFC were probed and manipulated in knock-in mice expressing the Cre recombinase under the endogenous parvalbumin promoter. Notably, we found that excitatory synaptic transmission onto these neurons was decreased in mice showing helplessness, a behavioral state that is thought to resemble features of human depression. Furthermore, selective suppression of PV interneurons in the mPFC using hM4Di, a DREADD (designer receptor exclusively activated by designer drug), promoted helplessness, indicating that activation of these neurons during stress promotes the establishment of resilient behavior. Our results reveal a cellular mechanism of mPFC dysfunction that may contribute to the emergence of maladaptive behavioral responses in the face of adverse life events. Copyright © 2015 the authors 0270-6474/15/353201-06$15.00/0.

Fractal analysis of polyferric chloride-humic acid (PFC-HA) flocs in different topological spaces.

PubMed

Wang, Yili; Lu, Jia; Baiyu, Du; Shi, Baoyou; Wang, Dongsheng

2009-01-01

The fractal dimensions in different topological spaces of polyferric chloride-humic acid (PFC-HA) flocs, formed in flocculating different kinds of humic acids (HA) water at different initial pH (9.0, 7.0, 5.0) and PFC dosages, were calculated by effective density-maximum diameter, image analysis, and N2 absorption-desorption methods, respectively. The mass fractal dimensions (Df) of PFC-HA flocs were calculated by bi-logarithm relation of effective density with maximum diameter and Logan empirical equation. The Df value was more than 2.0 at initial pH of 7.0, which was 11% and 13% higher than those at pH 9.0 and 5.0, respectively, indicating the most compact flocs formed in flocculated HA water at initial pH of 7.0. The image analysis for those flocs indicates that after flocculating the HA water at initial pH greater than 7.0 with PFC flocculant, the fractal dimensions of D2 (logA vs. logdL) and D3 (logVsphere VS. logdL) of PFC-HA flocs decreased with the increase of PFC dosages, and PFC-HA flocs showed a gradually looser structure. At the optimum dosage of PFC, the D2 (logA vs. logdL) values of the flocs show 14%-43% difference with their corresponding Df, and they even had different tendency with the change of initial pH values. However, the D2 values of the flocs formed at three different initial pH in HA solution had a same tendency with the corresponding Dr. Based on fractal Frenkel-Halsey-Hill (FHH) adsorption and desorption equations, the pore surface fractal dimensions (Ds) for dried powders of PFC-HA flocs formed in HA water with initial pH 9.0 and 7.0 were all close to 2.9421, and the Ds values of flocs formed at initial pH 5.0 were less than 2.3746. It indicated that the pore surface fractal dimensions of PFC-HA flocs dried powder mainly show the irregularity from the mesopore-size distribution and marcopore-size distribution.

Neuron number and size in prefrontal cortex of children with autism.

PubMed

Courchesne, Eric; Mouton, Peter R; Calhoun, Michael E; Semendeferi, Katerina; Ahrens-Barbeau, Clelia; Hallet, Melodie J; Barnes, Cynthia Carter; Pierce, Karen

2011-11-09

Autism often involves early brain overgrowth, including the prefrontal cortex (PFC). Although prefrontal abnormality has been theorized to underlie some autistic symptoms, the cellular defects that cause abnormal overgrowth remain unknown. To investigate whether early brain overgrowth in children with autism involves excess neuron numbers in the PFC. DESIGN, SETTING, AND CASES: Postmortem prefrontal tissue from 7 autistic and 6 control male children aged 2 to 16 years was examined by expert anatomists who were blinded to diagnostic status. Number and size of neurons were quantified using stereological methods within the dorsolateral (DL-PFC) and mesial (M-PFC) subdivisions of the PFC. Cases were from the eastern and southeastern United States and died between 2000 and 2006. Mean neuron number and size in the DL-PFC and M-PFC were compared between autistic and control postmortem cases. Correlations of neuron number with deviation in brain weight from normative values for age were also performed. Children with autism had 67% more neurons in the PFC (mean, 1.94 billion; 95% CI, 1.57-2.31) compared with control children (1.16 billion; 95% CI, 0.90-1.42; P = .002), including 79% more in DL-PFC (1.57 billion; 95% CI, 1.20-1.94 in autism cases vs 0.88 billion; 95% CI, 0.66-1.10 in controls; P = .003) and 29% more in M-PFC (0.36 billion; 95% CI, 0.33-0.40 in autism cases vs 0.28 billion; 95% CI, 0.23-0.34 in controls; P = .009). Brain weight in the autistic cases differed from normative mean weight for age by a mean of 17.6% (95% CI, 10.2%-25.0%; P = .001), while brains in controls differed by a mean of 0.2% (95% CI, -8.7% to 9.1%; P = .96). Plots of counts by weight showed autistic children had both greater total prefrontal neuron counts and brain weight for age than control children. In this small preliminary study, brain overgrowth in males with autism involved an abnormal excess number of neurons in the PFC.

Investigation of stormwater quality improvements utilizing permeable friction course (PFC).

DOT National Transportation Integrated Search

2010-09-01

This report describes research into the water quality and hydraulics of the Permeable Friction Course (PFC). : Water quality monitoring of 3 locations in the Austin area indicates up to a 90 percent reduction in pollutant : discharges from PFC compar...

Prefrontal atrophy, disrupted NREM slow waves, and impaired hippocampal-dependent memory in aging

PubMed Central

Mander, Bryce A.; Rao, Vikram; Lu, Brandon; Saletin, Jared M.; Lindquist, John R.; Ancoli-Israel, Sonia; Jagust, William; Walker, Matthew P.

2014-01-01

Aging has independently been associated with regional brain atrophy, reduced non-rapid eye movement (NREM) slow-wave activity (SWA), and impaired long-term retention of episodic memories. However, that the interaction of these factors represents a neuropatholgical pathway associated with cognitive decline in later life remains unknown. Here, we show that age-related medial prefrontal cortex (mPFC) grey-matter atrophy is associated with reduced NREM SWA activity in older adults, the extent to which statistically mediates the impairment of overnight sleep-dependent memory retention. Moreover, this memory impairment was further associated with persistent hippocampal activation and reduced task-related hippocampal-prefrontal cortex connectivity, potentially representing impoverished hippocampal-neocortical memory transformation. Together, these data support a model in which age-related mPFC atrophy diminishes SWA, the functional consequence of which is impaired long-term memory. Such findings suggest that sleep disruption in the elderly, mediated by structural brain changes, represent a novel contributing factor to age-related cognitive decline in later life. PMID:23354332

Differential effects of insular and ventromedial prefrontal cortex lesions on risky decision-making

PubMed Central

Bechara, A.; Damasio, H.; Aitken, M. R. F.; Sahakian, B. J.; Robbins, T. W.

2008-01-01

The ventromedial prefrontal cortex (vmPFC) and insular cortex are implicated in distributed neural circuitry that supports emotional decision-making. Previous studies of patients with vmPFC lesions have focused primarily on decision-making under uncertainty, when outcome probabilities are ambiguous (e.g. the Iowa Gambling Task). It remains unclear whether vmPFC is also necessary for decision-making under risk, when outcome probabilities are explicit. It is not known whether the effect of insular damage is analogous to the effect of vmPFC damage, or whether these regions contribute differentially to choice behaviour. Four groups of participants were compared on the Cambridge Gamble Task, a well-characterized measure of risky decision-making where outcome probabilities are presented explicitly, thus minimizing additional learning and working memory demands. Patients with focal, stable lesions to the vmPFC (n = 20) and the insular cortex (n = 13) were compared against healthy subjects (n = 41) and a group of lesion controls (n = 12) with damage predominantly affecting the dorsal and lateral frontal cortex. The vmPFC and insular cortex patients showed selective and distinctive disruptions of betting behaviour. VmPFC damage was associated with increased betting regardless of the odds of winning, consistent with a role of vmPFC in biasing healthy individuals towards conservative options under risk. In contrast, patients with insular cortex lesions failed to adjust their bets by the odds of winning, consistent with a role of the insular cortex in signalling the probability of aversive outcomes. The insular group attained a lower point score on the task and experienced more ‘bankruptcies’. There were no group differences in probability judgement. These data confirm the necessary role of the vmPFC and insular regions in decision-making under risk. Poor decision-making in clinical populations can arise via multiple routes, with functionally dissociable effects of vmPFC and insular cortex damage. PMID:18390562

Involvement of the Cannabinoid CB1 Receptor in Modulation of Dopamine Output in the Prefrontal Cortex Associated with Food Restriction in Rats

PubMed Central

Biggio, Francesca; Utzeri, Cinzia; Lallai, Valeria; Licheri, Valentina; Lutzu, Stefano; Mostallino, Maria Cristina; Secci, Pietro Paolo; Biggio, Giovanni; Sanna, Enrico

2014-01-01

Increase in dopamine output on corticolimbic structures, such as medial prefrontal cortex (mPFC) and nucleus accumbens, has been related to reward effects associated with palatable food or food presentation after a fasting period. The endocannabinoid system regulates feeding behavior through a modulatory action on different neurotransmitter systems, including the dopaminergic system. To elucidate the involvement of type 1 cannabinoid receptors in the regulation of dopamine output in the mPFC associated with feeding in hungry rats, we restricted the food availability to a 2-h period daily for 3 weeks. In food-restricted rats the extracellular dopamine concentration in the mPFC increased starting 80 min before food presentation and returned to baseline after food removal. These changes were attenuated in animals treated with the CB1 receptor antagonist SR141716. To better understand how food restriction can change the response of mesocortical dopaminergic neurons, we studied several components of the neuronal circuit that regulates dopamine output in the mPFC. Patch-clamp experiments revealed that the inhibitory effect of the CB1 receptor agonist WIN 55,212-2 on GABAergic sIPSC frequency was diminished in mPFC neurons of FR compared to fed ad libitum rats. The basal sIPSC frequency resulted reduced in mPFC neurons of food-restricted rats, suggestive of an altered regulation of presynaptic GABA release; these changes were accompanied by an enhanced excitability of mPFC and ventral tegmental area neurons. Finally, type 1 cannabinoid receptor expression in the mPFC was reduced in food-restricted rats. Together, our data support an involvement of the endocannabinoid system in regulation of dopamine release in the mPFC through changes in GABA inhibitory synapses and suggest that the emphasized feeding-associated increase in dopamine output in the mPFC of food-restricted rats might be correlated with an altered expression and function of type 1 cannabinoid receptor in this brain region. PMID:24632810

Involvement of the cannabinoid CB1 receptor in modulation of dopamine output in the prefrontal cortex associated with food restriction in rats.

PubMed

Dazzi, Laura; Talani, Giuseppe; Biggio, Francesca; Utzeri, Cinzia; Lallai, Valeria; Licheri, Valentina; Lutzu, Stefano; Mostallino, Maria Cristina; Secci, Pietro Paolo; Biggio, Giovanni; Sanna, Enrico

2014-01-01

Increase in dopamine output on corticolimbic structures, such as medial prefrontal cortex (mPFC) and nucleus accumbens, has been related to reward effects associated with palatable food or food presentation after a fasting period. The endocannabinoid system regulates feeding behavior through a modulatory action on different neurotransmitter systems, including the dopaminergic system. To elucidate the involvement of type 1 cannabinoid receptors in the regulation of dopamine output in the mPFC associated with feeding in hungry rats, we restricted the food availability to a 2-h period daily for 3 weeks. In food-restricted rats the extracellular dopamine concentration in the mPFC increased starting 80 min before food presentation and returned to baseline after food removal. These changes were attenuated in animals treated with the CB1 receptor antagonist SR141716. To better understand how food restriction can change the response of mesocortical dopaminergic neurons, we studied several components of the neuronal circuit that regulates dopamine output in the mPFC. Patch-clamp experiments revealed that the inhibitory effect of the CB1 receptor agonist WIN 55,212-2 on GABAergic sIPSC frequency was diminished in mPFC neurons of FR compared to fed ad libitum rats. The basal sIPSC frequency resulted reduced in mPFC neurons of food-restricted rats, suggestive of an altered regulation of presynaptic GABA release; these changes were accompanied by an enhanced excitability of mPFC and ventral tegmental area neurons. Finally, type 1 cannabinoid receptor expression in the mPFC was reduced in food-restricted rats. Together, our data support an involvement of the endocannabinoid system in regulation of dopamine release in the mPFC through changes in GABA inhibitory synapses and suggest that the emphasized feeding-associated increase in dopamine output in the mPFC of food-restricted rats might be correlated with an altered expression and function of type 1 cannabinoid receptor in this brain region.

Differential effects of insular and ventromedial prefrontal cortex lesions on risky decision-making.

PubMed

Clark, L; Bechara, A; Damasio, H; Aitken, M R F; Sahakian, B J; Robbins, T W

2008-05-01

The ventromedial prefrontal cortex (vmPFC) and insular cortex are implicated in distributed neural circuitry that supports emotional decision-making. Previous studies of patients with vmPFC lesions have focused primarily on decision-making under uncertainty, when outcome probabilities are ambiguous (e.g. the Iowa Gambling Task). It remains unclear whether vmPFC is also necessary for decision-making under risk, when outcome probabilities are explicit. It is not known whether the effect of insular damage is analogous to the effect of vmPFC damage, or whether these regions contribute differentially to choice behaviour. Four groups of participants were compared on the Cambridge Gamble Task, a well-characterized measure of risky decision-making where outcome probabilities are presented explicitly, thus minimizing additional learning and working memory demands. Patients with focal, stable lesions to the vmPFC (n = 20) and the insular cortex (n = 13) were compared against healthy subjects (n = 41) and a group of lesion controls (n = 12) with damage predominantly affecting the dorsal and lateral frontal cortex. The vmPFC and insular cortex patients showed selective and distinctive disruptions of betting behaviour. VmPFC damage was associated with increased betting regardless of the odds of winning, consistent with a role of vmPFC in biasing healthy individuals towards conservative options under risk. In contrast, patients with insular cortex lesions failed to adjust their bets by the odds of winning, consistent with a role of the insular cortex in signalling the probability of aversive outcomes. The insular group attained a lower point score on the task and experienced more 'bankruptcies'. There were no group differences in probability judgement. These data confirm the necessary role of the vmPFC and insular regions in decision-making under risk. Poor decision-making in clinical populations can arise via multiple routes, with functionally dissociable effects of vmPFC and insular cortex damage.

