Many philosophers have argued that statistical evidence regarding group characteristics (particularly stereotypical ones) can create normative conflicts between the requirements of epistemic rationality and our moral obligations to each other. In a recent article, Johnson-King and Babic argue that such conflicts can usually be avoided: what ordinary morality requires, they argue, epistemic rationality permits. In this article, we show that as data get large, Johnson-King and Babic’s approach becomes less plausible. More constructively, we build on their project and develop a (...) generalized model of reasoning about stereotypes under which one can indeed avoid normative conflicts, even in a big data world, when data contain some noise. In doing so, we also articulate a general approach to rational belief updating for noisy data. (shrink)

With the advancement of internet and the emergence of network globalization, security has always been a major concern. During the trial operation, the management control platform discussed in this article included more than 600 network security vulnerabilities in the industry, with dozens of incidents, which were promptly dealt with and rectified, effectively improving the level of network security management and protection in the industry. As networks are very much vulnerable to denial of service attacks, much more emphasis has been given (...) to security. By improving their network security, network administrators have often tried their best. To attempt penetration testing, it is the best way of ensuring the system security. With the development of information technology, the security requirement of information system is increasing day by day. The use of penetration testing technology is conducive to the realization of accurate positioning, accurate detection, and active alarm of security vulnerabilities, and the optimization of monitoring and rectification of the combination of network security management control system. Taking penetration testing technology as one of the core elements of management and control, the risk index model is optimized to make network security management controllable and efficient, and effectively achieve management and control objectives. (shrink)

This comparison of time in Augustine with time in Husserl demonstrates first that both authors connect with the Platonic tradition, where ideal existence has primacy, and time appears at the moment of configuration of finite and sensible reality. It explains the conception of time in both authors, showing that the fundamental coincidence is ‘distension’, and that ‘traces’ of memory predominate in Augustine, whereas Husserl maintains a more elaborate doctrine of peculiarity of the constituting acts.

Today’s youth find it extremely difficult to look beyond the present, in large part due to the precariousness of the labour market. Unconditional basic income, meanwhile, is emerging as the economic and social policy that is attracting most interest as an alternative not only to the conditional minimum income programmes, but also to the increasing unemployment and precarious conditions of employment. This survey study, conducted among students at the University of the Basque Country (UPV/EHU) in 2021 (n = 709), explores (...) the attitudes of young people towards basic income. Findings reveal strong support among Basque youth for basic income, citing its potential to enhance personal freedom and improve living conditions. While previous studies have already found that young people tend to be more supportive of basic income, this research fills a gap in the literature by analysing in depth young people’s attitudes and beliefs about this policy proposal. (shrink)

In order to correct the deficiencies of intrusion detection technology, the entire computer and network security system are needed to be more perfect. This work proposes an improved k-means algorithm and an improved Apriori algorithm applied in data mining technology to detect network intrusion and security maintenance. The classical KDDCUP99 dataset has been utilized in this work for performing the experimentation with the improved algorithms. The algorithm’s detection rate and false alarm rate are compared with the experimental data before the (...) improvement. The outcomes of proposed algorithms are analyzed in terms of various simulation parameters like average time, false alarm rate, absolute error as well as accuracy value. The results show that the improved algorithm advances the detection efficiency and accuracy using the designed detection model. The improved and tested detection model is then applied to a new intrusion detection system. After intrusion detection experiments, the experimental results show that the proposed system improves detection accuracy and reduces the false alarm rate. A significant improvement of 90.57% can be seen in detecting new attack type intrusion detection using the proposed algorithm. (shrink)

We comment on the proposition “that lower temperatures and especially greater seasonal variation in temperature call for individuals and societies to adopt … a greater degree of self-control” (Van Lange et al., sect. 3, para. 4) for which we cannot find empirical support in a large data set with data-driven analyses. After providing greater nuance in our theoretical review, we suggest that Van Lange et al. revisit their model with an eye toward the social determinants of self-control.

The data with the advancement of information technology are increasing on daily basis. The data mining technique has been applied to various fields. The complexity and execution time are the major factors viewed in existing data mining techniques. With the rapid development of database technology, many data storage increases, and data mining technology has become more and more important and expanded to various fields in recent years. Association rule mining is the most active research technique of data mining. Data mining (...) technology is used for potentially useful information extraction and knowledge from big data sets. The results demonstrate that the precision ratio of the presented technique is high comparable to other existing techniques with the same recall rate, i.e., the R-tree algorithm. The proposed technique by the mining effectively controls the noise data, and the precision rate is also kept very high, which indicates the highest accuracy of the technique. This article makes a systematic and detailed analysis of data mining technology by using the Apriori algorithm. (shrink)

