According to berkley's review, women have a higher risk of suffering from pain than men. If this is true, there should be more frequent and more intense activity both in the pain excitatory system and in the pain inhibitory system of women than of men. Consequently, it remains unclear whether the overall effect at the end is more pain or less pain in women. This conclusion fits the weak sex differences observed for experimental and clinical pain as shown (...) by BERKLEY's review of the literature. (shrink)

Stroke remains one of the leading causes of various disabilities, including debilitating motor and language impairments. Though various treatments exist, post-stroke impairments frequently become chronic, dramatically reducing daily life quality, and requiring specific rehabilitation. A critical goal of chronic stroke rehabilitation is to induce, usually through behavioral training, experience-dependent plasticity processes in order to promote functional recovery. However, the efficiency of such interventions is typically modest, and very little is known regarding the neural dynamics underpinning recovery processes and possible biomarkers (...) of their efficiency. Some studies have emphasized specific alterations of excitatory–inhibitory balance within distributed neural networks as an important recovery correlate. Neural processes sensitive to these alterations, such as task-dependent oscillatory activity in beta as well as alpha bands, may be candidate biomarkers of chronic stroke functional recovery. In this review, we discuss the results of studies on motor and language recovery with a focus on oscillatory processes centered around the beta band and their modulations during functional recovery in chronic stroke. The discussion is based on a framework where task-dependent modulations of beta and alpha oscillatory activity, generated by the deep cortical excitatory–inhibitory microcircuits, serve as a neural mechanism of domain-general top-down control processes. We discuss the findings, their limitations, and possible directions for future research. (shrink)

Autism spectrum disorders (ASD) are thought to result in part from altered cortical excitatory-inhibitory balance; this pathophysiology may impact the generation of oscillations on EEG. We investigated premotor-parietal cortical physiology associated with praxis, which has strong theoretical and empirical associations with ASD symptomatology. 25 children with high-functioning ASD (HFA) and 33 controls performed a praxis task involving the pantomiming of tool use, while EEG was recorded. We assessed task-related modulation of signal power in alpha and beta frequency (...) bands. Compared with controls, subjects with HFA showed 27% less left central (motor/premotor) beta (18-22 Hz) event-related desynchronization (ERD) (p = 0.030), as well as 24% less left parietal alpha (7-13 Hz) ERD (p = 0.046). Within the HFA group, blunting of central ERD attenuation was associated with impairments in clinical measures of praxis imitation (r = -0.4; p = 0.04) and increased autism severity (r = 0.48; p = 0.016). The modulation of central beta activity is associated, among other things, with motor imagery, which may be necessary for imitation. Impaired imitation has been associated with core features of ASD. Altered modulation of oscillatory activity may be mechanistically involved in those aspects of motor network function that relate to the core symptoms of ASD. (shrink)

Backgrounds: Transcranial direct current stimulation is a non-invasive brain stimulation technique for the treatment of several psychiatric disorders, e.g., mood disorders and schizophrenia. Therapeutic effects of tDCS are suggested to be produced by bi-directional changes in cortical activities, i.e., increased/decreased cortical excitability via anodal/cathodal stimulation. Although tDCS provides a promising approach for the treatment of psychiatric disorders, its neurobiological mechanisms remain to be explored.Objectives: To review recent findings from neurophysiological, chemical, and brain-network studies, and consider how tDCS ameliorates psychiatric conditions.Findings: (...) Enhancement of excitatory synaptic transmissions through anodal tDCS stimulation is likely to facilitate glutamate transmission and suppress gamma-aminobutyric acid transmission in the cortex. On the other hand, it positively or negatively modulates the activities of dopamine, serotonin, and acetylcholine transmissions in the central nervous system. These neural events by tDCS may change the balance between excitatory and inhibitory inputs. Specifically, multi-session tDCS is thought to promote/regulate information processing efficiency in the cerebral cortical circuit, which induces long-term potentiation by synthesizing various proteins.Conclusions: This review will help understand putative mechanisms underlying the clinical benefits of tDCS from the perspective of neurotransmitters, network dynamics, intracellular events, and related modalities of the brain function. (shrink)