Ventromedial Prefrontal Cortex Is Critical for Helping Others Who Are Suffering.

PubMed

Beadle, Janelle N; Paradiso, Sergio; Tranel, Daniel

2018-01-01

Neurological patients with damage to the ventromedial prefrontal cortex (vmPFC) are reported to display reduced empathy toward others in their daily lives in clinical case studies. However, the empathic behavior of patients with damage to the vmPFC has not been measured experimentally in response to an empathy-eliciting event. This is important because characterizing the degree to which patients with damage to the vmPFC have lower empathic behavior will allow for the development of targeted interventions to improve patients' social skills and in turn will help family members to better understand their impairments so they can provide appropriate supports. For the first time, we induced empathy using an ecologically-valid empathy induction in neurological patients with damage to the vmPFC and measured their empathic emotional responses and behavior in real time. Eight neurological patients with focal damage to the vmPFC were compared to demographically-matched brain-damaged and healthy comparison participants. Patients with damage to the vmPFC gave less money in the empathy condition to a person who was suffering (a confederate) than comparison participants. This provides the first direct experimental evidence that the vmPFC is critical for empathic behavior toward individuals who are suffering.

Reward and social valuation deficits following ventromedial prefrontal damage.

PubMed

Moretti, Laura; Dragone, Davide; di Pellegrino, Giuseppe

2009-01-01

Lesion and imaging studies have implicated the ventromedial prefrontal cortex (vmPFC) in economic decisions and social interactions, yet its exact functions remain unclear. Here, we investigated the hypothesis that the vmPFC represents the subjective value or desirability of future outcomes during social decision-making. Both vmPFC-damaged patients and control participants acted as the responder in a single-round ultimatum game. To test outcome valuation, we contrasted concrete, immediately available gains with abstract, future ones. To test social valuation, we contrasted interactions with a human partner and those involving a computer. We found that, compared to controls, vmPFC patients substantially reduced their acceptance rate of unfair offers from a human partner, but only when financial gains were presented as abstract amounts to be received later. When the gains were visible and readily available, the vmPFC patients' acceptance of unfair offers was normal. Furthermore, unlike controls, vmPFC patients did not distinguish between unfair offers from a human agent and those from a computerized opponent. We conclude that the vmPFC encodes the expected value of abstract, future goals in a common neural currency that takes into account both reward and social signals in order to optimize economic decision-making.

Past makes future: role of pFC in prediction.

PubMed

Fuster, Joaquín M; Bressler, Steven L

2015-04-01

The pFC enables the essential human capacities for predicting future events and preadapting to them. These capacities rest on both the structure and dynamics of the human pFC. Structurally, pFC, together with posterior association cortex, is at the highest hierarchical level of cortical organization, harboring neural networks that represent complex goal-directed actions. Dynamically, pFC is at the highest level of the perception-action cycle, the circular processing loop through the cortex that interfaces the organism with the environment in the pursuit of goals. In its predictive and preadaptive roles, pFC supports cognitive functions that are critical for the temporal organization of future behavior, including planning, attentional set, working memory, decision-making, and error monitoring. These functions have a common future perspective and are dynamically intertwined in goal-directed action. They all utilize the same neural infrastructure: a vast array of widely distributed, overlapping, and interactive cortical networks of personal memory and semantic knowledge, named cognits, which are formed by synaptic reinforcement in learning and memory acquisition. From this cortex-wide reservoir of memory and knowledge, pFC generates purposeful, goal-directed actions that are preadapted to predicted future events.

G proteins in rat prefrontal cortex (PFC) are differentially activated as a function of oxygen status and PFC region.

PubMed

Hambrecht, V S; Vlisides, P E; Row, B W; Gozal, D; Baghdoyan, H A; Lydic, R

2009-03-01

This study tested the hypothesis that activation of guanine nucleotide binding (G) proteins in rat prefrontal cortex (PFC) is altered by hypoxia. G protein activation by the cholinergic agonist carbachol and the opioid agonist DAMGO was quantified using [(35)S]GTPgammaS autoradiography. G protein activation was expressed as nCi/g tissue in the PFC of 18 rats exposed for 14 consecutive days to sustained hypoxia (10% O(2)), intermittent hypoxia (10% and 21% O(2) alternating every 90 s), or room air (21% O(2)). Relative to basal levels of G protein activation, carbachol and DAMGO increased G protein activation by approximately 70% across all oxygen concentrations. Compared to the room air condition, sustained hypoxia caused a significant increase in G protein activation in frontal association (FrA) region of the PFC. Region-specific comparisons revealed that intermittent and sustained hypoxia caused greater DAMGO-stimulated G protein activation in the FrA than in the pre-limbic (PrL). The data show for the first time that hypoxia increased G protein activation in PFC. The results suggest the potential for hypoxia-induced enhancements in G protein activation to alter PFC function.

Ventromedial prefrontal damage reduces mind-wandering and biases its temporal focus

PubMed Central

Bertossi, Elena

2016-01-01

Mind-wandering, an ubiquitous expression of humans’ mental life, reflects a drift of attention away from the current task towards self-generated thoughts, and has been associated with activity in the brain default network. To date, however, little is understood about the contribution of individual nodes of this network to mind-wandering. Here, we investigated whether the ventromedial prefrontal cortex (vmPFC) is critically involved in mind-wandering, by studying the propensity to mind-wander in patients with lesion to the vmPFC (vmPFC patients), control patients with lesions not involving the vmPFC, and healthy individuals. Participants performed three tasks varying in cognitive demands while their thoughts were periodically sampled, and a self-report scale of daydreaming in daily life. vmPFC patients exhibited reduced mind-wandering rates across tasks, and claimed less frequent daydreaming, than both healthy and brain-damaged controls. vmPFC damage reduced off-task thoughts related to the future, while it promoted those about the present. These results indicate that vmPFC critically supports mind-wandering, possibly by helping to construct future-related scenarios and thoughts that have the potential to draw attention inward, away from the ongoing tasks. PMID:27445210

77 FR 15841 - Notice of Passenger Facility Charge (PFC) Approvals and Disapprovals

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-16

... PFC approvals and disapprovals under the provisions of the Aviation Safety and Capacity Expansion Act... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration Notice of Passenger Facility Charge (PFC) Approvals and Disapprovals AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Monthly...

14 CFR 158.3 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... PASSENGER FACILITY CHARGES (PFC'S) General § 158.3 Definitions. The following definitions apply in this part... agency's PFC account. These costs may include reasonable monthly financial account charges and... revenue generated by a public airport (1) through any lease, rent, fee, PFC or other charge collected...

Tagging of Breast Tumors for Excision and Specimen Radiography and of Sentinel Nodes for Ultrasound-Guided Localization Using Novel Particulate Agents

DTIC Science & Technology

2000-08-01

optimized the dose. This year we worked on coloring that agent and sentinel node detection. Scope: We could not color the radiopaque perfluorocarbon ( PFC ...We aimed to accomplish these two goals using perfluorocarbon ( PFC ) emulsions. Because it was known that PFC emulsions, that can be radiopaque...discussed our results to hypothesis #1: When a radiopaque perfluorocarbon ( PFC ) emulsion is injected in the lesion it will mark the lesion for days and will

Acute cocaine induced deficits in cognitive performance in rhesus macaque monkeys treated with baclofen

PubMed Central

Porrino, Linda J.; Hampson, Robert E.; Opris, Ioan; Deadwyler, Samuel A.

2013-01-01

Rationale Acute and/or chronic exposure to cocaine can affect cognitive performance, which may influence rate of recovery during treatment. Objective Effects of the GABA-B receptor agonist baclofen were assessed for potency to reverse the negative influence of acute, pre-session, intravenous (IV) injection of cocaine on cognitive performance in Macaca mulatta nonhuman primates. Methods Animals were trained to perform a modified delayed match to sample (DMS) task incorporating two types of trials with varying degrees of cognitive load that had different decision requirements in order to correctly utilize information retained over the delay interval. The effects of cocaine (0.2, 0.4, and 0.6 mg/kg, IV) alone and in combination with baclofen (0.29 and 0.40 mg/kg, IV) were examined with respect to sustained performance levels. Brain metabolic activity during performance of the task was assessed using PET imaged uptake of [18F]-fluorodeoxyglucose. Results Acute cocaine injections produced a dose-dependent decline in DMS performance selective for trials of high cognitive load. The GABA-receptor agonist baclofen, co-administered with cocaine, reversed task performance back to nondrug (saline IV) control levels. Simultaneous assessment of PET-imaged brain metabolic activity in prefrontal cortex (PFC) showed alterations by cocaine compared to PFC metabolic activation in nondrug (saline, IV) control DMS sessions, but like performance, PFC activation was returned to control levels by baclofen (0.40 mg/kg, IV) injected with cocaine. Conclusions The results show that baclofen, administered at a relatively high dose, reversed the cognitive deficits produced by acute cocaine intoxication that may have implications for use in chronic drug exposure. PMID:22836369

Comprehensive neural networks for guilty feelings in young adults.

PubMed

Nakagawa, Seishu; Takeuchi, Hikaru; Taki, Yasuyuki; Nouchi, Rui; Sekiguchi, Atsushi; Kotozaki, Yuka; Miyauchi, Carlos Makoto; Iizuka, Kunio; Yokoyama, Ryoichi; Shinada, Takamitsu; Yamamoto, Yuki; Hanawa, Sugiko; Araki, Tsuyoshi; Hashizume, Hiroshi; Kunitoki, Keiko; Sassa, Yuko; Kawashima, Ryuta

2015-01-15

Feelings of guilt are associated with widespread self and social cognitions, e.g., empathy, moral reasoning, and punishment. Neural correlates directly related to the degree of feelings of guilt have not been detected, probably due to the small numbers of subjects, whereas there are growing numbers of neuroimaging studies of feelings of guilt. We hypothesized that the neural networks for guilty feelings are widespread and include the insula, inferior parietal lobule (IPL), amygdala, subgenual cingulate cortex (SCC), and ventromedial prefrontal cortex (vmPFC), which are essential for cognitions of guilt. We investigated the association between regional gray matter density (rGMD) and feelings of guilt in 764 healthy young students (422 males, 342 females; 20.7 ± 1.8 years) using magnetic resonance imaging and the guilty feeling scale (GFS) for the younger generation which comprises interpersonal situation (IPS) and rule-breaking situation (RBS) scores. Both the IPS and RBS were negatively related to the rGMD in the right posterior insula (PI). The IPS scores were negatively correlated with rGMD in the left anterior insula (AI), right IPL, and vmPFC using small volume correction. A post hoc analysis performed on the significant clusters identified through these analyses revealed that rGMD activity in the right IPL showed a significant negative association with the empathy quotient. These findings at the whole-brain level are the widespread comprehensive neural network regions for guilty feelings. Interestingly, the novel finding in this study is that the PI was implicated as a common region for feelings of guilt with interaction between the IPS and RBS. Additionally, the neural networks including the IPL were associated with empathy and with regions implicated in moral reasoning (AI and vmPFC), and punishment (AI). Copyright © 2014 Elsevier Inc. All rights reserved.

Neural correlates of confidence during item recognition and source memory retrieval: evidence for both dual-process and strength memory theories.

PubMed

Hayes, Scott M; Buchler, Norbou; Stokes, Jared; Kragel, James; Cabeza, Roberto

2011-12-01

Although the medial-temporal lobes (MTL), PFC, and parietal cortex are considered primary nodes in the episodic memory network, there is much debate regarding the contributions of MTL, PFC, and parietal subregions to recollection versus familiarity (dual-process theory) and the feasibility of accounts on the basis of a single memory strength process (strength theory). To investigate these issues, the current fMRI study measured activity during retrieval of memories that differed quantitatively in terms of strength (high vs. low-confidence trials) and qualitatively in terms of recollection versus familiarity (source vs. item memory tasks). Support for each theory varied depending on which node of the episodic memory network was considered. Results from MTL best fit a dual-process account, as a dissociation was found between a right hippocampal region showing high-confidence activity during the source memory task and bilateral rhinal regions showing high-confidence activity during the item memory task. Within PFC, several left-lateralized regions showed greater activity for source than item memory, consistent with recollective orienting, whereas a right-lateralized ventrolateral area showed low-confidence activity in both tasks, consistent with monitoring processes. Parietal findings were generally consistent with strength theory, with dorsal areas showing low-confidence activity and ventral areas showing high-confidence activity in both tasks. This dissociation fits with an attentional account of parietal functions during episodic retrieval. The results suggest that both dual-process and strength theories are partly correct, highlighting the need for an integrated model that links to more general cognitive theories to account for observed neural activity during episodic memory retrieval.

