Biology subjects

Peters, J.

Publications and source records attributed to Peters, J..

At least 91 records · Page 5Linked to original sources

bioRxiv2020

Temporal discounting in adolescents and adults with Tourette syndrome

BackgroundTourette syndrome is a neurodevelopmental disorder with the clinical hallmarks of motor and phonic tics which are associated with hyperactivity in dopaminergic networks. Dopaminergic hyperactivity in the basal ganglia has previously been linked to increased sensitivity to positive reinforcement and increases in choice impulsivity. ObjectiveWe address whether this extends to changes in temporal discounting, where impulsivity is operationalized as an increased preference to choose smaller-but-sooner over larger-but-later rewards. Results are discussed with respect to neural models of temporal discounting, dopaminergic alterations in Tourette syndrome and the developmental trajectory of temporal discounting. MethodsIn the first study we included nineteen adolescent patients with Tourette syndrome and nineteen age- and education matched controls. In the second study, we compared twenty-five adult patients with Tourette syndrome and twenty-five age- and education-matched controls. ResultsIn the light of the dopaminergic hyperactivity model, we predicted differences in temporal discounting in patients with Tourette syndrome. However, computational modeling of choice behavior using hierarchical Bayesian parameter estimation revealed reduced impulsive choice in adolescent patients, and no group differences in adults. ConclusionWe speculate that adolescents might show reduced discounting due to improved inhibitory functions that also affect choice impulsivity and/or the developmental trajectory of executive control functions. The absence of an effect in adults might be due to differences in the clinical population (e.g. patients who acquired successful tic inhibition during adolescence might have gone into remission). Future studies would benefit from adopting longitudinal approaches to further elucidate the developmental trajectory of these effects.

neuroscience↗

bioRxiv2020

Dopaminergic modulation of human inter-temporal choice: a diffusion model analysis using the D2-receptor-antagonist haloperidol.

The neurotransmitter dopamine is implicated in diverse functions, including reward processing, reinforcement learning and cognitive control. The tendency to discount future rewards in value over time has long been discussed in the context of potential dopaminergic modulation. Here we examined the effect of a single dose of the D2 receptor antagonist Haloperidol (2mg) on temporal discounting. Our approach extends previous human pharmacological studies in two ways. First, we applied state-of-the-art computational modeling based on the drift diffusion model to comprehensively examine choice dynamics. Second, we examined dopaminergic modulation of reward magnitude effects on temporal discounting. Drift diffusion modeling revealed reduced temporal discounting and substantially faster non-decision times under Haloperidol. Temporal discounting was substantially increased for low vs. high reward magnitudes, but this magnitude effect was largely unaffected by Haloperidol. These results were corroborated by model-free analyses as well as modeling via more standard approaches using softmax action selection. We previously reported elevated caudate activation under Haloperidol in this sample of participants, supporting the idea that Haloperidol elevated dopamine neurotransmission, e.g. by blocking inhibitory feedback via presynaptic D2 autoreceptors. The present modeling results show that during inter-temporal choice, this leads to attenuated temporal discounting and increased response vigor (shorter non-decision times).

neuroscience↗

bioRxiv2019

Attenuated directed exploration during reinforcement learning in gambling disorder

