Stereotyped Activity Research Articles

Dynamic model of whole cortex reveals disassortative hub structure in the intracortical connectome

The brain exhibits complex spatio-temporal patterns of activity. In particular, its baseline neural activity for idle subjects or animals has a specific structure, also called functional connectivity (FC): cortical areas experience correlated fluctuations at rest as revealed by imaging techniques (e.g., fMRI, EEG and MEG). Moreover, these correlation patterns become more expressed or suppressed depending on the engaged task. The putative function for this stereotypical background activity has been actively questioned by the neuroscience community. A Bayesian hypothesis is that it reflects the variety of possible coactivations of cortical areas for usual tasks, forming a prior representation of the environment and interactions wherewith. The present study relies on our recently developed model [1] in which noise diffusion is constrained by intracortical white-matter projections to reproduce FC observed in experimental data (fMRI BOLD signal). In this model, noise has a functional role and represents the variability of neural activity during tasks. This model allows us to explore the role of various parameters in shaping FC, such as the local nonlinear dynamics of cortical areas. More importantly, we can infer the efficacies of intracortical projections, also called effective connectivity (EC), from experimental data. EC plays a crucial role in shaping FC and differs from the structural connectivity (SC) that is typically obtained using diffusion tensor imaging (DTI), which estimates the density of white-matter fibers. It is important to notice that the efficacies of these fibers may differ from their density, due to the concentration of synapses formed at their end, the type of neurotransmitters associated and the excitability of target neural populations. In the end, our model combines anatomical SC and activity FC to evaluate what drives the neural dynamics, embodied in EC. Practically, directed EC can be estimated using two matrices of empirical FC, namely FC0 for correlations with zero time shift and FCτ for correlations with a given time shift τ>0. We apply our method to infer the intracortical EC from experimental fMRI data that consists of ~20 minutes of recording for 25 idle subjects. The model reproduces both empirical FC0 and FCτ matrices with a Pearson correlation coefficient of 0.65. The recovered EC connectivity is significantly asymmetric, with a value of 0.3 for an index that scales from 0 for symmetric matrices to 1 for asymmetric matrices. Moreover, EC exhibits hubs that have either strong incoming or outgoing weights, but not both. This disassortative property is expected to exert a strong influence in shaping the whole network dynamics.

Interfacing 3D Engineered Neuronal Cultures to Micro-Electrode Arrays: An Innovative In Vitro Experimental Model.

Currently, large-scale networks derived from dissociated neurons growing and developing in vitro on extracellular micro-transducer devices are the gold-standard experimental model to study basic neurophysiological mechanisms involved in the formation and maintenance of neuronal cell assemblies. However, in vitro studies have been limited to the recording of the electrophysiological activity generated by bi-dimensional (2D) neural networks. Nonetheless, given the intricate relationship between structure and dynamics, a significant improvement is necessary to investigate the formation and the developing dynamics of three-dimensional (3D) networks. In this work, a novel experimental platform in which 3D hippocampal or cortical networks are coupled to planar Micro-Electrode Arrays (MEAs) is presented. 3D networks are realized by seeding neurons in a scaffold constituted of glass microbeads (30-40 µm in diameter) on which neurons are able to grow and form complex interconnected 3D assemblies. In this way, it is possible to design engineered 3D networks made up of 5-8 layers with an expected final cell density. The increasing complexity in the morphological organization of the 3D assembly induces an enhancement of the electrophysiological patterns displayed by this type of networks. Compared with the standard 2D networks, where highly stereotyped bursting activity emerges, the 3D structure alters the bursting activity in terms of duration and frequency, as well as it allows observation of more random spiking activity. In this sense, the developed 3D model more closely resembles in vivo neural networks.