Low-dimensional attractor for neural activity from local field potentials in optogenetic mice

PubMed Central

Oprisan, Sorinel A.; Lynn, Patrick E.; Tompa, Tamas; Lavin, Antonieta

2015-01-01

We used optogenetic mice to investigate possible nonlinear responses of the medial prefrontal cortex (mPFC) local network to light stimuli delivered by a 473 nm laser through a fiber optics. Every 2 s, a brief 10 ms light pulse was applied and the local field potentials (LFPs) were recorded with a 10 kHz sampling rate. The experiment was repeated 100 times and we only retained and analyzed data from six animals that showed stable and repeatable response to optical stimulations. The presence of nonlinearity in our data was checked using the null hypothesis that the data were linearly correlated in the temporal domain, but were random otherwise. For each trail, 100 surrogate data sets were generated and both time reversal asymmetry and false nearest neighbor (FNN) were used as discriminating statistics for the null hypothesis. We found that nonlinearity is present in all LFP data. The first 0.5 s of each 2 s LFP recording were dominated by the transient response of the networks. For each trial, we used the last 1.5 s of steady activity to measure the phase resetting induced by the brief 10 ms light stimulus. After correcting the LFPs for the effect of phase resetting, additional preprocessing was carried out using dendrograms to identify “similar” groups among LFP trials. We found that the steady dynamics of mPFC in response to light stimuli could be reconstructed in a three-dimensional phase space with topologically similar “8”-shaped attractors across different animals. Our results also open the possibility of designing a low-dimensional model for optical stimulation of the mPFC local network. PMID:26483665

Reduced Cortical Gray Matter Volume In Male Adolescents With Substance And Conduct Problems

PubMed Central

Dalwani, Manish; Sakai, Joseph T.; Mikulich-Gilbertson, Susan K.; Tanabe, Jody; Raymond, Kristen; McWilliams, Shannon K.; Thompson, Laetitia L.; Banich, Marie T.; Crowley, Thomas J.

2011-01-01

Boys with serious conduct and substance problems (“Antisocial Substance Dependence” (ASD)) repeatedly make impulsive and risky decisions in spite of possible negative consequences. Because prefrontal cortex (PFC) is involved in planning behavior in accord with prior rewards and punishments, structural abnormalities in PFC could contribute to a person's propensity to make risky decisions. Methods We acquired high-resolution structural images of 25 male ASD patients (ages 14–18 years) and 19 controls of similar ages using a 3T MR system. We conducted whole-brain voxel-based morphometric analysis (p<0.05, corrected for multiple comparisons at whole-brain cluster-level) using Statistical Parametric Mapping version-5 and tested group differences in regional gray matter (GM) volume with analyses of covariance, adjusting for total GM volume, age, and IQ; we further adjusted between-group analyses for ADHD and depression. As secondary analyses, we tested for negative associations between GM volume and impulsivity within groups and separately, GM volume and symptom severity within patients using whole-brain regression analyses. Results ASD boys had significantly lower GM volume than controls in left dorsolateral PFC (DLPFC), right lingual gyrus and bilateral cerebellum, and significantly higher GM volume in right precuneus. Left DLPFC GM volume showed negative association with impulsivity within controls and negative association with substance dependence severity within patients. Conclusions ASD boys show reduced GM volumes in several regions including DLPFC, a region highly relevant to impulsivity, disinhibition, and decision-making, and cerebellum, a region important for behavioral regulation, while they showed increased GM in precuneus, a region associated with self-referential and self-centered thinking. PMID:21592680

Prefrontal electroencephalographic activity during the working memory processes involved in a sexually motivated task in male rats.

PubMed

Hernández-González, Marisela; Almanza-Sepúlveda, Mayra Linné; Olvera-Cortés, María Esther; Gutiérrez-Guzmán, Blanca Erika; Guevara, Miguel Angel

2012-08-01

The prefrontal cortex is involved in working memory functions, and several studies using food or drink as rewards have demonstrated that the rat is capable of performing tasks that involve working memory. Sexual activity is another highly-rewarding, motivated behaviour that has proven to be an efficient incentive in classical operant tasks. The objective of this study was to determine whether the functional activity of the medial prefrontal cortex (mPFC) changes in relation to the working memory processes involved in a sexually motivated task performed in male rats. Thus, male Wistar rats implanted in the mPFC were subjected to a nonmatching-to-sample task in a T-maze using sexual interaction as a reinforcer during a 4-day training period. On the basis of their performance during training, the rats were classified as 'good-learners' or 'bad-learners'. Only the good-learner rats showed an increase in the absolute power of the 8-13 Hz band during both the sample and test runs; a finding that could be related to learning of the working memory elements entailed in the task. During the maintenance phase only (i.e., once the rule had been learned well), the good-learner rats also showed an increased correlation of the 8-13 Hz band during the sample run, indicating that a high degree of coupling between the prefrontal cortices is necessary for the processing required to allow the rats to make correct decisions in the maintenance phase. Taken together, these data show that mPFC activity changes in relation to the working memory processes involved in a sexually motivated task in male rats.

Neural Correlates of Confidence during Item Recognition and Source Memory Retrieval: Evidence for Both Dual-process and Strength Memory Theories

PubMed Central

Hayes, Scott M.; Buchler, Norbou; Stokes, Jared; Kragel, James; Cabeza, Roberto

2012-01-01

Although the medial-temporal lobes (MTL), PFC, and parietal cortex are considered primary nodes in the episodic memory network, there is much debate regarding the contributions of MTL, PFC, and parietal subregions to recollection versus familiarity (dual-process theory) and the feasibility of accounts on the basis of a single memory strength process (strength theory). To investigate these issues, the current fMRI study measured activity during retrieval of memories that differed quantitatively in terms of strength (high vs. low-confidence trials) and qualitatively in terms of recollection versus familiarity (source vs. item memory tasks). Support for each theory varied depending on which node of the episodic memory network was considered. Results from MTL best fit a dual-process account, as a dissociation was found between a right hippocampal region showing high-confidence activity during the source memory task and bilateral rhinal regions showing high-confidence activity during the item memory task. Within PFC, several left-lateralized regions showed greater activity for source than item memory, consistent with recollective orienting, whereas a right-lateralized ventrolateral area showed low-confidence activity in both tasks, consistent with monitoring processes. Parietal findings were generally consistent with strength theory, with dorsal areas showing low-confidence activity and ventral areas showing high-confidence activity in both tasks. This dissociation fits with an attentional account of parietal functions during episodic retrieval. The results suggest that both dual-process and strength theories are partly correct, highlighting the need for an integrated model that links to more general cognitive theories to account for observed neural activity during episodic memory retrieval. PMID:21736454

Event-related fMRI studies of episodic encoding and retrieval: meta-analyses using activation likelihood estimation.

PubMed

Spaniol, Julia; Davidson, Patrick S R; Kim, Alice S N; Han, Hua; Moscovitch, Morris; Grady, Cheryl L

2009-07-01

The recent surge in event-related fMRI studies of episodic memory has generated a wealth of information about the neural correlates of encoding and retrieval processes. However, interpretation of individual studies is hampered by methodological differences, and by the fact that sample sizes are typically small. We submitted results from studies of episodic memory in healthy young adults, published between 1998 and 2007, to a voxel-wise quantitative meta-analysis using activation likelihood estimation [Laird, A. R., McMillan, K. M., Lancaster, J. L., Kochunov, P., Turkeltaub, P. E., & Pardo, J. V., et al. (2005). A comparison of label-based review and ALE meta-analysis in the stroop task. Human Brain Mapping, 25, 6-21]. We conducted separate meta-analyses for four contrasts of interest: episodic encoding success as measured in the subsequent-memory paradigm (subsequent Hit vs. Miss), episodic retrieval success (Hit vs. Correct Rejection), objective recollection (e.g., Source Hit vs. Item Hit), and subjective recollection (e.g., Remember vs. Know). Concordance maps revealed significant cross-study overlap for each contrast. In each case, the left hemisphere showed greater concordance than the right hemisphere. Both encoding and retrieval success were associated with activation in medial-temporal, prefrontal, and parietal regions. Left ventrolateral prefrontal cortex (PFC) and medial-temporal regions were more strongly involved in encoding, whereas left superior parietal and dorsolateral and anterior PFC regions were more strongly involved in retrieval. Objective recollection was associated with activation in multiple PFC regions, as well as multiple posterior parietal and medial-temporal areas, but not hippocampus. Subjective recollection, in contrast, showed left hippocampal involvement. In summary, these results identify broadly consistent activation patterns associated with episodic encoding and retrieval, and subjective and objective recollection, but also subtle differences among these processes.

Childhood abuse and reduced cortical thickness in brain regions involved in emotional processing.

PubMed

Gold, Andrea L; Sheridan, Margaret A; Peverill, Matthew; Busso, Daniel S; Lambert, Hilary K; Alves, Sonia; Pine, Daniel S; McLaughlin, Katie A

2016-10-01

Alterations in gray matter development represent a potential pathway through which childhood abuse is associated with psychopathology. Several prior studies find reduced volume and thickness of prefrontal (PFC) and temporal cortex regions in abused compared with nonabused adolescents, although most prior research is based on adults and volume-based measures. This study tests the hypothesis that child abuse, independent of parental education, predicts reduced cortical thickness in prefrontal and temporal cortices as well as reduced gray mater volume (GMV) in subcortical regions during adolescence. Structural MRI scans were obtained from 21 adolescents exposed to physical and/or sexual abuse and 37 nonabused adolescents (ages 13-20). Abuse was operationalized using dichotomous and continuous measures. We examined associations between abuse and brain structure in several a priori-defined regions, controlling for parental education, age, sex, race, and total brain volume for subcortical GMV. Significance was evaluated at p < .05 with a false discovery rate correction. Child abuse exposure and severity were associated with reduced thickness in ventromedial prefrontal cortex (PFC), right lateral orbitofrontal cortex, right inferior frontal gyrus, bilateral parahippocampal gyrus (PHG), left temporal pole, and bilateral inferior, right middle, and right superior temporal gyri. Neither abuse measure predicted cortical surface area or subcortical GMV. Bilateral PHG thickness was inversely related to externalizing symptoms. Child abuse, an experience characterized by a high degree of threat, is associated with reduced cortical thickness in ventromedial and ventrolateral PFC and medial and lateral temporal cortex in adolescence. Reduced PHG thickness may be a mediator linking abuse with externalizing psychopathology, although prospective research is needed to evaluate this possibility. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Structural and functional alterations in the prefrontal cortex after post-weaning social isolation: relationship with species-typical and deviant aggression.

PubMed

Biro, Laszlo; Toth, Mate; Sipos, Eszter; Bruzsik, Biborka; Tulogdi, Aron; Bendahan, Samuel; Sandi, Carmen; Haller, Jozsef

2017-05-01

Although the inhibitory control of aggression by the prefrontal cortex (PFC) is the cornerstone of current theories of aggression control, a number of human and laboratory studies showed that the execution of aggression increases PFC activity; moreover, enhanced activation was observed in aggression-related psychopathologies and laboratory models of abnormal aggression. Here, we investigated these apparently contradictory findings in the post-weaning social isolation paradigm (PWSI), an established laboratory model of abnormal aggression. When studied in the resident-intruder test as adults, rats submitted to PWSI showed increased attack counts, increased share of bites directed towards vulnerable body parts of opponents (head, throat, and belly) and reduced social signaling of attacks. These deviations from species-typical behavioral characteristics were associated with a specific reduction in the thickness of the right medial PFC (mPFC), a bilateral decrease in dendritic and glial density, and reduced vascularization on the right-hand side of the mPFC. Thus, the early stressor interfered with mPFC development. Despite these structural deficits, aggressive encounters enhanced the activation of the mPFC in PWSI rats as compared to controls. A voxel-like functional analysis revealed that overactivation was restricted to a circumscribed sub-region, which contributed to the activation of hypothalamic centers involved in the initiation of biting attacks as shown by structural equation modeling. These findings demonstrate that structural alterations and functional hyperactivity can coexist in the mPFC of rats exposed to early stressors, and suggest that the role of the mPFC in aggression control is more complex than suggested by the inhibitory control theory.

Serum metabolome biomarkers associate low-level environmental perfluorinated compound exposure with oxidative /nitrosative stress in humans.

PubMed

Wang, Xiaofei; Liu, Liangpo; Zhang, Weibing; Zhang, Jie; Du, Xiaoyan; Huang, Qingyu; Tian, Meiping; Shen, Heqing

2017-10-01

Previous in vivo and in vitro studies have linked perfluorinated compound (PFC) exposure with metabolic interruption, but the inter-species difference and high treatment doses usually make the results difficult to be extrapolated to humans directly. The best strategy for identifying the metabolic interruption may be to establish the direct correlations between monitored PFCs data and metabolic data on human samples. In this study, serum metabolome data and PFC concentrations were acquired for a Chinese adult male cohort. The most abundant PFCs are PFOA and PFOS with concentration medians 7.56 and 12.78 nM, respectively; in together they count around 81.6% of the total PFCs. PFC concentration-related serum metabolic profile changes and the related metabolic biomarkers were explored by using partial least squares-discriminant analysis (PLS-DA). Respectively taking PFOS, PFOA and total PFC as the classifiers, serum metabolome can be differentiated between the lowest dose group (1st quartile PFCs) and the highest PFC dose group (4th quartile PFCs). Ten potential PFC biomarkers were identified, mainly involving in pollutant detoxification, antioxidation and nitric oxide (NO) signal pathways. These suggested that low-level environmental PFC exposure has significantly adverse impacts on glutathione (GSH) cycle, Krebs cycle, nitric oxide (NO) generation and purine oxidation in humans. To the best of our knowledge, this is the first report investigating the association of environmental PFC exposure with human serum metabolome alteration. Given the important biological functions of the identified biomarkers, we suggest that PFC could increase the metabolism syndromes risk including diabetes and cardiovascular diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

Neuromodulation of Prefrontal Cortex in Non-Human Primates by Dopaminergic Receptors during Rule-Guided Flexible Behavior and Cognitive Control

PubMed Central

Vijayraghavan, Susheel; Major, Alex J.; Everling, Stefan

2017-01-01

The prefrontal cortex (PFC) is indispensable for several higher-order cognitive and executive capacities of primates, including representation of salient stimuli in working memory (WM), maintenance of cognitive task set, inhibition of inappropriate responses and rule-guided flexible behavior. PFC networks are subject to robust neuromodulation from ascending catecholaminergic systems. Disruption of these systems in PFC has been implicated in cognitive deficits associated with several neuropsychiatric disorders. Over the past four decades, a considerable body of work has examined the influence of dopamine on macaque PFC activity representing spatial WM. There has also been burgeoning interest in neuromodulation of PFC circuits involved in other cognitive functions of PFC, including representation of rules to guide flexible behavior. Here, we review recent neuropharmacological investigations conducted in our laboratory and others of the role of PFC dopamine receptors in regulating rule-guided behavior in non-human primates. Employing iontophoresis, we examined the effects of local manipulation of dopaminergic subtypes on neuronal activity during performance of rule-guided pro- and antisaccades, an experimental paradigm sensitive to PFC integrity, wherein deficits in performance are reliably observed in many neuropsychiatric disorders. We found dissociable effects of dopamine receptors on neuronal activity for rule representation and oculomotor responses and discuss these findings in the context of prior studies that have examined the role of dopamine in spatial delayed response tasks, attention, target selection, abstract rules, visuomotor learning and reward. The findings we describe here highlight the common features, as well as heterogeneity and context dependence of dopaminergic neuromodulation in regulating the efficacy of cognitive functions of PFC in health and disease. PMID:29259545

Increased dopamine transporter function as a mechanism for dopamine hypoactivity in the adult infralimbic medial prefrontal cortex following adolescent social stress.