Gambling disorder is a behavioral addiction associated with impairments in value-based decision-making and behavioral flexibility and might be linked to changes in the dopamine system. Maximizing long-term rewards requires a flexible trade-off between the exploitation of known options and the exploration of novel options for information gain. This exploration-exploitation trade-off is thought to depend on dopamine neurotransmission. We hypothesized that human gamblers would show a reduction in directed (uncertainty-based) exploration, accompanied by changes in brain activity in a fronto-parietal exploration-related network. Twenty-three frequent, non-treatment seeking gamblers and twenty-three healthy matched controls (all male) performed a four-armed bandit task during functional magnetic resonance-imaging. Computational modeling using hierarchical Bayesian parameter estimation revealed signatures of directed exploration, random exploration, and perseveration in both groups. Gamblers showed a reduction in directed exploration, whereas random exploration and perseveration were similar between groups. Neuroimaging revealed no evidence for group differences in neural representations of basic task variables (expected value, prediction errors). Our hypothesis of reduced frontal pole recruitment in gamblers was not supported. Exploratory analyses revealed that during directed exploration, gamblers showed reduced parietal cortex and substantia-nigra / ventral-tegmental-area activity. Cross-validated classification analyses revealed that connectivity in an exploration-related network was predictive of group status, suggesting that connectivity patterns might be more predictive of problem gambling than univariate effects. Findings reveal specific reductions in strategic exploration gamblers that might be linked to altered processing in a fronto-parietal network and/or changes in dopamine neurotransmission implicated in gambling disorder. Significance statementWiehler et al. report that gamblers rely less on the strategic exploration of unknown, but potentially better rewards during reward learning. This is reflected in a related network of brain activity. Parameters of this network can be used to predict the presence of problem gambling behavior in participants.

neuroscience↗

bioRxiv2019

Dopamine and risky decision-making in pathological and problem gamblers.

Gambling disorder is a behavioral addiction that is associated with impairments in value-based decision-making such as increased temporal discounting and reduced risk-aversion. Dopamine regulates learning and decision-making by modulating information processing throughout fronto-striatal circuits. Although the role of alterations in dopamine neurotransmission in the etiology of gambling disorder is controversial, preliminary evidence suggests that specifically increasing frontal dopamine levels might improve cognitive functioning in pathological and problem gamblers. We therefore examined whether increasing frontal dopamine levels via the catechol-O-methyltransferase (COMT) inhibitor tolcapone would reduce risky choice in a group of pathological and problem gamblers (n=14) in a repeated-measures counter-balanced placebo-controlled double-blind study. Choice data were fit using hierarchical Bayesian parameter estimation and a modeling scheme that combined a risky choice model with the drift diffusion model to account for both choices and response time distributions. Model comparison revealed that the data were best accounted for by a variant of the drift diffusion model with a non-linear modulation of trial-wise drift rates by value differences, confirming recent findings. Contrary to our hypothesis, risk-taking was slightly increased under tolcapone vs. placebo (Cohens d = -.281). Examination of drug effects on diffusion model parameters revealed an increase in the value-dependency of the drift rate (Cohens d = .932) with a simultaneous reduction in the maximum drift rate (Cohens d = -1.84). These results add to previous work on the potential role of COMT inhibitors in behavioral addictions, and show no consistent beneficial effect of tolcapone on risky choice in gambling disorder. Modeling results add to mounting evidence for the applicability of diffusion models in value-based decision-making. Future work should focus on individual genetic, clinical and cognitive factors that might account for the heterogeneity in the effects of COMT inhibition.

neuroscience↗

bioRxiv2019

Modeling and treating GRIN2A developmental and epileptic encephalopathy in mice

NMDA receptors (NMDAR) play crucial roles in excitatory synaptic transmission. Rare variants of GRIN2A, which encodes the GluN2A NMDAR subunit, are associated with several intractable neurodevelopmental disorders, including developmental and epileptic encephalopathy (DEE). A de novo missense variant, p.Ser644Gly (c.1930A>G), was identified in a child with DEE, and Grin2a knockin mice were generated to model and extend understanding of this intractable childhood disease. Homozygous and heterozygous mutant mice exhibit altered hippocampal morphology at two weeks of age, and homozygotes exhibit lethal tonic-clonic seizures in the third week. Heterozygous adult mice display a variety of distinct features, including resistance to electrically induced partial seizures, as well as hyperactivity and repetitive and reduced anxiety behaviors. Multielectrode recordings of mutant neuronal networks reveal hyperexcitability and altered bursting and synchronicity. When expressed in heterologous cells, mutant receptors exhibit enhanced NMDAR agonist potency and slow deactivation following rapid removal of glutamate, as occurs at synapses. Consistent with these observations, NMDAR-mediated synaptic currents in hippocampal slices from mutant mice show a prolonged deactivation time course. Standard antiepileptic drug monotherapy was ineffective in the patient, but combined treatment of NMDAR antagonists with antiepileptic drugs substantially reduced the seizure burden albeit without appreciable developmental improvement. Chronic treatment of homozygous mutant mouse pups with NMDAR antagonists delayed the onset of lethal seizures but did not prevent them. These studies illustrate the power of modeling severe neurodevelopmental seizure disorders using multiple experimental modalities and suggest their extended utility in identifying and evaluating new therapies.