Stiff Person Syndrome is a rare autoimmune disorder associated with antibodies against glutamic acid decarboxylase, the key enzyme in γ -aminobutyric acid synthesis. In order to investigate the role of cerebral benzodiazepinereceptor binding in SPS, we performed [ 11 C]flumazenil positron emission tomography in a female patient with SPS compared to nine healthy controls. FMZ is a radioligand to the postsynaptic central benzodiazepine receptor which is co-localized with the GABA-A receptor. In the SPS patient, we found a global reduction (...) of cortical FMZ binding. In addition, distinct local clusters of reduced radiotracer binding were observed. These data provide first in vivo evidence for a reduced postsynaptic GABA-A receptor availability which may reflect the loss of GABAergic neuronal inhibition in SPS. (shrink)

En 1988, la fouille sous‑marine du port de Thasos permettait l’extraction d’un imposant carreau de marbre, en même temps que d’autres blocs entassés en avant de la jetée antique. En 2017, un nouvel examen de la pierre, qui appartenait originellement à l’élévation d’un édifice de l’agora toute proche, a révélé une inscription rendue très difficilement lisible par un séjour prolongé dans l’eau de mer. Le Peuple des Thasiens y honorait son patron, Caius Octavius, proconsul de Macédoine en 60‑59 av. (...) J.‑C. (shrink)

Using delay differential equations to study mathematical models of Parkinson's disease and Huntington's disease is important to show how important it is for synchronization between basal ganglia loops to work together. We used the delay circuit RLC (resistor, inductor, capacitor) model to show how the direct pathway and the indirect pathway in the basal ganglia excite and inhibit the motor cortex, respectively. A term has been added to the mathematical model without time delay in the case of the hyperdirect pathway. (...) It is proposed to add a non-linear term to adjust the synchronization. We studied Hopf bifurcation conditions for the proposed models. The desynchronization of response times between the direct pathway and the indirect pathway leads to different symptoms of Parkinson's disease. Tremor appears when the response time in the indirect pathway increases at rest. The simulation confirmed that tremor occurs and the motor cortex is in an inhibited state. The direct pathway can increase the time delay in the dopaminergic pathway, which significantly increases the activity of the motor cortex. The hyperdirect pathway regulates the activity of the motor cortex. The simulation showed bradykinesia occurs when we switch from one movement to another that is less exciting for the motor cortex. A decrease of GABA in the striatum or delayed excitation of the substantia nigra from the subthalamus may be a major cause of Parkinson's disease. An increase in the response time delay in one of the pathways results in the chaotic movement characteristic of Huntington's disease. (shrink)

Many biologically active compounds including neurotransmitters, metabolic precursors, and certain drugs are accumulated intracellularly by transporters that are coupled to the transmembrane Na+ gradient. Amino acid neurotransmitter transporters play a key role in the regulation of extracellular amino acid concentrations and termination of neurotransmission in the CNSAbbreviations: CNS, central nervous system; GABA, γ‐aminobutyric acid; cDNA, complementary deoxyribonucleic acid; mRNA, messenger ribonucleic acid; NMDA, N‐methyl‐D‐aspartate; PKC, protein kinase C; PMA, phorbol 12‐myristate 13‐acetate; DAG, diacyl glycerol; R59022, DAG kinase inhibitor; AA, (...) arachidonic acid; ACHC, cis‐3‐aminocyclohexanecarboxylic acid; GAT‐A, ACHC‐sensitive GABA transporter; GAT‐B, β‐alanine‐sensitive GABA transporter; GLY‐1 and GLYT‐1, glycine transporters; PROT‐1, proline transporter; BGT‐1, betaine transporter.. Transporters for the major amino acid neurotransmitters glutamate, GABA, and glycine are found in both neurons and glial cells. Recent work has resulted in the identification of cDNAs encoding several amino acid neurotransmitter transport proteins, all of which belong to the Na+‐and Cl−‐dependent transporter gene family. The diversity of this family suggests a degree of transporter heterogeneity that is greater than that indicated by biochemical and pharmacological studies. (shrink)

We recently described a novel form of stress‐associated bidirectional plasticity at GABA synapses onto hypothalamic parvocellular neuroendocrine cells (PNCs), the apex of the hypothalamus‐pituitary‐adrenal axis. This plasticity may contribute to neuroendocrine adaptation. However, this GABA synapse plasticity likely does not translate into a simple more and less of inhibition because the ionic driving force for Cl−, the primary charge carrier for GABAA receptors, is dynamic. Specifically, stress impairs a Cl− extrusion mechanism in PNCs. This not only renders the (...) steady‐state GABA response less hyperpolarizing but also makes PNCs susceptible to the activity‐dependent accumulation of Cl−. Accordingly, GABA synapse plasticity impacts both the robustness of GABA voltage response and dynamic Cl− loading, imposing nonlinear influences on PNC excitability during circuit activities. This theoretical consideration predicts roles for GABA transmission far more versatile than canonical inhibition. We propose potential impacts of GABA synapse plasticity on the experience‐dependent fine‐tuning of neuroendocrine stress responses. (shrink)

In this note an allusion recreated from Seneca’s De providentia is rescued as it was hidden in the Octavius of Minucius Felix, which recovers and adapted some topics from the Senecan text in a few brief lines which have been hitherto practically unnoticed; if the allusion is verified, a more recent reading of Seneca’s writing would make full argumentative sense.