Phasic activity of dopaminergic neurons in the ventral tegmental area or substantia nigra compacta has been suggested to encode reward-prediction error signal for reinforcement learning. Recent studies have shown that the lateral habenula neurons exhibit a similar response, but for nonrewarding or punishment signals. Hence, the transient signaling role of LHb neurons is opposite that of DA neurons and also that of several other brain nuclei such as the border region of the globus pallidus internal segment and the rostral medial (...) tegmentum. Previous theoretical models have investigated the neural circuit mechanism underlying reward-based phasic activity of DA neurons, but the feasibility of a larger neural circuit model to account for the observed reward-based phasic activity in other brain nuclei such as the LHb has yet to be shown. Here, we propose a large-scale neural circuit model and show that parallel excitatory and inhibitory pathways underlie the learned neural responses across multiple brain regions. Specifically, the model can account for the phasic neural activity observed in the GPb, LHb, RMTg, and VTA/SNc. Based on sensitivity analysis, the model is found to be robust against changes in the overall neural connectivity strength. The model also predicts that striosomes play a key role in the phasic activity of VTA/SNc and LHb neurons by encoding previous and expected rewards. Taken together, our model identifies the important role of parallel neural circuit pathways in accounting for phasic activity across multiple brain areas during reward and punishment processing. (shrink)

Neuroconstructivism, Vol. 1: How the Brain Constructs Cognition implies that brain functioning depends on biofeedback and ecological trajectories. Using the building blocks of Boolean algebra known as logic gates and models of distributed control systems, I suggest that levels of regulatory states are responsible for optimal, pathological, and developmental processes. I include the impact of regulatory and nonregulatory functions on structural development.

The cellular basis of motor learning in the cerebellum has been attributed mostly to long-term depression (LTD) at excitatory parallel fiber (PF)-Purkinje cell (PC) synapses. LTD is induced when PFs are activated in conjunction with a climbing fiber (CF), the other excitatory input to PCs. Recently, by using whole-cell patch-clamp recording from PCs in cerebellar slices, a new form of synaptic plasticity was discovered. Stimulation of excitatory CFs induced a long-lasting (usually longer than 30 min) of 30 (...) sec) and the durations of RP (>30 min) strongly suggests that some intracellular biochemical machinery is involved. Pharmacological evidence suggests that protein kinases are involved in RP of inhibitory synapses and LTD of excitatory PF synapses. Besides the well-described LTD, RP could be a cellular mechanism that plays an important role in motor learning. (shrink)

Neural activity varies continually from moment to moment. Such temporal variability (TV) has been highlighted as a functionally specific brain property playing a fundamental role in cognition. We sought to investigate the mechanisms involved in TV changes between two basic behavioral states, namely having the eyes open (EO) or eyes closed (EC) in vivo in humans. To these ends we acquired BOLD fMRI, ASL, and [18F]-fluoro-deoxyglucose PET in a group of healthy participants (n = 15), along with BOLD fMRI and (...) [18F]-flumazenil PET in a separate group (n = 19). Focusing on an EO- vs EC-sensitive region in the occipital cortex (identified in an independent sample), we show that TV is constrained in the EO condition compared to EC. This reduction is correlated with an increase in energy consumption and with regional GABAA receptor density. This suggests that the modulation of TV by behavioral state involves an increase in overall neural activity that is related to an increased effect from GABAergic inhibition in addition to any excitatory changes. These findings contribute to our understanding of the mechanisms underlying activity variability in the human brain and its control. (shrink)

A general conceptual framework for large-scale neocortical dynamics based on data from many laboratories is applied to a variety of experimental designs, spatial scales, and brain states. Partly distinct, but interacting local processes (e.g., neural networks) arise from functional segregation. Global processes arise from functional integration and can facilitate (top down) synchronous activity in remote cell groups that function simultaneously at several different spatial scales. Simultaneous local processes may help drive (bottom up) macroscopic global dynamics observed with electroencephalography (EEG) or (...) magnetoencephalography (MEG). A local/global dynamic theory that is consistent with EEG data and the proposed conceptual framework is outlined. This theory is neutral about properties of neural networks embedded in macroscopic fields, but its global component makes several qualitative and semiquantitative predictions about EEG measures of traveling and standing wave phenomena. A more general “metatheory” suggests what large-scale quantitative theories of neocortical dynamics may be like when more accurate treatment of local and nonlinear effects is achieved. The theory describes the dynamics of excitatory and inhibitory synaptic action fields. EEG and MEG provide large-scale estimates of modulation of these synaptic fields around background levels. Brain states are determined by neuromodulatory control parameters. Purely local states are dominated by local feedback gains and rise and decay times of postsynaptic potentials. Dominant local frequencies vary with brain region. Other states are purely global, with moderate to high coherence over large distances. Multiple global mode frequencies arise from a combination of delays in corticocortical axons and neocortical boundary conditions. Global frequencies are identical in all cortical regions, but most states involve dynamic interactions between local networks and the global system. EEG frequencies may involve a “matching” of local resonant frequencies with one or more of the many, closely spaced global frequencies. Key Words: binding problem; cell assemblies; coherence; EEG; limit cycles; neocortical dynamics; pacemakers; phase locking; spatial scale; standing waves; synchronization. Footnotes1 The relationship between the synaptic action fields proposed in the target article and cell assemblies is clarified with Figure R1 (p. 416) of the Response. (This figure was not available to Commentators. (shrink)