Para além dos déficits: interação e atenção conjunta em crianças com autismo

As desordens do espectro autista são descritas por déficits persistentes na interação e comunicação social, além de padrão restrito, repetitivo e estereotipado de comportamentos, interesses e atividades. Apesar dessa descrição dominante – a partir dos déficits –, na literatura também há autores que lançam olhares aos comportamentos para além dos déficits. Nessa perspectiva, o objetivo deste trabalho foi investigar como se dão os processos de interação social em crianças com autismo em contexto familiar, mais especificamente analisando os processos de atenção conjunta. Estudos de casos múltiplos foram conduzidos com duas crianças de cinco anos diagnosticadas com o transtorno. Por dois meses, foram feitas videogravações semanais das crianças no contexto familiar. Com base no referencial da Rede de Significações, as cenas foram mapeadas e transcritas, e as interações analisadas por meio da noção de fluxo interacional. Apesar da presença de comportamentos e interesses repetitivos e estereotipados nos dois casos, verificou-se a ocorrência de recursos comunicativos na interação, a qual se deu, muitas vezes, em situações de contraposição ou evitação social. Além desses comportamentos, verificou-se o estabelecimento de atenção conjunta e processos de negociação de interesses por parte das crianças. A evidência de tais comportamentos coloca como necessária maior exploração do tema, já que apontam para algumas potencialidades, mesmo que através de modos particulares nessas crianças.

Race and the First-Person Shooter: Challenging the Video Gamer in BioShock Infinite

This article argues that the 2013 first-person shooter (FPS) video game BioShock Infinite (2K Games) challenges gamers in its representations of race. Launched in 2007, the BioShock franchise has a reputation for thoughtful dystopian narratives, beautiful retro worlds, and addictive gameplay. As the latest installment in an award-winning franchise, BioShock Infinite entices players on reputation alone. Although the game's marketing presents it as a clichéd FPS game with a stereotypical white male hero and nonstop action, BioShock Infinite regularly interrogates its own models of hegemonic power through both the narrative and the gameplay. This article tracks the ways in which the game encourages the player to notice and engage with white supremacism and race relations in an allegorical American context. The early twentieth-century world of Columbia functions not only as a playground for the player but also as a proving ground where social mores are repeatedly tested. Practices such as lynching, segregation, and phrenology are woven into the narrative and the player must sometimes literally decide whether to endorse or oppose the racism modeled in the game. The hack-and-slash gameplay also becomes inextricable from the racial identities and views of both the protagonist and his enemies. In this way, BioShock Infinite balances gaming as entertainment with gaming as education and contributes to the broader debate around the social function of video games.

Abnormal transsulfuration metabolism and reduced antioxidant capacity in Chinese children with autism spectrum disorders

Autism spectrum disorder (ASD) is a neurological disorder that presents a spectrum of qualitative impairments in social interaction, communication, as well as restricted and stereotyped behavioral patterns, interests, and activities. Several studies have suggested that the etiology of ASD can be partly explained by oxidative stress. However, the implications of abnormal transsulfuration metabolism and oxidative stress, and their relation with ASD are still unclear. The purpose of this study was to evaluate several transsulfuration pathway metabolites in Chinese participants diagnosed with ASD, to better understand their role in the etiology of this disorder. Fifty children (39 male, 11 female) diagnosed with ASD and 50 age- and gender-matched non-ASD children (i.e., control group) were included in this study. This prospective blinded study was undertaken to assess transsulfuration and oxidative metabolites, including levels of homocysteine (Hcy), cysteine (Cys), total glutathione (tGSH), reduced glutathione (GSH), oxidized glutathione (GSSG), and glutathione ratio (GSH/GSSG). The clinical severity of ASD was evaluated with the Childhood Autism Rating Scale (CARS), and the autistic children's present behavior was measured by the Autism Behavior Checklist (ABC). The results indicated that Hcy and GSSG levels were significantly higher in children diagnosed with ASD, Cys, tGSH and GSH levels as well as the GSH/GSSG ratio showed remarkably lower values in ASD children compared to control subjects. Hcy levels correlated significantly with increasing CARS scores and GSSG levels in children with ASD. Our results suggest that an abnormal transsulfuration metabolism and reduced antioxidant capacity (i.e., hyperhomocysteinemia and increased oxidative stress), and Hcy level appears to have a potentially negative impact on clinical severity of autistic disorder.

Trophic factor-induced activity 'signature' regulates the functional expression of postsynaptic excitatory acetylcholine receptors required for synaptogenesis.

