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1.  Response Inhibition during Cue Reactivity in Problem Gamblers: An fMRI Study 
PLoS ONE  2012;7(3):e30909.
Disinhibition over drug use, enhanced salience of drug use and decreased salience of natural reinforcers are thought to play an important role substance dependence. Whether this is also true for pathological gambling is unclear. To understand the effects of affective stimuli on response inhibition in problem gamblers (PRGs), we designed an affective Go/Nogo to examine the interaction between response inhibition and salience attribution in 16 PRGs and 15 healthy controls (HCs).
Four affective blocks were presented with Go trials containing neutral, gamble, positive or negative affective pictures. The No-Go trials in these blocks contained neutral pictures. Outcomes of interest included percentage of impulsive errors and mean reaction times in the different blocks. Brain activity related to No-Go trials was assessed to measure response inhibition in the various affective conditions and brain activity related to Go trials was assessed to measure salience attribution.
PRGs made fewer errors during gamble and positive trials than HCs, but were slower during all trials types. Compared to HCs, PRGs activated the dorsolateral prefrontal cortex, anterior cingulate and ventral striatum to a greater extent while viewing gamble pictures. The dorsal lateral and inferior frontal cortex were more activated in PRGs than in HCs while viewing positive and negative pictures. During neutral inhibition, PRGs were slower but similar in accuracy to HCs, and showed more dorsolateral prefrontal and anterior cingulate cortex activity. In contrast, during gamble and positive pictures PRGs performed better than HCs, and showed lower activation of the dorsolateral and anterior cingulate cortex.
This study shows that gambling-related stimuli are more salient for PRGs than for HCs. PRGs seem to rely on compensatory brain activity to achieve similar performance during neutral response inhibition. A gambling-related or positive context appears to facilitate response inhibition as indicated by lower brain activity and fewer behavioural errors in PRGs.
PMCID: PMC3316530  PMID: 22479305
2.  Brain activation patterns associated with cue reactivity and craving in abstinent problem gamblers, heavy smokers and healthy controls: an fMRI study 
Addiction Biology  2010;15(4):491-503.
Abnormal cue reactivity is a central characteristic of addiction, associated with increased activity in motivation, attention and memory related brain circuits. In this neuroimaging study, cue reactivity in problem gamblers (PRG) was compared with cue reactivity in heavy smokers (HSM) and healthy controls (HC). A functional magnetic resonance imaging event-related cue reactivity paradigm, consisting of gambling, smoking-related and neutral pictures, was employed in 17 treatment-seeking non-smoking PRG, 18 non-gambling HSM, and 17 non-gambling and non-smoking HC. Watching gambling pictures (relative to neutral pictures) was associated with higher brain activation in occipitotemporal areas, posterior cingulate cortex, parahippocampal gyrus and amygdala in PRG compared with HC and HSM. Subjective craving in PRG correlated positively with brain activation in left ventrolateral prefrontal cortex and left insula. When comparing the HSM group with the two other groups, no significant differences in brain activity induced by smoking cues were found. In a stratified analysis, the HSM subgroup with higher Fagerström Test for Nicotine Dependence scores (FTND M = 5.4) showed higher brain activation in ventromedial prefrontal cortex, rostral anterior cingulate cortex, insula and middle/superior temporal gyrus while watching smoking-related pictures (relative to neutral pictures) than the HSM subgroup with lower FTND scores (FTND M = 2.9) and than non-smoking HC. Nicotine craving correlated with activation in left prefrontal and left amygdala when viewing smoking-related pictures in HSM. Increased regional responsiveness to gambling pictures in brain regions linked to motivation and visual processing is present in PRG, similar to neural mechanisms underlying cue reactivity in substance dependence. Increased brain activation in related fronto-limbic brain areas was present in HSM with higher FTND scores compared with HSM with lower FTND scores.
PMCID: PMC3014110  PMID: 20840335
Addiction; cue reactivity; fMRI; impulse control disorder; nicotine dependence; pathological gambling
3.  Getting a grip on problem gambling: what can neuroscience tell us? 
In problem gamblers, diminished cognitive control and increased impulsivity is present compared to healthy controls. Moreover, impulsivity has been found to be a vulnerability marker for the development of pathological gambling (PG) and problem gambling (PrG) and to be a predictor of relapse. In this review, the most recent findings on functioning of the brain circuitry relating to impulsivity and cognitive control in PG and PrG are discussed. Diminished functioning of several prefrontal areas and of the anterior cingulate cortex (ACC) indicate that cognitive-control related brain circuitry functions are diminished in PG and PrG compared to healthy controls. From the available cue reactivity studies on PG and PrG, increased responsiveness towards gambling stimuli in fronto-striatal reward circuitry and brain areas related to attentional processing is present compared to healthy controls. At this point it is unresolved whether PG is associated with hyper- or hypo-activity in the reward circuitry in response to monetary cues. More research is needed to elucidate the complex interactions for reward responsivity in different stages of gambling and across different types of reward. Conflicting findings from basic neuroscience studies are integrated in the context of recent neurobiological addiction models. Neuroscience studies on the interface between cognitive control and motivational processing are discussed in light of current addiction theories.
Clinical implications: We suggest that innovation in PG therapy should focus on improvement of dysfunctional cognitive control and/or motivational functions. The implementation of novel treatment methods like neuromodulation, cognitive training and pharmacological interventions as add-on therapies to standard treatment in PG and PrG, in combination with the study of their effects on brain-behavior mechanisms could prove an important clinical step forward towards personalizing and improving treatment results in PG.
PMCID: PMC4033022  PMID: 24904328
pathological gambling; disordered gambling; reward sensitivity; impulsivity; cue reactivity; response inhibition; review; addictive behaviors
4.  Time course of attentional bias for gambling information in problem gambling 
There is a wealth of evidence showing enhanced attention towards drug-related information (i.e. attentional bias) in substance abusers. However, little is known about attentional bias in deregulated behaviors without substance use such as abnormal gambling. This study examined whether problem gamblers (PrG, as assessed through self-reported gambling-related craving and gambling dependence severity) exhibit attentional bias for gambling-related cues.
Forty PrG and 35 control participants performed a change detection task using the flicker paradigm, in which two images differing in only one aspect are repeatedly flashed on the screen until the participant is able to report the changing item. In our study, the changing item was either neutral or related to gambling. Eye movements were recorded, which made it possible to measure both initial orienting of attention as well as its maintenance on gambling information.
Direct (eye-movements) and indirect (change in detection latency) measures of attention in individuals with problematic gambling behaviors suggested the occurrence of both engagement and of maintenance attentional biases towards gambling-related visual cues. Compared to non-problematic gamblers, PrG exhibited (1) faster reaction times to gambling-cues as compared to neutral cues, (2) higher percentage of initial saccades directed toward gambling pictures; (3) an increased fixation duration and fixation count on gambling pictures. In the PrG group, measures of gambling-related attentional bias were not associated with craving for gambling and gambling dependence severity. Theoretical and clinical implications of these results are discussed.
PMCID: PMC3792789  PMID: 21688874
Gambling; Attentional bias; Dependence; Eye-tracking; Craving
5.  PTSD symptom severity is associated with increased recruitment of top-down attentional control in a trauma-exposed sample☆ 
NeuroImage : Clinical  2014;7:19-27.
Recent neuroimaging work suggests that increased amygdala responses to emotional stimuli and dysfunction within regions mediating top down attentional control (dorsomedial frontal, lateral frontal and parietal cortices) may be associated with the emergence of anxiety disorders, including posttraumatic stress disorder (PTSD). This report examines amygdala responsiveness to emotional stimuli and the recruitment of top down attention systems as a function of task demands in a population of U.S. military service members who had recently returned from combat deployment in Afghanistan/Iraq. Given current interest in dimensional aspects of pathophysiology, it is worthwhile examining patients who, while not meeting full PTSD criteria, show clinically significant functional impairment.
Fifty-seven participants with sub-threshold levels of PTSD symptoms completed the affective Stroop task while undergoing fMRI. Participants with PTSD or depression at baseline were excluded.
Greater PTSD symptom severity scores were associated with increased amygdala activation to emotional, particularly positive, stimuli relative to neutral stimuli. Furthermore, greater PTSD symptom severity was associated with increased superior/middle frontal cortex response during task conditions relative to passive viewing conditions. In addition, greater PTSD symptom severity scores were associated with: (i) increased activation in the dorsolateral prefrontal, lateral frontal, inferior parietal cortices and dorsomedial frontal cortex/dorsal anterior cingulate cortex (dmFC/dACC) in response to emotional relative to neutral stimuli; and (ii) increased functional connectivity during emotional trials, particularly positive trials, relative to neutral trials between the right amygdala and dmFC/dACC, left caudate/anterior insula cortex, right lentiform nucleus/caudate, bilateral inferior parietal cortex and left middle temporal cortex.
We suggest that these data may reflect two phenomena associated with increased PTSD symptomatology in combat-exposed, but PTSD negative, armed services members. First, these data indicate increased emotional responsiveness by: (i) the positive relationship between PTSD symptom severity and amygdala responsiveness to emotional relative to neutral stimuli; (ii) greater BOLD response as a function of PTSD symptom severity in regions implicated in emotion (striatum) and representation (occipital and temporal cortices) during emotional relative to neutral conditions; and (iii) increased connectivity between the amygdala and regions implicated in emotion (insula/caudate) and representation (middle temporal cortex) as a function of PTSD symptom severity during emotional relative to neutral trials. Second, these data indicate a greater need for the recruitment of regions implicated in top down attention as indicated by (i) greater BOLD response in superior/middle frontal gyrus as a function of PTSD symptom severity in task relative to view conditions; (ii) greater BOLD response in dmFC/dACC, lateral frontal and inferior parietal cortices as a function of PTSD symptom severity in emotional relative to neutral conditions and (iii) greater functional connectivity between the amygdala and inferior parietal cortex as a function of PTSD symptom severity during emotional relative to neutral conditions.
•Greater PTSD symptoms associated with increased amygdala activation to emotional stimuli•PTSD symptoms associated with greater top down attention response in task and emotion conditions•PTSD symptoms were associated with slower reaction times.•Increased top down attention recruitment may compensate for heightened emotional responses.
PMCID: PMC4299952  PMID: 25610763
Post-traumatic stress disorder; Emotion attention; Amygdala; Top down attention
6.  Abnormalities of functional brain networks in pathological gambling: a graph-theoretical approach 
Functional neuroimaging studies of pathological gambling (PG) demonstrate alterations in frontal and subcortical regions of the mesolimbic reward system. However, most investigations were performed using tasks involving reward processing or executive functions. Little is known about brain network abnormalities during task-free resting state in PG. In the present study, graph-theoretical methods were used to investigate network properties of resting state functional magnetic resonance imaging data in PG. We compared 19 patients with PG to 19 healthy controls (HCs) using the Graph Analysis Toolbox (GAT). None of the examined global metrics differed between groups. At the nodal level, pathological gambler showed a reduced clustering coefficient in the left paracingulate cortex and the left juxtapositional lobe (supplementary motor area, SMA), reduced local efficiency in the left SMA, as well as an increased node betweenness for the left and right paracingulate cortex and the left SMA. At an uncorrected threshold level, the node betweenness in the left inferior frontal gyrus was decreased and increased in the caudate. Additionally, increased functional connectivity between fronto-striatal regions and within frontal regions has also been found for the gambling patients. These findings suggest that regions associated with the reward system demonstrate reduced segregation but enhanced integration while regions associated with executive functions demonstrate reduced integration. The present study makes evident that PG is also associated with abnormalities in the topological network structure of the brain during rest. Since alterations in PG cannot be explained by direct effects of abused substances on the brain, these findings will be of relevance for understanding functional connectivity in other addictive disorders.
PMCID: PMC3784685  PMID: 24098282
fMRI; graph theory; network; connectivity; pathological gambling; reward; behavioral addiction; small world
7.  Striatal connectivity changes following gambling wins and near-misses: Associations with gambling severity 
NeuroImage : Clinical  2014;5:232-239.
Frontostriatal circuitry is implicated in the cognitive distortions associated with gambling behaviour. ‘Near-miss’ events, where unsuccessful outcomes are proximal to a jackpot win, recruit overlapping neural circuitry with actual monetary wins. Personal control over a gamble (e.g., via choice) is also known to increase confidence in one's chances of winning (the ‘illusion of control’).