In amblyopia, abnormal visual experience during development leads to an enduring loss of visual acuity in adulthood. Physiological studies in animal models suggest that intracortical GABAergic inhibition may mediate visual deficits in amblyopia. To better understand the relationship between visual cortical γ-aminobutyric acid (GABA) and perceptual suppression in persons with amblyopia (PWA), we employed magnetic resonance spectroscopy (MRS) to quantify GABA levels in both PWA and normally-sighted persons (NSP). In the same individuals, we obtained psychophysical measures of perceptual (...) suppression for a variety of ocular configurations. In PWA, we found a robust negative correlation between the depth of amblyopia (the difference in visual acuity between the amblyopic and non-amblyopic eyes) and GABA concentration that was specific to visual cortex and was not observed in a sensorimotor cortical control region. Moreover, lower levels of visual cortical GABA were associated with weaker perceptual suppression of the fellow eye by the amblyopic eye and stronger suppression of the amblyopic eye by the fellow eye. Taken together, our findings provide evidence that intracortical GABAergic inhibition is an important component of the pathology of human amblyopia and suggest possible therapeutic interventions to restore vision in the amblyopic eye through enhancement of visual cortical GABAergic signaling in PWA. (shrink)

The dialogue Octavius by Minucius Felix is a point of reception in the legacy of Ciceronian skeptical fideism, and as such it deserves its place in the history of skeptical fideism. Drawing on his Ciceronian model, Minucius depicts a skeptical fideist—Caecilius—struggling to hold on to his religious traditions in the face of the challenges posed by the new religion of Christianity. But Minucius himself is a convert to the new religion and writes in its defense. And this authorial intent (...) distorts the skeptical fideism which Minucius found in Cicero’s De natura deorum by adding credulous and/or dogmatic elements that are ill-fitted to skeptical fideism but well-suited to his authorial intention of answering all available objections to Christianity in the hopes of winning converts. (shrink)

En la recensión se presenta la obra de Byung-Chul Han, quien a través de una serie de comparaciones entre el budismo Zen y la filosofía moderna occidental pretende señalar la riqueza del pensamiento oriental y las posibilidades que brinda al desarrollo de la filosofía contemporánea.

A pesar de matices y variaciones de significado, la intencionalidad husserliana sigue al servicio de la verdad como adaequatio, adaptada al orden monádico de la conciencia trascendental. Sin embargo, en la conciencia interna del tiempo se ve la dificultad de interpretar intencionalmente la esfera pasiva de la conciencia, con lo cual peligra la vocación por la verdad de la intencionalidad. A partir de la constitución eidética, se busca una génesis pasiva del sentido ideal intencional, sin perder su referencia egológica. Despite (...) the nuances and variations in meaning, Husserlian intentionality continues to be at the service of truth as adaequatio, adapted to the monadic order of transcendental consciousness. However, the internal consciousness of time reveals the difficulty of interpreting the passive sphere of consciousness intentionally, which jeopardizes intentionality's vocation for truth. On the basis of eidetic constitution, a passive genesis of ideal intentional meaning is sought, which does not lose its reference to the ego. (shrink)

A partir de la divergencia de M. Foucault con Th. Hobbes con respecto a la guerra como principio y fundamento del poder, se muestra la importancia de esa diferencia conceptual para los análisis políticos contemporáneos. Foucault sostiene que, en las sociedades modernas de Occidente, la comunidad política, y más precisamente la política misma, ha sido el terreno de la guerra librada por otros medios. Por extensión, esta tesis significa invertir el principio de von Clausewitz; a saber, que la guerra es (...) la continuación de la política por otros medios. On the basis of the difference between M. Foucault and Th. Hobbes regarding war as a principle and foundation of power, the article shows the importance of this conceptual difference for contemporary political analyses. Foucault argues that in modern Western societies, the political community and, more specifically, politics itself, has been the space of a war waged by other means. By extension, this thesis entails the inversion of von Clausewitz's principle, namely, that war is the continuation of politics by other means. A partir da divergência de M. Foucault com Th. Hobbes sobre a guerra como princípio e fundamento do poder, mostra-se a importância dessa diferença conceitual para as análises políticas contemporâneas. Foucault sustenta que, nas sociedades modernas do Ocidente, a comunidade política, e mais precisamente a política em si, tem sido o terreno da guerra travada por outros meios. Por extensão, esta tese significa inverter o princípio de von Clausewitz; a saber, que a guerra é a continuação da política por outros meios. (shrink)