Highly coordinated and coincidental patterns of activity-dependent mechanisms (“fire together wire together”) are thought to serve as inductive signals during synaptogenesis, enabling neuronal pairing between specific sub-sets of excitatory partners. However, neither the nature of activity triggers, nor the “activity signature” of long-term neuronal firing in developing/regenerating neurons have yet been fully defined. Using a highly tractable model system comprising of identified cholinergic neurons from Lymnaea, we have discovered that intrinsic trophic factors present in the Lymnaea brain-conditioned medium (CM) act as a natural trigger for activity patterns in post- but not the presynaptic neuron. Using microelectrode array recordings, we demonstrate that trophic factors trigger stereotypical activity patterns that include changes in frequency, activity and variance. These parameters were reliable indicators of whether a neuron expressed functional excitatory or inhibitory nAChRs and synapse formation. Surprisingly, we found that the post- but not the presynaptic cell exhibits these changes in activity patterns, and that the functional expression of excitatory nAChRs required neuronal somata, de novo protein synthesis and voltage gated calcium channels. In summary, our data provides novel insights into trophic factor mediated actions on neuronal activity and its specific regulation of nAChR expression.

Gradual emergence of spontaneous correlated brain activity during fading of general anesthesia in rats: Evidences from fMRI and local field potentials

Intrinsic brain activity is characterized by the presence of highly structured networks of correlated fluctuations between different regions of the brain. Such networks encompass different functions, whose properties are known to be modulated by the ongoing global brain state and are altered in several neurobiological disorders. In the present study, we induced a deep state of anesthesia in rats by means of a ketamine/medetomidine peritoneal injection, and analyzed the time course of the correlation between the brain activity in different areas while anesthesia spontaneously decreased over time. We compared results separately obtained from fMRI and local field potentials (LFPs) under the same anesthesia protocol, finding that while most profound phases of anesthesia can be described by overall sparse connectivity, stereotypical activity and poor functional integration, during lighter states different frequency-specific functional networks emerge, endowing the gradual restoration of structured large-scale activity seen during rest. Noteworthy, our in vivo results show that those areas belonging to the same functional network (the default-mode) exhibited sustained correlated oscillations around 10Hz throughout the protocol, suggesting the presence of a specific functional backbone that is preserved even during deeper phases of anesthesia. Finally, the overall pattern of results obtained from both imaging and in vivo-recordings suggests that the progressive emergence from deep anesthesia is reflected by a corresponding gradual increase of organized correlated oscillations across the cortex.

Behavioral Attitudes in Different Cultures: Russian-Speaking New Comers vs. Native Israel Citizens

AbstractGroups of Russian-speaking and native Israel citizens (adults and adolescents) were compared according to their behavioral attitudes by using the BASE test— a projective questionnaire for the estimation of behavioral attitudes (search activity, stereotyped activity, chaotic activity and renunciation of search). Native citizens, girls and adult women, displayed a lower level of stereotyped activity and a higher level of chaotic activity in comparison to their Russian-speaking peers. The ratio between search activity and stereotyped activity was higher in native citizens. Authors propose that the difference between groups is determined by the difference in the traditions of growing up in Israel and in former USSR: the conditions for growing up are more free and with less pressure and requirements towards children in Israel. It can decrease an attitude towards the stereotyped behavior and increase not only the tendency towards search activity but also toward chaotic activity thus increasing the longevity of maturation.

Cytosolic calcium ions exert a major influence on the firing rate and maintenance of pacemaker activity in guinea-pig sinus node.

The sino-atrial node (SAN) provides the electrical stimulus to initiate every heart beat. Cellular processes underlying this activity have been debated extensively, especially with regards to the role of intracellular calcium. We have used whole-cell application of 1,2-bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA), a rapid calcium chelator, to guinea pig isolated SAN myocytes to assess the effect of rapid reduction of intracellular calcium on SAN cell electrical activity. High-dose (10 mM) BAPTA induced rapid and complete cessation of rhythmic action potential (AP) firing (time to cessation 5.5 ± 1.7 s). Over a range of concentrations, BAPTA induced slowing of action potential firing and disruption of rhythmic activity, which was dose-dependent in its time of onset. Exposure to BAPTA was associated with stereotyped action potential changes similar to those previously reported in the presence of ryanodine, namely depolarization of the most negative diastolic potential, prolongation of action potentials and a reduction in action potential amplitude. These experiments are consistent with the view that cytosolic calcium is essential to the maintenance of rhythmic pacemaker activity.