neuroscience↗

bioRxiv2019

Dopaminergic modulation of the exploration/exploitation trade-off in human decision-making

A central issue in reinforcement learning and decision-making is whether to exploit knowledge of reward values, or to explore novel options. Although it is widely hypothesized that dopamine neurotransmission plays a key role in regulating this balance, causal evidence for a role of dopamine in human exploration is still lacking. Here, we use a combination of computational modeling, pharmacological intervention and functional magnetic resonance imaging (fMRI) to test for a causal effect of dopamine transmission on the exploration-exploitation trade-off in humans. 31 healthy male subjects performed a restless four-armed bandit task in a within-subjects design under three drug conditions: 150mg of the dopamine precursor L-dopa, 2mg of the D2 receptor antagonist haloperidol, and placebo. In all conditions, choice behavior was best explained by an extension of an established Bayesian learning model accounting for perseveration, uncertainty-based exploration and random exploration. Uncertainty-based exploration was attenuated under L-dopa compared to placebo and haloperidol. There was no evidence for a modulation of prediction error signaling or categorical effects of exploration/exploitation under L-dopa, whereas model-based fMRI revealed that L-dopa attenuated neural representations of overall uncertainty in insula and dorsal anterior cingulate cortex. Our results highlight the computational role of these regions in exploration and suggest that dopamine modulates exploration by modulating how this circuit tracks accumulating uncertainty during decision-making.

neuroscience↗

bioRxiv2019

Genetic determinants of lipids and cardiovascular disease outcomes: a wide-angled Mendelian randomization investigation

AimsTo systematically investigate causal relationships between circulating lipids and cardiovascular outcomes, using a Mendelian randomization approach.\n\nMethods and ResultsIn the primary analysis, we performed two-sample multivariable Mendelian randomization using data from participants of European ancestry. We also conducted univariable analyses using inverse-variance weighted and robust methods, and gene-specific analyses using variants that can be considered as proxies for specific lipid-lowering medications. We obtained associations with lipid fractions from the Global Lipids Genetics Consortium, a meta-analysis of 188,577 participants, and genetic associations with cardiovascular outcomes from 367,703 participants in UK Biobank.\n\nFor LDL-cholesterol, in addition to the expected positive associations with coronary artery disease (CAD) risk (odds ratio per 1 standard deviation increase [OR], 1.45; 95% confidence interval [95%CI] 1.35-1.57) and other atheromatous outcomes (ischemic cerebrovascular disease and peripheral vascular disease), we found independent associations of genetically-predicted LDL-cholesterol with abdominal aortic aneurysm (OR 1.75; 95%CI 1.40-2.17), and aortic valve stenosis (OR 1.46; 95%CI 1.25-1.70). Genetically-predicted triglyceride levels were positively associated with CAD (OR 1.25; 95%CI 1.12-1.40), aortic valve stenosis (OR 1.29; 95%CI 1.04-1.61), and hypertension (OR 1.17; 95%CI 1.07-1.27), but inversely associated with venous thromboembolism (OR 0.79; 95%CI 0.67-0.93). The positive associations of genetically-predicted LDL-cholesterol and triglycerides with heart failure and aortic stenosis appeared to be mediated by CAD.\n\nConclusionLowering LDL-cholesterol is likely to prevent abdominal aortic aneurysm and aortic stenosis, in addition to CAD and other atheromatous cardiovascular outcomes. Lowering triglycerides is likely to prevent CAD and aortic valve stenosis, but may increase risk of thromboembolism.

epidemiology↗

bioRxiv2019

The drift diffusion model as the choice rule in inter-temporal and risky choice: a case study in medial orbitofrontal cortex lesion patients and controls.