Deep brain stimulation is a clinical intervention for the treatment of movement disorders. It has also been applied to the treatment of psychiatric disorders such as depression, anorexia nervosa, obsessive-compulsive disorder, and schizophrenia. Psychiatric disorders including schizophrenia, bipolar disorder, and major depression can lead to psychosis, which can cause patients to lose touch with reality. The ventral tegmental area, located near the midline of the midbrain, is an important region involved in psychosis. However, the clinical application of electrical stimulation of (...) the VTA to treat psychotic diseases has been limited, and related mechanisms have not been thoroughly studied. In the present study, hyperlocomotion and stereotyped behaviors of the mice were employed to mimic and evaluate the positive-psychotic-like behaviors. We attempted to treat positive psychotic-like behaviors by electrically stimulating the VTA in mice and exploring the neural mechanisms behind behavioral effects. Local field potential recording and in vivo fiber photometry to observe the behavioral effects and changes in neural activities caused by DBS in the VTA of mice. Optogenetic techniques were used to verify the neural mechanisms underlying the behavioral effects induced by DBS. Our results showed that electrical stimulation of the VTA activates local gamma-aminobutyric acid neurons, and dopamine neurons, reduces hyperlocomotion, and relieves stereotyped behaviors induced by MK-801 injection. The results of optogenetic manipulation showed that the activation of the VTA GABA neurons, but not DA neurons, is involved in the alleviation of hyperlocomotion and stereotyped behaviors. We visualized changes in the activity of specific types in specific brain areas induced by DBS, and explored the neural mechanism of DBS in alleviating positive psychotic-like behaviors. This preclinical study not only proposes new technical means of exploring the mechanism of DBS, but also provides experimental justification for the clinical treatment of psychotic diseases by electrical stimulation of the VTA. (shrink)

Attention-deficit/hyperactivity disorder (ADHD) is currently defined as a cognitive/behavioral developmental disorder where all clinical criteria are behavioral. Inattentiveness, overactivity, and impulsiveness are presently regarded as the main clinical symptoms. The dynamic developmental behavioral theory is based on the hypothesis that altered dopaminergic function plays a pivotal role by failing to modulate nondopaminergic (primarily glutamate and GABA) signal transmission appropriately. A hypofunctioning mesolimbic dopamine branch produces altered reinforcement of behavior and deficient extinction of previously reinforced behavior. This gives rise to (...) delay aversion, development of hyperactivity in novel situations, impulsiveness, deficient sustained attention, increased behavioral variability, and failure to “inhibit” responses (“disinhibition”). A hypofunctioning mesocortical dopamine branch will cause attention response deficiencies (deficient orienting responses, impaired saccadic eye movements, and poorer attention responses toward a target) and poor behavioral planning (poor executive functions). A hypofunctioning nigrostriatal dopamine branch will cause impaired modulation of motor functions and deficient nondeclarative habit learning and memory. These impairments will give rise to apparent developmental delay, clumsiness, neurological “soft signs,” and a “failure to inhibit” responses when quick reactions are required. Hypofunctioning dopamine branches represent the main individual predispositions in the present theory. The theory predicts that behavior and symptoms in ADHD result from the interplay between individual predispositions and the surroundings. The exact ADHD symptoms at a particular time in life will vary and be influenced by factors having positive or negative effects on symptom development. Altered or deficient learning and motor functions will produce special needs for optimal parenting and societal styles. Medication will to some degree normalize the underlying dopamine dysfunction and reduce the special needs of these children. The theory describes how individual predispositions interact with these conditions to produce behavioral, emotional, and cognitive effects that can turn into relatively stable behavioral patterns. Key Words: catecholamine; clumsiness; dopamine; hyperkinesis; hyperkinetic disorder; impulsivity; monoamine; neuromodulator; overactivity; pollutants; reinforcement; reward; verbally governed behavior; soft signs; variability. (shrink)

Newborn neurons are generated in the adult hippocampus from a pool of self‐renewing stem cells located in the subgranular zone (SGZ) of the dentate gyrus. Their activation, proliferation, and maturation depend on a host of environmental and cellular factors but, until recently, the contribution of local neuronal circuitry to this process was relatively unknown. In their recent publication, Song and colleagues have uncovered a novel circuit‐based mechanism by which release of the neurotransmitter, γ‐aminobutyric acid (GABA), from parvalbumin‐expressing (PV) interneurons, (...) can hold radial glia‐like (RGL) stem cells of the adult SGZ in a quiescent state. This tonic GABAergic signal, dependent upon the activation of γ2 subunit‐containing GABAA receptors of RGL stem cells, can thus prevent their proliferation and subsequent maturation or return them to quiescence if previously activated. PV interneurons are thus capable of suppressing neurogenesis during periods of high network activity and facilitating neurogenesis when network activity is low. (shrink)

Tackling impaired bioenergetics in multiple sclerosis has been recently recognized as an innovative approach with therapeutic potential. Guanidinoacetic acid is an experimental nutrient that plays a significant role in high-energy phosphate metabolism. The preliminary trials suggest beneficial effects of supplemental GAA in MS, with GAA augments biomarkers of brain energy metabolism and improves patient-reported features of the disease. GAA can also impact other metabolic footprints of MS, including demyelination, oxidative stress, and GABA-glutamate imbalance. In this mini-review article, we summarize (...) studies evaluating GAA effectiveness in MS, explore mechanisms of GAA action, and discuss the challenges of using dietary GAA as an element of MS therapy. (shrink)