Abstract T MP70: Genetic Deletion of the Prostaglandin E2 EP3 Receptor Improves Outcomes after Experimental Intracerebral Hemorrhage in Young and Old Mice

Intracerebral hemorrhage (ICH) is a type of hemorrhagic stroke associated with high mortality and morbidity rates. Prolonged and unbalanced inflammatory responses after hemorrhagic stroke may negatively contribute to secondary brain injury. Prostaglandin E2 (PGE 2 ) is an important mediator of inflammation and plays a role in several neurologic disorders. PGE 2 has selective high affinity toward its membrane-bound G-protein-coupled receptors EP1, EP2, EP3, and EP4, which together arbitrate its neuromodulatory effects. We have previously shown in a middle cerebral artery occlusion model of ischemia/reperfusion-induced brain injury and a striatal NMDA-induced excitotoxicity model that mice pretreated intracerebroventricularly with a selective EP3 receptor agonist have larger brain lesions when compared to control mice. In the present study, we investigated whether EP3 receptor deletion (EP3 -/- ) would lead to improved anatomical and functional outcomes in young (2-4mo) and aged (22-24mo) C57BL/6 mice after inducing a hemorrhagic stroke using the collagenase model of ICH (n=8-10 for all groups). Neurobehavioral testing, including video-recording of home cage activity and neurological deficit scoring was performed at 24h, 48h, and 72h post-ICH. At 72h, mice were transcardially perfused and brains isolated for Cresyl Violet staining and lesion volume quantification. In both young and aged mice, smaller brain lesion volumes were seen for the EP3 -/- when compared to age-matched wildtype controls (p<0.05). Further, the aged EP3 -/- displayed significantly better neurologic recovery at 72h, as identified by both behavioral tests (p<0.01). Interestingly, the aged EP3 -/- showed significantly reduced ambulatory and stereotypic activity at 24h post-ictus (p<0.005). No significant behavioral differences were seen in the young cohort. Collectively, these results indicate a dynamic role of the EP3 receptor in mediating anatomical and functional outcomes following ICH. Additional studies are needed in order to clarify the mechanisms involved and identify potential therapeutic paradigms for alleviating the initial PGE 2 -EP3 receptor associated toxicity and promoting its later beneficial effects.

Temeljne informacije o zdravstvenoj njezi osoba s autizmom

Autism is a biological disorder of a brain development. The symptoms of autism appear mostly in the first three years and they stay present for the rest of the life. Nowadays, autistic disorders are seen as pervasive developmental disorders, for which a pervasive defect of numerous developmental areas, for example social interaction and communication, or the appearance of stereotypic behavior, interests or activities, is considered characteristic. Such a behavior pattern influences the possibility to satisfy the basic human needs, and therefore the quality of life. In order to increase the quality of life for people with autism and their families, the role of the nurse is extremely important. As autism stays present during the whole life, the nursing care includes activities on all levels of health protection during all developmental stages of autistic people. Special emphasis is put on the improvement of the life conditions and the person’s perception of its own reality of life. The role of nurses in the increase of the quality of life for people with autism and their families is based on the satisfaction of basic human needs.

Mapping the stereotyped behaviour of freely moving fruit flies.

A frequent assumption in behavioural science is that most of an animal's activities can be described in terms of a small set of stereotyped motifs. Here, we introduce a method for mapping an animal's actions, relying only upon the underlying structure of postural movement data to organize and classify behaviours. Applying this method to the ground-based behaviour of the fruit fly, Drosophila melanogaster, we find that flies perform stereotyped actions roughly 50% of the time, discovering over 100 distinguishable, stereotyped behavioural states. These include multiple modes of locomotion and grooming. We use the resulting measurements as the basis for identifying subtle sex-specific behavioural differences and revealing the low-dimensional nature of animal motions.