Sequential sampling models such as the drift diffusion model have a long tradition in research on perceptual decision-making, but mounting evidence suggests that these models can account for response time distributions that arise during reinforcement learning and value-based decision-making. Building on this previous work, we implemented the drift diffusion model as the choice rule in inter-temporal choice (temporal discounting) and risky choice (probability discounting) using a hierarchical Bayesian estimation scheme. We validated our approach in data from nine patients with focal lesions to the ventromedial prefrontal cortex / medial orbitofrontal cortex (vmPFC/mOFC) and nineteen age- and education-matched controls. Choice model parameters estimated via standard softmax action selection were reliably reproduced using the drift diffusion model as the choice rule, both for temporal discounting and risky choice. Model comparison revealed that, for both tasks, the data were best accounted for by a variant of the drift diffusion model including a non-linear mapping from value-differences to trial-wise drift rates. Posterior predictive checks of the winning models revealed a reasonably good fit to individual participants reaction time distributions. We then applied this modeling framework and 1) reproduced our previous results regarding temporal discounting in vmPFC/mOFC patients and 2) showed in a previously unpublished data set on risky choice that vmPFC/mOFC patients exhibit increased risk-taking relative to controls. Analyses of diffusion model parameters revealed that vmPFC/mOFC damage abolished neither value sensitivity nor asymptote of the drift rate. Rather, it substantially increased non-decision times and reduced response caution during risky choice. Our results highlight that novel insights can be gained from applying sequential sampling models in studies of inter-temporal and risky decision-making in cognitive neuroscience.

neuroscience↗

bioRxiv2019

Modulating pathogenesis with Mobile-CRISPRi

Pathogens express a set of proteins required for establishing and maintaining an infection, termed virulence life-style genes (VLGs). Due to their outsized importance in pathogenesis, VLG products are attractive targets for the next generation of antimicrobials. However, precise manipulation of VLG expression in the context of infection is technically challenging, limiting our ability to understand the roles of VLGs in pathogenesis and accordingly design effective inhibitors. We previously developed a suite of gene knockdown tools that are transferred by conjugation and stably integrate into pathogen genomes that we call \"Mobile-CRISPRi\". Here we show the efficacy of Mobile-CRISPRi in controlling VLG expression in a murine infection model. We optimize Mobile-CRISPRi in Pseudomonas aeruginosa for use in a murine model of pneumonia by tuning the expression of CRISPRi components to avoid non-specific toxicity. As a proof of principle, we demonstrate that knockdown of a VLG encoding the type III secretion system (T3SS) activator ExsA blocks effector protein secretion in culture and attenuates virulence in mice. We anticipate that Mobile-CRISPRi will be a valuable tool to probe the function of VLGs across many bacterial species and pathogenesis models.\n\nImportanceAntibiotic resistance is a growing threat to global health. To optimize the use of our existing antibiotics and identify new targets for future inhibitors, understanding the fundamental drivers of bacterial growth in the context of the host immune response is paramount. Historically these genetic drivers have been difficult to manipulate, as they are requisite for pathogen survival. Here, we provide the first application of Mobile-CRISPRi to study virulence life-style genes in mouse models of lung infection through partial gene perturbation. We envision the use of Mobile-CRISPRi in future pathogenesis models and antibiotic target discovery efforts.

microbiology↗

bioRxiv2018

Genetically distinct clinical subsets, and associations with asthma and eosinophil abundance, within Eosinophilic Granulomatosis with Polyangiitis