Source preference in which equally distributed risks may be valued differently has been receiving increasing attention. Using subjects recruited in Berkeley, Fox and Tversky demonstrate a familiarity bias in source preference—betting on a less than even-chance event based on San Francisco temperature is valued more than betting on a better than even-chance event based on Istanbul temperature. Neophobia is associated with the amygdala which is GABA-rich and is known to be modulated by benzodiazepines as anxiolytic agents that enhance the (...) activity of the GABAA receptor in processing anxiety and fear. This leads to our hypothesis that familiarity bias in decision making may be explained by polymorphic variations in this receptor mediated by anxiety regulation in the amygdala. In two companion studies involving Beijing-based subjects, we examine 10 single nucleotide polymorphisms of GABRB2 and find 7 SNPs each showing negative association between familiarity bias—preference for betting on parity of Beijing temperature over Tokyo temperature—and having at least one minor allele. In an imaging genetics study of a subsample of subjects based on the SNP with the most balanced allelic distribution, we find that subjects’ familiarity bias in terms of risk aversion towards bets on the parity of the temperature of 20 Chinese cities is negatively associated with their post-scanning familiarity ratings of the cities only for those with no minor allele in this SNP. Moreover, familiarity bias is positively associated with activation in the right amygdala along with the brain’s attention networks. Overall, our findings help discriminate between ambiguity aversion and familiarity bias in source preference and supports our gene–brain–behavior hypothesis of GABAergic modulation of amygdala activation in response to familiarity towards the source of uncertainty. (shrink)

Computerized relaxation training has been suggested as an effective and easily accessible intervention for individuals with psychological distress. To better elucidate the neural mechanism that underpins the effects of relaxation training, we investigated whether a 10-session computerized relaxation training program changed prefrontal gamma-aminobutyric acid levels and cerebral blood flow in women with psychological distress. We specifically focused on women since they were reported to be more vulnerable to develop stress-related disorders than men. Nineteen women with psychological distress but without a (...) diagnosis of psychiatric disorders received the 10-day computerized relaxation training program that consisted of 30-min cognitive-relaxation training and 10-min breathing-relaxation training per day. At baseline and post-intervention, perceived stress levels, anxiety, fatigue, and sleep quality were assessed by self-report questionnaires. Brain magnetic resonance spectroscopy and arterial spin labeling scans were also performed before and after the intervention to evaluate GABA levels and relative CBF in the prefrontal region. Levels of perceived stress, anxiety, fatigue, and sleep quality improved following 10 sessions of computerized relaxation training, resulting in a significant relief in composite scores of stress-related symptoms. The prefrontal GABA levels decreased, while relative CBF increased after the intervention. In addition, a greater increase in relative prefrontal CBF was associated with better composite scores of stress-related symptoms following the intervention. The current findings suggest that computerized relaxation training may improve stress-related symptoms through modulating the prefrontal GABA levels and CBF in women with psychological distress. (shrink)

Recent studies have provided evidence of associations between neurochemistry and reading (dis)ability (Pugh et al., 2014). Based on a long history of studies indicating that fluent reading entails the automatic convergence of the written and spoken forms of language and our recently proposed Neural Noise Hypothesis (Hancock et al., 2017), we hypothesized that individual differences in cross-modal integration would mediate, at least partially, the relationship between neurochemical concentrations and reading. Cross-modal integration was measured in 231 children using a two-alternative forced (...) choice cross-modal matching task with three language conditions (letters, words, and pseudowords) and two levels of difficulty within each language condition. Neurometabolite concentrations of Choline (Cho), Glutamate (Glu), gamma-Aminobutyric (GABA), and N- acetyl-aspartate (NAA) were then measured in a subset of this sample (n = 70) with Magnetic Resonance Spectroscopy (MRS). A structural equation mediation model revealed that the effect of cross-modal word matching mediated the relationship between increased Glu (which has been proposed to be an index of neural noise) and poorer reading ability. In addition, the effect of cross-modal word matching fully mediated a relationship between increased Cho and poorer reading ability. Multilevel mixed effects models confirmed that lower Cho predicted faster cross-modal matching reaction time, specifically in the hard word condition. These Cho... (shrink)