Using psychophysiological interaction (PPI) analyses, we examined changes in functional connectivity as regular gamblers and non-gambling participants played a slot-machine game that delivered wins, near-misses and full-misses, and manipulated personal control. We focussed on connectivity with striatal seed regions, and associations with gambling severity, using voxel-wise regression.
For the interaction term of near-misses (versus full-misses) by personal choice (participant-chosen versus computer-chosen), ventral striatal connectivity with the insula, bilaterally, was positively correlated with gambling severity. In addition, some effects for the contrast of wins compared to all non-wins were observed at an uncorrected (p < .001) threshold: there was an overall increase in connectivity between the striatal seeds and left orbitofrontal cortex and posterior insula, and a negative correlation for gambling severity with the connectivity between the right ventral striatal seed and left anterior cingulate cortex.
These findings corroborate the ‘non-categorical’ nature of reward processing in gambling: near-misses and full-misses are objectively identical outcomes that are processed differentially. Ventral striatal connectivity with the insula correlated positively with gambling severity in the illusion of control contrast, which could be a risk factor for the cognitive distortions and loss-chasing that are characteristic of problem gambling.
PMCID: PMC4110887  PMID: 25068112
Gambling; Connectivity; fMRI; Reward; Near-miss; Addiction
8.  Executive attention control and emotional responding in attention-deficit/hyperactivity disorder — A functional MRI study 
NeuroImage : Clinical  2015;9:545-554.
There are suggestions that patients with attention-deficit/hyperactivity disorder (ADHD) show impairment in executive attention control and emotion regulation. This study investigated emotion regulation as a function of the recruitment of executive attention in patients with ADHD.
Thirty-five healthy children/adolescents (mean age = 13.91) and twenty-six children/adolescents with ADHD (mean age = 14.53) participated in this fMRI study. They completed the affective Stroop paradigm viewing positive, neutral and negative images under varying cognitive loads. A 3-way ANOVA (diagnosis-by-condition-by-emotion) was conducted on the BOLD response data. Following this, 2 3-way ANOVAs (diagnosis-by-condition-by-emotion) were applied to context-dependent psychophysiological interaction (gPPI) analyses generated from a dorsomedial frontal cortex and an amygdala seed (identified from the BOLD response ANOVA main effects of condition and emotion respectively).
A diagnosis-by-condition interaction within dorsomedial frontal cortex revealed reduced recruitment of dorsomedial frontal cortex as a function of increased task demands in the children/adolescents with ADHD relative to healthy children/adolescents. The level of reduction in recruitment of dorsomedial frontal cortex was significantly correlated with symptom severity (total and hyperactivity) measured by Conner's Parent Report Scale in the children/adolescents with ADHD. In addition, analysis of gPPI data from a dorsomedial frontal cortex seed revealed significant diagnosis-by-condition interactions within lateral frontal cortex; connectivity between dorsomedial frontal cortex and lateral frontal cortex was reduced in the patients with ADHD relative to comparison youth during congruent and incongruent task trials relative to view trials. There were no interactions of group, or main effect of group, within the amygdala in the BOLD response ANOVA (though children/adolescents with ADHD showed increased responses to positive images within temporal cortical regions during task trials; identified by the diagnosis-by-condition-by-emotion interaction). However, analysis of gPPI data from an amygdala seed revealed decreased connectivity between amygdala and lentiform nucleus in the presence of emotional stimuli in children/adolescents with ADHD (diagnosis-by-emotion interaction).
The current study demonstrated disrupted recruitment of regions implicated in executive function and impaired connectivity within those regions in children/adolescents with ADHD. There were also indications of heightened representation of emotional stimuli in patients with ADHD. However, as the findings were specific for positive stimuli, the suggestion of a general failure in emotion regulation in ADHD was not supported.
•ADHD showed decreased dorsomedial frontal cortex activity with increased cognitive demand.•Decreased dorsomedial frontal cortex activity was correlated with symptom severity of ADHD.•Connectivity of dorsomedial frontal cortex–lateral frontal cortex was compromised in ADHD.•ADHD showed increased activities in emotional responding areas to positive emotional stimuli.
PMCID: PMC4632075  PMID: 26640766
Attention-deficit/hyperactivity disorder; Affective Stroop; Executive attention; Emotion regulation; fMRI
9.  An fMRI study of risk-taking following wins and losses: Implications for the gambler’s fallacy 
Human brain mapping  2011;32(2):271-281.
Human decision-making involving independent events is often biased and affected by prior outcomes. Using a controlled task that allows us to manipulate prior outcomes, the present study examined the effect of prior outcomes on subsequent decisions in a group of young adults. We found that participants were more risk-seeking after losing a gamble (Riskloss) than after winning a gamble (Riskwin), a pattern resembling the gambler’s fallacy. Functional MRI data revealed that decisions after Riskloss were associated with increased activation in the frontoparietal network, but decreased activation in the caudate and ventral striatum. The increased risk-seeking behavior after a loss showed a trend of positive correlation with activation in the frontoparietal network and the left lateral orbitofrontal cortex but a trend of negative correlation with activation in the amgydala and caudate. In addition, there was a trend of positive correlation between feedback-related activation in the left lateral frontal cortex and subsequent increased risk-seeking behavior. These results suggest that a strong cognitive control mechanism but a weak affective decision-making and reinforcement learning mechanism that usually contribute to flexible, goal-directed decisions can lead to decision biases involving random events. This has significant implications for our understanding of the gambler’s fallacy and human decision making under risk.
PMCID: PMC3429350  PMID: 21229615
Amygdala; Decision Making; Emotion; Frontal Cortex; functional MRI; Gambler’s Fallacy; Orbitofrontal Cortex; Reinforcement Learning; Striatum
10.  In Vivo and In Vitro Analyses of Regulation of the Pheromone-Responsive prgQ Promoter by the PrgX Pheromone Receptor Protein 
Journal of Bacteriology  2012;194(13):3386-3394.
Expression of conjugative transfer and virulence functions of the Enterococcus faecalis antibiotic resistance plasmid pCF10 is regulated by the interaction of the pheromone receptor protein PrgX with two DNA binding operator sites (XBS1 and XBS2) upstream from the transcription start site of the prgQ operon (encoding the pCF10 transfer machinery) and by posttranscriptional mechanisms. Occupancy of both binding sites by PrgX dimers results in repression of the prgQ promoter. Structural and genetic studies suggest that the peptide pheromone cCF10 functions by binding to PrgX and altering its oligomerization state, resulting in reduced occupancy of XBSs and increased prgQ transcription. The DNA binding activity of PrgX has additional indirect regulatory effects on prgQ transcript levels related to the position of the convergently transcribed prgX operon. This has complicated interpretation of previous analyses of the control of prgQ expression by PrgX. We report here the results of in vivo and in vitro experiments examining the direct effects of PrgX on transcription from the prgQ promoter, as well as quantitative correlation between the concentrations of XBSs, PrgX protein, and prgQ promoter activity in vivo. The results of electrophoretic mobility shift assays and quantitative analysis of prgQ transcription in vitro and in vivo support the predicted roles of the PrgX DNA binding sites in prgQ transcription regulation. The results also suggest the existence of other factors that impede PrgX repression or enhance its antagonism by cCF10 in vivo.
PMCID: PMC3434730  PMID: 22544272
11.  A Latent Class Analysis of Pathological-Gambling Criteria Among High School Students: Associations With Gambling, Risk and Health/Functioning Characteristics 
Journal of addiction medicine  2014;8(6):421-430.
To identify subtypes of adolescent gamblers based on the 10 Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria for pathological gambling and the 9 Diagnostic and Statistical Manual of Mental Disorders, fifth edition criteria for gambling disorder and to examine associations between identified subtypes with gambling, other risk behaviors, and health/functioning characteristics.
Using cross-sectional survey data from 10 high schools in Connecticut (N = 3901), we conducted latent class analysis to classify adolescents who reported past-year gambling into gambling groups on the basis of items from the Massachusetts Gambling Screen. Adolescents also completed questions assessing demographic information, substance use (cigarette, marijuana, alcohol, and other drugs), gambling behaviors (relating to gambling formats, locations, motivations, and urges), and health/functioning characteristics (eg, extracurricular activities, mood, aggression, and body mass index).
The optimal solution consisted of 4 classes that we termed low-risk gambling (86.4%), at-risk chasing gambling (7.6%), at-risk negative consequences gambling (3.7%), and problem gambling (PrG) (2.3%). At-risk and PrG classes were associated with greater negative functioning and more gambling behaviors. Different patterns of associations between at-risk and PrG classes were also identified.
Adolescent gambling classifies into 4 classes, which are differentially associated with demographic, gambling patterns, risk behaviors, and health/functioning characteristics. Early identification and interventions for adolescent gamblers should be sensitive to the heterogeneity of gambling subtypes.
PMCID: PMC4667944  PMID: 25275877
adolescents; gambling; latent class analysis
12.  Inhibitory behavioral control: A stochastic dynamic causal modeling study comparing cocaine dependent subjects and controls 
NeuroImage : Clinical  2015;7:837-847.
Cocaine dependence is associated with increased impulsivity in humans. Both cocaine dependence and impulsive behavior are under the regulatory control of cortico-striatal networks. One behavioral laboratory measure of impulsivity is response inhibition (ability to withhold a prepotent response) in which altered patterns of regional brain activation during executive tasks in service of normal performance are frequently found in cocaine dependent (CD) subjects studied with functional magnetic resonance imaging (fMRI). However, little is known about aberrations in specific directional neuronal connectivity in CD subjects. The present study employed fMRI-based dynamic causal modeling (DCM) to study the effective (directional) neuronal connectivity associated with response inhibition in CD subjects, elicited under performance of a Go/NoGo task with two levels of NoGo difficulty (Easy and Hard). The performance on the Go/NoGo task was not significantly different between CD subjects and controls. The DCM analysis revealed that prefrontal–striatal connectivity was modulated (influenced) during the NoGo conditions for both groups. The effective connectivity from left (L) anterior cingulate cortex (ACC) to L caudate was similarly modulated during the Easy NoGo condition for both groups. During the Hard NoGo condition in controls, the effective connectivity from right (R) dorsolateral prefrontal cortex (DLPFC) to L caudate became more positive, and the effective connectivity from R ventrolateral prefrontal cortex (VLPFC) to L caudate became more negative. In CD subjects, the effective connectivity from L ACC to L caudate became more negative during the Hard NoGo conditions. These results indicate that during Hard NoGo trials in CD subjects, the ACC rather than DLPFC or VLPFC influenced caudate during response inhibition.
•Dynamic causal modeling was used to study response inhibition in cocaine dependence.•A Go/NoGo task with two levels of NoGo difficulty (Easy and Hard) was used.•Patients and controls used anterior cingulate cortex to control caudate during Easy NoGo.•Controls used dorsolateral/ventrolateral prefrontal cortex to control caudate during Hard NoGo.•Patients continued using anterior cingulate cortex to control caudate during Hard NoGo.
PMCID: PMC4459041  PMID: 26082893
Dynamic casual modeling; Impulsivity; Inhibitory control; Cocaine dependence
13.  Cartilage boundary lubrication synergism is mediated by hyaluronan concentration and PRG4 concentration and structure 
Proteoglycan 4 (PRG4) and hyaluronan (HA) are key synovial fluid constituents that contribute synergistically to cartilage boundary lubrication; however, the effects of their concentrations as well as their structure, both of which can be altered in osteoarthritis, on this functional synergism are unknown. The objectives of this study were to evaluate cartilage boundary lubricating ability of 1) PRG4 + HA in solution at constant HA concentration in a range of PRG4 concentrations, 2) constant PRG4 concentration in a range of HA concentrations, 3) HA + reduced/alkylated (R/A) PRG4, and 4) hylan G-F 20 + PRG4.
Static and kinetic friction coefficients (μstatic,Neq, <μkinetic,Neq>) were measured using a previously characterized cartilage-cartilage boundary mode friction test for the following concentrations of purified PRG4 and HA: Test 1: HA (1.5 MDa, 3.3 mg/mL) + PRG4 from 4.5 – 1500 μg/mL; Test 2: PRG4 (450, 150, 45 μg/mL) + HA (1.5 MDa) from 0.3 – 3.3 mg/mL. Test 3: hylan G-F 20 (3. 3 mg/mL) + PRG4 (450 μg/mL). Test 4: HA (3.3 mg/mL) + R/A PRG4 (450 μg/mL). ANOVA was used to compare lubricants within (comparing 6 lubricants of interest) and between (comparing 3 lubricants of interest) test sequences, with Tukey and Fishers post-hoc testing respectively.
