Neuroscience Models Research Articles

Arkheia: Data Management and Communication for Open Computational Neuroscience.

Two trends have been unfolding in computational neuroscience during the last decade. First, a shift of focus to increasingly complex and heterogeneous neural network models, with a concomitant increase in the level of collaboration within the field (whether direct or in the form of building on top of existing tools and results). Second, a general trend in science toward more open communication, both internally, with other potential scientific collaborators, and externally, with the wider public. This multi-faceted development toward more integrative approaches and more intense communication within and outside of the field poses major new challenges for modelers, as currently there is a severe lack of tools to help with automatic communication and sharing of all aspects of a simulation workflow to the rest of the community. To address this important gap in the current computational modeling software infrastructure, here we introduce Arkheia. Arkheia is a web-based open science platform for computational models in systems neuroscience. It provides an automatic, interactive, graphical presentation of simulation results, experimental protocols, and interactive exploration of parameter searches, in a web browser-based application. Arkheia is focused on automatic presentation of these resources with minimal manual input from users. Arkheia is written in a modular fashion with a focus on future development of the platform. The platform is designed in an open manner, with a clearly defined and separated API for database access, so that any project can write its own backend translating its data into the Arkheia database format. Arkheia is not a centralized platform, but allows any user (or group of users) to set up their own repository, either for public access by the general population, or locally for internal use. Overall, Arkheia provides users with an automatic means to communicate information about not only their models but also individual simulation results and the entire experimental context in an approachable graphical manner, thus facilitating the user's ability to collaborate in the field and outreach to a wider audience.

A Neuroscience-Oriented Research Approach to Borderline Personality Disorder

Traditionally, the study of personality disorders had been based on psychoanalytic or behavioral models. Over the past two decades, there has been an emerging neuroscience model of borderline personality disorder (BPD) grounded in the concept of BPD as a condition in which dysfunctional neural circuits underlie its pathological dimensions, some of which include emotion dysregulation (broadly encompassing affective instability, negative affectivity, and hyperarousal), abnormal interpersonal functioning, and impulsive aggression. This article, initiated at a joint Columbia University-Cornell University Think Tank on BPD with representation from the Icahn School of Medicine at Mount Sinai, suggests how to advance research in BPD by studying the dimensions that underlie BPD in addition to studying the disorder as a unitary diagnostic entity. We suggest that linking the underlying neurobiological abnormalities to behavioral symptoms of the disorder can inform a research agenda to better understand BPD with its multiple presentations.

Brain anatomy of the 4-day-old European rabbit.

The European rabbit (Oryctolagus cuniculus) is a widely used model in fundamental, medical and veterinary neurosciences. Besides investigations in adults, rabbit pups are relevant to study perinatal neurodevelopment and early behaviour. To date, the rabbit is also the only species in which a pheromone - the mammary pheromone (MP) - emitted by lactating females and active on neonatal adaptation has been described. The MP is crucial since it contributes directly to nipple localisation and oral seizing in neonates, i.e. to their sucking success. It may also be one of the non-photic cues arising from the mother, which stimulates synchronisation of the circadian system during pre-visual developmental stages. Finally, the MP promotes neonatal odour associative and appetitive conditioning in a remarkably rapid and efficient way. For these different reasons, the rabbit offers a currently unique opportunity to determine pheromonal-induced brain processing supporting adaptation early in life. Therefore, it is of interest to create a reference work of the newborn rabbit pup brain, which may constitute a tool for future multi-disciplinary and multi-approach research in this model, and allow comparisons related to the neuroethological basis of social and feeding behaviour among newborns of various species. Here, in line with existing experimental studies, and based on original observations, we propose a functional anatomical description of brain sections in 4-day-old rabbits with a particular focus on seven brain regions which appear important for neonatal perception of sensory signals emitted by the mother, circadian adaptation to the short and single daily nursing of the mother in the nest, and expression of specific motor actions involved in nipple localisation and milk intake. These brain regions involve olfactory circuits, limbic-related areas important in reward, motivation, learning and memory formation, homeostatic areas engaged in food anticipation, and regions implicated in circadian rhythm and arousal, as well as in motricity.