Differential diagnosis of motor symptoms, for example, akinesia, may be difficult in clinical neuropsychiatry. Symptoms may be either of neurologic origin, for example, Parkinson's disease, or of psychiatric origin, for example, catatonia, leading to a so-called “conflict of paradigms.” Despite their different origins, symptoms may appear more or less clinically similar. Possibility of dissociation between origin and clinical appearance may reflect functional brain organisation in general, and cortical-cortical/subcortical relations in particular. It is therefore hypothesized that similarities and differences between Parkinson's (...) disease and catatonia may be accounted for by distinct kinds of modulation between cortico-cortical and cortico-subcortical relations. Catatonia can be characterized by concurrent motor, emotional, and behavioural symptoms. The different symptoms may be accounted for by dysfunction in orbitofrontal-prefrontal/parietal cortical connectivity reflecting “horizontal modulation” of cortico-cortical relation. Furthermore, alteration in “top-down modulation” reflecting “vertical modulation” of caudate and other basal ganglia by GABA-ergic mediated orbitofrontal cortical deficits may account for motor symptoms in catatonia. Parkinson's disease, in contrast, can be characterized by predominant motor symptoms. Motor symptoms may be accounted for by altered “bottom-up modulation” between dopaminergic mediated deficits in striatum and premotor/motor cortex. Clinical similarities between Parkinson's disease and catatonia with respect to akinesia may be related with involvement of the basal ganglia in both disorders. Clinical differences with respect to emotional and behavioural symptoms may be related with involvement of different cortical areas, that is, orbitofrontal/parietal and premotor/motor cortex implying distinct kinds of modulation – “vertical” and “horizontal” modulation, respectively. Key Words: Bottom-up modulation; catatonia; horizontal modulation; Parkinson's disease; top-down modulation; vertical modulation. (shrink)

Injury to the central or peripheral nervous system is often associated with persistent pain. After ischemic injury to the spinal cord, rats develop severe mechanical allodynia-like symptoms, expressed as a pain-like response to innocuous stimuli. In its short-lasting phase the allodynia can be relieved with the [gamma]-aminobutyric acid (GABA)-B receptor agonist baclofen, which also reverses the hyperexcitability of dorsal horn interneurons to mechanical stimuli. Furthermore, there is a reduction in GABA immunoreactivity in the dorsal horn of allodynic rats. (...) Clinical neuropathic pain of peripheral and central origin often cannot be relieved by opiates at doses that do not cause side effects. The loss of sensitivity to opiates may be associated with the up-regulation of endogenous antiopioid substances, such as the neuropeptide cholecystokinin (CCK). CCK and its receptor (CCK-R) protein is normally not detectable in rat dorsal root ganglion cells. After peripheral nerve section, both CCK and CCK-R are up-regulated in the dorsal root ganglia. Furthermore, CI 988, an antagonist of the CCK-B receptor, chronically coadministered with morphine, reduces autotomy, a behavior that may be a sign of neuropathic pain following peripheral nerve section. Thus, opiate insensitivity may be due to the release of CCK from injured primary afferents. Similarly, in the chronic phase of the spinal ischemic model of central pain, the allodynia-like symptom is not relieved by systemic morphine, but is significantly reversed by the CCK-B antagonist. Consequently, up-regulation of CCK and CCK-R in the CNS may also underlie opiate drug insensitivity following CNS injury. Thus, dysfunction of central inhibition involving GABA and endogenous opioids may be a factor underlying the development of sensory abnormalities and/or pain following injury to neural tissue. (shrink)

The neurotransmitters GABA and glutamate have been suggested to play a role in Major Depressive Disorder (MDD) through an imbalance between cortical inhibition and excitation. This effect has been highlighted in higher brain areas, such as the prefrontal cortex, but has also been posited in basic sensory cortices. Based on this, magnetic resonance spectroscopy (MRS) was used to investigate potential changes to GABA+ and glutamate+glutamine (Glx) concentrations within the occipital cortex in MDD patients (n = 25) and healthy (...) controls (n = 25). No difference in occipital GABA+ or Glx concentrations, nor in the GABA+/Glx ratio, was found between groups. An analysis of an extended MDD patient and unmatched control dataset (n = 90) found no correlation between metabolite concentrations and depressive symptoms. These results were integrated with prior studies through metabolite-specific meta-analyses, revealing no difference in occipital GABA and Glx concentrations between patients and controls. An effect of publication year on GABA group differences was found, suggesting that previously reported results may have been artifacts of measurement accuracy. Taken together, our results suggest that, contrary to some prior reports, MRS measurements of occipital GABA and Glx do not differ between MDD patients and controls. (shrink)

The way the central nervous system (CNS) responds to diverse stimuli is contingent upon the specific brain state of the individual, including sleep and wakefulness. Despite the wealth of readout parameters and data delineating the brain states, the primary mechanisms are yet to be identified. Here we highlight the role of astrocytes, with a specific emphasis on chloride (Cl−) homeostasis as a modulator of brain states. Neuronal activity is regulated by the concentration of ions that determine excitability. Astrocytes, as the (...) CNS homeostatic cells, are recognised for their proficiency in maintaining dynamic homeostasis of ions, known as ionostasis. Nevertheless, the contribution of astrocyte‐driven ionostasis to the genesis of brain states or their response to sleep‐inducing pharmacological agents has been overlooked. Our objective is to underscore the significance of astrocytic Cl− homeostasis, elucidating how it may underlie the modulation of brain states. We endeavour to contribute to a comprehensive understanding of the interplay between astrocytes and brain states. (shrink)