Abstract“Sign stimuli” elicit specific patterns of behavior when an organism's motivation is appropriate. In the toad, visually released prey-catching involves orienting toward the prey, approaching, fixating, and snapping. For these action patterns to be selected and released, the prey must be recognized and localized in space. Toads discriminate prey from nonprey by certain spatiotemporal stimulus features. The stimulus-response relations are mediated by innate releasing mechanisms (RMs) with recognition properties partly modifiable by experience. Striato-pretecto-tectal connectivity determines the RM's recognition and localization (...) properties, whereas medialpallio-thalamo-tectal circuitry makes the system sensitive to changes in internal state and to prior history of exposure to stimuli. RMs encode the diverse stimulus conditions referring to the same prey object through different combinations of “specialized” tectal neurons, involving cells selectively tuned to prey features. The prey-selective neurons express the outcome of information processing in functional units consisting of interconnected cells. Excitatory and inhibitory interactions among feature-sensitive tectal and pretectal neurons specify the perceptual operations involved in distinguishing the prey from its background, selecting its features, and discriminating it from predators. Other connections indicate stimulus location. The results of these analyses are transmitted by specialized neurons projecting from the tectum to bulbar/spinal motor systems, providing a sensorimotor interface. Specific combinations of such projective neurons – mediating feature- and space-related messages – form “command releasing systems” that activate corresponding motor pattern generators for appropriate prey-catching action patterns. (shrink)

This selective review explores biologically inspired learning as a model for intelligent robot control and sensing technology on the basis of specific examples. Hebbian synaptic learning is discussed as a functionally relevant model for machine learning and intelligence, as explained on the basis of examples from the highly plastic biological neural networks of invertebrates and vertebrates. Its potential for adaptive learning and control without supervision, the generation of functional complexity, and control architectures based on self-organization is brought forward. Learning without (...) prior knowledge based on excitatory and inhibitory neural mechanisms accounts for the process through which survival-relevant or task-relevant representations are either reinforced or suppressed. The basic mechanisms of unsupervised biological learning drive synaptic plasticity and adaptation for behavioral success in living brains with different levels of complexity. The insights collected here point toward the Hebbian model as a choice solution for “intelligent” robotics and sensor systems. Keywords: Hebbian learning; synaptic plasticity; neural networks; self-organization; brain; reinforcement; sensory processing; robot control . (shrink)

Does motor behavior early in development have the same signatures of habituation, dishabituation, and Spencer-Thompson dishabituation known from infant perception and cognition? And do these signatures explain the choice preferences in A not B motor decision tasks? We provide new empirical evidence that gives an affirmative answer to the first question together with a unified neural dynamic model that gives an affirmative answer to the second question.In the perceptual and cognitive domains, habituation is the weakening of an orientation response to (...) a stimulus over perceptual experience. Switching to a novel stimulus leads to dishabituation, the re-establishment of the orientation response. In Spencer-Thompson dishabituation, the renewed orientation response transfers to the original stimulus. The change in orientation responses over perceptual experience explains infants' behavior in preferential looking tasks: Familiarity preference early during exposure and novelty preference late during exposure. In the motor domain, perseveration in the A not B task could be interpreted as a form of familiarity preference. There are hints that this preference reverses after enough experience with the familiar movement. We provide a unified account for habituation and patterns of preferential selection in which neural dynamic fields generate perceptual or motor representations. The build-up of activation in excitatory fields leads to familiarity preference, the build-up of activation in inhibitory fields leads to novelty preference. We show that the model accounts for the new experimental evidence for motor habituation, but is also compatible with earlier accounts for perceptual habituation and motor perseveration. We discuss how excitatory and inhibitory memory traces may regulate exploration and exploitation for both orientation to objects and motor behaviors. (shrink)