This study demonstrates that both PRG4 and HA concentration, as well as PRG4 disulfide-bonded structure, can alter the cartilage boundary lubricating ability of PRG4 + HA solutions. The boundary lubricating ability of high MW HA + PRG4 solutions was limited by very low concentrations of PRG4. Decreased concentrations of high MW HA also limited the cartilage boundary lubricating ability of HA + PRG4 solutions, with the effect exacerbated by low PRG4 concentrations. The reduction of friction by addition of PRG4 to a cross-linked HA viscosupplement product, but not with addition of R/A PRG4 to HA, is consistent with a non-covalent mechanism of interaction where tertiary and quaternary PRG4 structure are important.
Collectively, these results demonstrate that deficiency of either or both PRG4 and HA, or alterations in PRG4 structure, may be detrimental to SF cartilage boundary lubricating function. This study provides further insight into the nature of cartilage boundary lubrication and advancement towards potential formulation of new intra-articular biotherapeutic treatments for osteoarthritis using PRG4 ± HA.
PMCID: PMC4678696  PMID: 26666513
Cartilage; Hyaluronan; Proteoglycan 4; Boundary Lubrication
14.  Why are Some Games More Addictive than Others: The Effects of Timing and Payoff on Perseverance in a Slot Machine Game 
Manipulating different behavioral characteristics of gambling games can potentially affect the extent to which individuals persevere at gambling, and their transition to problematic behaviors. This has potential impact for mobile gambling technologies and responsible gambling interventions. Two laboratory models pertinent to this are the partial reinforcement extinction effect (PREE) and the trial spacing effect. Both of these might speed up or delay the acquisition and extinction of conditioned behavior. We report an experiment that manipulated the rate of reinforcement and inter trial interval (ITI) on a simulated slot machine where participants were given the choice between gambling and skipping on each trial, before perseverative gambling was measured in extinction, followed by measurements of the illusion of control, depression and impulsivity. We hypothesized that longer ITI’s in conjunction with the low rates of reinforcement observed in gambling would lead to greater perseverance. We further hypothesized, given that timing is known to be important in displaying illusory control and potentially in persevering in gambling, that prior exposure to longer intervals might affect illusions of control. An interaction between ITI and rate of reinforcement was observed, as low reinforced gamblers with a long ITI gambled for longer. Respondents also displayed extinction and a PREE. Gamblers exposed to a higher rate of reinforcement gambled for longer in acquisition. Impulsivity was associated with extended perseverance in extinction, and more depressed gamblers in the high reinforcement short ITI group persevered for longer. Performance in the contingency judgment failed to support the second hypothesis: the only significant contrast observed was that participants became better calibrated as the task progressed.
PMCID: PMC4735408  PMID: 26869955
gambling; impulsivity; associative learning; behavior; addictive; reinforcement schedule; slot machine
15.  Cyclic loading increases friction and changes cartilage surface integrity in lubricin-mutant mouse knees 
Arthritis and Rheumatism  2012;64(2):465-473.
To investigate the effects of lubricin gene dosage and cyclic loading on whole joint coefficient of friction and articular cartilage surface integrity in mouse knee joints.
Joints from mice with 2 (Prg4+/+), 1 (Prg4+/−), or no (Prg4−/−) functioning lubricin alleles were subjected to 26 hours of cyclic loading using a custom-built pendulum. Coefficient of friction values were measured at multiple time points. Contralateral control joints were left unloaded. Following testing, joints were examined for histologic evidence of damage and cell viability.
At baseline, the coefficient of friction values in Prg4−/− mice were significantly higher than those in Prg4+/+ and Prg4+/− mice (P < 0.001). Cyclic loading continuously increased the coefficient of friction in Prg4−/− mouse joints. In contrast, Prg4+/− and Prg4+/+ mouse joints had no coefficient of friction increases during the first 4 hours of loading. After 26 hours of loading, joints from all genotypes had increased coefficient of friction values compared to baseline and unloaded controls. Significantly greater increases occurred in Prg4−/− and Prg4+/− mouse joints compared to Prg4+/+ mouse joints. The coefficient of friction values were not significantly associated with histologic evidence of damage or loss of cell viability.
Our findings indicate that mice lacking lubricin have increased baseline coefficient of friction values and are not protected against further increases caused by loading. Prg4+/− mice are indistinguishable from Prg4+/+ mice at baseline, but have significantly greater coefficient of friction values following 26 hours of loading. Lubricin dosage affects joint properties during loading, and may have clinical implications in patients for whom injury or illness alters lubricin abundance.
PMCID: PMC3252402  PMID: 21905020
16.  Binding of Porphyromonas gingivalis Fimbriae to Proline-Rich Glycoproteins in Parotid Saliva via a Domain Shared by Major Salivary Components 
Infection and Immunity  1998;66(5):2072-2077.
Porphyromonas gingivalis, a putative periodontopathogen, can bind to human saliva through its fimbriae. We previously found that salivary components from the submandibular and sublingual glands bind to P. gingivalis fimbriae and that acidic proline-rich protein (PRP) and statherin function as receptor molecules for fimbriae. In this study, we investigated the fimbria-binding components in parotid saliva. Fractionated human parotid saliva by gel-filtration chromatography was immobilized onto nitrocellulose membranes for the overlay assay following sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The salivary components on the membrane were allowed to interact with fimbriae purified from P. gingivalis ATCC 33277, and the interacted fimbriae were probed with anti-fimbria antibodies. The fimbriae were shown to bind to two forms of proline-rich glycoproteins (PRGs) as well as to acidic PRPs and statherin. Moreover, fimbriae bound to several components of smaller molecular size which appeared to be acidic PRP variants and basic PRPs. Fimbriae bound strongly to the purified PRGs adsorbed onto hydroxyapatite (HAP) beads. In contrast, PRGs in solution failed to inhibit the fimbrial binding to the immobilized PRGs on the HAP beads. These findings suggest that the appearance of binding site(s) of PRGs can be ascribed to their conformational changes. We previously identified the distinct segments within PRP and statherin molecules that are involved in fimbrial binding. The peptides analogous to the binding regions of PRP and statherin (i.e., PRP-C and STN-C) markedly inhibit the binding of fimbriae to PRP and statherin immobilized on the HAP beads, respectively. The PRP-C significantly inhibited the binding of fimbriae to PRG-coated HAP beads as well as to PRP on HAP beads. The peptide did not affect the binding of fimbriae to statherin, whereas the STN-C showed no effect on the fimbrial binding to PRPs or PRGs. In the overlay assay, the PRP-C clearly diminished the interactions between the fimbriae and the various salivary components, including PRPs, the PRGs, and the components with smaller molecular sizes but not statherin. These results strongly suggest that fimbriae bind to salivary components (except statherin) via common peptide segments. It is also suggested that fimbriae bind to saliva through the two distinct binding domains of receptory salivary components: (i) PRGs and PRPs and (ii) statherin.
PMCID: PMC108165  PMID: 9573091
17.  Characterization of the Sequence Specificity Determinants Required for Processing and Control of Sex Pheromone by the Intramembrane Protease Eep and the Plasmid-Encoded Protein PrgY▿  
Journal of Bacteriology  2007;190(4):1172-1183.
Conjugative transfer of the Enterococcus faecalis plasmid pCF10 is induced by the peptide pheromone cCF10 when recipient-produced cCF10 is detected by donors. cCF10 is produced by proteolytic processing of the signal sequence of a chromosomally encoded lipoprotein (CcfA). In donors, endogenously produced cCF10 is carefully controlled to prevent constitutive expression of conjugation functions, an energetically wasteful process, except in vivo, where endogenous cCF10 induces a conjugation-linked virulence factor. Endogenous cCF10 is controlled by two plasmid-encoded products; a membrane protein PrgY reduces pheromone levels in donors, and a secreted inhibitor peptide iCF10 inhibits the residual endogenous pheromone that escapes PrgY control. In this study we genetically determined the amino acid specificity determinants within PrgY, cCF10, and the cCF10 precursor that are necessary for cCF10 processing and for PrgY-mediated control. We showed that amino acid residues 125 to 241 of PrgY are required for specific recognition of cCF10 and that PrgY recognizes determinants within the heptapeptide cCF10 sequence, supporting a direct interaction between PrgY and mature cCF10. In addition, we found that a regulated intramembrane proteolysis (RIP) family pheromone precursor-processing protein Eep recognizes amino acids N-terminal to cCF10 in the signal sequence of CcfA. These results support a model where Eep directly targets pheromone precursors for RIP and PrgY interacts directly with the mature cCF10 peptide during processing. Despite evidence that both PrgY and Eep associate with cCF10 in or near the membrane, results presented here indicate that these two proteins function independently.
PMCID: PMC2238190  PMID: 18083822
18.  RNA-Mediated Reciprocal Regulation between Two Bacterial Operons Is RNase III Dependent 
mBio  2011;2(5):e00189-11.
In bacteria, RNAs regulate gene expression and function via several mechanisms. An RNA may pair with complementary sequences in a target RNA to impact transcription, translation, or degradation of the target. Control of conjugation of pCF10, a pheromone response plasmid of Enterococcus faecalis, is a well-characterized system that serves as a model for the regulation of gene expression in bacteria by intercellular signaling. The prgQ operon, whose products mediate conjugation, is negatively regulated by two products of the prgX operon, Anti-Q, a small RNA, and PrgX, the transcriptional repressor of the prgQ promoter. Here we show that Qs, an RNA from the 5′ end of the prgQ operon, represses expression of PrgX by targeting prgX mRNA for cleavage by RNase III. Our results demonstrate that the prgQ and prgX operons each use RNAs to negatively regulate gene expression from the opposing operon by different mechanisms. Such reciprocal regulation between two operons using RNAs has not been previously demonstrated. Furthermore, these results show that Qs is an unusually versatile RNA, serving three separate functions in the regulation of conjugation. Understanding the potential versatility of RNAs and their various roles in gene regulatory networks will allow us to better understand how cells regulate complex behavior.
Importance Bacteria use RNA to regulate gene expression by a variety of mechanisms. The prgQ and prgX operons of pCF10, a conjugative plasmid of Enterococcus faecalis, have been shown to negatively regulate one another by a variety of mechanisms. One of these mechanisms involves Anti-Q, a small RNA from the prgX operon that prevents gene expression from the prgQ operon. In this work, we find that Qs, an RNA from the prgQ operon, negatively regulates gene expression from the prgX operon. These findings have a number of implications. (i) The Anti-Q and Qs RNAs act by different mechanisms, highlighting the variety of ways in which bacteria can regulate gene expression using RNAs. (ii) Reciprocal regulation between operons mediated by small RNAs has not been previously described, deepening our understanding of how bacteria regulate complex behavior. (iii) Additional roles for Qs have been described, demonstrating the versatility of this RNA.
Bacteria use RNA to regulate gene expression by a variety of mechanisms. The prgQ and prgX operons of pCF10, a conjugative plasmid of Enterococcus faecalis, have been shown to negatively regulate one another by a variety of mechanisms. One of these mechanisms involves Anti-Q, a small RNA from the prgX operon that prevents gene expression from the prgQ operon. In this work, we find that Qs, an RNA from the prgQ operon, negatively regulates gene expression from the prgX operon. These findings have a number of implications. (i) The Anti-Q and Qs RNAs act by different mechanisms, highlighting the variety of ways in which bacteria can regulate gene expression using RNAs. (ii) Reciprocal regulation between operons mediated by small RNAs has not been previously described, deepening our understanding of how bacteria regulate complex behavior. (iii) Additional roles for Qs have been described, demonstrating the versatility of this RNA.
PMCID: PMC3181467  PMID: 21954305
19.  Genetic analysis of a region of the Enterococcus faecalis plasmid pCF10 involved in positive regulation of conjugative transfer functions. 
Journal of Bacteriology  1995;177(8):2107-2117.