Based on brain imaging findings, we present a model according to which addiction emerges as an imbalance in the information processing and integration among various brain circuits and functions. The dysfunctions reflect (a) decreased sensitivity of reward circuits, (b) enhanced sensitivity of memory circuits to conditioned expectations to drugs and drug cues, stress reactivity, and (c) negative mood, and a weakened control circuit. Although initial experimentation with a drug of abuse is largely a voluntary behavior, continued drug use can eventually (...) impair neuronal circuits in the brain that are involved in free will, turning drug use into an automatic compulsive behavior. The ability of addictive drugs to co‐opt neurotransmitter signals between neurons (including dopamine, glutamate, and GABA) modifies the function of different neuronal circuits, which begin to falter at different stages of an addiction trajectory. Upon exposure to the drug, drug cues or stress this results in unrestrained hyperactivation of the motivation/drive circuit that results in the compulsive drug intake that characterizes addiction. (shrink)

Discussions of the object as a key to understanding central aspects of modern and contemporary art. Artists increasingly refer to "post-object-based" work while theorists engage with material artifacts in culture. A focus on "object-based" learning treats objects as vectors for dialogue across disciplines. Virtual imaging enables the object to be abstracted or circumvented, while immaterial forms of labor challenge materialist theories. This anthology surveys such reappraisals of what constitutes the "objectness" of production, with art as its focus. Among the topics (...) it examines are the relation of the object to subjectivity; distinctions between objects and things; the significance of the object's transition from inert mass to tool or artifact; and the meanings of the everyday in the found object, repetition in the replicated or multiple object, loss in the absent object, and abjection in the formless or degraded object. It also explores artistic positions that are anti-object; theories of the experimental, liminal or mental object; and the role of objects in performance. The object becomes a prism through which to reread contemporary art and better understand its recent past. Artists surveyed include Georges Adéagbo, Art in Ruins, Iain Baxter, Louise Bourgeois, Pavel Büchler, Lygia Clark, Claude Closky, Brian Collier, Jimmie Durham, Fischli & Weiss, Luca Frei, Meschac Gaba, Isa Genzken, Gruppe Geflecht, Eva Hesse, Mike Kelley, John Latham, Antje Majewski, Gustav Metzger, Cady Noland, Gabriel Orozco, Adrian Piper, Falke Pisano, Eva Rothschild, Aura Satz, Kenneth Snelson, Hito Steyerl, Josef Strau, Alina Szapocznikow, Joëlle Tuerlinckx, Erwin Wurm Writers include Homi K. Bhabha, Jack Burnham, Ewa Lajer-Burcharth, Lynne Cooke, Gillo Dorfles, Jean Fisher, Ferreira Gullar, Charles Harrison, Paulo Herkenhoff, Julia Kristeva, Bruno Latour, Bracha Lichtenberg-Ettinger, Jean-François Lyotard, Lev Manovich, Ursula Meyer, Bruno Munari, Georges Perec, Hans-Jörg Rheinberger, Dieter Roelstraete, Howard Singerman, Nancy Spector, Marcus Steinweg, Anne Wagner, Gérard Wajcman, Slavoj Zizek. (shrink)

Disorders of consciousness and the self are at the forefront of schizophrenia symptomatology. Patients are impaired in feeling themselves as the authors of their thoughts and actions. In addition, their flow of consciousness is disrupted, and thought fragmentation has been suggested to be involved in the patients’ difficulties in feeling as being one unique, unchanging self across time. Both impairments are related to self disorders, and both have been investigated at the experimental level. Here we review evidence that both mechanisms (...) of motor control and the temporal structure of signal processing are impaired in schizophrenia patients. Based on this review, we propose that the sequencing of action and perception plays a key role in the patients’ impairments. Furthermore, the millisecond time scale of the disorders, as well as the impaired sequencing, highlights the cooperation between brain networks including the cerebellum, as proposed by Andreasen (1999). We examine this possibility in the light of recent knowledge on the anatomical and physiological properties of the cerebellum, its role in timing, and its involvement in known physiological impairments in patients with schizophrenia, e.g., resting states and brain dynamics. A disruption in communication between networks involving the cerebellum, related to known impairments in dopamine, glutamate and GABA transmission, may help to better explain why patients experience reduced attunement with the external world and possibly with themselves. (shrink)