Eosinophilic granulomatosis with polyangiitis (EGPA: formerly Churg-Strauss syndrome) is a rare inflammatory disease of unknown cause. 30% of patients have anti-neutrophil cytoplasm antibodies (ANCA) specific for myeloperoxidase (MPO). We performed a genome-wide association study (GWAS) of EGPA, testing 7.5 million genetic variants in 684 cases and 6,838 controls. Case-control analyses were performed for EGPA as a whole, and stratified by ANCA. To increase power, we used a conditional false discovery rate method to leverage findings from GWASs of related phenotypes. In total, 11 variants were associated with EGPA, two specifically with ANCA-negative EGPA, and one (HLA-DQ) with MPO+ANCA EGPA. Many variants were associated with asthma, eosinophilic and immune-mediated diseases and, strikingly, nine were associated with eosinophil count in the general population. Through Mendelian randomisation, we show that a primary tendency to eosinophilia underlies EGPA susceptibility. We demonstrate that EGPA comprises two genetically and clinically distinct syndromes, with ANCA-negative EGPA genetically more similar to asthma. MPO+ ANCA EGPA is an eosinophilic autoimmune disease sharing certain clinical features and an MHC association with MPO+ ANCA-associated vasculitis, while ANCA-negative EGPA may instead have a mucosal/barrier dysfunction origin. Five identified candidate genes are targets of therapies in development, supporting their exploration in EGPA.

genetics↗

bioRxiv2018

A phylogeography of the second plague pandemic revealed through the analysis of historical Y. pestis genomes

The second plague pandemic (14th - 18th century AD), caused by the bacterium Yersinia pestis, is infamous for its initial wave, the Black Death (1346-1353 AD), and its repeated scourges in Europe and the vicinity until the Early Modern Era. Here, we report 32 ancient Y. pestis genomes spanning the 14th to 17th century AD through the analysis of human remains from nine European archaeological sites. Our data support an initial entry of the bacterium from Eastern Europe and the absence of genetic diversity during the Black Death as well as low diversity during local outbreaks thereafter. Moreover, analysis of post-Black Death genomes shows the diversification of a Y. pestis lineage into multiple genetically distinct clades that may have given rise to more than one disease reservoir in, or close to, Europe. Finally, we show the loss of a genomic region that includes virulence-associated genes in strains associated with late stages of the second plague pandemic (17th - 18th century AD). This deletion could not be detected in extant strains within our modern dataset, though it was identified in a today-extinct lineage associated with the first plague pandemic (6th - 8th century AD), suggesting convergent evolution during both pandemic events.

evolutionary biology↗

bioRxiv2018

Ancient Yersinia pestis genomes from across Western Europe reveal early diversification during the First Pandemic (541-750)

The first historically documented pandemic caused by Yersinia pestis started as the Justinianic Plague in 541 within the Roman Empire and continued as the so-called First Pandemic until 750. Although palaeogenomic studies have previously identified the causative agent as Y. pestis, little is known about the bacteriums spread, diversity and genetic history over the course of the pandemic.\n\nTo elucidate the microevolution of the bacterium during this time period, we screened human remains from 20 sites in Austria, Britain, Germany, France and Spain for Y. pestis DNA and reconstructed six new genomes. We present a novel methodological approach assessing SNPs in ancient bacterial genomes, facilitating qualitative analyses of low coverage genomes from a metagenomic background. Phylogenetic analysis reveals the existence of previously undocumented Y. pestis diversity during the 6th-7th centuries, and provides evidence for the presence of multiple distinct Y. pestis strains in Europe. We offer genetic evidence for the presence of the Justinianic Plague in the British Isles, previously only hypothesized from ambiguous documentary accounts, as well as southern France and Spain, and that southern Germany seems to have been affected by at least two distinct Y. pestis strains. Four of the reported strains form a polytomy similar to others seen across the Y. pestis phylogeny, associated with the Second and Third Pandemics. We identified a deletion of a 45 kb genomic region in the most recent First Pandemic strain affecting two virulence factors, intriguingly overlapping with a deletion found in 17th-18th-century genomes of the Second Pandemic.\n\nSignificance StatementThe first historically reported pandemic attributed to Yersinia pestis started with the Justinianic Plague (541-544) and continued for around 200 years as the so-called First Pandemic. To date, only one Y. pestis strain from this pandemic has been reconstructed using ancient DNA. In this study, we present six new genomes from Britain, France, Germany and Spain, demonstrating the geographic range of plague during the First pandemic and showing microdiversity in the Early Medieval Period. Moreover, we detect similar genome decay during the First and Second Pandemic (17th to 18th century) that includes the same two virulence factors, thus providing an example of potential convergent evolution of Y. pestis during large scale epidemics.