PubMed

Novick, Andrew M; Forster, Gina L; Hassell, James E; Davies, Daniel R; Scholl, Jamie L; Renner, Kenneth J; Watt, Michael J

2015-10-01

Being bullied during adolescence is associated with later mental illnesses characterized by deficits in cognitive tasks mediated by prefrontal cortex (PFC) dopamine (DA). Social defeat of adolescent male rats, as a model of teenage bullying victimization, results in medial PFC (mPFC) dopamine (DA) hypofunction in adulthood that is associated with increased drug seeking and working memory deficits. Increased expression of the DA transporter (DAT) is also seen in the adult infralimbic mPFC following adolescent defeat. We propose the functional consequence of this increased DAT expression is enhanced DA clearance and subsequently decreased infralimbic mPFC DA availability. To test this, in vivo chronoamperometry was used to measure changes in accumulation of the DA signal following DAT blockade, with increased DAT-mediated clearance being reflected by lower DA signal accumulation. Previously defeated rats and controls were pre-treated with the norepinephrine transporter (NET) inhibitor desipramine (20 mg/kg, ip.) to isolate infralimbic mPFC DA clearance to DAT, then administered the selective DAT inhibitor GBR-12909 (20 or 40 mg/kg, sc.). Sole NET inhibition with desipramine produced no differences in DA signal accumulation between defeated rats and controls. However, rats exposed to adolescent social defeat demonstrated decreased DA signal accumulation compared to controls in response to both doses of GBR-12909, indicating greater DAT-mediated clearance of infralimbic mPFC DA. These results suggest that protracted increases in infralimbic mPFC DAT function represent a mechanism by which adolescent social defeat stress produces deficits in adult mPFC DA activity and corresponding behavioral and cognitive dysfunction. Copyright © 2015 Elsevier Ltd. All rights reserved.

Reductions in Cortico-Striatal Hyperconnectivity Accompany Successful Treatment of Obsessive-Compulsive Disorder with Dorsomedial Prefrontal rTMS

PubMed Central

Dunlop, Katharine; Woodside, Blake; Olmsted, Marion; Colton, Patricia; Giacobbe, Peter; Downar, Jonathan

2016-01-01

Obsessive-compulsive disorder (OCD) is a disabling illness with high rates of nonresponse to conventional treatments. OCD pathophysiology is believed to involve abnormalities in cortico-striatal-thalamic-cortical circuits through regions such as dorsomedial prefrontal cortex (dmPFC) and ventral striatum. These regions may constitute therapeutic targets for neuromodulation treatments, such as repetitive transcranial magnetic stimulation (rTMS). However, the neurobiological predictors and correlates of successful rTMS treatment for OCD are unclear. Here, we used resting-state functional magnetic resonance imaging (fMRI) to identify neural predictors and correlates of response to 20–30 sessions of bilateral 10 Hz dmPFC-rTMS in 20 treatment-resistant OCD patients, with 40 healthy controls as baseline comparators. A region of interest in the dmPFC was used to generate whole-brain functional connectivity maps pre-treatment and post treatment. Ten of 20 patients met the response criteria (⩾50% improvement on Yale-Brown Obsessive-Compulsive Scale, YBOCS); response to dmPFC-rTMS was sharply bimodal. dmPFC-rTMS responders had higher dmPFC-ventral striatal connectivity at baseline. The degree of reduction in this connectivity, from pre- to post-treatment, correlated to the degree of YBOCS symptomatic improvement. Baseline clinical and psychometric data did not predict treatment response. In summary, reductions in fronto-striatal hyperconnectivity were associated with treatment response to dmPFC-rTMS in OCD. This finding is consistent with previous fMRI studies of deep brain stimulation in OCD, but opposite to previous reports on mechanisms of dmPFC-rTMS in major depression. fMRI could prove useful in predicting the response to dmPFC-rTMS in OCD. PMID:26440813

Reductions in Cortico-Striatal Hyperconnectivity Accompany Successful Treatment of Obsessive-Compulsive Disorder with Dorsomedial Prefrontal rTMS.

PubMed

Dunlop, Katharine; Woodside, Blake; Olmsted, Marion; Colton, Patricia; Giacobbe, Peter; Downar, Jonathan

2016-04-01

Obsessive-compulsive disorder (OCD) is a disabling illness with high rates of nonresponse to conventional treatments. OCD pathophysiology is believed to involve abnormalities in cortico-striatal-thalamic-cortical circuits through regions such as dorsomedial prefrontal cortex (dmPFC) and ventral striatum. These regions may constitute therapeutic targets for neuromodulation treatments, such as repetitive transcranial magnetic stimulation (rTMS). However, the neurobiological predictors and correlates of successful rTMS treatment for OCD are unclear. Here, we used resting-state functional magnetic resonance imaging (fMRI) to identify neural predictors and correlates of response to 20-30 sessions of bilateral 10 Hz dmPFC-rTMS in 20 treatment-resistant OCD patients, with 40 healthy controls as baseline comparators. A region of interest in the dmPFC was used to generate whole-brain functional connectivity maps pre-treatment and post treatment. Ten of 20 patients met the response criteria (⩾50% improvement on Yale-Brown Obsessive-Compulsive Scale, YBOCS); response to dmPFC-rTMS was sharply bimodal. dmPFC-rTMS responders had higher dmPFC-ventral striatal connectivity at baseline. The degree of reduction in this connectivity, from pre- to post-treatment, correlated to the degree of YBOCS symptomatic improvement. Baseline clinical and psychometric data did not predict treatment response. In summary, reductions in fronto-striatal hyperconnectivity were associated with treatment response to dmPFC-rTMS in OCD. This finding is consistent with previous fMRI studies of deep brain stimulation in OCD, but opposite to previous reports on mechanisms of dmPFC-rTMS in major depression. fMRI could prove useful in predicting the response to dmPFC-rTMS in OCD.

Chemogenetic Activation of an Extinction Neural Circuit Reduces Cue-Induced Reinstatement of Cocaine Seeking.

PubMed

Augur, Isabel F; Wyckoff, Andrew R; Aston-Jones, Gary; Kalivas, Peter W; Peters, Jamie

2016-09-28

The ventromedial prefrontal cortex (vmPFC) has been shown to negatively regulate cocaine-seeking behavior, but the precise conditions by which vmPFC activity can be exploited to reduce cocaine relapse are currently unknown. We used viral-mediated gene transfer of designer receptors (DREADDs) to activate vmPFC neurons and examine the consequences on cocaine seeking in a rat self-administration model of relapse. Activation of vmPFC neurons with the Gq-DREADD reduced reinstatement of cocaine seeking elicited by cocaine-associated cues, but not by cocaine itself. We used a retro-DREADD approach to confine the Gq-DREADD to vmPFC neurons that project to the medial nucleus accumbens shell, confirming that these neurons are responsible for the decreased cue-induced reinstatement of cocaine seeking. The effects of vmPFC activation on cue-induced reinstatement depended on prior extinction training, consistent with the reported role of this structure in extinction memory. These data help define the conditions under which chemogenetic activation of extinction neural circuits can be exploited to reduce relapse triggered by reminder cues. The ventromedial prefrontal cortex (vmPFC) projection to the nucleus accumbens shell is important for extinction of cocaine seeking, but its anatomical proximity to the relapse-promoting projection from the dorsomedial prefrontal cortex to the nucleus accumbens core makes it difficult to selectively enhance neuronal activity in one pathway or the other using traditional pharmacotherapy (e.g., systemically administered drugs). Viral-mediated gene delivery of an activating Gq-DREADD to vmPFC and/or vmPFC projections to the nucleus accumbens shell allows the chemogenetic exploitation of this extinction neural circuit to reduce cocaine seeking and was particularly effective against relapse triggered by cocaine reminder cues. Copyright © 2016 the authors 0270-6474/16/3610174-07$15.00/0.

Influence of highly distinctive structural properties on the excitability of pyramidal neurons in monkey visual and prefrontal cortices

PubMed Central

Amatrudo, Joseph M.; Weaver, Christina M.; Crimins, Johanna L.; Hof, Patrick R.; Rosene, Douglas L.; Luebke, Jennifer I.

2012-01-01

Whole-cell patch-clamp recordings and high-resolution 3D morphometric analyses of layer 3 pyramidal neurons in in vitro slices of monkey primary visual cortex (V1) and dorsolateral granular prefrontal cortex (dlPFC) revealed that neurons in these two brain areas possess highly distinctive structural and functional properties. Area V1 pyramidal neurons are much smaller than dlPFC neurons, with significantly less extensive dendritic arbors and far fewer dendritic spines. Relative to dlPFC neurons, V1 neurons have a significantly higher input resistance, depolarized resting membrane potential and higher action potential (AP) firing rates. Most V1 neurons exhibit both phasic and regular-spiking tonic AP firing patterns, while dlPFC neurons exhibit only tonic firing. Spontaneous postsynaptic currents are lower in amplitude and have faster kinetics in V1 than in dlPFC neurons, but are no different in frequency. Three-dimensional reconstructions of V1 and dlPFC neurons were incorporated into computational models containing Hodgkin-Huxley and AMPA- and GABAA-receptor gated channels. Morphology alone largely accounted for observed passive physiological properties, but led to AP firing rates that differed more than observed empirically, and to synaptic responses that opposed empirical results. Accordingly, modeling predicts that active channel conductances differ between V1 and dlPFC neurons. The unique features of V1 and dlPFC neurons are likely fundamental determinants of area-specific network behavior. The compact electrotonic arbor and increased excitability of V1 neurons support the rapid signal integration required for early processing of visual information. The greater connectivity and dendritic complexity of dlPFC neurons likely support higher level cognitive functions including working memory and planning. PMID:23035077

Multimodal Investigation of Network Level Effects Using Intrinsic Functional Connectivity, Anatomical Covariance, and Structure-to-Function Correlations in Unmedicated Major Depressive Disorder.

PubMed

Scheinost, Dustin; Holmes, Sophie E; DellaGioia, Nicole; Schleifer, Charlie; Matuskey, David; Abdallah, Chadi G; Hampson, Michelle; Krystal, John H; Anticevic, Alan; Esterlis, Irina

2018-04-01

Converging evidence suggests that major depressive disorder (MDD) affects multiple large-scale brain networks. Analyses of the correlation or covariance of regional brain structure and function applied to structural and functional MRI data may provide insights into systems-level organization and structure-to-function correlations in the brain in MDD. This study applied tensor-based morphometry and intrinsic connectivity distribution to identify regions of altered volume and intrinsic functional connectivity in data from unmedicated individuals with MDD (n=17) and healthy comparison participants (HC, n=20). These regions were then used as seeds for exploratory anatomical covariance and connectivity analyses. Reduction in volume in the anterior cingulate cortex (ACC) and lower structural covariance between the ACC and the cerebellum were observed in the MDD group. Additionally, individuals with MDD had significantly lower whole-brain intrinsic functional connectivity in the medial prefrontal cortex (mPFC). This mPFC region showed altered connectivity to the ventral lateral PFC (vlPFC) and local circuitry in MDD. Global connectivity in the ACC was negatively correlated with reported depressive symptomatology. The mPFC-vlPFC connectivity was positively correlated with depressive symptoms. Finally, we observed increased structure-to-function correlation in the PFC/ACC in the MDD group. Although across all analysis methods and modalities alterations in the PFC/ACC were a common finding, each modality and method detected alterations in subregions belonging to distinct large-scale brain networks. These exploratory results support the hypothesis that MDD is a systems level disorder affecting multiple brain networks located in the PFC and provide new insights into the pathophysiology of this disorder.

The Essential Role of Primate Orbitofrontal Cortex in Conflict-Induced Executive Control Adjustment

PubMed Central

Buckley, Mark J.; Tanaka, Keiji

2014-01-01

Conflict in information processing evokes trial-by-trial behavioral modulations. Influential models suggest that adaptive tuning of executive control, mediated by mid-dorsal lateral prefrontal cortex (mdlPFC) and anterior cingulate cortex (ACC), underlies these modulations. However, mdlPFC and ACC are parts of distributed brain networks including orbitofrontal cortex (OFC), posterior cingulate cortex (PCC), and superior-dorsal lateral prefrontal cortex (sdlPFC). Contributions of these latter areas in adaptive tuning of executive control are unknown. We trained monkeys to perform a matching task in which they had to resolve the conflict between two behavior-guiding rules. Here, we report that bilateral lesions in OFC, but not in PCC or sdlPFC, impaired selection between these competing rules. In addition, the behavioral adaptation that is normally induced by experiencing conflict disappeared in OFC-lesioned, but remained normal in PCC-lesioned or sdlPFC-lesioned monkeys. Exploring underlying neuronal processes, we found that the activity of neurons in OFC represented the conflict between behavioral options independent from the other aspects of the task. Responses of OFC neurons to rewards also conveyed information of the conflict level that the monkey had experienced along the course to obtain the reward. Our findings indicate dissociable functions for five closely interconnected cortical areas suggesting that OFC and mdlPFC, but not PCC or sdlPFC or ACC, play indispensable roles in conflict-dependent executive control of on-going behavior. Both mdlPFC and OFC support detection of conflict and its integration with the task goal, but in contrast to mdlPFC, OFC does not retain the necessary information for conflict-induced modulation of future decisions. PMID:25122901

Optogenetic Examination of Prefrontal-Amygdala Synaptic Development.