Prevailing theories of the neural basis of at least a subset of individuals with autism spectrum disorder include an imbalance of excitatory and inhibitory neurotransmission. These circuitry imbalances are commonly probed in adults using auditory steady-state responses to elicit coherent electrophysiological responses from intact circuitry. Challenges to the ASSR methodology occur during development, where the optimal ASSR driving frequency may be unknown. An alternative approach is the amplitude-modulated sweep in which the amplitude of a tone is modulated as (...) a sweep from 10 to 100 Hz over the course of ∼15 s. Phase synchrony of evoked responses, measured via intra-trial coherence, is recorded as a function of frequency. We applied such AM sweep stimuli bilaterally to 40 typically developing and 80 children with ASD, aged 6–18 years. Diagnoses were confirmed by DSM-5 criteria as well as autism diagnostic observation schedule observational assessment. Stimuli were presented binaurally during MEG recording and consisted of 20 AM swept stimuli with a duration of ∼30 s each. Peak intra-trial coherence values and peak response frequencies of source modeled responses were examined. First, the phase synchrony or inter-trial coherence of the ASSR is diminished in ASD; second, hemispheric bias in the ASSR, observed in typical development, is maintained in ASD, and third, that the frequency at which the peak response is obtained varies on an individual basis, in part dependent on age, and with altered developmental trajectories in ASD vs. TD. Finally, there appears an association between auditory steady-state phase synchrony and clinical assessment of language ability/impairment. We concluded that the AM sweep stimulus provides a mechanism for probing ASSR in an unbiased fashion, during developmental maturation of peak response frequency, peak frequencies vary, in part due to developmental age, and importantly, ITC at this peak frequency is diminished in ASD, with the degree of ITC disturbance related to clinically assessed language impairment. (shrink)

A technique for the bilateral activation of neural nets that leads to a functional asymmetry of two simulated ''cerebral hemispheres'' is described. The simulation is designed to perform object recognition, while exhibiting characteristics typical of human consciousness-specifically, the unitary nature of conscious attention, together with a dual awareness corresponding to the ''nucleus'' and ''fringe'' described by William James (1890). Sensory neural nets self-organize on the basis of five sensory features. The system is then taught arbitrary symbolic labels for a small (...) number of similar stimuli. Finally, the trained network is exposed to nonverbal stimuli for object recognition, leading to Gaussian activation of the ''sensory'' maps-with a peak at the location most closely related to the features of the external stimulus. ''Verbal'' maps are activated most strongly at the labeled location that lies closest to the peak on homologous sensory maps. On the verbal maps activation is characterized by both excitatory and inhibitory Gaussians (a Mexican hat), the parameters of which are determined by the relative locations of the verbal labels. Mutual homotopic inhibition across the ''corpus callosum'' then produces functional cerebral asymmetries, i.e., complementary activation of homologous ''association'' and ''frontal'' maps within a common focus of attention-a nucleus in the left hemisphere and a fringe in the right hemisphere. An object is recognized as corresponding to a known label when the total activation of both hemispheres (nucleus plus fringe) is strongest for that label. The functional dualities of the cerebral hemispheres are discussed in light of the nucleus/fringe asymmetry. (shrink)

Non-local phonological patterns can be difficult to analyze in the context of speech production models. Some patterns – e.g., vowel harmonies, nasal harmonies – can be readily analyzed to arise from temporal extension of articulatory gestures (i.e., spreading); such patterns can be viewed as articulatorily local. However, there are other patterns – e.g., nasal consonant harmony, laryngeal feature harmony – which cannot be analyzed as spreading; instead these patterns appear to enforce agreement between features of similar segments without affecting intervening (...) segments. Indeed, there are numerous typological differences between spreading harmonies and agreement harmonies, and this suggests that there is a mechanistic difference in the ways that spreading and agreement harmonies arise. This paper argues that in order to properly understand spreading and agreement patterns, the gestural framework of Articulatory Phonology must be enriched with respect to how targets of the vocal tract are controlled in planning and production. Specifically, it is proposed that production models should distinguish between excitatory and inhibitory articulatory gestures, and that gestures which are below a selection threshold can influence the state of the vocal tract, despite not being active. These ideas are motivated by several empirical phenomena, which include anticipatory posturing before production of a word form, and dissimilatory interactions in distractor-target response paradigms. Based on these ideas, a model is developed which provides two distinct mechanisms for the emergence of non-local phonological patterns. (shrink)