Estimation of artificial neuron parameters that obtain a required distribution of coupled system periods in a hybrid network

Rhythmic neuronal activity is a hallmark of many higher-level functions of the nervous system including the expression of rhythmic motor patterns and generation of behaviors such as cognition, memory, arousal, and sleep. Many rhythmic networks underlying these behaviors consist of one or more pacemaker neurons that are coupled with non-pacemaking neurons, and exhibit reliable stereotyped activity that however displays diverse levels of activity variability between networks – and sometimes those circuits that exhibit high levels of activity variability even depend upon their variability to accomplish some behavioral goal [1,2]. While it is understood that synaptic feedback from non-pacemaking neurons coupled to pacemaker neurons can limit variability of rhythmic activity [3,4], it is not yet understood how specific neuronal dynamics influence variability of the coupled network. Here we develop a theoretical approach to predict how network activity variability – as quantified by the probability distribution of observed periods – changes with altered phase response dynamics of non-pacemaking neurons, and demonstrate this theoretical approach’s predictive efficacy in hybrid networks established in the stomatogastric nervous system (STNS) of Cancer borealis. These hybrid networks consist of one biological pacemaker neuron (Anterior Burster/Pyloric Dilator complex [AB/PD]) and one artificial non-pacemaker neuron (designed to mimic the burst timing of the Lateral Pyloric [LP] neuron), which allows us to vary the phase response dynamics of the latter element. Our simple theoretical approach to predict the effects of network coupling on activity variability is based on three assumptions. First, within the range of variation of AB/PD neuron’ intrinsic period, it is assumed that there is always at least one stable fixed-point in the dynamics of the coupled system. Second, it is assumed that any drifting of the AP/PD neuron’s intrinsic period is significantly slower than the duration of one intrinsic period, so that the coupled system is capable of reaching a steady-state condition. Third, it is assumed that as the period of AB/PD varies, any changes in this neuron’s phase resetting curve (PRC) are negligibly small. The first two assumptions allow us to directly map an AB/PD neuron’s intrinsic period onto the network period in the coupled system. The last assumption allows us to recalculate the map for different intrinsic periods and predict the distribution of periods in the coupled network based upon the known distribution of intrinsic periods of AP/PD neuron. Using previously developed analyses [5] and a linear tS-tR curve for the artificial neuron we are able to qualitatively predict how slope and bias of the artificial neuron’s tS-tR curve affect the distribution of network periods. All experiments are performed using standard intracellular electrophysiological methods for the pyloric network of the STNS, and hybrid networks are established with the dynamic clamp.

Neurotrophins and spinal circuit function.

Work early in the last century emphasized the stereotyped activity of spinal circuits based on studies of reflexes. However, the last several decades have focused on the plasticity of these spinal circuits. These considerations began with studies of the effects of monoamines on descending and reflex circuits. In recent years new classes of compounds called growth factors that are found in peripheral nerves and the spinal cord have been shown to affect circuit behavior in the spinal cord. In this review we will focus on the effects of neurotrophins, particularly nerve growth factor (NGF), brain derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), on spinal circuits. We also discuss evidence that these molecules can modify functions including nociceptive behavior, motor reflexes and stepping behavior. Since these substances and their receptors are normally present in the spinal cord, they could potentially be useful in improving function in disease states and after injury. Here we review recent findings relevant to these translational issues.

Adaptive ability to cope with atypical or novel situations involving tool use: An fMRI approach

We investigated the neural mechanisms underlying the ability to cope in atypical or novel situations using tools. We hypothesized that two cognitive components support this ability: adaptive coordination (for adapting to situational demands) and cognitive inhibition (for inhibiting the incongruent actions afforded by tools). We had subjects choose novel tools for a given task or choose among familiar tools in an atypical situation, during which we examined cortical activation in their brains using functional magnetic resonance imaging. Neural activation during adaptive coordination was observed in the left lateral orbitofrontal cortex, inferior frontal gyrus and sulcus, middle and medial frontal gyrus, intraparietal sulcus, precentral sulcus, inferior temporal gyrus, supramarginal gyrus, the bilateral insula, anterior cingulate cortex, and the right callosal sulcus. Activation indicating cognitive inhibition was observed in the right middle and inferior frontal gyrus. These findings demonstrate that the left parietal region shapes basic action, whereas the right frontal region inhibits stereotypical action. The left frontal regions are thought to be linked to the processing of ambiguous actions and play key roles in coordinating actions, whereas other regions are involved in processing situational contexts. Our results may be important for understanding the neural systems underlying adaptability to daily social situations.