Current research on the neural basis of consciousness is based mainly on neuroimaging, physiology and psychophysics. This target article reviews what is known about biochemical factors that may contribute to the development of consciousness, based on loss of consciousness (i.e., coma). There are two theories of the biochemical mode of action of general anaesthetics. One is that anaesthesia is a direct (i.e., not receptor-mediated) effect of the anaesthetic on cellular neurophysiological function; the other is that some alteration of receptor function (...) occurs. General anaesthetics are mainly GABA agonists but some (such as ketamine) are glutamate antagonists. They also affect other systems, particularly cholinergic ones. There are various comas of metabolic origin. For example, a combination of small doses of the iron chelators desferrioxamine and prochlorperazine induce a profound and long lasting coma in humans. The mechanisms that might mediate this include redox mechanisms at the glutamate synapse, post-synaptic endocytosis of dopamine and iron, and intracellular iron-dopamine complexes, which are powerful dismuters of the superoxide anion. New findings in cell biology relating to endocytosis and recycling of receptors are discussed in a wider context. These biochemical events may induce coma by two mechanisms: (i) Consciousness may depend on widespread cortical (or cortico-thalamic) activation. (ii) Whereas these biochemical changes are widespread, only the changes in a subset of consciousness' neurons may count. An experimental program to distinguish between these two alternatives is proposed. (shrink)

Concept of ethics in Ādi-Granth, Sikh canon.

Are there sex differences in pain? For experimentally delivered somatic stimuli, females have lower thresholds, greater ability to discriminate, higher pain ratings, and less tolerance of noxious stimuli than males. These differences, however, are small, exist only for certain forms of stimulation and are affected by many situational variables such as presence of disease, experimental setting, and even nutritive status. For endogenous pains, women report more multiple pains in more body regions than men. With no obvious underlying rationale, some painful (...) diseases are more prevalent among females, others among males and, for many diseases, symptoms differ between females and males. Sex differences in attitudes exist that affect not only reporting, coping, and responses to treatment, but also measurement and treatment. So many variables are operative, however, that the most striking feature of sex differences in reported pain experience is the apparent overall lack of them. On the other hand, deduction from known biological sex differences suggests that these are powerful sex differences in the operation of pain mechanisms. First, the vaginal canal provides an additional route in women for internal trauma and invasion by pathological agents that puts them at greater risk for developing hyperalgesia in multiple body regions. Second, sex differences in temporal patterns are likely to give rise to sex differences in how pain is and stimuli are interpreted, a situation that could lead to a greater variability and wider range of pains without obvious peripheral pathology among females. Third, sex differences in the actions of sex hormones suggest pain-relevant differences in the operation of many neuroactive agents, opiate and nonopiate systems, nerve growth factor, and the sympathetic system. Thus, while inductive analysis of existing data demonstrate more similarities than differences in pain experience between females and males, deductive analysis suggests important operational sex differences in its production. (shrink)

Goal-directed spatial decision making video games combine spatial mapping, memory, and reward; all of which can involve hippocampal excitation through suppression of an inhibitory neurotransmitter, γ-aminobutyric acid. In this study, GABA was measured before and after 30 min of video game play within a voxel around the hippocampus. It was predicted that all participants would experience a decrease in GABA during gaming as a result of in-game rewards; and, those who were most competitive with the goal-directed spatial decision (...) making game would display lower hippocampal GABA concentrations after gaming. Those who were not competitive, because they were too skilled or not skilled enough, would demonstrate higher hippocampal GABA concentrations after gaming. While there were no significant differences in hippocampal GABA before and after gaming for gamers and non-gamers alike, there was a significant quadratic regression between performance on a spatial working memory task and post-gaming hippocampal GABA concentrations. (shrink)

In considering the rise of American Humanism, we will explore these developments, as expressed in the Free Religious Association (FRA) and the early Chicago School of Philosophy. Brief consideration will be given to the developments in the Unitarian Church in America which led to the formation of the FRA in 1867. The focus on the FRA will center on four key founders, Ralph Waldo Emerson, Octavius Brooks Frothingham, Francis Ellingwood Abbot and William James Potter. Following the World’s Congress of (...) Religions (1893) and the adoption of Abbot’s “free religion” in a revised constitution for Unitarianism in 1895, the emphasis shifts to the early philosophy department at the University of Chicago and the rise of Humanism. Contributions and influences on the development of Humanism by George Burman Foster, Edward Scribner Ames, and Albert Eustace Haydon will be explored. (shrink)

Vergil's plagiarism has been a theme for critics ever since Perellius Faustus made an anthology of his ‘furta’ and Quintus Octavius Avitus com-piled eight volumes of Оμоιóτησ, giving both the original passages and Vergil's adaptations of them . Much of this literature has survived in the commentary of Servius and in Book VI. of the Saturnalia of Macrobius. The study of his imitations and plagiarisms throws much light on Vergil's methods and aims of composition, and has frequently been attempted (...) in editions of his works. But one class of his plagiarisms differs considerably from the rest. Often in the Aenèid he incorporates phrases, either intact or slightly altered, from the Annales of Ennius. These differ from where he imitates Homer, because in them he does not have to translate from Greek into Latin and so remake the original into something new, and they differ, too, from his adaptations of some other earlier Latin poets, because Ennius was his only important forerunner who had written on the same heroic themes of war and the growth of Rome. (shrink)