evolutionary biology↗

bioRxiv2018

Identification of a genetic element required for spore killing in Neurospora

Meiotic drive elements like Spore killer-2 (Sk-2) in Neurospora are transmitted through sexual reproduction to the next generation in a biased manner. Sk-2 achieves this biased transmission through spore killing. Here, we identify rfk-1 as a gene required for the spore killing mechanism. The rfk-1 gene is associated with a 1,481 bp DNA interval (called AH36) near the right border of the 30 cM Sk-2 element, and its deletion eliminates the ability of Sk-2 to kill spores. The rfk-1 gene also appears to be sufficient for spore killing because its insertion into a non-Sk-2 isolate disrupts sexual reproduction after the initiation of meiosis. Although the complete rfk-1 transcript has yet to be defined, our data indicate that rfk-1 encodes a protein of at least 39 amino acids and that rfk-1 has evolved from a partial duplication of gene ncu07086. We also present evidence that rfk-1s location near the right border of Sk-2 is critical for the success of spore killing. Increasing the distance of rfk-1 from the right border of Sk-2 causes it to be inactivated by a genome defense process called meiotic silencing by unpaired DNA (MSUD), adding to accumulating evidence that MSUD exists, at least in part, to protect genomes from meiotic drive.

genetics↗

bioRxiv2018

Systemically administered MSCs given 24hrs after osteotomy do not affect bone formation in rat distraction osteogenesis

Distraction osteogenesis is a unique postnatal bone formation employed by orthopaedic surgeons to treat many conditions, however, the overall time to external frame removal can be extensive. Any strategies that accelerate healing would improve patient care. Distraction osteogenesis research in the past decade has shown that direct stem cell implantation enhances new bone formation. Systemic implantation would be more clinically desirable. Systemically delivered stem cells have been shown to home to a mandibular distraction site; however, effects on bone formation have not been studied. Ten-week-old, male Sprague-Dawley rats underwent surgery to implant an external fixator-distractor and an osteotomy was performed. Twenty-four hours postoperatively, each rat received tail vein injections of either saline or 10^6 fluorescently labeled primary mesenchymal stem cells. Animals in the validation groups were euthanized two days after surgery and the femora processed for histology. Animals in the experimental groups were given five days of latency, then the femur was lengthened once daily for five days (0.75mm/day, 3.75mm total). Following four weeks of consolidation, the animals were euthanized and the femora were evaluated by microCT and histology to quantify new bone formation. Labeled stem cells were found at the distraction site in validation animals. However, there were no differences in any bone or soft tissue outcomes. Systemic stem cell administration 24 hours after surgery does not improve DO outcomes. It is possible that the animal model was not challenging enough to discriminate any augmentation provided by stem cells.

bioengineering↗

bioRxiv2018

Sleep deprivation selectively up-regulates an amygdala-hypothalamic circuit involved in food reward

Sleep loss is associated with increased obesity risk, as demonstrated by correlations between sleep duration and change in body mass index or body fat percentage. Whereas previous studies linked this weight gain to disturbed endocrine parameters after sleep deprivation (SD) or restriction, neuroimaging studies revealed up-regulated neural processing of food rewards after sleep loss in reward-processing areas such as the anterior cingulate cortex, ventral striatum and insula. To tackle this ongoing debate between homeostatic versus hedonic factors underlying sleep loss-associated weight gain, we rigorously tested the association between SD and food cue processing using high-resolution fMRI and assessment of hormones. After taking blood samples from thirty-two lean, healthy men, they underwent fMRI while performing a neuroeconomic, value-based decision making task with snack food and trinket rewards following a full night of habitual sleep (HS) and a night of SD in a repeated-measures cross-over design. We found that des-acyl ghrelin concentrations were increased after SD compared with HS. Despite similar hunger ratings due to fasting in both conditions, participants were willing to spend more money on food items only after SD. Furthermore, fMRI data paralleled this behavioral finding, revealing a food reward-specific up-regulation of hypothalamic valuation signals and amygdala-hypothalamic coupling after a single night of SD. Behavioral and fMRI results were not significantly correlated with changes in acyl, des-acyl or total ghrelin concentrations. Our results indicate that increased food valuation after sleep loss is due to hedonic rather than hormonal mechanisms.