The prgB gene encodes the surface protein Asc10, which mediates cell aggregation resulting in high-frequency conjugative transfer of the pheromone-inducible tetracycline resistance plasmid pCF10 in Enterococcus faecalis. Previous Tn5 insertional mutagenesis and sequencing analysis of a 12-kb fragment of pCF10 indicated that a region containing prgX, -Q, -R, -S, and -T, located 3 to 6 kb upstream of prgB, is required to activate the expression of prgB. Complementation studies showed that the positive regulatory region functions in cis in an orientation-dependent manner (J. W. Chung and G. M. Dunny, Proc. Natl. Acad. Sci. USA 89:9020-9024, 1992). In order to determine the involvement of each gene in the activation of prgB, Tn5 insertional mutagenesis and exonuclease III deletion analyses of the regulatory region were carried out. The results indicate that prgQ and -S are required for the expression of prgB, while prgX, -R, and -T are not required. Western blot (immunoblot) analysis of these mutants shows that prgQ is also essential for the expression of prgA (encoding the surface exclusion protein Sec10), which is located between prgB and the positive-control region. Complementation analysis demonstrates that a cis-acting regulatory element is located in the prgQ region and that pCF10 sequences in an untranslated region 3' from prgQ are an essential component of the positive-control system. Analyses of various Tn5 insertions in pCF10 genes suggest that transcription reading into this transposon is terminated in E. faecalis but that outward-reading transcripts may initiate from within the ends of Tn5 or from the junction sequences.
PMCID: PMC176855  PMID: 7721703
20.  Analysis of the Amino Acid Sequence Specificity Determinants of the Enterococcal cCF10 Sex Pheromone in Interactions with the Pheromone-Sensing Machinery▿  
Journal of Bacteriology  2006;189(4):1399-1406.
The level of expression of conjugation genes in Enterococcus faecalis strains carrying the pheromone-responsive transferable plasmid pCF10 is determined by the ratio in the culture medium of two types of signaling peptides, a pheromone (cCF10) and an inhibitor (iCF10). Recent data have demonstrated that both peptides target the cytoplasmic receptor protein PrgX. However, the relative importance of the interaction of these peptides with the pCF10 protein PrgZ (which enhances import of cCF10) versus PrgX is not fully understood, and there is relatively little information about specific amino acid sequence determinants affecting the functional interactions of cCF10 with these proteins in vivo. To address these issues, we used a pheromone-inducible reporter gene system where various combinations of PrgX and PrgZ could be expressed in an isogenic host background to examine the biological activities of cCF10, iCF10, and variants of cCF10 isolated in a genetic screen. The results suggest that most of the amino acid sequence determinants of cCF10 pheromone activity affect interactions between the peptide and PrgX, although some sequence variants that affected peptide/PrgZ interactions were also identified. The results provide functional data to complement ongoing structural studies of PrgX and increase our understanding of the functional interactions of cCF10 and iCF10 with the pheromone-sensing machinery of pCF10.
PMCID: PMC1797347  PMID: 17098891
21.  Tuning the Brake While Raising the Stake: Network Dynamics during Sequential Decision-Making 
The Journal of Neuroscience  2016;36(19):5417-5426.
When gathering valued goods, risk and reward are often coupled and escalate over time, for instance, during foraging, trading, or gambling. This escalating frame requires agents to continuously balance expectations of reward against those of risk. To address how the human brain dynamically computes these tradeoffs, we performed whole-brain fMRI while healthy young individuals engaged in a sequential gambling task. Participants were repeatedly confronted with the option to continue with throwing a die to accumulate monetary reward under escalating risk, or the alternative option to stop to bank the current balance. Within each gambling round, the accumulation of gains gradually increased reaction times for “continue” choices, indicating growing uncertainty in the decision to continue. Neural activity evoked by “continue” choices was associated with growing activity and connectivity of a cortico-subcortical “braking” network that positively scaled with the accumulated gains, including pre-supplementary motor area (pre-SMA), inferior frontal gyrus, caudate, and subthalamic nucleus (STN). The influence of the STN on continue-evoked activity in the pre-SMA was predicted by interindividual differences in risk-aversion attitudes expressed during the gambling task. Furthermore, activity in dorsal anterior cingulate cortex (ACC) reflected individual choice tendencies by showing increased activation when subjects made nondefault “continue” choices despite an increasing tendency to stop, but ACC activity did not change in proportion with subjective choice uncertainty. Together, the results implicate a key role of dorsal ACC, pre-SMA, inferior frontal gyrus, and STN in computing the trade-off between escalating reward and risk in sequential decision-making.
SIGNIFICANCE STATEMENT Using a paradigm where subjects experienced increasing potential rewards coupled with increasing risk, this study addressed two unresolved questions in the field of decision-making: First, we investigated an “inhibitory” network of regions that has so far been investigated with externally cued action inhibition. In this study, we show that the dynamics in this network under increasingly risky decisions are predictive of subjects' risk attitudes. Second, we contribute to a currently ongoing debate about the anterior cingulate cortex's role in sequential foraging decisions by showing that its activity is related to making nondefault choices rather than to choice uncertainty.
PMCID: PMC4863066  PMID: 27170137
ACC; action selection; conflict; inhibition; pre-SMA
22.  Sex and Disease-Related Alterations of Anterior Insula Functional Connectivity in Chronic Abdominal Pain 
The Journal of Neuroscience  2014;34(43):14252-14259.
Resting-state functional magnetic resonance imaging has been used to investigate intrinsic brain connectivity in healthy subjects and patients with chronic pain. Sex-related differences in the frequency power distribution within the human insula (INS), a brain region involved in the integration of interoceptive, affective, and cognitive influences, have been reported. Here we aimed to test sex and disease-related alterations in the intrinsic functional connectivity of the dorsal anterior INS. The anterior INS is engaged during goal-directed tasks and modulates the default mode and executive control networks. By comparing functional connectivity of the dorsal anterior INS in age-matched female and male healthy subjects and patients with irritable bowel syndrome (IBS), a common chronic abdominal pain condition, we show evidence for sex and disease-related alterations in the functional connectivity of this region: (1) male patients compared with female patients had increased positive connectivity of the dorsal anterior INS bilaterally with the medial prefrontal cortex (PFC) and dorsal posterior INS; (2) female patients compared with male patients had greater negative connectivity of the left dorsal anterior INS with the left precuneus; (3) disease-related differences in the connectivity between the bilateral dorsal anterior INS and the dorsal medial PFC were observed in female subjects; and (4) clinical characteristics were significantly correlated to the insular connectivity with the dorsal medial PFC in male IBS subjects and with the precuneus in female IBS subjects. These findings are consistent with the INS playing an important role in modulating the intrinsic functional connectivity of major networks in the resting brain and show that this role is influenced by sex and diagnosis.
PMCID: PMC4205551  PMID: 25339739
fMRI; IBS; insula; pain; sex difference
23.  Cognitive processes underlying impaired decision-making under uncertainty in gambling disorder 
Addictive behaviors  2014;39(10):1533-1536.
Pathological gamblers display at the Iowa Gambling Task (IGT) a strong preference for choices featuring high immediate rewards, but higher unpredictable and more delayed losses. The present study aimed, by applying the Expectancy-Valence (EV) model to the IGT, at identifying impaired components of decision-making under uncertainty in pathological gamblers.
Twenty pathological gamblers and 20 non-gamblers performed the IGT. The EV model breaks down IGT performance into three cognitive processes: (i) the subjective weight that the individual assigns to gains versus losses (gain/loss parameter), (ii) the degree of prominence given to recently-obtained information, compared to past experience (recency parameter), and (iii) the consistency between learning and responding (consistency parameter).
Pathological gamblers obtained higher scores on the gain/loss parameter as compared to controls, indicating higher sensitivity to monetary gains. This measure was also correlated with the degree of gambling dependence severity. No between-group difference was observed in the recency and the consistency parameters.
These findings suggest that pathological gamblers’ strong preference for choices featuring high rewards but higher losses during the IGT is due to a hypersensitivity for large monetary gains, which might reflect a hypersensitivity in their reward systems. In contrast, we found in pathological gamblers no evidence of inability to integrate information across time, a function that has been shown previously to be linked to damage in the prefrontal cortex.
PMCID: PMC4114505  PMID: 24980287
decision-making; gambling disorder; cognitive modeling; sensitivity to reward
24.  25th Annual Computational Neuroscience Meeting: CNS-2016 