Housing environment influences stress-related hippocampal substrates and depression-like behavior

Rats are widely used animal models for biological psychiatry and neuroscience. Laboratory rats are typically housed in impoverished sensory environments. The lack of species-typical sensory environment might radically change the response of individual animals to stressful and/or threatening episodes. In this report, we demonstrate that behavioral and neural sequelae of chronic stress were modified by sensory environment of adult male rats. This includes effects of stress on the density of spines on CA3 hippocampal neurons, hippocampal neurogenesis and abundance of glucocorticoid or mineralocorticoid receptors. Enrichment also reduced depression-like behavior in a forced swim task. Stress and sensory enrichment evoked opposing effects on all the above endpoints. The sensory enrichment used in this report is of a relatively short duration provided during adulthood. This period excludes critical windows of greater plasticity during pre- and peripubertal stages. Our results suggest that standard housing practices for laboratory rats remain austere concerning sensory requirements of this species. Thus, even a moderate sensory enrichment is capable of reducing high stress-sensitivity and depressive-like behavior in standard laboratory rats.

Reduced-Reference Image Quality Assessment in Free-Energy Principle and Sparse Representation

The free-energy principle in recent studies of brain theory and neuroscience models the perception and understanding of the outside scene as an active inference process, in which the brain tries to account for the visual scene with an internal generative model. Specifically, with the internal generative model, the brain yields corresponding predictions for its encountered visual scenes. Then, the discrepancy between the visual input and its brain prediction should be closely related to the quality of perceptions. On the other hand, sparse representation has been evidenced to resemble the strategy of the primary visual cortex in the brain for representing natural images. With the strong neurobiological support for sparse representation, in this paper, we approximate the internal generative model with sparse representation and propose an image quality metric accordingly, which is named FSI (free-energy principle and sparse representation-based index for image quality assessment). In FSI, the reference and distorted images are, respectively, predicted by the sparse representation at first. Then, the difference between the entropies of the prediction discrepancies is defined to measure the image quality. Experimental results on four large-scale image databases confirm the effectiveness of the FSI and its superiority over representative image quality assessment methods. The FSI belongs to reduced-reference methods, and it only needs a single number from the reference image for quality estimation.

Development of stereotaxic recording system for awake marmosets (Callithrix jacchus)

The common marmoset has been proposed as a potential alternative to macaque monkey as a primate model for neuroscience and medical research. Here, we have newly developed a stereotaxic neuronal recording system for awake marmosets under the head-fixed condition by modifying that for macaque monkeys. Using this system, we recorded neuronal activity in the cerebral cortex of awake marmosets and successfully identified the primary motor cortex by intracortical microstimulation. Neuronal activities of deep brain structures, such as the basal ganglia, thalamus, and cerebellum, in awake marmosets were also successfully recorded referring to magnetic resonance images. Our system is suitable for functional mapping of the brain, since the large recording chamber allows access to arbitrary regions over almost the entire brain, and the recording electrode can be easily moved stereotaxically from one site to another. In addition, our system is desirable for neuronal recording during task performance to assess motor skills and cognitive function, as the marmoset sits in the marmoset chair and can freely use its hands. Moreover, our system can be used in combination with cutting-edge techniques, such as two-photon imaging and optogenetic manipulation. This recording system will contribute to boosting neuroscience and medical research using marmosets.

Selected Abstracts From the 2017 International Neuroethics Society Annual Meeting

Debates continue over whether the prevailing neuroscientific model of addiction as a brain disease informs questions around moral and criminal responsibility, but little empirical work has been conducted with those tasked to address this question in practical terms on a daily basis. We have explored this point over two studies, respectively sampling 110 and 276 Magistrates active in the UK. In the first study we asked them to consider a criminal sentencing scenario in which evidence of a defendant’s brain damage and impaired impulse control was presented. This neurological damage was attributed to either a (fictional) disease or to addiction. When the same neuropsychiatric profile resulted from disease, rather than heroin use and addiction, custodial sentences were significantly reduced. The pivotal factor denying addiction the mitigating power of disease was perceived choice in the initial acquisition; removing choice from addiction dramatically increased the odds of sentence reduction, while attaching choice to disease tended to aggravate or reverse earlier leniency. The second study presented another criminal sentencing scenario in which the defendant exhibited similar neurological impairment, but additionally included ‘mixed’ aetiologies in which either disease led to addiction or addiction led to disease. Our results confirm the dramatic effect which the aetiology of impairment can have on judgements of criminal responsibility, whilst moreover give suggestion that drug-use tips the balance in favour of the punitive element when weighing criminal sentencing decisions.