PubMed

Arruda-Carvalho, Maithe; Wu, Wan-Chen; Cummings, Kirstie A; Clem, Roger L

2017-03-15

A brain network comprising the medial prefrontal cortex (mPFC) and amygdala plays important roles in developmentally regulated cognitive and emotional processes. However, very little is known about the maturation of mPFC-amygdala circuitry. We conducted anatomical tracing of mPFC projections and optogenetic interrogation of their synaptic connections with neurons in the basolateral amygdala (BLA) at neonatal to adult developmental stages in mice. Results indicate that mPFC-BLA projections exhibit delayed emergence relative to other mPFC pathways and establish synaptic transmission with BLA excitatory and inhibitory neurons in late infancy, events that coincide with a massive increase in overall synaptic drive. During subsequent adolescence, mPFC-BLA circuits are further modified by excitatory synaptic strengthening as well as a transient surge in feedforward inhibition. The latter was correlated with increased spontaneous inhibitory currents in excitatory neurons, suggesting that mPFC-BLA circuit maturation culminates in a period of exuberant GABAergic transmission. These findings establish a time course for the onset and refinement of mPFC-BLA transmission and point to potential sensitive periods in the development of this critical network. SIGNIFICANCE STATEMENT Human mPFC-amygdala functional connectivity is developmentally regulated and figures prominently in numerous psychiatric disorders with a high incidence of adolescent onset. However, it remains unclear when synaptic connections between these structures emerge or how their properties change with age. Our work establishes developmental windows and cellular substrates for synapse maturation in this pathway involving both excitatory and inhibitory circuits. The engagement of these substrates by early life experience may support the ontogeny of fundamental behaviors but could also lead to inappropriate circuit refinement and psychopathology in adverse situations. Copyright © 2017 the authors 0270-6474/17/372976-10$15.00/0.

Differential Functional Connectivity Alterations of Two Subdivisions within the Right dlPFC in Parkinson's Disease

PubMed Central

Caspers, Julian; Mathys, Christian; Hoffstaedter, Felix; Südmeyer, Martin; Cieslik, Edna C.; Rubbert, Christian; Hartmann, Christian J.; Eickhoff, Claudia R.; Reetz, Kathrin; Grefkes, Christian; Michely, Jochen; Turowski, Bernd; Schnitzler, Alfons; Eickhoff, Simon B.

2017-01-01

Patients suffering from Parkinson's disease (PD) often show impairments in executive function (EF) like decision-making and action control. The right dorsolateral prefrontal cortex (dlPFC) has been strongly implicated in EF in healthy subjects and has repeatedly been reported to show alterations related to EF impairment in PD. Recently, two key regions for cognitive action control have been identified within the right dlPFC by co-activation based parcellation. While the posterior region is engaged in rather basal EF like stimulus integration and working memory, the anterior region has a more abstract, supervisory function. To investigate whether these functionally distinct subdivisions of right dlPFC are differentially affected in PD, we analyzed resting-state functional connectivity (FC) in 39 PD patients and 44 age- and gender-matched healthy controls. Patients were examined both after at least 12 h withdrawal of dopaminergic drugs (OFF) and under their regular dopaminergic medication (ON). We found that only the posterior right dlPFC subdivision shows FC alterations in PD, while the anterior part remains unaffected. PD-related decreased FC with posterior right dlPFC was found in the bilateral medial posterior parietal cortex (mPPC) and left dorsal premotor region (PMd) in the OFF state. In the medical ON, FC with left PMd normalized, while decoupling with bilateral mPPC remained. Furthermore, we observed increased FC between posterior right dlPFC and the bilateral dorsomedial prefrontal cortex (dmPFC) in PD in the ON state. Our findings point to differential disturbances of right dlPFC connectivity in PD, which relate to its hierarchical organization of EF processing by stronger affecting the functionally basal posterior aspect than the hierarchically higher anterior part. PMID:28611616

False memories and confabulation.

PubMed

Johnson, M K; Raye, C L

1998-04-01

Memory distortions range from the benign (thinking you mailed a check that you only thought about mailing), to the serious (confusing what you heard after a crime with what you actually saw), to the fantastic (claiming you piloted a spaceship). We review theoretical ideas and empirical evidence about the source monitoring processes underlying both true and false memories. Neuropsychological studies show that certain forms of brain damage (such as combined frontal and medial-temporal lesions) might result in profound source confusions, called confabulations. Neuroimaging techniques provide new evidence regarding more specific links between underlying brain mechanisms and the normal cognitive processes involved in evaluating memories. One hypothesis is that the right prefrontal cortex (PFC) subserves heuristic judgments based on easily assessed qualities (such as familiarity or perceptual detail) and the left PFC (or the right and left PFC together) subserves more systematic judgments requiring more careful analysis of memorial qualities or retrieval and evaluation of additional supporting or disconfirming information. Such heuristic and systematic processes can be disrupted not only by brain damage but also, for example, by hypnosis, social demands and motivational factors, suggesting caution in the methods used by `memory exploring' professions (therapists, police officers, lawyers, etc.) in order to avoid inducing false memories.

A neuroimaging investigation of attribute framing and individual differences

PubMed Central

Murch, Kevin B.

2014-01-01

Functional magnetic resonance imaging was used to evaluate the neural basis of framing effects. We tested the reflexive and reflective systems model of social cognition as it relates to framing. We also examined the relationships among frame susceptibility, intelligence and personality measures. Participants evaluated whether personal attributes applied to themselves from multiple perspectives and in positive and negative frames. Participants rated whether each statement was descriptive or not and endorsed positive frames more than negative frames. Individual differences on frame decisions enabled us to form high and low frame susceptibility groups. Endorsement of frame-consistent attributes was associated with personality factors, cognitive reflection and intelligence. Reflexive brain regions were associated with positive frames while reflective areas were associated with negative frames. Region of Interest analyses showed that frame-inconsistent responses were associated with increased activation within reflective cognitive control regions including the left dorsolateral prefrontal cortex (PFC), dorsomedial PFC and left ventrolateral PFC. Frame-consistent responses were associated with increased activation in the right orbitofrontal cortex. These results demonstrate that individual differences in frame susceptibility influence personal attribute evaluations. Overall, this study clarifies the neural correlates of the reflective and reflexive systems of social cognition as applied to decisions about social attributions. PMID:23988759

Neural Mechanisms of Information Storage in Visual Short-Term Memory

PubMed Central

Serences, John T.

2016-01-01

The capacity to briefly memorize fleeting sensory information supports visual search and behavioral interactions with relevant stimuli in the environment. Traditionally, studies investigating the neural basis of visual short term memory (STM) have focused on the role of prefrontal cortex (PFC) in exerting executive control over what information is stored and how it is adaptively used to guide behavior. However, the neural substrates that support the actual storage of content-specific information in STM are more controversial, with some attributing this function to PFC and others to the specialized areas of early visual cortex that initially encode incoming sensory stimuli. In contrast to these traditional views, I will review evidence suggesting that content-specific information can be flexibly maintained in areas across the cortical hierarchy ranging from early visual cortex to PFC. While the factors that determine exactly where content-specific information is represented are not yet entirely clear, recognizing the importance of task-demands and better understanding the operation of non-spiking neural codes may help to constrain new theories about how memories are maintained at different resolutions, across different timescales, and in the presence of distracting information. PMID:27668990

Photocatalytic fuel cell (PFC) and dye self-photosensitization photocatalytic fuel cell (DSPFC) with BiOCl/Ti photoanode under UV and visible light irradiation.

PubMed

Li, Kan; Xu, Yunlan; He, Yi; Yang, Chen; Wang, Yalin; Jia, Jinping

2013-04-02

A fuel cell that functioned as a photo fuel cell (PFC) when irradiated with UV light and as a dye self-photosensitization photo fuel cell (DSPFC) when irradiated with visible light was proposed and investigated in this study. The system included a BiOCl/Ti plate photoanode and a Pt cathode, and dye solutions were employed as fuel. Electricity was generated at the same time as the dyes were degraded. 26.2% and 24.4% Coulombic efficiency were obtained when 20 mL of 10 mg · L(-1) Rhodamine B solution was treated with UV for 2 h and visible light for 3 h, respectively. Irradiation with natural and artificial sunlight was also evaluated. UV and visible light could be utilized at the same time and the photogenerated current was observed. The mechanism of electricity generation in BiOCl/Ti PFC and DSPFC was studied through degradation of the colorless salicylic acid solution. Factors that affect the electricity generation and dye degradation performance, such as solution pH and cathode material, were also investigated and optimized.

Neural mechanisms of information storage in visual short-term memory.

PubMed

Serences, John T

2016-11-01

The capacity to briefly memorize fleeting sensory information supports visual search and behavioral interactions with relevant stimuli in the environment. Traditionally, studies investigating the neural basis of visual short term memory (STM) have focused on the role of prefrontal cortex (PFC) in exerting executive control over what information is stored and how it is adaptively used to guide behavior. However, the neural substrates that support the actual storage of content-specific information in STM are more controversial, with some attributing this function to PFC and others to the specialized areas of early visual cortex that initially encode incoming sensory stimuli. In contrast to these traditional views, I will review evidence suggesting that content-specific information can be flexibly maintained in areas across the cortical hierarchy ranging from early visual cortex to PFC. While the factors that determine exactly where content-specific information is represented are not yet entirely clear, recognizing the importance of task-demands and better understanding the operation of non-spiking neural codes may help to constrain new theories about how memories are maintained at different resolutions, across different timescales, and in the presence of distracting information. Copyright © 2016 Elsevier Ltd. All rights reserved.

Suppression of Striatal Prediction Errors by the Prefrontal Cortex in Placebo Hypoalgesia.

PubMed

Schenk, Lieven A; Sprenger, Christian; Onat, Selim; Colloca, Luana; Büchel, Christian

2017-10-04

Classical learning theories predict extinction after the discontinuation of reinforcement through prediction errors. However, placebo hypoalgesia, although mediated by associative learning, has been shown to be resistant to extinction. We tested the hypothesis that this is mediated by the suppression of prediction error processing through the prefrontal cortex (PFC). We compared pain modulation through treatment cues (placebo hypoalgesia, treatment context) with pain modulation through stimulus intensity cues (stimulus context) during functional magnetic resonance imaging in 48 male and female healthy volunteers. During acquisition, our data show that expectations are correctly learned and that this is associated with prediction error signals in the ventral striatum (VS) in both contexts. However, in the nonreinforced test phase, pain modulation and expectations of pain relief persisted to a larger degree in the treatment context, indicating that the expectations were not correctly updated in the treatment context. Consistently, we observed significantly stronger neural prediction error signals in the VS in the stimulus context compared with the treatment context. A connectivity analysis revealed negative coupling between the anterior PFC and the VS in the treatment context, suggesting that the PFC can suppress the expression of prediction errors in the VS. Consistent with this, a participant's conceptual views and beliefs about treatments influenced the pain modulation only in the treatment context. Our results indicate that in placebo hypoalgesia contextual treatment information engages prefrontal conceptual processes, which can suppress prediction error processing in the VS and lead to reduced updating of treatment expectancies, resulting in less extinction of placebo hypoalgesia. SIGNIFICANCE STATEMENT In aversive and appetitive reinforcement learning, learned effects show extinction when reinforcement is discontinued. This is thought to be mediated by prediction errors (i.e., the difference between expectations and outcome). Although reinforcement learning has been central in explaining placebo hypoalgesia, placebo hypoalgesic effects show little extinction and persist after the discontinuation of reinforcement. Our results support the idea that conceptual treatment beliefs bias the neural processing of expectations in a treatment context compared with a more stimulus-driven processing of expectations with stimulus intensity cues. We provide evidence that this is associated with the suppression of prediction error processing in the ventral striatum by the prefrontal cortex. This provides a neural basis for persisting effects in reinforcement learning and placebo hypoalgesia. Copyright © 2017 the authors 0270-6474/17/379715-09$15.00/0.

76 FR 12405 - Notice of Passenger Facility Charge (PFC) Approvals and Disapprovals

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-07

.... Mandatory pavement markings. Airport signage. Runway guard lights. Wildlife study. PFC application.... Runway 18/36 pavement maintenance. Runway 13/31 pavement maintenance. PFC administration fees. Brief... Use: Tractor with snow blower and snow plow. Airport security and access control upgrades--design...

14 CFR 158.65 - Reporting requirements: Collecting air carriers.

Code of Federal Regulations, 2010 CFR

2010-01-01

... TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Reporting, Recordkeeping and Audits § 158.65 Reporting requirements: Collecting air carriers. (a) Each air carrier collecting PFCs for a public... carrier and airport involved, (ii) The total PFC revenue collected, (iii) The total PFC revenue refunded...

14 CFR 158.65 - Reporting requirements: Collecting air carriers.

Code of Federal Regulations, 2013 CFR

2013-01-01

... TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Reporting, Recordkeeping and Audits § 158.65 Reporting requirements: Collecting air carriers. (a) Each air carrier collecting PFCs for a public... carrier and airport involved, (ii) The total PFC revenue collected, (iii) The total PFC revenue refunded...

14 CFR 158.21 - General.

Code of Federal Regulations, 2012 CFR

2012-01-01

... FACILITY CHARGES (PFC'S) Application and Approval § 158.21 General. This subpart specifies the consultation and application requirements under which a public agency may obtain approval to impose a PFC and use PFC revenue on a project. This subpart also establishes the procedure for the Administrator's review...