Recent pain research has concentrated heavily on excitatory processes. However, noxious stimuli activate excitatory and inhibitory systems. As failure of inhibition could underlie some forms of pathological pain, it may be argued that a full understanding of the mechanisms underlying the development of pain states can only come from a consideration of all the central sequelae of injurious stimuli. [berkley; blumberg et al.; coderre & katz; dickenson; mcmahon; weisenfeld-hallin et al.].

Ramachandran and Hirstein offer a number of interesting ideas about aesthetic preference. In this commentary I shall focus mainly on their ideas concerning peak shift and prototypicality. The authors give the example of a rat rewarded for responding to a rectangle and not rewarded for responding to a longer triangle . They argue that the rat will respond even more to a more elongated rectangle. In fact, two phenomena are involved here. Peak shift refers to the fact that the rat (...) responds more to a supernormal stimulus . Behavioural contrast refers to the fact that the rat responds more to the S++ than it did to the S+ before discrimination training took place. It does not detract from the authors’ main point, but we would be unlikely to find peak shift in the hypothetical experiment described. Peak shift only occurs when the S+ and the S- are very similar to each other . Let us say that we train a rat to respond to a 1000 Hz tone and not to respond to a 500 Hz tone. No peak shift will be found. We will find peak shift if the S+ is 1000 Hz and the S- is 950 Hz. The conventional explanation for this is that the animal shows generalization. A rat trained simply to respond to a 1000 Hz tone will also respond a bit less to one of 990 Hz, even less to one of 980 Hz, and so on. In discrimination training, our rat would have a strong tendency to respond to a 1000 Hz tone but, because of generalization from the 950 Hz tone, it would also have some tendency not to respond to it. If we subtract the inhibitory gradient around 950 Hz from the excitatory gradient around 1000 Hz, we will end up with maximal responding around, say, 1010 Hz . Intuitively, we would expect the rat to respond more to the S++ but also less vigorously than it had to the S+ before discrimination training was begun. This is because the inhibitory gradient has been subtracted from the excitatory gradient. Surprisingly, we find behavioural contrast; the rat responds more vigorously to the S++ than it had to the S+. Grossberg argues that this is because there is a tendency to keep amount of activation on a layer of cortex constant. (shrink)

An analysis of the underlying neurophysiology of aesthetics and religiousexperience allows for the development of an Aesthetic‐Religious Continuum. This continuumpertains to the variety of creative and spiritual experiences available to human beings. This mayalso lead to an understanding of the neurophysiological mechanism underlying both“positive” and “negative” aesthetics. An analysis of this continuumallows for the ability to understand the neurophenomenological aspects of a variety of humanexperiences ranging from relatively simple aesthetic experiences to profound spiritual and unitarystates such as those obtained during (...) meditation. However, it may be possible through aneuropsychological analysis to determine the similarities that exist across such experiences.Thus, certain parts of the brain may be functioning in similar ways during different experiences.It may be the case that the specific neuropsychological components of a given experience maydepend on the strength of the affectual response of the person and the ability to mark suchexperiences as significant. Further, even though similar structures may be functioning duringdifferent experiences, their inhibitory and excitatory interactions may be different. Finally, byconsidering the Aesthetic‐Religious Continuum, we may eventually arrive at a betterunderstanding of how we experience and define reality. (shrink)

We argue that prediction success maximization is a basic objective of cognition and cortex, that it is compatible with but distinct from prediction error minimization, that neither objective requires subtractive coding, that there is clear neurobiological evidence for the amplification of predicted signals, and that we are unconvinced by evidence proposed in support of subtractive coding. We outline recent discoveries showing that pyramidal cells on which our cognitive capabilities depend usually transmit information about input to their basal dendrites and amplify (...) that transmission when input to their distal apical dendrites provides a context that agrees with the feedforward basal input in that both are depolarizing, i.e., both are excitatory rather than inhibitory. Though these intracellular discoveries require a level of technical expertise that is beyond the current abilities of most neuroscience labs, they are not controversial and acclaimed as groundbreaking. We note that this cellular cooperative context-sensitivity greatly enhances the cognitive capabilities of the mammalian neocortex, and that much remains to be discovered concerning its evolution, development, and pathology. (shrink)