The Effect of DMEM and DMEM:F12 Culture Media on the Growth of SH-SY5Y Cells

The human neuroblastoma cell line, SH-SY5Y cells, is commonly used as an in vitro model for neuroscience and neurobiology research. SH-SY5Y cells were established during the 1970’s from the parental metastatic bone tumor, SK-N-SH cell line. The utilization of SH-SY5Y cells in neurobiology research is due to their resemblance to the human primary neuronal cells with several limitations, considering the cells are derived from malignant tumor cells. Since SH-SY5Y cells are widely cultured for research, several different culture media have been used to optimize the growth of the cells, including Eagle's Minimum Essential Medium (EMEM), Dulbecco’s modified Eagle’s medium (DMEM) and other recently developed culture media. The ability of SH-SY5Y cells to reach confluency in culture flasks ranges from 5 days to 15 days, depending on the culture media. Hence, the optimization of the culture media is crucial to achieve the fastest growth rate for the cells. The objective of the study is to evaluate the culture media for the proliferation of SH-SY5Y cells. We compared the growth rate of SH-SY5Y cells cultured in Dulbecco’s modified Eagle’s medium (DMEM) supplemented with 15% heat-inactivated fetal bovine serum (hiFBS), Dulbecco’s modified Eagle’s medium: Nutrientmixture F-12 (DMEM:F12) + supplemented with 15% hiFBS and DMEM:F12 supplemented with 10% hiFBS. In DMEM:F12 supplemented with 15% hiFBS, cells grew up to 6.67E+05 cells. In DMEM:F12 supplemented with 10%hiFBS, cells grew up to 5.28E+05 cells. In DMEM supplemented with 15% hiFBS, the cells grew up to 4.76E+05 cells. There was a significant difference between culture media DMEM:F12 supplemented with 15% hiFBS as compared to DMEM:F12 supplemented with 10%hiFBS and DMEM supplemented with 15% hiFBS (p 0.05).

PRISM BRAIN MAPPING – NEUROSCIENCE APPLICATION IN BUSINESS COACHING

The article addresses coaching as the emerging field of human development from the neuroscience perspective. Neuroscience explains human behavior in terms of activities of the brain, and therefore can make a major contribution to the effectiveness of the coaching process, as well as of the coaching relationship. Introducing neuroscientific models, methods and tools into the research in the field of coaching can raise the awareness of existing behavioral patterns of coaches as well as enhance understanding of the mechanism, which enable coaches to adapt their behaviors accordingly.
 In this paper we present the results of our preliminary study on the aptitudes and characteristics, which – from the neuroscience point of view, make coaches successful. As we have based our research on the neuroscience insights, we have chosen the neuroscience-based tool, PRISM Brain Mapping questionnaire, to measure aptitudes and preferred behaviors of successful coaches. From the perspective of our research, the most important issue was to investigate the most preferred behavioral patterns among successful coaches, versus the less experienced coaches, or beginners.
 Findings from our research can be useful in supporting professional development of coaches, by enabling them to assess their possible competence gap and to address it on the individual level. Now, it is scientifically proved that our brains have got plasticity, and therefore, one can change the behavioral patterns to better suit in the role of a good coach.

The neuroscience of depressive disorders: A brief review of the past and some considerations about the future.

Depression is a common and debilitating mental health condition whose underlying aetiology and pathophysiology is still relatively poorly understood. In this article, we first turn to the past and briefly review what neuroscientific investigations have taught us so far about depression. In doing so, we cover neurochemical, neuroendocrine, immunological, functional and structural anatomical, and cognitive levels of description. We then turn our attention to the future and discuss where the field might be moving in the years to come. We argue that future developments may rely on three important lines of enquiry: first, the development of an integrated neuroscientific model of depression and its treatment in which different levels of description can be mechanistically linked, and in which distinct pathophysiological trajectories leading to depressive symptomatology can be identified. Second, the continued search for potentially overlooked pathophysiological factors, especially outside the immediate boundaries of the brain. And third, the improvement in translation of neuroscientific insights to aid and advance clinical practice and research.