Analyse clinique d’un cas de complexification des phénomènes répétitifs dans l’autisme chez l’enfant

ObjectivesRestricted and repetitive stereotyped behaviours, activities, and interests (henceforth: RRSB) have always constituted a pathognomonic group of symptoms in autism. They formed part of Leo Kanner's first clinical descriptions in 1943 and are constitutive of contemporary accounts formalized in the international nosographical classifications. Over the last few years, the nature of the relationships between the different forms of RRSB has been the object of lively debate in the literature. While statistical studies have usually highlighted the heterogeneity of the observed RRSBs, clinical studies, in contrast, have generally emphasized the extent to which different RRSBs overlap in the same individual. Here, we develop the concept of “complexification” as a specific form of evolution of the different RRSBs exhibited by the autistic child. We put forward the hypothesis that certain continuity exists between the different RRSBs. MethodBased on three years of participating observation with an autistic child within an institutional context, we have categorized the different RRSBs he exhibits using a structural analysis methodology. We developed a complexity scale based on this case. ResultsThe different RRSBs presented by the child, over the three years of the study, are structurally homogeneous in the sense that they suggest an identity of structural properties: the same matrix organises the development and complexification of these RRSBs. DiscussionThe complexification of RRSBs is a process that entails that the clinician respects the initiatives of the autistic child. Respect favours the elaboration of an appeased social relationship and enables consensual learning experiences. ConclusionIn this study, we were able to evidence the existence of an overlap between different RRSBs of distinct levels of complexity. This suggests certain homogeneity and interdependence between the different types of RRSBs. Further research is necessary to better assess the incidence of this homogeneity on the evolution of the autistic child.

The Hypothesis That Anorexia Nervosa Is a Passion: Clarifications and Elaborations

The Hypothesis That Anorexia Nervosa Is a Passion:Clarifications and Elaborations Louis C. Charland (bio), Tony Hope (bio), Anne Stewart (bio), and Jacinta Tan (bio) Keywords Anorexia nervosa, passion, emotion, feeling, mood, authenticity, identity We are grateful for these two insightful commentaries, which both see novelty and value in the manner in which we invoke the hypothesis that anorexia nervosa is a passion, to help explain data from the Anorexia Experiences Study, which provides the basis of our inquiry. In this response, we wish to clarify and elaborate on our hypothesis; in particular, the difference between passions and moods, the manner in which our hypothesis touches on issues of authenticity and identity, and the compelling parallel with addiction. We also wish to emphasize that, in proposing the hypothesis that anorexia nervosa is a passion, our primary aim is not so much to exclude or replace alternative theoretical approaches. Our focus, really, is to argue that the hypothesis that anorexia nervosa is a passion adds something rich and unique to our current understanding of that condition, which is not fully or adequately captured by alternative accounts. Passions and Moods Hannah Bowden asks whether the descriptive theoretical virtues we attribute to ‘passion’ might also be accomplished by referring to “Heideggerian mood,” or “a form of Heideggerian mood in combination with certain beliefs” (Bowden 2013, 368). She explicitly asks how passions differ from moods. These are important questions. To begin, note that in her remarks Bowden is inquiring about the descriptive capabilities of the theoretical constructs ‘passion’ and ‘mood.’ Her concern is largely with phenomenological description. Now it is indeed true that we argue that ‘passion’ plays a pivotal role in the description of the clinical course and nature of anorexia nervosa, although admittedly we do not engage in phenomenology per se. However, what must be emphasized is that we also wish to argue that, properly understood, the construct ‘passion’ plays a theoretically irreducible and ineliminable role in the explanation of the clinical course of anorexia nervosa; in particular, the manner in which many of the feelings and emotions in anorexia nervosa [End Page 375] succeed one another in apparently rule-governed and even law-like ways. Our contention is that neither the concepts ‘emotion,’ ‘feeling,’ ‘mood,’ ‘belief,’ or any combination of these, can adequately describe or explain the complex progressive syndrome that is anorexia nervosa. Something like the concept of passion we invoke from Ribot is required. Although much work remains to be done, this at least is the essence of our case. We believe that it is an especially important theoretical virtue of the concept of passion that we employ that it helps to describe and explain, both how and why the anorexic syndrome can sometimes take the tragic, progressive, worsening, course it does. Indeed, at one point Ribot likens passions where there is a loss of control of this sort to an ‘avalanche.’ This compelling metaphor suggests a tightly bound, progressive, worsening, affective–intellectual–motivational syndrome that, in our view, cannot credibly be labeled or identified, described or explained, with moods, or simply moods plus certain beliefs. Furthermore, ‘passion’ in our view cannot be accounted for using other preexisting theoretical concepts, or any combination of these. Our claim is that the concept ‘passion’—and not simply the term—must be added (reinstated, to be precise) to our current existing theoretical framework. None of this is to say that moods might not play an important part in the phenomenological and clinical description of the anorexic syndrome, or its explanation. But that is an independent empirical question that we did not attempt to answer in our article. To further clarify, there are in fact quite a few important differences between moods and passions on our account. First, passions may initially be voluntarily chosen, whereas moods, normally, are not. Second, passions are tied to an ‘intentional object’ or fixed idea, whereas moods, normally, are not. Third, passions require the intellectual resources of reason and cognition, whereas moods, normally, do not. Fourth, passions are often tied to specific stereotypical action tendencies, whereas moods, normally, are not. Fifth, passions are stable and may endure for years, whereas moods tend to be more fleeting and temporary...