Sharpee, Tatyana O. | Destexhe, Alain | Kawato, Mitsuo | Sekulić, Vladislav | Skinner, Frances K. | Wójcik, Daniel K. | Chintaluri, Chaitanya | Cserpán, Dorottya | Somogyvári, Zoltán | Kim, Jae Kyoung | Kilpatrick, Zachary P. | Bennett, Matthew R. | Josić, Kresimir | Elices, Irene | Arroyo, David | Levi, Rafael | Rodriguez, Francisco B. | Varona, Pablo | Hwang, Eunjin | Kim, Bowon | Han, Hio-Been | Kim, Tae | McKenna, James T. | Brown, Ritchie E. | McCarley, Robert W. | Choi, Jee Hyun | Rankin, James | Popp, Pamela Osborn | Rinzel, John | Tabas, Alejandro | Rupp, André | Balaguer-Ballester, Emili | Maturana, Matias I. | Grayden, David B. | Cloherty, Shaun L. | Kameneva, Tatiana | Ibbotson, Michael R. | Meffin, Hamish | Koren, Veronika | Lochmann, Timm | Dragoi, Valentin | Obermayer, Klaus | Psarrou, Maria | Schilstra, Maria | Davey, Neil | Torben-Nielsen, Benjamin | Steuber, Volker | Ju, Huiwen | Yu, Jiao | Hines, Michael L. | Chen, Liang | Yu, Yuguo | Kim, Jimin | Leahy, Will | Shlizerman, Eli | Birgiolas, Justas | Gerkin, Richard C. | Crook, Sharon M. | Viriyopase, Atthaphon | Memmesheimer, Raoul-Martin | Gielen, Stan | Dabaghian, Yuri | DeVito, Justin | Perotti, Luca | Kim, Anmo J. | Fenk, Lisa M. | Cheng, Cheng | Maimon, Gaby | Zhao, Chang | Widmer, Yves | Sprecher, Simon | Senn, Walter | Halnes, Geir | Mäki-Marttunen, Tuomo | Keller, Daniel | Pettersen, Klas H. | Andreassen, Ole A. | Einevoll, Gaute T. | Yamada, Yasunori | Steyn-Ross, Moira L. | Alistair Steyn-Ross, D. | Mejias, Jorge F. | Murray, John D. | Kennedy, Henry | Wang, Xiao-Jing | Kruscha, Alexandra | Grewe, Jan | Benda, Jan | Lindner, Benjamin | Badel, Laurent | Ohta, Kazumi | Tsuchimoto, Yoshiko | Kazama, Hokto | Kahng, B. | Tam, Nicoladie D. | Pollonini, Luca | Zouridakis, George | Soh, Jaehyun | Kim, DaeEun | Yoo, Minsu | Palmer, S. E. | Culmone, Viviana | Bojak, Ingo | Ferrario, Andrea | Merrison-Hort, Robert | Borisyuk, Roman | Kim, Chang Sub | Tezuka, Taro | Joo, Pangyu | Rho, Young-Ah | Burton, Shawn D. | Bard Ermentrout, G. | Jeong, Jaeseung | Urban, Nathaniel N. | Marsalek, Petr | Kim, Hoon-Hee | Moon, Seok-hyun | Lee, Do-won | Lee, Sung-beom | Lee, Ji-yong | Molkov, Yaroslav I. | Hamade, Khaldoun | Teka, Wondimu | Barnett, William H. | Kim, Taegyo | Markin, Sergey | Rybak, Ilya A. | Forro, Csaba | Dermutz, Harald | Demkó, László | Vörös, János | Babichev, Andrey | Huang, Haiping | Verduzco-Flores, Sergio | Dos Santos, Filipa | Andras, Peter | Metzner, Christoph | Schweikard, Achim | Zurowski, Bartosz | Roach, James P. | Sander, Leonard M. | Zochowski, Michal R. | Skilling, Quinton M. | Ognjanovski, Nicolette | Aton, Sara J. | Zochowski, Michal | Wang, Sheng-Jun | Ouyang, Guang | Guang, Jing | Zhang, Mingsha | Michael Wong, K. Y. | Zhou, Changsong | Robinson, Peter A. | Sanz-Leon, Paula | Drysdale, Peter M. | Fung, Felix | Abeysuriya, Romesh G. | Rennie, Chris J. | Zhao, Xuelong | Choe, Yoonsuck | Yang, Huei-Fang | Mi, Yuanyuan | Lin, Xiaohan | Wu, Si | Liedtke, Joscha | Schottdorf, Manuel | Wolf, Fred | Yamamura, Yoriko | Wickens, Jeffery R. | Rumbell, Timothy | Ramsey, Julia | Reyes, Amy | Draguljić, Danel | Hof, Patrick R. | Luebke, Jennifer | Weaver, Christina M. | He, Hu | Yang, Xu | Ma, Hailin | Xu, Zhiheng | Wang, Yuzhe | Baek, Kwangyeol | Morris, Laurel S. | Kundu, Prantik | Voon, Valerie | Agnes, Everton J. | Vogels, Tim P. | Podlaski, William F. | Giese, Martin | Kuravi, Pradeep | Vogels, Rufin | Seeholzer, Alexander | Podlaski, William | Ranjan, Rajnish | Vogels, Tim | Torres, Joaquin J. | Baroni, Fabiano | Latorre, Roberto | Gips, Bart | Lowet, Eric | Roberts, Mark J. | de Weerd, Peter | Jensen, Ole | van der Eerden, Jan | Goodarzinick, Abdorreza | Niry, Mohammad D. | Valizadeh, Alireza | Pariz, Aref | Parsi, Shervin S. | Warburton, Julia M. | Marucci, Lucia | Tamagnini, Francesco | Brown, Jon | Tsaneva-Atanasova, Krasimira | Kleberg, Florence I. | Triesch, Jochen | Moezzi, Bahar | Iannella, Nicolangelo | Schaworonkow, Natalie | Plogmacher, Lukas | Goldsworthy, Mitchell R. | Hordacre, Brenton | McDonnell, Mark D. | Ridding, Michael C. | Zapotocky, Martin | Smit, Daniel | Fouquet, Coralie | Trembleau, Alain | Dasgupta, Sakyasingha | Nishikawa, Isao | Aihara, Kazuyuki | Toyoizumi, Taro | Robb, Daniel T. | Mellen, Nick | Toporikova, Natalia | Tang, Rongxiang | Tang, Yi-Yuan | Liang, Guangsheng | Kiser, Seth A. | Howard, James H. | Goncharenko, Julia | Voronenko, Sergej O. | Ahamed, Tosif | Stephens, Greg | Yger, Pierre | Lefebvre, Baptiste | Spampinato, Giulia Lia Beatrice | Esposito, Elric | et Olivier Marre, Marcel Stimberg | Choi, Hansol | Song, Min-Ho | Chung, SueYeon | Lee, Dan D. | Sompolinsky, Haim | Phillips, Ryan S. | Smith, Jeffrey | Chatzikalymniou, Alexandra Pierri | Ferguson, Katie | Alex Cayco Gajic, N. | Clopath, Claudia | Angus Silver, R. | Gleeson, Padraig | Marin, Boris | Sadeh, Sadra | Quintana, Adrian | Cantarelli, Matteo | Dura-Bernal, Salvador | Lytton, William W. | Davison, Andrew | Li, Luozheng | Zhang, Wenhao | Wang, Dahui | Song, Youngjo | Park, Sol | Choi, Ilhwan | Shin, Hee-sup | Choi, Hannah | Pasupathy, Anitha | Shea-Brown, Eric | Huh, Dongsung | Sejnowski, Terrence J. | Vogt, Simon M. | Kumar, Arvind | Schmidt, Robert | Van Wert, Stephen | Schiff, Steven J. | Veale, Richard | Scheutz, Matthias | Lee, Sang Wan | Gallinaro, Júlia | Rotter, Stefan | Rubchinsky, Leonid L. | Cheung, Chung Ching | Ratnadurai-Giridharan, Shivakeshavan | Shomali, Safura Rashid | Ahmadabadi, Majid Nili | Shimazaki, Hideaki | Nader Rasuli, S. | Zhao, Xiaochen | Rasch, Malte J. | Wilting, Jens | Priesemann, Viola | Levina, Anna | Rudelt, Lucas | Lizier, Joseph T. | Spinney, Richard E. | Rubinov, Mikail | Wibral, Michael | Bak, Ji Hyun | Pillow, Jonathan | Zaho, Yuan | Park, Il Memming | Kang, Jiyoung | Park, Hae-Jeong | Jang, Jaeson | Paik, Se-Bum | Choi, Woochul | Lee, Changju | Song, Min | Lee, Hyeonsu | Park, Youngjin | Yilmaz, Ergin | Baysal, Veli | Ozer, Mahmut | Saska, Daniel | Nowotny, Thomas | Chan, Ho Ka | Diamond, Alan | Herrmann, Christoph S. | Murray, Micah M. | Ionta, Silvio | Hutt, Axel | Lefebvre, Jérémie | Weidel, Philipp | Duarte, Renato | Morrison, Abigail | Lee, Jung H. | Iyer, Ramakrishnan | Mihalas, Stefan | Koch, Christof | Petrovici, Mihai A. | Leng, Luziwei | Breitwieser, Oliver | Stöckel, David | Bytschok, Ilja | Martel, Roman | Bill, Johannes | Schemmel, Johannes | Meier, Karlheinz | Esler, Timothy B. | Burkitt, Anthony N. | Kerr, Robert R. | Tahayori, Bahman | Nolte, Max | Reimann, Michael W. | Muller, Eilif | Markram, Henry | Parziale, Antonio | Senatore, Rosa | Marcelli, Angelo | Skiker, K. | Maouene, M. | Neymotin, Samuel A. | Seidenstein, Alexandra | Lakatos, Peter | Sanger, Terence D. | Menzies, Rosemary J. | McLauchlan, Campbell | van Albada, Sacha J. | Kedziora, David J. | Neymotin, Samuel | Kerr, Cliff C. | Suter, Benjamin A. | Shepherd, Gordon M. G. | Ryu, Juhyoung | Lee, Sang-Hun | Lee, Joonwon | Lee, Hyang Jung | Lim, Daeseob | Wang, Jisung | Lee, Heonsoo | Jung, Nam | Anh Quang, Le | Maeng, Seung Eun | Lee, Tae Ho | Lee, Jae Woo | Park, Chang-hyun | Ahn, Sora | Moon, Jangsup | Choi, Yun Seo | Kim, Juhee | Jun, Sang Beom | Lee, Seungjun | Lee, Hyang Woon | Jo, Sumin | Jun, Eunji | Yu, Suin | Goetze, Felix | Lai, Pik-Yin | Kim, Seonghyun | Kwag, Jeehyun | Jang, Hyun Jae | Filipović, Marko | Reig, Ramon | Aertsen, Ad | Silberberg, Gilad | Bachmann, Claudia | Buttler, Simone | Jacobs, Heidi | Dillen, Kim | Fink, Gereon R. | Kukolja, Juraj | Kepple, Daniel | Giaffar, Hamza | Rinberg, Dima | Shea, Steven | Koulakov, Alex | Bahuguna, Jyotika | Tetzlaff, Tom | Kotaleski, Jeanette Hellgren | Kunze, Tim | Peterson, Andre | Knösche, Thomas | Kim, Minjung | Kim, Hojeong | Park, Ji Sung | Yeon, Ji Won | Kim, Sung-Phil | Kang, Jae-Hwan | Lee, Chungho | Spiegler, Andreas | Petkoski, Spase | Palva, Matias J. | Jirsa, Viktor K. | Saggio, Maria L. | Siep, Silvan F. | Stacey, William C. | Bernar, Christophe | Choung, Oh-hyeon | Jeong, Yong | Lee, Yong-il | Kim, Su Hyun | Jeong, Mir | Lee, Jeungmin | Kwon, Jaehyung | Kralik, Jerald D. | Jahng, Jaehwan | Hwang, Dong-Uk | Kwon, Jae-Hyung | Park, Sang-Min | Kim, Seongkyun | Kim, Hyoungkyu | Kim, Pyeong Soo | Yoon, Sangsup | Lim, Sewoong | Park, Choongseok | Miller, Thomas | Clements, Katie | Ahn, Sungwoo | Ji, Eoon Hye | Issa, Fadi A. | Baek, JeongHun | Oba, Shigeyuki | Yoshimoto, Junichiro | Doya, Kenji | Ishii, Shin | Mosqueiro, Thiago S. | Strube-Bloss, Martin F. | Smith, Brian | Huerta, Ramon | Hadrava, Michal | Hlinka, Jaroslav | Bos, Hannah | Helias, Moritz | Welzig, Charles M. | Harper, Zachary J. | Kim, Won Sup | Shin, In-Seob | Baek, Hyeon-Man | Han, Seung Kee | Richter, René | Vitay, Julien | Beuth, Frederick | Hamker, Fred H. | Toppin, Kelly | Guo, Yixin | Graham, Bruce P. | Kale, Penelope J. | Gollo, Leonardo L. | Stern, Merav | Abbott, L. F. | Fedorov, Leonid A. | Giese, Martin A. | Ardestani, Mohammad Hovaidi | Faraji, Mohammad Javad | Preuschoff, Kerstin | Gerstner, Wulfram | van Gendt, Margriet J. | Briaire, Jeroen J. | Kalkman, Randy K. | Frijns, Johan H. M. | Lee, Won Hee | Frangou, Sophia | Fulcher, Ben D. | Tran, Patricia H. P. | Fornito, Alex | Gliske, Stephen V. | Lim, Eugene | Holman, Katherine A. | Fink, Christian G. | Kim, Jinseop S. | Mu, Shang | Briggman, Kevin L. | Sebastian Seung, H. | Wegener, Detlef | Bohnenkamp, Lisa | Ernst, Udo A. | Devor, Anna | Dale, Anders M. | Lines, Glenn T. | Edwards, Andy | Tveito, Aslak | Hagen, Espen | Senk, Johanna | Diesmann, Markus | Schmidt, Maximilian | Bakker, Rembrandt | Shen, Kelly | Bezgin, Gleb | Hilgetag, Claus-Christian | van Albada, Sacha Jennifer | Sun, Haoqi | Sourina, Olga | Huang, Guang-Bin | Klanner, Felix | Denk, Cornelia | Glomb, Katharina | Ponce-Alvarez, Adrián | Gilson, Matthieu | Ritter, Petra | Deco, Gustavo | Witek, Maria A. G. | Clarke, Eric F. | Hansen, Mads | Wallentin, Mikkel | Kringelbach, Morten L. | Vuust, Peter | Klingbeil, Guido | De Schutter, Erik | Chen, Weiliang | Zang, Yunliang | Hong, Sungho | Takashima, Akira | Zamora, Criseida | Gallimore, Andrew R. | Goldschmidt, Dennis | Manoonpong, Poramate | Karoly, Philippa J. | Freestone, Dean R. | Soundry, Daniel | Kuhlmann, Levin | Paninski, Liam | Cook, Mark | Lee, Jaejin | Fishman, Yonatan I. | Cohen, Yale E. | Roberts, James A. | Cocchi, Luca | Sweeney, Yann | Lee, Soohyun | Jung, Woo-Sung | Kim, Youngsoo | Jung, Younginha | Song, Yoon-Kyu | Chavane, Frédéric | Soman, Karthik | Muralidharan, Vignesh | Srinivasa Chakravarthy, V. | Shivkumar, Sabyasachi | Mandali, Alekhya | Pragathi Priyadharsini, B. | Mehta, Hima | Davey, Catherine E. | Brinkman, Braden A. W. | Kekona, Tyler | Rieke, Fred | Buice, Michael | De Pittà, Maurizio | Berry, Hugues | Brunel, Nicolas | Breakspear, Michael | Marsat, Gary | Drew, Jordan | Chapman, Phillip D. | Daly, Kevin C. | Bradle, Samual P. | Seo, Sat Byul | Su, Jianzhong | Kavalali, Ege T. | Blackwell, Justin | Shiau, LieJune | Buhry, Laure | Basnayake, Kanishka | Lee, Sue-Hyun | Levy, Brandon A. | Baker, Chris I. | Leleu, Timothée | Philips, Ryan T. | Chhabria, Karishma
BMC Neuroscience  2016;17(Suppl 1):54.