Zwischen ethischer Neutralität und Dehumanisierung

AbstractIt is an undoubted fact that neuroscientific models of explanation play a crucial role in the realms of science and public life. Besides some noteworthy theoretical problems (unserious experimental set-ups, mis- or overinterpretation, illegitimate analogies, etc.) there are also practical problems concerning the neuroscientific explanation monopoly. To bring those problems to light, it is reasonable to concentrate on a specific and currently prominent version of modelling – namely that undertaken by so-called biological psychiatry. In this article, it will be shown that the controversy concerning biological psychiatry is often guided by several misunderstandings and wrong-headed accusations. The article starts by giving a minimal definition of biological psychiatry which can be used as a common ground for further argumentation. It differentiates three subprojects of biological psychiatry and examines their risks and potentials in more detail. In sum, the article argues for a nuanced attitude towards biological psychiatry: If we are concerned with diagnostic practices and biological underpinnings of mental illnesses we are well-informed by the methods of biological psychiatry. However, if we want to know something about the nature of mental illnesses, we should imagine other projects which are theoretically much better equipped to answer ontological questions.

Behavioural lateralization in domestic pigs (Sus scrofa)—variations between motor functions and individuals

ABSTRACTMotor lateralization is hypothesized to depend on the complexity of the motor function, but it might at the same time reflect hemispheric dominance within an individual across motor functions. We investigated possible motor lateralization patterns in four motor functions of different complexity (snout use in a manipulative task, foot use in two-stepping tasks and tail curling) in the domestic pig, a tetrapod species relevant as farm animal but also as a model in human neuroscience. A significant majority of our sample showed individual biases for manipulation with their snout and for curling their tail. Interestingly, the tail curling was lateralized towards the right at the population level and showed stronger lateralization patterns than the snout. Using a cluster analysis with combined tail and snout laterality, we identified groups of individuals with different lateralization patterns across motor functions that potentially reflect the individuals’ hemispheric dominance. To conclude, our results suggest that pigs show lateralization patterns that depend on the motor function and on the individual. Such individual lateralization patterns might have broader implications for animal personality and welfare. Our study lays the methodological groundwork for future research on laterality in pigs.

Context-Specific Inhibition is Related to Craving in Alcohol Use Disorders: A Dangerous Imbalance.

Most contemporary neuroscientific models of alcohol use disorders (AUD) incorporate an imbalance between enhanced cue reactivity, which results in a strong urge to consume, and the impaired inhibitory control of that urge. While these phenomena have been frequently investigated separately, studies involving both aspects and thus precisely investigating the postulated imbalance are rare. In this study, inhibition was investigated in an addiction-specific context and individual craving levels were also examined. This study compared inhibition in alcohol-related and neutral contexts in patients with AUD and healthy controls, while also taking into account the individual amount of craving. All subjects performed a Go/NoGo task involving neutral and alcohol-related NoGo trials, while their brain activity was recorded using multichannel electroencephalography. The map strength and topography of the N2 and P3 components of the NoGo event-related potentials were compared between groups and contexts using whole-scalp randomization-based methods. The effects of interest were further investigated with sLORETA source analysis. For the N2 component, the context by craving interaction was strong for map strength and map topography. The source analysis indicated that in subjects with high craving, alcohol-related context led to enhanced and prolonged activation in the posterior cingulate and premotor cortical areas. This interaction was specific for craving, but not for diagnostic classification. The amplitude of the P3 component was reduced in subjects with AUD, which replicated previous findings. In subjects with strong craving, the conflict reflected in the NoGo-N2 was enhanced in the alcohol-related context. Such enhanced conflict probably makes the successful inhibition of the urge to drink in high-risk situations even more difficult for this subgroup of patients and should therefore be addressed in individualized treatment planning.

The Agent Brain: A Review of Non-invasive Brain Stimulation Studies on Sensing Agency.