14 CFR 158.21 - General.

Code of Federal Regulations, 2013 CFR

2013-01-01

... FACILITY CHARGES (PFC'S) Application and Approval § 158.21 General. This subpart specifies the consultation and application requirements under which a public agency may obtain approval to impose a PFC and use PFC revenue on a project. This subpart also establishes the procedure for the Administrator's review...

14 CFR 158.65 - Reporting requirements: Collecting air carriers.

Code of Federal Regulations, 2011 CFR

2011-01-01

... TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Reporting, Recordkeeping and Audits § 158.65 Reporting requirements: Collecting air carriers. (a) Each air carrier collecting PFCs for a public... carrier and airport involved, (ii) The total PFC revenue collected, (iii) The total PFC revenue refunded...

14 CFR 158.65 - Reporting requirements: Collecting air carriers.

Code of Federal Regulations, 2012 CFR

2012-01-01

... TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Reporting, Recordkeeping and Audits § 158.65 Reporting requirements: Collecting air carriers. (a) Each air carrier collecting PFCs for a public... carrier and airport involved, (ii) The total PFC revenue collected, (iii) The total PFC revenue refunded...

14 CFR 158.21 - General.

Code of Federal Regulations, 2014 CFR

2014-01-01

... FACILITY CHARGES (PFC'S) Application and Approval § 158.21 General. This subpart specifies the consultation and application requirements under which a public agency may obtain approval to impose a PFC and use PFC revenue on a project. This subpart also establishes the procedure for the Administrator's review...

14 CFR 158.65 - Reporting requirements: Collecting air carriers.

Code of Federal Regulations, 2014 CFR

2014-01-01

... TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Reporting, Recordkeeping and Audits § 158.65 Reporting requirements: Collecting air carriers. (a) Each air carrier collecting PFCs for a public... carrier and airport involved, (ii) The total PFC revenue collected, (iii) The total PFC revenue refunded...

14 CFR 158.67 - Recordkeeping and auditing: Public agency.

Code of Federal Regulations, 2011 CFR

2011-01-01

... TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Reporting, Recordkeeping and Audits § 158.67 Recordkeeping and auditing: Public agency. (a) Each public agency shall keep any unliquidated PFC... interest bearing instruments used by the public agency's airport capital fund. Interest earned on such PFC...

14 CFR 158.67 - Recordkeeping and auditing: Public agency.

Code of Federal Regulations, 2014 CFR

2014-01-01

... TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Reporting, Recordkeeping and Audits § 158.67 Recordkeeping and auditing: Public agency. (a) Each public agency shall keep any unliquidated PFC... interest bearing instruments used by the public agency's airport capital fund. Interest earned on such PFC...

14 CFR 158.21 - General.

Code of Federal Regulations, 2010 CFR

2010-01-01

... FACILITY CHARGES (PFC'S) Application and Approval § 158.21 General. This subpart specifies the consultation and application requirements under which a public agency may obtain approval to impose a PFC and use PFC revenue on a project. This subpart also establishes the procedure for the Administrator's review...

14 CFR 158.67 - Recordkeeping and auditing: Public agency.

Code of Federal Regulations, 2012 CFR

2012-01-01

... TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Reporting, Recordkeeping and Audits § 158.67 Recordkeeping and auditing: Public agency. (a) Each public agency shall keep any unliquidated PFC... interest bearing instruments used by the public agency's airport capital fund. Interest earned on such PFC...

14 CFR 158.67 - Recordkeeping and auditing: Public agency.

Code of Federal Regulations, 2013 CFR

2013-01-01

... TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Reporting, Recordkeeping and Audits § 158.67 Recordkeeping and auditing: Public agency. (a) Each public agency shall keep any unliquidated PFC... interest bearing instruments used by the public agency's airport capital fund. Interest earned on such PFC...

14 CFR 158.21 - General.

Code of Federal Regulations, 2011 CFR

2011-01-01

... FACILITY CHARGES (PFC'S) Application and Approval § 158.21 General. This subpart specifies the consultation and application requirements under which a public agency may obtain approval to impose a PFC and use PFC revenue on a project. This subpart also establishes the procedure for the Administrator's review...

5-HT2a receptor in mPFC influences context-guided reconsolidation of object memory in perirhinal cortex.

PubMed

Morici, Juan Facundo; Miranda, Magdalena; Gallo, Francisco Tomás; Zanoni, Belén; Bekinschtein, Pedro; Weisstaub, Noelia V

2018-05-02

Context-dependent memories may guide adaptive behavior relaying in previous experience while updating stored information through reconsolidation. Retrieval can be triggered by partial and shared cues. When the cue is presented, the most relevant memory should be updated. In a contextual version of the object recognition task, we examined the effect of medial PFC (mPFC) serotonin 2a receptor (5-HT2aR) blockade during retrieval in reconsolidation of competing objects memories. We found that mPFC 5-HT2aR controls retrieval and reconsolidation of object memories in the perirhinal cortex (PRH), but not in the dorsal hippocampus in rats. Also, reconsolidation of objects memories in PRH required a functional interaction between the ventral hippocampus and the mPFC. Our results indicate that in the presence of conflicting information at retrieval, mPFC 5-HT2aR may facilitate top-down context-guided control over PRH to control the behavioral response and object memory reconsolidation. © 2018, Morici et al.

Rostro-caudal and dorso-ventral gradients in medial and lateral prefrontal cortex during cognitive control of affective and cognitive interference.

PubMed

Rahm, Christoffer; Liberg, Benny; Wiberg-Kristoffersen, Maria; Aspelin, Peter; Msghina, Mussie

2013-04-01

Characterizing the anatomical substrates of major brain functions such as cognition and emotion is of utmost importance to the ongoing efforts of understanding the nature of psychiatric ailments and their potential treatment. The aim of our study was to investigate how the brain handles affective and cognitive interferences on cognitive processes. Functional magnetic resonance imaging investigation was performed on healthy individuals, comparing the brain oxygenation level dependent activation patterns during affective and cognitive counting Stroop tasks. The affective Stroop task activated rostral parts of medial prefrontal cortex (PFC) and rostral and ventral parts of lateral PFC, while cognitive Stroop activated caudal parts of medial PFC and caudal and dorsal parts of lateral PFC. Our findings suggest that the brain may handle affective and cognitive interference on cognitive processes differentially, with affective interference preferentially activating rostral and ventral PFC networks and cognitive interference activating caudal and dorsal PFC networks. © 2013 The Authors. Scandinavian Journal of Psychology © 2013 The Scandinavian Psychological Associations.

Dysregulation of prefrontal cortex-mediated slow evolving limbic dynamics drives stress-induced emotional pathology

PubMed Central

Hultman, Rainbo; Mague, Stephen D.; Li, Qiang; Katz, Brittany M.; Michel, Nadine; Lin, Lizhen; Wang, Joyce; David, Lisa K.; Blount, Cameron; Chandy, Rithi; Carlson, David; Ulrich, Kyle; Carin, Lawrence; Dunson, David; Kumar, Sunil; Deisseroth, Karl; Moore, Scott D.; Dzirasa, Kafui

2016-01-01

Summary Circuits distributed across cortico-limbic brain regions compose the networks that mediate emotional behavior. The prefrontal cortex (PFC) regulates ultraslow (<1Hz) dynamics across these networks, and PFC dysfunction is implicated in stress-related illnesses including major depressive disorder (MDD). To uncover the mechanism whereby stress-induced changes in PFC circuitry alter emotional networks to yield pathology, we used a multi-disciplinary approach including in vivo recordings in mice and chronic social-defeat stress. Our network model, inferred using machine learning, linked stress-induced behavioral pathology to the capacity of PFC to synchronize amygdala and VTA activity. Direct stimulation of PFC-amygdala circuitry with DREADDs normalized PFC-dependent limbic synchrony in stress-susceptible animals and restored normal behavior. In addition to providing insights into MDD mechanisms, our findings demonstrate an interdisciplinary approach that can be used to identify the large-scale network changes that underlie complex emotional pathologies and the specific network nodes that can be used to develop targeted interventions. PMID:27346529

Closing the gate in the limbic striatum: prefrontal suppression of hippocampal and thalamic inputs

PubMed Central

Calhoon, Gwendolyn G.; O’Donnell, Patricio

2013-01-01

SUMMARY Many brain circuits control behavior by integrating information arising from separate inputs onto a common target neuron. Neurons in the ventral striatum (VS) receive converging excitatory afferents from the prefrontal cortex (PFC), hippocampus (HP), and thalamus, among other structures, and the integration of these inputs is critical for shaping goal-directed behaviors. Although HP inputs have been described as gating PFC throughput in the VS, recent data reveal that the VS desynchronizes from the HP during epochs of burst-like PFC activity related to decision-making. It is therefore possible that PFC inputs locally attenuate responses to other glutamatergic inputs to the VS. Here, we found that delivering trains of stimuli to the PFC suppresses HP- and thalamus-evoked synaptic responses in the VS, in part through activation of inhibitory processes. This interaction may enable the PFC to exert influence on basal ganglia loops during decision-making instances with minimal disturbance from ongoing contextual inputs. PMID:23583113

5-HT2a receptor in mPFC influences context-guided reconsolidation of object memory in perirhinal cortex

PubMed Central

Morici, Juan Facundo; Miranda, Magdalena; Gallo, Francisco Tomás; Zanoni, Belén; Bekinschtein, Pedro

2018-01-01

Context-dependent memories may guide adaptive behavior relaying in previous experience while updating stored information through reconsolidation. Retrieval can be triggered by partial and shared cues. When the cue is presented, the most relevant memory should be updated. In a contextual version of the object recognition task, we examined the effect of medial PFC (mPFC) serotonin 2a receptor (5-HT2aR) blockade during retrieval in reconsolidation of competing objects memories. We found that mPFC 5-HT2aR controls retrieval and reconsolidation of object memories in the perirhinal cortex (PRH), but not in the dorsal hippocampus in rats. Also, reconsolidation of objects memories in PRH required a functional interaction between the ventral hippocampus and the mPFC. Our results indicate that in the presence of conflicting information at retrieval, mPFC 5-HT2aR may facilitate top-down context-guided control over PRH to control the behavioral response and object memory reconsolidation. PMID:29717980

Reduced prefrontal connectivity in psychopathy.

PubMed

Motzkin, Julian C; Newman, Joseph P; Kiehl, Kent A; Koenigs, Michael

2011-11-30

Linking psychopathy to a specific brain abnormality could have significant clinical, legal, and scientific implications. Theories on the neurobiological basis of the disorder typically propose dysfunction in a circuit involving ventromedial prefrontal cortex (vmPFC). However, to date there is limited brain imaging data to directly test whether psychopathy may indeed be associated with any structural or functional abnormality within this brain area. In this study, we employ two complementary imaging techniques to assess the structural and functional connectivity of vmPFC in psychopathic and non-psychopathic criminals. Using diffusion tensor imaging, we show that psychopathy is associated with reduced structural integrity in the right uncinate fasciculus, the primary white matter connection between vmPFC and anterior temporal lobe. Using functional magnetic resonance imaging, we show that psychopathy is associated with reduced functional connectivity between vmPFC and amygdala as well as between vmPFC and medial parietal cortex. Together, these data converge to implicate diminished vmPFC connectivity as a characteristic neurobiological feature of psychopathy.

Reduced Prefrontal Connectivity in Psychopathy

PubMed Central

Motzkin, Julian C.; Newman, Joseph P.; Kiehl, Kent A.; Koenigs, Michael

2012-01-01

Linking psychopathy to a specific brain abnormality could have significant clinical, legal, and scientific implications. Theories on the neurobiological basis of the disorder typically propose dysfunction in a circuit involving ventromedial prefrontal cortex (vmPFC). However, to date there is limited brain imaging data to directly test whether psychopathy may indeed be associated with any structural or functional abnormality within this brain area. In this study, we employ two complementary imaging techniques to assess the structural and functional connectivity of vmPFC in psychopathic and non-psychopathic criminals. Using diffusion tensor imaging, we show that psychopathy is associated with reduced structural integrity in the right uncinate fasciculus, the primary white matter connection between vmPFC and anterior temporal lobe. Using functional magnetic resonance imaging, we show that psychopathy is associated with reduced functional connectivity between vmPFC and amygdala as well as between vmPFC and medial parietal cortex. Together, these data converge to implicate diminished vmPFC connectivity as a characteristic neurobiological feature of psychopathy. PMID:22131397

Dorsomedial Prefrontal Cortex Contribution to Behavioral and Nucleus Accumbens Neuronal Responses to Incentive Cues

PubMed Central

Ishikawa, Akinori; Ambroggi, Frederic; Nicola, Saleem M.; Fields, Howard L.

2008-01-01

Cue-elicited phasic changes in firing of nucleus accumbens (NAc) neurons can facilitate reward-seeking behavior. Here, we test the hypothesis that the medial prefrontal cortex (mPFC), which sends a dense glutamatergic projection to the NAc core, contributes to NAc neuronal firing responses to reward-predictive cues. Rats trained to perform an operant response to a cue for sucrose were implanted with recording electrodes in the core of the NAc and microinjection cannulas in the dorsal mPFC (dmPFC). The cue-evoked firing of NAc neurons was reduced by bilateral injection of GABAA and GABAB agonists into the dmPFC concomitant with loss of behavioral responding to the cue. In addition, unilateral dmPFC inactivation reduced ipsilateral cue excitations and contralateral cue inhibitions. These findings indicate that cue-evoked excitations and inhibitions of NAc core neurons depend on dmPFC projections to the NAc and that these phasic changes contribute to the behavioral response to reward-predictive cues. PMID:18463262

An Integrated Multilevel Converter with Sigma Delta Control for LED Lighting

NASA Astrophysics Data System (ADS)

Gerber, Daniel L.