The brain, rather than being homogeneous, displays an almost infinite topological genus, since it is punctured with a high number of “cavities”. We might think to the brain as a sponge equipped with countless, uniformly placed, holes. Here we show how these holes, termed topological vortexes, stand for nesting, non-concentric brain signal cycles resulting from the activity of inhibitory neurons. Such inhibitory spike activity is inversely correlated with its counterpart, i.e., the excitatory spike activity propagating throughout the (...) whole brain tissue. We illustrate how Pascal’s triangles and linear and nonlinear arithmetic octahedrons are capable of describing the three-dimensional random walks generated by the inhbitory/excitatory activity of the nervous tissue. In case of nonlinear 3D paths, the trajectories of excitatory spiking oscillations can be depicted as the operation of filling the numbers of octahedrons in the form of “islands of numbers”: this leads to excitatory neuronal assemblies, spaced out by empty areas of inhibitory neuronal assemblies. These mathematical procedures allow us to describe the topology of a brain of infinite genus, to represent inhibitory neurons in terms of Betti numbers and to highlight how spike diffusion in neural tissues is generated by the random activation of tiny groups of excitatory neurons. Our approach suggests the existence of a strong mathematical background subtending the intricate oscillatory activity of the central nervous system. (shrink)

The target article is well in accordance with recent theoretical advances considering the complex large-scale brain network organization underlying emotions. Given current limitations of the methods in brain science, however, research is faced with the difficult question as to how it will be possible to elucidate the complex nonlinear interactions, the neurotransmitters involved, and the excitatory or inhibitory nature of neural processes underlying human emotion in such networks. Moreover, while investigating the network properties of neural processes underlying emotions, (...) it is also important to keep in mind that specific brain structures, or specific brain networks, generate specific emotions. Thus, while aiming at elucidating complex large-scale brain networks of emotion, it is important to identify emotional specificity of, or within, these networks. (shrink)

This paper explores multiple experimental interventions in molecular biology. By “multiple,” we mean that molecular biologists often use different modes of experimental interventions in a series of experiments for one and the same subject. In performing such a series of experiment, scientists may use different modes of interventions to realize plural goals such as testing given hypotheses and exploring novel phenomena. In order to illustrate this claim, we develop a framework of multiple modes of experimental interventions to analyze a series (...) of experiments for a single subject. Our argument begins with a brief characterization of Craver and Darden’s taxonomy of experiments, because the taxonomy they have made implies various modes of interventions. We propose to extract two interventional directions and two interventional effects from their taxonomy as the basis of classification. The vertical or inter-level direction means that an intervention is performed between different levels of organization and the horizontal or inter-stage direction means that an intervention is performed between different stages of a mechanism. Interventions may produce an excitatory or an inhibitory effect. As a consequence, we can classify modes of interventions according to different directions and effects. We illustrate our claims by doing a case study of the PaJaMo experiment, which is a series of experiments for a single subject. The final goal in this paper is to provide a taxonomy of characteristics of experimentation in which the PaJaMo experiment is adequately located. (shrink)

This article examines three aspects of the problem of understanding Benjamin Libet’s idea of conscious will causally interacting with certain neural activities involved in generating overt bodily movements. The first is to grasp the notion of cause involved, and we suggest a definition. The second is to form an idea of by what neural structure(s) and mechanism(s) a conscious will may control the motor activation. We discuss the possibility that the acts of control have to do with levels of supplementary (...) motor area activity and with the activation of populations of excitatory and inhibitory interneurons. The third aspect is to conceive of the main features of Libet’s proposed conscious mental field (CMF). We consider both an ontological and an epistemological interpretation of the CMF being nonphysical. In an attempt to refute the idea that Libet’s dualist mind–brain interactionism would violate the law of conservation of energy, we suggest that a CMF may alter the probability of the ion-channel gating by influencing structures of a size to which quantum mechanics needs to be applied. We argue that given the suggested definition of cause, and given the epistemological interpretation of the CMF being nonphysical, nothing would necessarily rule out that an element of a CMF, conscious will, may causally interact with neural activities in the brain. This defense of the idea of conscious will being causally efficacious has a bearing not only on the understanding of the mind–brain relation but also on the free will debate. (shrink)