Table of contents
A1 Functional advantages of cell-type heterogeneity in neural circuits
Tatyana O. Sharpee
A2 Mesoscopic modeling of propagating waves in visual cortex
Alain Destexhe
A3 Dynamics and biomarkers of mental disorders
Mitsuo Kawato
F1 Precise recruitment of spiking output at theta frequencies requires dendritic h-channels in multi-compartment models of oriens-lacunosum/moleculare hippocampal interneurons
Vladislav Sekulić, Frances K. Skinner
F2 Kernel methods in reconstruction of current sources from extracellular potentials for single cells and the whole brains
Daniel K. Wójcik, Chaitanya Chintaluri, Dorottya Cserpán, Zoltán Somogyvári
F3 The synchronized periods depend on intracellular transcriptional repression mechanisms in circadian clocks.
Jae Kyoung Kim, Zachary P. Kilpatrick, Matthew R. Bennett, Kresimir Josić
O1 Assessing irregularity and coordination of spiking-bursting rhythms in central pattern generators
Irene Elices, David Arroyo, Rafael Levi, Francisco B. Rodriguez, Pablo Varona
O2 Regulation of top-down processing by cortically-projecting parvalbumin positive neurons in basal forebrain
Eunjin Hwang, Bowon Kim, Hio-Been Han, Tae Kim, James T. McKenna, Ritchie E. Brown, Robert W. McCarley, Jee Hyun Choi
O3 Modeling auditory stream segregation, build-up and bistability
James Rankin, Pamela Osborn Popp, John Rinzel
O4 Strong competition between tonotopic neural ensembles explains pitch-related dynamics of auditory cortex evoked fields
Alejandro Tabas, André Rupp, Emili Balaguer-Ballester
O5 A simple model of retinal response to multi-electrode stimulation
Matias I. Maturana, David B. Grayden, Shaun L. Cloherty, Tatiana Kameneva, Michael R. Ibbotson, Hamish Meffin
O6 Noise correlations in V4 area correlate with behavioral performance in visual discrimination task
Veronika Koren, Timm Lochmann, Valentin Dragoi, Klaus Obermayer
O7 Input-location dependent gain modulation in cerebellar nucleus neurons
Maria Psarrou, Maria Schilstra, Neil Davey, Benjamin Torben-Nielsen, Volker Steuber
O8 Analytic solution of cable energy function for cortical axons and dendrites
Huiwen Ju, Jiao Yu, Michael L. Hines, Liang Chen, Yuguo Yu
O9 C. elegans interactome: interactive visualization of Caenorhabditis elegans worm neuronal network
Jimin Kim, Will Leahy, Eli Shlizerman
O10 Is the model any good? Objective criteria for computational neuroscience model selection
Justas Birgiolas, Richard C. Gerkin, Sharon M. Crook
O11 Cooperation and competition of gamma oscillation mechanisms
Atthaphon Viriyopase, Raoul-Martin Memmesheimer, Stan Gielen
O12 A discrete structure of the brain waves
Yuri Dabaghian, Justin DeVito, Luca Perotti
O13 Direction-specific silencing of the Drosophila gaze stabilization system
Anmo J. Kim, Lisa M. Fenk, Cheng Lyu, Gaby Maimon
O14 What does the fruit fly think about values? A model of olfactory associative learning
Chang Zhao, Yves Widmer, Simon Sprecher,Walter Senn
O15 Effects of ionic diffusion on power spectra of local field potentials (LFP)
Geir Halnes, Tuomo Mäki-Marttunen, Daniel Keller, Klas H. Pettersen,Ole A. Andreassen, Gaute T. Einevoll
O16 Large-scale cortical models towards understanding relationship between brain structure abnormalities and cognitive deficits
Yasunori Yamada
O17 Spatial coarse-graining the brain: origin of minicolumns
Moira L. Steyn-Ross, D. Alistair Steyn-Ross
O18 Modeling large-scale cortical networks with laminar structure
Jorge F. Mejias, John D. Murray, Henry Kennedy, Xiao-Jing Wang
O19 Information filtering by partial synchronous spikes in a neural population
Alexandra Kruscha, Jan Grewe, Jan Benda, Benjamin Lindner
O20 Decoding context-dependent olfactory valence in Drosophila
Laurent Badel, Kazumi Ohta, Yoshiko Tsuchimoto, Hokto Kazama
P1 Neural network as a scale-free network: the role of a hub
B. Kahng
P2 Hemodynamic responses to emotions and decisions using near-infrared spectroscopy optical imaging
Nicoladie D. Tam
P3 Phase space analysis of hemodynamic responses to intentional movement directions using functional near-infrared spectroscopy (fNIRS) optical imaging technique
Nicoladie D.Tam, Luca Pollonini, George Zouridakis
P4 Modeling jamming avoidance of weakly electric fish
Jaehyun Soh, DaeEun Kim
P5 Synergy and redundancy of retinal ganglion cells in prediction
Minsu Yoo, S. E. Palmer
P6 A neural field model with a third dimension representing cortical depth
Viviana Culmone, Ingo Bojak
P7 Network analysis of a probabilistic connectivity model of the Xenopus tadpole spinal cord
Andrea Ferrario, Robert Merrison-Hort, Roman Borisyuk
P8 The recognition dynamics in the brain
Chang Sub Kim
P9 Multivariate spike train analysis using a positive definite kernel
Taro Tezuka
P10 Synchronization of burst periods may govern slow brain dynamics during general anesthesia
Pangyu Joo
P11 The ionic basis of heterogeneity affects stochastic synchrony
Young-Ah Rho, Shawn D. Burton, G. Bard Ermentrout, Jaeseung Jeong, Nathaniel N. Urban
P12 Circular statistics of noise in spike trains with a periodic component
Petr Marsalek
P14 Representations of directions in EEG-BCI using Gaussian readouts
Hoon-Hee Kim, Seok-hyun Moon, Do-won Lee, Sung-beom Lee, Ji-yong Lee, Jaeseung Jeong
P15 Action selection and reinforcement learning in basal ganglia during reaching movements
Yaroslav I. Molkov, Khaldoun Hamade, Wondimu Teka, William H. Barnett, Taegyo Kim, Sergey Markin, Ilya A. Rybak
P17 Axon guidance: modeling axonal growth in T-Junction assay
Csaba Forro, Harald Dermutz, László Demkó, János Vörös
P19 Transient cell assembly networks encode persistent spatial memories
Yuri Dabaghian, Andrey Babichev
P20 Theory of population coupling and applications to describe high order correlations in large populations of interacting neurons
Haiping Huang
P21 Design of biologically-realistic simulations for motor control
Sergio Verduzco-Flores
P22 Towards understanding the functional impact of the behavioural variability of neurons
Filipa Dos Santos, Peter Andras
P23 Different oscillatory dynamics underlying gamma entrainment deficits in schizophrenia
Christoph Metzner, Achim Schweikard, Bartosz Zurowski
P24 Memory recall and spike frequency adaptation
James P. Roach, Leonard M. Sander, Michal R. Zochowski
P25 Stability of neural networks and memory consolidation preferentially occur near criticality
Quinton M. Skilling, Nicolette Ognjanovski, Sara J. Aton, Michal Zochowski
P26 Stochastic Oscillation in Self-Organized Critical States of Small Systems: Sensitive Resting State in Neural Systems
Sheng-Jun Wang, Guang Ouyang, Jing Guang, Mingsha Zhang, K. Y. Michael Wong, Changsong Zhou
P27 Neurofield: a C++ library for fast simulation of 2D neural field models
Peter A. Robinson, Paula Sanz-Leon, Peter M. Drysdale, Felix Fung, Romesh G. Abeysuriya, Chris J. Rennie, Xuelong Zhao
P28 Action-based grounding: Beyond encoding/decoding in neural code
Yoonsuck Choe, Huei-Fang Yang
P29 Neural computation in a dynamical system with multiple time scales
Yuanyuan Mi, Xiaohan Lin, Si Wu
P30 Maximum entropy models for 3D layouts of orientation selectivity
Joscha Liedtke, Manuel Schottdorf, Fred Wolf
P31 A behavioral assay for probing computations underlying curiosity in rodents
Yoriko Yamamura, Jeffery R. Wickens
P32 Using statistical sampling to balance error function contributions to optimization of conductance-based models
Timothy Rumbell, Julia Ramsey, Amy Reyes, Danel Draguljić, Patrick R. Hof, Jennifer Luebke, Christina M. Weaver
P33 Exploration and implementation of a self-growing and self-organizing neuron network building algorithm
Hu He, Xu Yang, Hailin Ma, Zhiheng Xu, Yuzhe Wang
P34 Disrupted resting state brain network in obese subjects: a data-driven graph theory analysis
Kwangyeol Baek, Laurel S. Morris, Prantik Kundu, Valerie Voon
P35 Dynamics of cooperative excitatory and inhibitory plasticity
Everton J. Agnes, Tim P. Vogels
P36 Frequency-dependent oscillatory signal gating in feed-forward networks of integrate-and-fire neurons
William F. Podlaski, Tim P. Vogels
P37 Phenomenological neural model for adaptation of neurons in area IT
Martin Giese, Pradeep Kuravi, Rufin Vogels
P38 ICGenealogy: towards a common topology of neuronal ion channel function and genealogy in model and experiment
Alexander Seeholzer, William Podlaski, Rajnish Ranjan, Tim Vogels
P39 Temporal input discrimination from the interaction between dynamic synapses and neural subthreshold oscillations
Joaquin J. Torres, Fabiano Baroni, Roberto Latorre, Pablo Varona
P40 Different roles for transient and sustained activity during active visual processing
Bart Gips, Eric Lowet, Mark J. Roberts, Peter de Weerd, Ole Jensen, Jan van der Eerden
P41 Scale-free functional networks of 2D Ising model are highly robust against structural defects: neuroscience implications
Abdorreza Goodarzinick, Mohammad D. Niry, Alireza Valizadeh
P42 High frequency neuron can facilitate propagation of signal in neural networks
Aref Pariz, Shervin S. Parsi, Alireza Valizadeh
P43 Investigating the effect of Alzheimer’s disease related amyloidopathy on gamma oscillations in the CA1 region of the hippocampus
Julia M. Warburton, Lucia Marucci, Francesco Tamagnini, Jon Brown, Krasimira Tsaneva-Atanasova
P44 Long-tailed distributions of inhibitory and excitatory weights in a balanced network with eSTDP and iSTDP
Florence I. Kleberg, Jochen Triesch
P45 Simulation of EMG recording from hand muscle due to TMS of motor cortex
Bahar Moezzi, Nicolangelo Iannella, Natalie Schaworonkow, Lukas Plogmacher, Mitchell R. Goldsworthy, Brenton Hordacre, Mark D. McDonnell, Michael C. Ridding, Jochen Triesch
P46 Structure and dynamics of axon network formed in primary cell culture
Martin Zapotocky, Daniel Smit, Coralie Fouquet, Alain Trembleau
P47 Efficient signal processing and sampling in random networks that generate variability
Sakyasingha Dasgupta, Isao Nishikawa, Kazuyuki Aihara, Taro Toyoizumi
P48 Modeling the effect of riluzole on bursting in respiratory neural networks
Daniel T. Robb, Nick Mellen, Natalia Toporikova
P49 Mapping relaxation training using effective connectivity analysis
Rongxiang Tang, Yi-Yuan Tang
P50 Modeling neuron oscillation of implicit sequence learning
Guangsheng Liang, Seth A. Kiser, James H. Howard, Jr., Yi-Yuan Tang
P51 The role of cerebellar short-term synaptic plasticity in the pathology and medication of downbeat nystagmus
Julia Goncharenko, Neil Davey, Maria Schilstra, Volker Steuber
P52 Nonlinear response of noisy neurons
Sergej O. Voronenko, Benjamin Lindner
P53 Behavioral embedding suggests multiple chaotic dimensions underlie C. elegans locomotion
Tosif Ahamed, Greg Stephens
P54 Fast and scalable spike sorting for large and dense multi-electrodes recordings
Pierre Yger, Baptiste Lefebvre, Giulia Lia Beatrice Spampinato, Elric Esposito, Marcel Stimberg et Olivier Marre
P55 Sufficient sampling rates for fast hand motion tracking
Hansol Choi, Min-Ho Song
P56 Linear readout of object manifolds
SueYeon Chung, Dan D. Lee, Haim Sompolinsky
P57 Differentiating models of intrinsic bursting and rhythm generation of the respiratory pre-Bötzinger complex using phase response curves
Ryan S. Phillips, Jeffrey Smith
P58 The effect of inhibitory cell network interactions during theta rhythms on extracellular field potentials in CA1 hippocampus