High brightness LEDs have become a mainstream lighting technology due to their efficiency, life span, and environmental benefits. As such, the lighting industry values LED drivers with low cost, small form factor, and long life span. Additional specifications that define a high quality LED driver are high efficiency, high power factor, wide-range dimming, minimal flicker, and a galvanically isolated output. The flyback LED driver is a popular topology that satisfies all these specifications, but it requires a bulky and costly flyback transformer. In addition, its passive methods for cancelling AC power ripple require electrolytic capacitors, which have been known to have life span issues. This dissertation details the design, construction, and verification of a novel LED driver that satisfies all the specifications. In addition, it does not require a flyback transformer or electrolytic capacitors, thus marking an improvement over the flyback driver on size, cost, and life span. This dissertation presents an integrated circuit (IC) LED driver, which features a pair of generalized multilevel converters that are controlled via sigma-delta modulation. The first is a multilevel rectifier responsible for power factor correction (PFC) and dimming. The PFC rectifier employs a second order sigma-delta loop to precisely control the input current harmonics and amplitude. The second is a bidirectional multilevel inverter used to cancel AC power ripple from the DC bus. This ripple-cancellation module transfers energy to and from a storage capacitor. It uses a first order sigma-delta loop with a preprogrammed waveform to swing the storage capacitor voltage. The system also contains an output stage that powers the LEDs with DC and provides for galvanic isolation. The output stage consists of an H-bridge stack that connects to the output through a small toroid transformer. The IC LED driver was simulated and prototyped on an ABCD silicon test chip. Testing and verification indicates functional performance for all the modules in the LED driver. The driver exhibits moderate efficiency at half voltage. Although the part was only testable to half voltage, loss models predict that its efficiency would be much higher at full voltage. The driver also meets specifications on the line current harmonics and ripple cancellation. This dissertation introduces multilevel circuit techniques to the IC and LED research space. The prototype's functional performance indicates that integrated multilevel converters are a viable topology for lighting and other similar applications.

An Improved Power Quality BIBRED Converter-Based VSI-Fed BLDC Motor Drive

NASA Astrophysics Data System (ADS)

Singh, Bhim; Bist, Vashist

2014-01-01

This paper presents an IHQRR (integrated high-quality rectifier regulator) BIBRED (boost integrated buck rectifier energy storage DC-DC) converter-based VSI (voltage source inverter)-fed BLDC (brushless DC) motor drive. The speed control of BLDC motor is achieved by controlling the DC link voltage of the VSI using a single voltage sensor. This allows VSI to operate in fundamental frequency switching mode for electronic commutation of BLDC motor which reduces the switching losses due to high-frequency switching used in conventional approach of PWM (pulse width modulation)-based VSI-fed BLDC motor drive. A BIBRED converter is operated in a dual-DCM (discontinuous conduction mode) thus using a voltage follower approach for PFC (power factor correction) and DC link voltage control. The performance of the proposed drive is evaluated for improved power quality over a wide range of speed control and supply voltage variation for demonstrating the behavior of proposed drive. The power quality indices thus obtained are within the recommended limits by international PQ (power quality) standards such as IEC 61000-3-2.

A new model predictive control algorithm by reducing the computing time of cost function minimization for NPC inverter in three-phase power grids.

PubMed

Taheri, Asghar; Zhalebaghi, Mohammad Hadi

2017-11-01

This paper presents a new control strategy based on finite-control-set model-predictive control (FCS-MPC) for Neutral-point-clamped (NPC) three-level converters. Containing some advantages like fast dynamic response, easy inclusion of constraints and simple control loop, makes the FCS-MPC method attractive to use as a switching strategy for converters. However, the large amount of required calculations is a problem in the widespread of this method. In this way, to resolve this problem this paper presents a modified method that effectively reduces the computation load compare with conventional FCS-MPC method and at the same time does not affect on control performance. The proposed method can be used for exchanging power between electrical grid and DC resources by providing active and reactive power compensations. Experiments on three-level converter for three Power Factor Correction (PFC), inductive and capacitive compensation modes verify the good and comparable performance. The results have been simulated using MATLAB/SIMULINK software. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

The influence of offspring, parity, and oxytocin on cognitive flexibility during the postpartum period.

PubMed

Albin-Brooks, Christopher; Nealer, Connor; Sabihi, Sara; Haim, Achikam; Leuner, Benedetta

2017-03-01

Pregnancy and the postpartum period are times of profound behavioral change including alterations in cognitive function. This has been most often studied using hippocampal-dependent tasks assessing spatial learning and memory. However, less is known about the cognitive effects of motherhood for tasks that rely on areas other than the hippocampus. We have previously shown that postpartum females perform better on the extradimensional phase of an attentional set shifting task, a measure of cognitive flexibility which is dependent on the medial prefrontal cortex (mPFC). The present experiments aimed to extend this work by examining the importance of postpartum stage as well as offspring and parity in driving improved mPFC cognitive function during motherhood. We also examined whether the neuropeptide oxytocin, which plays a role in regulating numerous maternal functions, mediates enhanced cognitive flexibility during motherhood. Our results demonstrate that compared to virgin females, cognitive flexibility is enhanced in mothers regardless of postpartum stage and is not affected by parity since both first (primiparous) and second (biparous) time mothers showed the enhancement. Moreover, we found that improved cognitive flexibility in mothers requires the presence of offspring, as removal of the pups abolished the cognitive enhancement in postpartum females. Lastly, using an oxytocin receptor antagonist, we demonstrate that oxytocin signaling in the mPFC is necessary for the beneficial effects of motherhood on cognitive flexibility. Together, these data provide insights into the temporal, experiential and hormonal factors which regulate mPFC-dependent cognitive function during the postpartum period. Copyright © 2017 Elsevier Inc. All rights reserved.

Strengthening of Existing Episodic Memories Through Non-invasive Stimulation of Prefrontal Cortex in Older Adults with Subjective Memory Complaints

PubMed Central

Manenti, Rosa; Sandrini, Marco; Gobbi, Elena; Cobelli, Chiara; Brambilla, Michela; Binetti, Giuliano; Cotelli, Maria

2017-01-01

Episodic memory is critical to daily life functioning. This type of declarative memory declines with age and is the earliest cognitive function to be compromised in Alzheimer’s disease (AD). Subjective memory complaints are commonly reported by older adults and have been considered a risk factor for developing AD. The possibilities for prevention of memory disorders in older adults have increased substantially in recent years. Previous studies have shown that anodal transcranial Direct Current Stimulation (tDCS) applied over the left lateral prefrontal cortex (PFC) after a contextual reminder strengthened existing verbal episodic memories, conceivably through reconsolidation, in elderly people. In this study, we hypothesized that anodal tDCS applied over the left lateral PFC after a contextual reminder would improve delayed memory retrieval relative to placebo (sham) stimulation in elderly individuals with SMC. Twenty-two subjects learned a list of words. Twenty-four hour later, tDCS (anodal or placebo) was applied over the left lateral PFC after a contextual reminder. Memory retrieval was tested 48h and 30 days later. These findings showed that anodal tDCS over the left lateral PFC strengthened existing episodic memories, a behavioral effect documented by improved recognition up to 30 days, relative to placebo stimulation. This study suggests that tDCS after a contextual reminder can induce long-lasting beneficial effects by facilitating the consolidation processes and opens up the possibility to design specific non-invasive interventions aimed at preventing memory decline in this at-risk population. PMID:29259554

Polyfluorinated compounds in dust from homes, offices, and vehicles as predictors of concentrations in office workers' serum.

PubMed

Fraser, Alicia J; Webster, Thomas F; Watkins, Deborah J; Strynar, Mark J; Kato, Kayoko; Calafat, Antonia M; Vieira, Verónica M; McClean, Michael D

2013-10-01

We aimed to characterize levels of polyfluorinated compounds (PFCs) in indoor dust from offices, homes, and vehicles; to investigate factors that may affect PFC levels in dust; and to examine the associations between PFCs in dust and office workers' serum. Dust samples were collected in 2009 from offices, homes, and vehicles of 31 individuals in Boston, MA and analyzed for nineteen PFCs, including perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), fluorotelomer alcohols (FTOHs), and sulfonamidoethanols (FOSEs). Serum was collected from each participant and analyzed for eight PFCs including PFOA and PFOS. Perfluorononanoate, PFOA, perfluoroheptanoate, perfluorohexanoate, PFOS and 8:2 FTOH had detection frequencies >50% in dust from all three microenvironments. The highest geometric mean concentration in office dust was for 8:2 FTOH (309ng/g), while PFOS was highest in homes (26.9ng/g) and vehicles (15.8ng/g). Overall, offices had the highest PFC concentrations, particularly for longer-chain carboxylic acids and FTOHs. Perfluorobutyrate was prevalent in homes and vehicles, but not offices. PFOA serum concentrations were not associated with PFC dust levels after adjusting for PFC concentrations in office air. Dust concentrations of most PFCs are higher in offices than in homes and vehicles. However, indoor dust may not be a significant source of exposure to PFCs for office workers. This finding suggests that our previously published observation of an association between FTOH concentrations in office air and PFOA concentrations in office workers was not due to confounding by PFCs in dust. © 2013.

Functional near infrared spectroscopy as a potential biological assessment of addiction recovery: preliminary findings.

PubMed

Dempsey, Jared P; Harris, Kitty S; Shumway, Sterling T; Kimball, Thomas G; Herrera, J Caleb; Dsauza, Cynthia M; Bradshaw, Spencer D

2015-03-01

Addiction science has primarily utilized self-report, continued substance use, and relapse factors to explore the process of recovery. However, the entry into successful abstinence substantially reduces our assessment abilities. Advances in neuroscience may be the key to objective understanding, treating, and monitoring long-term success in addiction recovery. To explore functional near infrared spectroscopy (fNIR) as a viable technique in the assessment of addiction-cue reactivity. Specifically, prefrontal cortex (PFC) activation to alcohol cues was explored among formally alcohol-dependent individuals, across varying levels of successful abstinence. The aim of the investigation was to identify patterns of PFC activation change consistent with duration of abstinence. A total of 15 formally alcohol-dependent individuals, with abstinence durations ranging from 1 month to 10 years, viewed alcohol images during fNIR PFC assessment. Participants also subjectively rated the same images for affect and arousal level. Subjective ratings of alcohol cues did not significantly correlate with duration of abstinence. As expected, days of abstinence did not significantly correlate with neutral cue fNIR reactivity. However, for alcohol cues, fNIR results showed increased days of abstinence was associated with decreased activation within the dorsolateral and dorsomedial prefrontal cortex regions. The present results suggest that fNIR may be a viable tool in the assessment of addiction-cue reactivity. RESULTS also support previous findings on the importance of dorsolateral and dorsomedial PFC in alcohol-cue activation. The findings build upon these past results suggesting that fNIR-assessed activation may represent a robust biological marker of successful addiction recovery.

Polyfluorinated compounds in dust from homes, offices, and vehicles as predictors of concentrations in office workers’ serum

PubMed Central

Fraser, Alicia J; Webster, Thomas F; Watkins, Deborah J; Strynar, Mark J; Kato, Kayoko; Calafat, Antonia M; Vieira, Verónica M; McClean, Michael D

2013-01-01

We aimed to characterize levels of polyfluorinated compounds (PFCs) in indoor dust from offices, homes, and vehicles; to investigate factors that may affect PFC levels in dust; and to examine the associations between PFCs in dust and office workers’ serum. Dust samples were collected in 2009 from offices, homes, and vehicles of 31 individuals in Boston, MA and analyzed for nineteen PFCs, including perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), fluorotelomer alcohols (FTOHs), and sulfonamidoethanols (FOSEs). Serum was collected from each participant and analyzed for eight PFCs including PFOA and PFOS. Perfluorononanoate, PFOA, perfluoroheptanoate, perfluorohexanoate, PFOS and 8:2 FTOH had detection frequencies >50% in dust from all three microenvironments. The highest geometric mean concentration in office dust was for 8:2 FTOH (309 ng/g), while PFOS was highest in homes (26.9 ng/g) and vehicles (15.8 ng/g). Overall, offices had the highest PFC concentrations, particularly for longer-chain carboxylic acids and FTOHs. Perfluorobutyrate was prevalent in homes and vehicles, but not offices. PFOA serum concentrations were not associated with PFC dust levels after adjusting for PFC concentrations in office air. Dust concentrations of most PFCs are higher in offices than in homes and vehicles. However, indoor dust may not be a significant source of exposure to PFCs for office workers. This finding suggests that our previously published observation of an association between FTOH concentrations in office air and PFOA concentrations in office workers was not due to confounding by PFCs in dust. PMID:24041736

Stress during a Critical Postnatal Period Induces Region-Specific Structural Abnormalities and Dysfunction of the Prefrontal Cortex via CRF1

PubMed Central

Yang, Xiao-Dun; Liao, Xue-Mei; Uribe-Mariño, Andrés; Liu, Rui; Xie, Xiao-Meng; Jia, Jiao; Su, Yun-Ai; Li, Ji-Tao; Schmidt, Mathias V; Wang, Xiao-Dong; Si, Tian-Mei

2015-01-01

During the early postnatal period, environmental influences play a pivotal role in shaping the development of the neocortex, including the prefrontal cortex (PFC) that is crucial for working memory and goal-directed actions. Exposure to stressful experiences during this critical period may disrupt the development of PFC pyramidal neurons and impair the wiring and function of related neural circuits. However, the molecular mechanisms of the impact of early-life stress on PFC development and function are not well understood. In this study, we found that repeated stress exposure during the first postnatal week hampered dendritic development in layers II/III and V pyramidal neurons in the dorsal agranular cingulate cortex (ACd) and prelimbic cortex (PL) of neonatal mice. The deleterious effects of early postnatal stress on structural plasticity persisted to adulthood only in ACd layer V pyramidal neurons. Most importantly, concurrent blockade of corticotropin-releasing factor receptor 1 (CRF1) by systemic antalarmin administration (20 μg/g of body weight) during early-life stress exposure prevented stress-induced apical dendritic retraction and spine loss in ACd layer V neurons and impairments in PFC-dependent cognitive tasks. Moreover, the magnitude of dendritic regression, especially the shrinkage of apical branches, of ACd layer V neurons predicted the degree of cognitive deficits in stressed mice. Our data highlight the region-specific effects of early postnatal stress on the structural plasticity of prefrontal pyramidal neurons, and suggest a critical role of CRF1 in modulating early-life stress-induced prefrontal abnormalities. PMID:25403725