Effects of Cellular Homeostatic Intrinsic Plasticity on Dynamical and Computational Properties of Biological Recurrent Neural Networks

Homeostatic intrinsic plasticity (HIP) is a ubiquitous cellular mechanism regulating neuronal activity, cardinal for the proper functioning of nervous systems. In invertebrates, HIP is critical for orchestrating stereotyped activity patterns. The functional impact of HIP remains more obscure in vertebrate networks, where higher order cognitive processes rely on complex neural dynamics. The hypothesis has emerged that HIP might control the complexity of activity dynamics in recurrent networks, with important computational consequences. However, conflicting results about the causal relationships between cellular HIP, network dynamics, and computational performance have arisen from machine-learning studies. Here, we assess how cellular HIP effects translate into collective dynamics and computational properties in biological recurrent networks. We develop a realistic multiscale model including a generic HIP rule regulating the neuronal threshold with actual molecular signaling pathways kinetics, Dale's principle, sparse connectivity, synaptic balance, and Hebbian synaptic plasticity (SP). Dynamic mean-field analysis and simulations unravel that HIP sets a working point at which inputs are transduced by large derivative ranges of the transfer function. This cellular mechanism ensures increased network dynamics complexity, robust balance with SP at the edge of chaos, and improved input separability. Although critically dependent upon balanced excitatory and inhibitory drives, these effects display striking robustness to changes in network architecture, learning rates, and input features. Thus, the mechanism we unveil might represent a ubiquitous cellular basis for complex dynamics in neural networks. Understanding this robustness is an important challenge to unraveling principles underlying self-organization around criticality in biological recurrent neural networks.