neuroscience↗

bioRxiv2017

A potential link between gambling addiction severity and central dopamine levels -- evidence from spontaneous eye blink rates in gamblers and controls

Accumulating evidence points at similarities between substance use disorders and pathological gambling on the behavioral and neural level. In substance addiction, dysregulation of striatal dopamine transmission has been consistently revealed. Due to the neurotoxicity of stimulating substances, it is still debated if this constitutes mainly a consequence of recurrent substance abuse or a vulnerability marker for addiction disorders. For gambling addiction, no clear association with striatal dopamine levels has been unveiled so far. With its presumably negligible dopaminergic toxicity, possible differences in striatal dopamine transmission in gambling addiction might therefore constitute a vulnerability marker. Spontaneous eye blink rate (sEBR) is controversially discussed as a potential proxy measure for striatal dopamine levels. Here we examined sEBR in 21 male problem gamblers and 20 healthy control participants. In addition, participants completed a screening questionnaire for overall psychopathology and self-reported measures of alcohol and nicotine consumption. We found no significant difference in sEBR between gamblers and controls. However, in gamblers, sEBR was negatively associated with addiction severity and positively associated with psychopathology. A final exploratory analysis revealed that healthy controls with low sEBR displayed higher alcohol and nicotine consumption than healthy participants with high sEBR. Although the association between dopamine transmission and sEBR is still debated, our findings reveal that sEBR is sensitive to inter-individual differences in addiction severity in problem gamblers.

neuroscience↗

bioRxiv2017

Cortical Entropy Values Correlate With Brain Scale-Free Dynamics

A two-dimensional shadow may encompass more information than its corresponding three-dimensional object. If we rotate the object, we achieve a pool of observed shadows from different angulations, gradients, shapes and variable length contours that make it possible for us to increase our available information. Starting from this simple observation, we show how informational entropies might turn out to be useful in the evaluation of scale-free dynamics in the brain. Indeed, brain activity exhibits a scale-free distribution, which appears as a straight line when plotted in a log power versus log frequency plot. A variation in the scale-free exponent and in the line scaling slope may occur during different functional neurophysiological states. Here we show that modifications in scaling slope are associated with variations in Renyi entropy, a generalization of Shannon informational entropy. From a three-dimensional objects perspective, by changing its orientation (standing for the cortical scale-free exponent), we detect different two-dimensional shadows from different perception angles (standing for Renyi entropy in different brain areas). We perform simulations showing how, starting from known values of Renyi entropy (easily detectable in brain fMRIs or EEG traces), it is feasible to calculate the scaling slope in a given moment and a given brain area. Because changes in scale-free cortical dynamics modify brain activity, suggests the possibility of novel insights in mind reading and description of the forces required for transcranial stimulation.

neuroscience↗

bioRxiv2017

Just One Brain Activity

The term brain activity refers to a wide range of mental faculties that can be assessed either on anatomical/functional micro-, meso- and macro-spatiotemporal scales of observation, or on intertwined levels with mutual interactions. Here we show, based on novel topological findings, how every brain activity encompassed in a given anatomical or functional level necessarily displays a counterpart in others. Different brain activities are able to scatter, collide and combine, merging, condensing and stitching together in a testable and quantifiable way. We point out how, despite their local cortical functional differences, all the mental processes, from perception to emotions, from cognition to mind wandering, may be reduced to a single, general brain activity that takes place in dimensions higher than the classical 3D plus time. In physics, the term duality refers to the case where two seemingly different systems turn out to be equivalent. Our framework permits a topological duality among different brain activities and neuro-techniques, because it holds for all the types of spatio-temporal nervous functions, independent of their cortical location, inter- and intra-level relationships, strength, magnitude and boundaries.

neuroscience↗