According to philosophy of mind and neuroscientific models, the sense of agency can be defined as the sense that I am the one that is generating an action and causing its effects. Such ability to sense ourselves as causal agents is critical for the definition of intentional behavior and is a primary root for human interaction skills. The present mini-review aims at discussing evidences from non-invasive brain stimulation (NIBS) studies targeting functional correlates of different aspects of agency and evidences on the way stimulation techniques affect such core feature of human subjective experience. Clinical and brain imaging studies helped in defining a neural network mediating agency-related processes, which includes the dorsolateral prefrontal cortex (dlPFC), the cingulate cortex (CC), the supplementary and pre-supplementary motor areas (SMA and pre-SMA), the posterior parietal cortex (PPC) and its inferior regions and the cerebellum. However, while the plurality of those structures mirrors the complexity of the phenomenon, their actual roles with respect to different components of the experience of agency have been primarily explored via correlational techniques, without a clear evidence about their causal significance with respect to the integration of sensorimotor information, intentionalization, and action monitoring processes. Therefore, insights into the specific causal role of different cortical structures can be specified by using NIBS techniques, in order to provide improved understanding into the bases of our ability vs. inability to properly act in complex social contexts.

Generative models for network neuroscience: prospects and promise.

Network neuroscience is the emerging discipline concerned with investigating the complex patterns of interconnections found in neural systems, and identifying principles with which to understand them. Within this discipline, one particularly powerful approach is network generative modelling, in which wiring rules are algorithmically implemented to produce synthetic network architectures with the same properties as observed in empirical network data. Successful models can highlight the principles by which a network is organized and potentially uncover the mechanisms by which it grows and develops. Here, we review the prospects and promise of generative models for network neuroscience. We begin with a primer on network generative models, with a discussion of compressibility and predictability, and utility in intuiting mechanisms, followed by a short history on their use in network science, broadly. We then discuss generative models in practice and application, paying particular attention to the critical need for cross-validation. Next, we review generative models of biological neural networks, both at the cellular and large-scale level, and across a variety of species including Caenorhabditis elegans, Drosophila, mouse, rat, cat, macaque and human. We offer a careful treatment of a few relevant distinctions, including differences between generative models and null models, sufficiency and redundancy, inferring and claiming mechanism, and functional and structural connectivity. We close with a discussion of future directions, outlining exciting frontiers both in empirical data collection efforts as well as in method and theory development that, together, further the utility of the generative network modelling approach for network neuroscience.

Salience network dynamics underlying successful resistance of temptation.

Self-control and the ability to resist temptation are critical for successful completion of long-term goals. Contemporary models in cognitive neuroscience emphasize the primary role of prefrontal cognitive control networks in aligning behavior with such goals. Here, we use gaze pattern analysis and dynamic functional connectivity fMRI data to explore how individual differences in the ability to resist temptation are related to intrinsic brain dynamics of the cognitive control and salience networks. Behaviorally, individuals exhibit greater gaze distance from target location (e.g. higher distractibility) during presentation of tempting erotic images compared with neutral images. Individuals whose intrinsic dynamic functional connectivity patterns gravitate toward configurations in which salience detection systems are less strongly coupled with visual systems resist tempting distractors more effectively. The ability to resist tempting distractors was not significantly related to intrinsic dynamics of the cognitive control network. These results suggest that susceptibility to temptation is governed in part by individual differences in salience network dynamics and provide novel evidence for involvement of brain systems outside canonical cognitive control networks in contributing to individual differences in self-control.

Cerebral metabolic correlates of attention networks in Alzheimer's Disease: A study of the Stroop