An 11-Year-Old Boy With Asperger’s Disorder Presenting With Aggression

“Alan” is an 11-year-old boy who was first seen in our clinic 3 years ago. His parents’ chief complaint at admission was Alan’s physically aggressive behavior at home, in particular toward his mother, as well as fights with children and teachers at school. Alan reportedly met his early developmental motor and cognitive milestones, but he showed difficulties with temper control and frustration tolerance as a toddler, having “significant fits” and biting other children. In preschool, Alan’s behavior was generally without significant aggression exceptwhen hismother was there to volunteer. In kindergarten, his parents reported, his behavior was managed with the help of a teacher who was very consistent with discipline and structure, but the followingyear,hisfirst-grade teacher providedmuch less structure, and Alan started getting into fights again with other children. His behavior also worsened at home; for instance, he would fight a neighbor boy and “the kids would scratch each other bloody.” The parents started family counseling at that time, which did not reduce the problem behaviors. In second grade, at the end of the first trimester, Alan reportedly “lost it.” After a family session, he “cleared the entire desk of the therapist” and “threatened to hurt the therapist.” At home, he would take knives from kitchen drawers and threaten family members. He would “shut down” and not talk about his feelings or thoughts. He was referred by the outpatient psychotherapist to the emergencydepartment and was subsequently treated in a day hospital program, which did reduce his outbursts. He was not put on medication. Discharge diagnoses were mood disorder not otherwise specified, rule out depressive disorder, and rule out anxiety disorder. After discharge, Alan was referred to our clinic. He continued to struggle with aggressive outbursts. When he was told to do minor chores or homework, he “would never do it.” Sometimes he would be “good” in themorning, but hismoodwasusually irritable, and little things would set off explosive outbursts, with yelling, throwing things, and punching people around him, resulting inbruises;his parentshad someconcern about the safety of Alan’s sibling, as well as their own safety. He had such outbursts approximately four times per week, each lasting 30 to 45 minutes. His parents also reported an apparent “female authority problem”; Alan responded much better to male authority figures than to women. During a review of Alan’s developmental history, his parents reported that their son had poor eye contact since early age and that he would “suppress” emotions and had a flat affect. They also noted that Alan did well approaching adults but did not attach emotionally to other children and struggled with making same-age friends. His own perception, however, was that he had many friends. Alan was always very much interested in science and was an expert in dinosaurs and rocks. “While other kids look at things in museums and move on,” he would read all the information he could get. Alan excelled in memorizing other people’s names and faces and after years would recognize someone he had seen only once. He was also noted to struggle with change in routines and to fidget with his hands. There was no history of abuse, contact with drugs or alcohol, mania, anxiety, ormajormedical illness. The family environmentwas reported as stable. Alan has one sibling, and no psychiatric family history was reported. Alan had never been hospitalized; he had been seen by three outpatient family therapists in the past, and, as noted, he had been in day hospital treatment. Alan himself reported that at times he did “not feel good,” but he denied depression or anxiety. He acknowledged having fights with other children but did not elaborate on circumstances. He reported hearing “animal voices” fromunder his bed or from the closet, but he could not really make them out. He felt there were ghosts and monsters in his room, and he was afraid of somebody pulling him down under his bed. When he looked, he reported seeing a lot of “stuff under his bed,” but denied seeing monsters. On further questioning, Alan said he thought those voices could be from the wind or his parents, but he was not certain about the absence of monsters. He had these experiencesmostly in thedarkness, atnight.Hedenied paranoia or ideas of reference.

Lasting neurobehavioral abnormalities in rats after neonatal activation of serotonin 1A and 1B receptors: possible mechanisms for serotonin dysfunction in autistic spectrum disorders

Perinatal exposure of rats to selective serotonin reuptake inhibitors (SSRIs) produces sensory and social abnormalities paralleling those seen in autistic spectrum disorders (ASDs). However, the possible mechanism(s) by which this exposure produces behavioral abnormalities is unclear. We hypothesized that the lasting effects of neonatal SSRI exposure are a consequence of abnormal stimulation of 5-HT1A and/or 5-HT1B receptors during brain development. We examined whether such stimulation would result in lasting sensory and social deficits in rats in a manner similar to SSRIs using both direct agonist stimulation of receptors as well as selective antagonism of these receptors during SSRI exposure. Male and female rat pups were treated from postnatal days 8 to 21. In Experiment 1, pups received citalopram (20 mg/kg/day), saline, (±)-8-hydroxy-dipropylaminotetralin hydrobromide (8-OH-DPAT; 0.5 mg/kg/day) or 7-trifluoromethyl-4(4-methyl-1-piperazinyl)-pyrrolo[1,2-a]-quinoxaline dimaleate (CGS-12066B; 10 mg/kg/day). In Experiment 2, a separate cohort of pups received citalopram (20 mg/kg/day), or saline which was combined with either N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclo-hexanecarboxamide maleate (WAY-100635; 0.6 mg/kg/day) or N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)-1-1'-biphenyl-4-carboxamide (GR-127935; 6 mg/kg/day) or vehicle. Rats were then tested in paradigms designed to assess sensory and social response behaviors at different time points during development. Direct and indirect neonatal stimulation of 5-HT1A or 5-HT1B receptors disrupts sensory processing, produces neophobia, increases stereotypic activity, and impairs social interactions in manner analogous to that observed in ASD. Increased stimulation of 5-HT1A and 5-HT1B receptors plays a significant role in the production of lasting social and sensory deficits in adult animals exposed as neonates to SSRIs.