Alexandra Pierri Chatzikalymniou, Katie Ferguson, Frances K. Skinner
P59 Expansion recoding through sparse sampling in the cerebellar input layer speeds learning
N. Alex Cayco Gajic, Claudia Clopath, R. Angus Silver
P60 A set of curated cortical models at multiple scales on Open Source Brain
Padraig Gleeson, Boris Marin, Sadra Sadeh, Adrian Quintana, Matteo Cantarelli, Salvador Dura-Bernal, William W. Lytton, Andrew Davison, R. Angus Silver
P61 A synaptic story of dynamical information encoding in neural adaptation
Luozheng Li, Wenhao Zhang, Yuanyuan Mi, Dahui Wang, Si Wu
P62 Physical modeling of rule-observant rodent behavior
Youngjo Song, Sol Park, Ilhwan Choi, Jaeseung Jeong, Hee-sup Shin
P64 Predictive coding in area V4 and prefrontal cortex explains dynamic discrimination of partially occluded shapes
Hannah Choi, Anitha Pasupathy, Eric Shea-Brown
P65 Stability of FORCE learning on spiking and rate-based networks
Dongsung Huh, Terrence J. Sejnowski
P66 Stabilising STDP in striatal neurons for reliable fast state recognition in noisy environments
Simon M. Vogt, Arvind Kumar, Robert Schmidt
P67 Electrodiffusion in one- and two-compartment neuron models for characterizing cellular effects of electrical stimulation
Stephen Van Wert, Steven J. Schiff
P68 STDP improves speech recognition capabilities in spiking recurrent circuits parameterized via differential evolution Markov Chain Monte Carlo
Richard Veale, Matthias Scheutz
P69 Bidirectional transformation between dominant cortical neural activities and phase difference distributions
Sang Wan Lee
P70 Maturation of sensory networks through homeostatic structural plasticity
Júlia Gallinaro, Stefan Rotter
P71 Corticothalamic dynamics: structure, number of solutions and stability of steady-state solutions in the space of synaptic couplings
Paula Sanz-Leon, Peter A. Robinson
P72 Optogenetic versus electrical stimulation of the parkinsonian basal ganglia. Computational study
Leonid L. Rubchinsky, Chung Ching Cheung, Shivakeshavan Ratnadurai-Giridharan
P73 Exact spike-timing distribution reveals higher-order interactions of neurons
Safura Rashid Shomali, Majid Nili Ahmadabadi, Hideaki Shimazaki, S. Nader Rasuli
P74 Neural mechanism of visual perceptual learning using a multi-layered neural network
Xiaochen Zhao, Malte J. Rasch
P75 Inferring collective spiking dynamics from mostly unobserved systems
Jens Wilting, Viola Priesemann
P76 How to infer distributions in the brain from subsampled observations
Anna Levina, Viola Priesemann
P77 Influences of embedding and estimation strategies on the inferred memory of single spiking neurons
Lucas Rudelt, Joseph T. Lizier, Viola Priesemann
P78 A nearest-neighbours based estimator for transfer entropy between spike trains
Joseph T. Lizier, Richard E. Spinney, Mikail Rubinov, Michael Wibral, Viola Priesemann
P79 Active learning of psychometric functions with multinomial logistic models
Ji Hyun Bak, Jonathan Pillow
P81 Inferring low-dimensional network dynamics with variational latent Gaussian process
Yuan Zaho, Il Memming Park
P82 Computational investigation of energy landscapes in the resting state subcortical brain network
Jiyoung Kang, Hae-Jeong Park
P83 Local repulsive interaction between retinal ganglion cells can generate a consistent spatial periodicity of orientation map
Jaeson Jang, Se-Bum Paik
P84 Phase duration of bistable perception reveals intrinsic time scale of perceptual decision under noisy condition
Woochul Choi, Se-Bum Paik
P85 Feedforward convergence between retina and primary visual cortex can determine the structure of orientation map
Changju Lee, Jaeson Jang, Se-Bum Paik
P86 Computational method classifying neural network activity patterns for imaging data
Min Song, Hyeonsu Lee, Se-Bum Paik
P87 Symmetry of spike-timing-dependent-plasticity kernels regulates volatility of memory
Youngjin Park, Woochul Choi, Se-Bum Paik
P88 Effects of time-periodic coupling strength on the first-spike latency dynamics of a scale-free network of stochastic Hodgkin-Huxley neurons
Ergin Yilmaz, Veli Baysal, Mahmut Ozer
P89 Spectral properties of spiking responses in V1 and V4 change within the trial and are highly relevant for behavioral performance
Veronika Koren, Klaus Obermayer
P90 Methods for building accurate models of individual neurons
Daniel Saska, Thomas Nowotny
P91 A full size mathematical model of the early olfactory system of honeybees
Ho Ka Chan, Alan Diamond, Thomas Nowotny
P92 Stimulation-induced tuning of ongoing oscillations in spiking neural networks
Christoph S. Herrmann, Micah M. Murray, Silvio Ionta, Axel Hutt, Jérémie Lefebvre
P93 Decision-specific sequences of neural activity in balanced random networks driven by structured sensory input
Philipp Weidel, Renato Duarte, Abigail Morrison
P94 Modulation of tuning induced by abrupt reduction of SST cell activity
Jung H. Lee, Ramakrishnan Iyer, Stefan Mihalas
P95 The functional role of VIP cell activation during locomotion
Jung H. Lee, Ramakrishnan Iyer, Christof Koch, Stefan Mihalas
P96 Stochastic inference with spiking neural networks
Mihai A. Petrovici, Luziwei Leng, Oliver Breitwieser, David Stöckel, Ilja Bytschok, Roman Martel, Johannes Bill, Johannes Schemmel, Karlheinz Meier
P97 Modeling orientation-selective electrical stimulation with retinal prostheses
Timothy B. Esler, Anthony N. Burkitt, David B. Grayden, Robert R. Kerr, Bahman Tahayori, Hamish Meffin
P98 Ion channel noise can explain firing correlation in auditory nerves
Bahar Moezzi, Nicolangelo Iannella, Mark D. McDonnell
P99 Limits of temporal encoding of thalamocortical inputs in a neocortical microcircuit
Max Nolte, Michael W. Reimann, Eilif Muller, Henry Markram
P100 On the representation of arm reaching movements: a computational model
Antonio Parziale, Rosa Senatore, Angelo Marcelli
P101 A computational model for investigating the role of cerebellum in acquisition and retention of motor behavior
Rosa Senatore, Antonio Parziale, Angelo Marcelli
P102 The emergence of semantic categories from a large-scale brain network of semantic knowledge
K. Skiker, M. Maouene
P103 Multiscale modeling of M1 multitarget pharmacotherapy for dystonia
Samuel A. Neymotin, Salvador Dura-Bernal, Alexandra Seidenstein, Peter Lakatos, Terence D. Sanger, William W. Lytton
P104 Effect of network size on computational capacity
Salvador Dura-Bernal, Rosemary J. Menzies, Campbell McLauchlan, Sacha J. van Albada, David J. Kedziora, Samuel Neymotin, William W. Lytton, Cliff C. Kerr
P105 NetPyNE: a Python package for NEURON to facilitate development and parallel simulation of biological neuronal networks
Salvador Dura-Bernal, Benjamin A. Suter, Samuel A. Neymotin, Cliff C. Kerr, Adrian Quintana, Padraig Gleeson, Gordon M. G. Shepherd, William W. Lytton
P107 Inter-areal and inter-regional inhomogeneity in co-axial anisotropy of Cortical Point Spread in human visual areas
Juhyoung Ryu, Sang-Hun Lee
P108 Two bayesian quanta of uncertainty explain the temporal dynamics of cortical activity in the non-sensory areas during bistable perception
Joonwon Lee, Sang-Hun Lee
P109 Optimal and suboptimal integration of sensory and value information in perceptual decision making
Hyang Jung Lee, Sang-Hun Lee
P110 A Bayesian algorithm for phoneme Perception and its neural implementation
Daeseob Lim, Sang-Hun Lee
P111 Complexity of EEG signals is reduced during unconsciousness induced by ketamine and propofol
Jisung Wang, Heonsoo Lee
P112 Self-organized criticality of neural avalanche in a neural model on complex networks
Nam Jung, Le Anh Quang, Seung Eun Maeng, Tae Ho Lee, Jae Woo Lee
P113 Dynamic alterations in connection topology of the hippocampal network during ictal-like epileptiform activity in an in vitro rat model
Chang-hyun Park, Sora Ahn, Jangsup Moon, Yun Seo Choi, Juhee Kim, Sang Beom Jun, Seungjun Lee, Hyang Woon Lee
P114 Computational model to replicate seizure suppression effect by electrical stimulation
Sora Ahn, Sumin Jo, Eunji Jun, Suin Yu, Hyang Woon Lee, Sang Beom Jun, Seungjun Lee
P115 Identifying excitatory and inhibitory synapses in neuronal networks from spike trains using sorted local transfer entropy
Felix Goetze, Pik-Yin Lai
P116 Neural network model for obstacle avoidance based on neuromorphic computational model of boundary vector cell and head direction cell
Seonghyun Kim, Jeehyun Kwag
P117 Dynamic gating of spike pattern propagation by Hebbian and anti-Hebbian spike timing-dependent plasticity in excitatory feedforward network model
Hyun Jae Jang, Jeehyun Kwag
P118 Inferring characteristics of input correlations of cells exhibiting up-down state transitions in the rat striatum
Marko Filipović, Ramon Reig, Ad Aertsen, Gilad Silberberg, Arvind Kumar
P119 Graph properties of the functional connected brain under the influence of Alzheimer’s disease
Claudia Bachmann, Simone Buttler, Heidi Jacobs, Kim Dillen, Gereon R. Fink, Juraj Kukolja, Abigail Morrison
P120 Learning sparse representations in the olfactory bulb
Daniel Kepple, Hamza Giaffar, Dima Rinberg, Steven Shea, Alex Koulakov
P121 Functional classification of homologous basal-ganglia networks
Jyotika Bahuguna,Tom Tetzlaff, Abigail Morrison, Arvind Kumar, Jeanette Hellgren Kotaleski
P122 Short term memory based on multistability
Tim Kunze, Andre Peterson, Thomas Knösche
P123 A physiologically plausible, computationally efficient model and simulation software for mammalian motor units
Minjung Kim, Hojeong Kim
P125 Decoding laser-induced somatosensory information from EEG
Ji Sung Park, Ji Won Yeon, Sung-Phil Kim
P126 Phase synchronization of alpha activity for EEG-based personal authentication
Jae-Hwan Kang, Chungho Lee, Sung-Phil Kim
P129 Investigating phase-lags in sEEG data using spatially distributed time delays in a large-scale brain network model
Andreas Spiegler, Spase Petkoski, Matias J. Palva, Viktor K. Jirsa
P130 Epileptic seizures in the unfolding of a codimension-3 singularity
Maria L. Saggio, Silvan F. Siep, Andreas Spiegler, William C. Stacey, Christophe Bernard, Viktor K. Jirsa
P131 Incremental dimensional exploratory reasoning under multi-dimensional environment
Oh-hyeon Choung, Yong Jeong
P132 A low-cost model of eye movements and memory in personal visual cognition
Yong-il Lee, Jaeseung Jeong
P133 Complex network analysis of structural connectome of autism spectrum disorder patients
Su Hyun Kim, Mir Jeong, Jaeseung Jeong
P134 Cognitive motives and the neural correlates underlying human social information transmission, gossip
Jeungmin Lee, Jaehyung Kwon, Jerald D. Kralik, Jaeseung Jeong
P135 EEG hyperscanning detects neural oscillation for the social interaction during the economic decision-making
Jaehwan Jahng, Dong-Uk Hwang, Jaeseung Jeong
P136 Detecting purchase decision based on hyperfrontality of the EEG
Jae-Hyung Kwon, Sang-Min Park, Jaeseung Jeong
P137 Vulnerability-based critical neurons, synapses, and pathways in the Caenorhabditis elegans connectome
Seongkyun Kim, Hyoungkyu Kim, Jerald D. Kralik, Jaeseung Jeong
P138 Motif analysis reveals functionally asymmetrical neurons in C. elegans
Pyeong Soo Kim, Seongkyun Kim, Hyoungkyu Kim, Jaeseung Jeong
P139 Computational approach to preference-based serial decision dynamics: do temporal discounting and working memory affect it?