Age-related reduced prefrontal-amygdala structural connectivity is associated with lower trait anxiety

PubMed Central

Clewett, David; Bachman, Shelby; Mather, Mara

2014-01-01

Objective A current neuroanatomical model of anxiety posits that greater structural connectivity between the amygdala and ventral prefrontal cortex (vPFC) facilitates regulatory control over the amygdala and helps reduce anxiety. However, some neuroimaging studies have reported contradictory findings, demonstrating a positive rather than negative association between trait anxiety and amygdala-vPFC white matter integrity. To help reconcile these findings, we tested the regulatory hypothesis of anxiety circuitry using aging as a model of white matter decline in the amygdala-vPFC pathway. Methods We used probabilistic tractography to trace connections between the amygdala and vPFC in 21 younger, 18 middle-aged, and 15 healthy older adults. The resulting tract estimates were used to extract three indices of white-matter integrity: fractional anisotropy (FA), radial diffusivity (RD) and axial diffusivity (AD). The relationship between these amygdala-vPFC structural connectivity measures and age and State-Trait Anxiety Inventory (STAI) scores were assessed. Results The tractography results revealed age-related decline in the FA (p = .005) and radial diffusivity (p = .002) of the amygdala-vPFC pathway. Contrary to the regulatory hypothesis, we found a positive rather than negative association between trait anxiety and right amygdala-vPFC FA (p = .01). Conclusion These findings argue against the notion that greater amygdala-vPFC structural integrity facilitates better anxiety outcomes in healthy adults. Instead, our results suggest that white matter degeneration in this network relates to lower anxiety in older adults. PMID:24635708

Social Isolation During the Critical Period Reduces Synaptic and Intrinsic Excitability of a Subtype of Pyramidal Cell in Mouse Prefrontal Cortex.

PubMed

Yamamuro, Kazuhiko; Yoshino, Hiroki; Ogawa, Yoichi; Makinodan, Manabu; Toritsuka, Michihiro; Yamashita, Masayuki; Corfas, Gabriel; Kishimoto, Toshifumi

2018-03-01

Juvenile social experience is crucial for the functional development of forebrain regions, especially the prefrontal cortex (PFC). We previously reported that social isolation for 2 weeks after weaning induces prefrontal cortex dysfunction and hypomyelination. However, the effect of social isolation on physiological properties of PFC neuronal circuit remained unknown. Since hypomyelination due to isolation is prominent in deep-layer of medial PFC (mPFC), we focused on 2 types of Layer-5 pyramidal cells in the mPFC: prominent h-current (PH) cells and nonprominent h-current (non-PH) cells. We found that a 2-week social isolation after weaning leads to a specific deterioration in action potential properties and reduction in excitatory synaptic inputs in PH cells. The effects of social isolation on PH cells, which involve reduction in functional glutamatergic synapses and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/N-methyl-d-aspartate charge ratio, are specific to the 2 weeks after weaning and to the mPFC. We conclude that juvenile social experience plays crucial roles in the functional development in a subtype of Layer-5 pyramidal cells in the mPFC. Since these neurons project to subcortical structures, a deficit in social experience during the critical period may result in immature neural circuitry between mPFC and subcortical targets. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Language learning without control: the role of the PFC.

PubMed

Friederici, Angela D; Mueller, Jutta L; Sehm, Bernhard; Ragert, Patrick

2013-05-01

Learning takes place throughout lifetime but differs in infants and adults because of the development of the PFC, a brain region responsible for cognitive control. To test this hypothesis, adults were investigated in a language learning paradigm under inhibitory, cathodal transcranial direct current stimulation over PFC. The experiment included a learning session interspersed with test phases and a test-only session. The stimulus material required the learning of grammatical dependencies between two elements in a novel language. In a parallel design, cathodal transcranial direct current stimulation over the left PFC, right PFC, or sham stimulation was applied during the learning session but not during the test-only session. Event-related brain potentials (ERPs) were recorded during both sessions. Whereas no ERP learning effects were observed during the learning session, different ERP learning effects as a function of prior stimulation type were found during the test-only session, although behavioral learning success was equal across conditions. With sham stimulation, the ERP learning effect was reflected in a centro-parietal N400-like negativity indicating lexical processes. Inhibitory stimulation over the left PFC, but not over the right PFC, led to a late positivity similar to that previously observed in prelinguistic infants indicating associative learning. The present data demonstrate that adults can learn with and without cognitive control using different learning mechanisms. In the presence of cognitive control, adult language learning is lexically guided, whereas it appears to be associative in nature when PFC control is downregulated.

Network structure underlying resolution of conflicting non-verbal and verbal social information.

PubMed

Watanabe, Takamitsu; Yahata, Noriaki; Kawakubo, Yuki; Inoue, Hideyuki; Takano, Yosuke; Iwashiro, Norichika; Natsubori, Tatsunobu; Takao, Hidemasa; Sasaki, Hiroki; Gonoi, Wataru; Murakami, Mizuho; Katsura, Masaki; Kunimatsu, Akira; Abe, Osamu; Kasai, Kiyoto; Yamasue, Hidenori

2014-06-01

Social judgments often require resolution of incongruity in communication contents. Although previous studies revealed that such conflict resolution recruits brain regions including the medial prefrontal cortex (mPFC) and posterior inferior frontal gyrus (pIFG), functional relationships and networks among these regions remain unclear. In this functional magnetic resonance imaging study, we investigated the functional dissociation and networks by measuring human brain activity during resolving incongruity between verbal and non-verbal emotional contents. First, we found that the conflict resolutions biased by the non-verbal contents activated the posterior dorsal mPFC (post-dmPFC), bilateral anterior insula (AI) and right dorsal pIFG, whereas the resolutions biased by the verbal contents activated the bilateral ventral pIFG. In contrast, the anterior dmPFC (ant-dmPFC), bilateral superior temporal sulcus and fusiform gyrus were commonly involved in both of the resolutions. Second, we found that the post-dmPFC and right ventral pIFG were hub regions in networks underlying the non-verbal- and verbal-content-biased resolutions, respectively. Finally, we revealed that these resolution-type-specific networks were bridged by the ant-dmPFC, which was recruited for the conflict resolutions earlier than the two hub regions. These findings suggest that, in social conflict resolutions, the ant-dmPFC selectively recruits one of the resolution-type-specific networks through its interaction with resolution-type-specific hub regions. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

75 FR 3954 - Agency Information Collection Activity Seeking OMB Approval

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-25

... (PFC). DATES: Please submit comments by February 24, 2010. FOR FURTHER INFORMATION CONTACT: Carla...: Passenger Facility Charge (PFC) Application. Type of Request: Extension without change of a currently...: 49 U.S.C. 40117 authorizes airports to impose passenger facility charges (PFC). This program requires...

Remember the source: dissociating frontal and parietal contributions to episodic memory.

PubMed

Donaldson, David I; Wheeler, Mark E; Petersen, Steve E

2010-02-01

Event-related fMRI studies reveal that episodic memory retrieval modulates lateral and medial parietal cortices, dorsal middle frontal gyrus (MFG), and anterior PFC. These regions respond more for recognized old than correctly rejected new words, suggesting a neural correlate of retrieval success. Despite significant efforts examining retrieval success regions, their role in retrieval remains largely unknown. Here we asked the question, to what degree are the regions performing memory-specific operations? And if so, are they all equally sensitive to successful retrieval, or are other factors such as error detection also implicated? We investigated this question by testing whether activity in retrieval success regions was associated with task-specific contingencies (i.e., perceived targetness) or mnemonic relevance (e.g., retrieval of source context). To do this, we used a source memory task that required discrimination between remembered targets and remembered nontargets. For a given region, the modulation of neural activity by a situational factor such as target status would suggest a more domain-general role; similarly, modulations of activity linked to error detection would suggest a role in monitoring and control rather than the accumulation of evidence from memory per se. We found that parietal retrieval success regions exhibited greater activity for items receiving correct than incorrect source responses, whereas frontal retrieval success regions were most active on error trials, suggesting that posterior regions signal successful retrieval whereas frontal regions monitor retrieval outcome. In addition, perceived targetness failed to modulate fMRI activity in any retrieval success region, suggesting that these regions are retrieval specific. We discuss the different functions that these regions may support and propose an accumulator model that captures the different pattern of responses seen in frontal and parietal retrieval success regions.

14 CFR 158.27 - Review of applications.

Code of Federal Regulations, 2014 CFR

2014-01-01

...) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Application and Approval § 158.27 Review of applications. (a... statutory deadline for the Administrator's decision. Upon receipt of the supplement, the Administrator... agency and the airport at which the PFC is to be imposed; (2) A brief description of the PFC project, the...

14 CFR 158.25 - Applications.

Code of Federal Regulations, 2013 CFR

2013-01-01

... PASSENGER FACILITY CHARGES (PFC'S) Application and Approval § 158.25 Applications. (a) General. This section specifies the information the public agency must file when applying for authority to impose a PFC and for authority to use PFC revenue on a project. A public agency may apply for such authority at any commercial...

14 CFR 158.25 - Applications.

Code of Federal Regulations, 2014 CFR

2014-01-01

... PASSENGER FACILITY CHARGES (PFC'S) Application and Approval § 158.25 Applications. (a) General. This section specifies the information the public agency must file when applying for authority to impose a PFC and for authority to use PFC revenue on a project. A public agency may apply for such authority at any commercial...

14 CFR 158.1 - Applicability.

Code of Federal Regulations, 2011 CFR

2011-01-01

... PASSENGER FACILITY CHARGES (PFC'S) General § 158.1 Applicability. This part applies to passenger facility charges (PFC's) as may be approved by the Administrator of the Federal Aviation Administration (FAA) and... procedures for reducing funds to a large or medium hub airport that imposes a PFC. [Doc. No. FAA-2000-7402...

14 CFR 158.25 - Applications.

Code of Federal Regulations, 2011 CFR

2011-01-01

... PASSENGER FACILITY CHARGES (PFC'S) Application and Approval § 158.25 Applications. (a) General. This section specifies the information the public agency must file when applying for authority to impose a PFC and for authority to use PFC revenue on a project. A public agency may apply for such authority at any commercial...

14 CFR 158.19 - Requirement for competition plans.

Code of Federal Regulations, 2014 CFR

2014-01-01

... (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) General § 158.19 Requirement for competition plans. (a) Beginning in fiscal year 2001, no public agency may impose a PFC with respect to a covered... to PFC authority approved prior to April 5, 2000. (b) The Administrator will review any plan...

14 CFR 158.83 - Informal resolution.

Code of Federal Regulations, 2014 CFR

2014-01-01

... PASSENGER FACILITY CHARGES (PFC'S) Termination § 158.83 Informal resolution. The Administrator shall... § 158.71, the Administrator cannot determine that PFC revenue is being used for the approved projects in accordance with the terms of the Administrator's approval to impose a PFC for those projects or with 49 U.S.C...

14 CFR 158.19 - Requirement for competition plans.

Code of Federal Regulations, 2010 CFR

2010-01-01

... (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) General § 158.19 Requirement for competition plans. (a) Beginning in fiscal year 2001, no public agency may impose a PFC with respect to a covered... to PFC authority approved prior to April 5, 2000. (b) The Administrator will review any plan...

14 CFR 158.83 - Informal resolution.

Code of Federal Regulations, 2012 CFR

2012-01-01

... PASSENGER FACILITY CHARGES (PFC'S) Termination § 158.83 Informal resolution. The Administrator shall... § 158.71, the Administrator cannot determine that PFC revenue is being used for the approved projects in accordance with the terms of the Administrator's approval to impose a PFC for those projects or with 49 U.S.C...

14 CFR 158.19 - Requirement for competition plans.

Code of Federal Regulations, 2012 CFR

2012-01-01

... (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) General § 158.19 Requirement for competition plans. (a) Beginning in fiscal year 2001, no public agency may impose a PFC with respect to a covered... to PFC authority approved prior to April 5, 2000. (b) The Administrator will review any plan...

14 CFR 158.83 - Informal resolution.

Code of Federal Regulations, 2010 CFR

2010-01-01

... PASSENGER FACILITY CHARGES (PFC'S) Termination § 158.83 Informal resolution. The Administrator shall... § 158.71, the Administrator cannot determine that PFC revenue is being used for the approved projects in accordance with the terms of the Administrator's approval to impose a PFC for those projects or with 49 U.S.C...

14 CFR 158.19 - Requirement for competition plans.

Code of Federal Regulations, 2013 CFR

2013-01-01

... (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) General § 158.19 Requirement for competition plans. (a) Beginning in fiscal year 2001, no public agency may impose a PFC with respect to a covered... to PFC authority approved prior to April 5, 2000. (b) The Administrator will review any plan...

14 CFR 158.83 - Informal resolution.

Code of Federal Regulations, 2013 CFR

2013-01-01

... PASSENGER FACILITY CHARGES (PFC'S) Termination § 158.83 Informal resolution. The Administrator shall... § 158.71, the Administrator cannot determine that PFC revenue is being used for the approved projects in accordance with the terms of the Administrator's approval to impose a PFC for those projects or with 49 U.S.C...

14 CFR 158.1 - Applicability.

Code of Federal Regulations, 2014 CFR

2014-01-01

... PASSENGER FACILITY CHARGES (PFC'S) General § 158.1 Applicability. This part applies to passenger facility charges (PFC's) as may be approved by the Administrator of the Federal Aviation Administration (FAA) and... procedures for reducing funds to a large or medium hub airport that imposes a PFC. [Doc. No. FAA-2000-7402...