Patients with Alzheimer's Disease (AD) show difficulties with attention. Cognitive neuroscience models posit that attention can be broken down into alerting, orienting, and executive networks. We used the Stroop Color-Word test to interrogate the neural correlates of attention deficits in AD. We hypothesized that the Word, Color, and Color-Word conditions of the Stroop would all tap into the alerting and orienting networks. The Color-Word condition would additionally tap into the executive network. A ratio of Color-Word to Color naming performance would isolate the executive network from the others. To identify the neural underpinnings of attention in AD we correlated performance on the Stroop with brain metabolic activity. Sixty-six patients with probable AD completed [18F] fluorodeoxyglucose PET scanning and neuropsychological testing. Analysis was conducted with SPM12 (p<0.001 uncorrected, extent threshold 50 voxels). Performance on the Word, Color, and Color-Word conditions directly correlated with metabolic rate in right inferior parietal lobules/intraparietal sulci. The Color-Word/Color ratio revealed associations with metabolic rate in right medial prefrontal cortex and insula/operculum. Overall findings were largely consistent with the hypothesized neuroanatomical substrates of the alerting, orienting, and executive networks. As such, attention deficits in AD reflect compromise to multiple large-scale networks.

Greater delay discounting among girls, but not boys, with ADHD correlates with cognitive control

ABSTRACTCognitive neuroscience models suggest both reward valuation and cognitive control contribute to reward-based decision-making. The current study examined the relationship between cognitive control and delay discounting (i.e., choosing smaller, immediate over larger, delayed rewards) in a large sample of boys and girls diagnosed with attention-deficit/hyperactivity disorder (ADHD; N = 95) and typically developing control children (TD; N = 59). Specifically, we examined performance on multiple measures of cognitive control (i.e., Go/No-Go task, Stop Signal task, and Spatial Span task) and delay discounting (i.e., Classic Delay Discounting and Real-Time Delay Discounting tasks), as well as the relationship between these measures. Results indicated that sex moderated the effects of group on task performance. Specifically, girls with ADHD, but not boys with the disorder, exhibited atypical delay discounting of real-time rewards. Results from correlational analyses indicated that delay discounting and cognitive control were not significantly correlated in the overall sample. Multiple regression analyses demonstrated that among girls with ADHD poorer spatial working memory and inhibitory control predicted greater real-time discounting. Collectively, findings provide support for distinct patterns of cognitive control and delay discounting among school-aged girls and boys with ADHD. Additionally, findings suggest that among girls with ADHD, those who exhibit relatively poor working memory and inhibitory control might be a particularly vulnerable subgroup with the greatest propensity to exhibit maladaptive decision-making.

Identifying affective personality profiles: A latent profile analysis of the Affective Neuroscience Personality Scales

Based on evolutionary theory, a recent model in affective neuroscience delineated six emotional brain systems at the core of human personality: SEEKING, CARING, PLAYFULNESS, FEAR, ANGER, SADNESS. The Affective Neuroscience Personality Scales (ANPS) assess their functioning. Using a person-centred approach of the ANPS, this study: (i) examined the existence of latent personality profiles, (ii) studied their gender invariance, (iii) assessed their longitudinal (4 years) stability, and (iv) explored how they relate to several intrapersonal, interpersonal, and emotion regulation skills. Latent Profile Analysis in 2 samples (Canadian, longitudinal, N = 520; French, cross-sectional, N = 830) found that, qualitatively, 3 profiles characterized both populations and genders, with one distinction for the second profile where the French women endorsed slightly higher and lower scores for, respectively, the negative and positive emotions. Whilst not being quantitatively similar across genders, the personality profiles remained consistent across time in the longitudinal sample. Associations between profiles and intrapersonal (e.g. depression), interpersonal (e.g. empathy), and emotion regulation skills measures (e.g. emotional intelligence) offered concurrent validity evidence. This person centred approach to ANPS offers a holistic and parsimonious way to study affective personality dimensions. It opens promising avenues for future studies on the predictive value of ANPS profiles, and for personality-targeted interventions.

Model of Illusions and Virtual Reality.

In Virtual Reality (VR) it is possible to induce illusions in which users report and behave as if they have entered into altered situations and identities. The effect can be robust enough for participants to respond “realistically,” meaning behaviors are altered as if subjects had been exposed to the scenarios in reality. The circumstances in which such VR illusions take place were first introduced in the 80's. Since then, rigorous empirical evidence has explored a wide set of illusory experiences in VR. Here, we compile this research and propose a neuroscientific model explaining the underlying perceptual and cognitive mechanisms that enable illusions in VR. Furthermore, we describe the minimum instrumentation requirements to support illusory experiences in VR, and discuss the importance and shortcomings of the generic model.