Sangsup Yoon, Jaehyung Kwon, Sewoong Lim, Jaeseung Jeong
P141 Social stress induced neural network reconfiguration affects decision making and learning in zebrafish
Choongseok Park, Thomas Miller, Katie Clements, Sungwoo Ahn, Eoon Hye Ji, Fadi A. Issa
P142 Descriptive, generative, and hybrid approaches for neural connectivity inference from neural activity data
JeongHun Baek, Shigeyuki Oba, Junichiro Yoshimoto, Kenji Doya, Shin Ishii
P145 Divergent-convergent synaptic connectivities accelerate coding in multilayered sensory systems
Thiago S. Mosqueiro, Martin F. Strube-Bloss, Brian Smith, Ramon Huerta
P146 Swinging networks
Michal Hadrava, Jaroslav Hlinka
P147 Inferring dynamically relevant motifs from oscillatory stimuli: challenges, pitfalls, and solutions
Hannah Bos, Moritz Helias
P148 Spatiotemporal mapping of brain network dynamics during cognitive tasks using magnetoencephalography and deep learning
Charles M. Welzig, Zachary J. Harper
P149 Multiscale complexity analysis for the segmentation of MRI images
Won Sup Kim, In-Seob Shin, Hyeon-Man Baek, Seung Kee Han
P150 A neuro-computational model of emotional attention
René Richter, Julien Vitay, Frederick Beuth, Fred H. Hamker
P151 Multi-site delayed feedback stimulation in parkinsonian networks
Kelly Toppin, Yixin Guo
P152 Bistability in Hodgkin–Huxley-type equations
Tatiana Kameneva, Hamish Meffin, Anthony N. Burkitt, David B. Grayden
P153 Phase changes in postsynaptic spiking due to synaptic connectivity and short term plasticity: mathematical analysis of frequency dependency
Mark D. McDonnell, Bruce P. Graham
P154 Quantifying resilience patterns in brain networks: the importance of directionality
Penelope J. Kale, Leonardo L. Gollo
P155 Dynamics of rate-model networks with separate excitatory and inhibitory populations
Merav Stern, L. F. Abbott
P156 A model for multi-stable dynamics in action recognition modulated by integration of silhouette and shading cues
Leonid A. Fedorov, Martin A. Giese
P157 Spiking model for the interaction between action recognition and action execution
Mohammad Hovaidi Ardestani, Martin Giese
P158 Surprise-modulated belief update: how to learn within changing environments?
Mohammad Javad Faraji, Kerstin Preuschoff, Wulfram Gerstner
P159 A fast, stochastic and adaptive model of auditory nerve responses to cochlear implant stimulation
Margriet J. van Gendt, Jeroen J. Briaire, Randy K. Kalkman, Johan H. M. Frijns
P160 Quantitative comparison of graph theoretical measures of simulated and empirical functional brain networks
Won Hee Lee, Sophia Frangou
P161 Determining discriminative properties of fMRI signals in schizophrenia using highly comparative time-series analysis
Ben D. Fulcher, Patricia H. P. Tran, Alex Fornito
P162 Emergence of narrowband LFP oscillations from completely asynchronous activity during seizures and high-frequency oscillations
Stephen V. Gliske, William C. Stacey, Eugene Lim, Katherine A. Holman, Christian G. Fink
P163 Neuronal diversity in structure and function: cross-validation of anatomical and physiological classification of retinal ganglion cells in the mouse
Jinseop S. Kim, Shang Mu, Kevin L. Briggman, H. Sebastian Seung, the EyeWirers
P164 Analysis and modelling of transient firing rate changes in area MT in response to rapid stimulus feature changes
Detlef Wegener, Lisa Bohnenkamp, Udo A. Ernst
P165 Step-wise model fitting accounting for high-resolution spatial measurements: construction of a layer V pyramidal cell model with reduced morphology
Tuomo Mäki-Marttunen, Geir Halnes, Anna Devor, Christoph Metzner, Anders M. Dale, Ole A. Andreassen, Gaute T. Einevoll
P166 Contributions of schizophrenia-associated genes to neuron firing and cardiac pacemaking: a polygenic modeling approach
Tuomo Mäki-Marttunen, Glenn T. Lines, Andy Edwards, Aslak Tveito, Anders M. Dale, Gaute T. Einevoll, Ole A. Andreassen
P167 Local field potentials in a 4 × 4 mm2 multi-layered network model
Espen Hagen, Johanna Senk, Sacha J. van Albada, Markus Diesmann
P168 A spiking network model explains multi-scale properties of cortical dynamics
Maximilian Schmidt, Rembrandt Bakker, Kelly Shen, Gleb Bezgin, Claus-Christian Hilgetag, Markus Diesmann, Sacha Jennifer van Albada
P169 Using joint weight-delay spike-timing dependent plasticity to find polychronous neuronal groups
Haoqi Sun, Olga Sourina, Guang-Bin Huang, Felix Klanner, Cornelia Denk
P170 Tensor decomposition reveals RSNs in simulated resting state fMRI
Katharina Glomb, Adrián Ponce-Alvarez, Matthieu Gilson, Petra Ritter, Gustavo Deco
P171 Getting in the groove: testing a new model-based method for comparing task-evoked vs resting-state activity in fMRI data on music listening
Matthieu Gilson, Maria AG Witek, Eric F. Clarke, Mads Hansen, Mikkel Wallentin, Gustavo Deco, Morten L. Kringelbach, Peter Vuust
P172 STochastic engine for pathway simulation (STEPS) on massively parallel processors
Guido Klingbeil, Erik De Schutter
P173 Toolkit support for complex parallel spatial stochastic reaction–diffusion simulation in STEPS
Weiliang Chen, Erik De Schutter
P174 Modeling the generation and propagation of Purkinje cell dendritic spikes caused by parallel fiber synaptic input
Yunliang Zang, Erik De Schutter
P175 Dendritic morphology determines how dendrites are organized into functional subunits
Sungho Hong, Akira Takashima, Erik De Schutter
P176 A model of Ca2+/calmodulin-dependent protein kinase II activity in long term depression at Purkinje cells
Criseida Zamora, Andrew R. Gallimore, Erik De Schutter
P177 Reward-modulated learning of population-encoded vectors for insect-like navigation in embodied agents
Dennis Goldschmidt, Poramate Manoonpong, Sakyasingha Dasgupta
P178 Data-driven neural models part II: connectivity patterns of human seizures
Philippa J. Karoly, Dean R. Freestone, Daniel Soundry, Levin Kuhlmann, Liam Paninski, Mark Cook
P179 Data-driven neural models part I: state and parameter estimation
Dean R. Freestone, Philippa J. Karoly, Daniel Soundry, Levin Kuhlmann, Mark Cook
P180 Spectral and spatial information processing in human auditory streaming
Jaejin Lee, Yonatan I. Fishman, Yale E. Cohen
P181 A tuning curve for the global effects of local perturbations in neural activity: Mapping the systems-level susceptibility of the brain
Leonardo L. Gollo, James A. Roberts, Luca Cocchi
P182 Diverse homeostatic responses to visual deprivation mediated by neural ensembles
Yann Sweeney, Claudia Clopath
P183 Opto-EEG: a novel method for investigating functional connectome in mouse brain based on optogenetics and high density electroencephalography
Soohyun Lee, Woo-Sung Jung, Jee Hyun Choi
P184 Biphasic responses of frontal gamma network to repetitive sleep deprivation during REM sleep
Bowon Kim, Youngsoo Kim, Eunjin Hwang, Jee Hyun Choi
P185 Brain-state correlate and cortical connectivity for frontal gamma oscillations in top-down fashion assessed by auditory steady-state response
Younginha Jung, Eunjin Hwang, Yoon-Kyu Song, Jee Hyun Choi
P186 Neural field model of localized orientation selective activation in V1
James Rankin, Frédéric Chavane
P187 An oscillatory network model of Head direction and Grid cells using locomotor inputs
Karthik Soman, Vignesh Muralidharan, V. Srinivasa Chakravarthy
P188 A computational model of hippocampus inspired by the functional architecture of basal ganglia
Karthik Soman, Vignesh Muralidharan, V. Srinivasa Chakravarthy
P189 A computational architecture to model the microanatomy of the striatum and its functional properties
Sabyasachi Shivkumar, Vignesh Muralidharan, V. Srinivasa Chakravarthy
P190 A scalable cortico-basal ganglia model to understand the neural dynamics of targeted reaching
Vignesh Muralidharan, Alekhya Mandali, B. Pragathi Priyadharsini, Hima Mehta, V. Srinivasa Chakravarthy
P191 Emergence of radial orientation selectivity from synaptic plasticity
Catherine E. Davey, David B. Grayden, Anthony N. Burkitt
P192 How do hidden units shape effective connections between neurons?
Braden A. W. Brinkman, Tyler Kekona, Fred Rieke, Eric Shea-Brown, Michael Buice
P193 Characterization of neural firing in the presence of astrocyte-synapse signaling
Maurizio De Pittà, Hugues Berry, Nicolas Brunel
P194 Metastability of spatiotemporal patterns in a large-scale network model of brain dynamics
James A. Roberts, Leonardo L. Gollo, Michael Breakspear
P195 Comparison of three methods to quantify detection and discrimination capacity estimated from neural population recordings
Gary Marsat, Jordan Drew, Phillip D. Chapman, Kevin C. Daly, Samual P. Bradley
P196 Quantifying the constraints for independent evoked and spontaneous NMDA receptor mediated synaptic transmission at individual synapses
Sat Byul Seo, Jianzhong Su, Ege T. Kavalali, Justin Blackwell
P199 Gamma oscillation via adaptive exponential integrate-and-fire neurons
LieJune Shiau, Laure Buhry, Kanishka Basnayake
P200 Visual face representations during memory retrieval compared to perception
Sue-Hyun Lee, Brandon A. Levy, Chris I. Baker
P201 Top-down modulation of sequential activity within packets modeled using avalanche dynamics
Timothée Leleu, Kazuyuki Aihara
Q28 An auto-encoder network realizes sparse features under the influence of desynchronized vascular dynamics
Ryan T. Philips, Karishma Chhabria, V. Srinivasa Chakravarthy
PMCID: PMC5001212  PMID: 27534393
25.  Catechol-O-methyltransferase (COMT) influences the connectivity of the prefrontal cortex at rest 
Neuroimage  2013;68:49-54.
Catechol-O-methyltransferase (COMT) modulates dopamine in the prefrontal cortex (PFC) and influences PFC dopamine-dependent cognitive task performance. A human COMT polymorphism (Val158Met) alters enzyme activity and is associated with both the activation and functional connectivity of the PFC during task performance, particularly working memory. Here, we used functional magnetic resonance imaging and a data-driven, independent components analysis (ICA) approach to compare resting state functional connectivity within the executive control network (ECN) between young, male COMT Val158 (n = 27) and Met158 (n = 28) homozygotes. COMT genotype effects on grey matter were assessed using voxel-based morphometry. COMT genotype significantly modulated functional connectivity within the ECN, which included the head of the caudate, and anterior cingulate and frontal cortical regions. Val158 homozygotes showed greater functional connectivity between a cluster within the left ventrolateral PFC and the rest of the ECN (using a threshold of Z > 2.3 and a family-wise error cluster significance level of p < 0.05). This difference occurred in the absence of any alterations in grey matter. Our data show that COMT Val158Met affects the functional connectivity of the PFC at rest, complementing its prominent role in the activation and functional connectivity of this region during cognitive task performance. The results suggest that genotype-related differences in prefrontal dopaminergic tone result in neuroadaptive changes in basal functional connectivity, potentially including subtle COMT genotype-dependent differences in the relative coupling of task-positive and task-negative regions, which could in turn contribute to its effects on brain activation, connectivity, and behaviour.
► We studied the impact of COMT Val158Met genotype on resting state connectivity. ► We compared resting state functional connectivity in Val/Val vs. Met/Met men. ► We focussed on the predominantly prefrontal (PFC) executive control network (ECN). ► The ECN was identified using a group ICA approach. ► We found greater resting PFC functional connectivity in Val/Val vs. Met/Met men.
PMCID: PMC3566589  PMID: 23228511
Resting state network; Dopamine; Working memory; Prefrontal cortex; Polymorphism; fMRI

Results 1-25 (1948320)