The recent discovery of the medullary circuit driving “hunger responses” – reduced thermogenesis and promoted feeding – has greatly expanded our knowledge on the central neural networks for energy homeostasis. However, how hypothalamic hunger and satiety signals generated under fasted and fed conditions, respectively, control the medullary autonomic and somatic motor mechanisms remains unknown. Here, in reviewing this field, we propose two hypothalamomedullary neural pathways for hunger and satiety signaling. To trigger hunger signaling, neuropeptide Y activates a group of neurons (...) in the paraventricular hypothalamic nucleus (PVH), which then stimulate an excitatory pathway to the medullary circuit to drive the hunger responses. In contrast, melanocortin‐mediated satiety signaling activates a distinct group of PVH neurons, which then stimulate a putatively inhibitory pathway to the medullary circuit to counteract the hunger signaling. The medullary circuit likely contains inhibitory and excitatory premotor neurons whose alternate phasic activation generates the coordinated masticatory motor rhythms to promote feeding. (shrink)

Depth electrode recordings in the human mesial frontal cortex have revealed individual neurons with mirror properties. A third of these cells have excitatory properties during action execution and inhibitory properties during action observation. These cells provide the neural mechanism that implements the functions of layers 3+4 of the shared circuits model (SCM).

The commentaries on our target article have raised important issues about central neuroplasticity and its role in persistent pain states. Some suggest that central neuroplasticity plays nothing more than a minor role in persistent pain, while others argue that persistent pain depends critically on peripheral inputs for its maintenance. Some stress that persistent pain relies to a large extent on changes in the brain and on centrifugal inputs from brain to spinal cord, whereas others argue that it depends on alterations (...) in inhibitory as well as excitatory systems. We attempt to addresseach of the commentators' points, while defending our position that central neuroplasticity is critical to pathological persistent pain states. (shrink)

The spinal mechanisms of action of opioids under normal conditions are reasonably well understood. The spinal effects of opioids can be enhanced or reduced depending on pathology and activity in other segmental and nonsegmental pathways. This plasticity will be considered in relation to the control of different pain states using opioids. The complex and contradictory findings on the supraspinal actions of opioids are explicable in terms of heterogeneous descending pathways to different spinal targets using multiple transmitters and receptors – therefore (...) opioids can both increase and decrease activity in descending pathways. These pathways could exhibit considerable plasticity. There is increasing evidence that delta opioid receptor agonists have the potential to replace morphine as major analgesics with reduced side-effect profiles. The concept of preemptive analgesia, based on preventing the induction of some of the negative plastic influences on opioid controls and the detrimental effects of pain, is sound, but experimental verification in the clinical setting is difficult. For example, a delayed compensatory upregulation of inhibitory systems, particularly in inflammation, may counter persistent painful inputs. Combination therapy with opioids may be beneficial in many pain states where either negative influences are blocked or inhibitory controls are enhanced. Finally, developmental aspects of these systems are discussed in connection with the treatment of pain in young children, where inhibitory systems in the spinal cord are immature. (shrink)

Background Human brain organoids are a valuable research tool for studying brain development, physiology, and pathology. Yet, a host of potential ethical concerns are inherent in their creation. There is a growing group of bioethicists who acknowledge the moral imperative to develop brain organoid technologies and call for caution in this research. Although a relatively new technology, brain organoids and their uses are already being discussed in media literature. Media literature informs the public and policymakers but has the potential for (...) utopian or dystopian distortions. Thus, it is important to understand how this technology is portrayed to the public. Methods To investigate how brain organoids are displayed to the public, we conducted a systematic review of media literature indexed in the Nexis Uni database from 2013–2019. News and media source articles passing exclusion criteria (_n_ = 93) were scored to evaluate tone and relevant themes. Themes were validated with a pilot sample before being applied to the dataset. Thematic analysis assessed article tone, reported potential for the technology, and the scientific, social, and ethical contexts surrounding brain organoids research. Results Brain organoid publications became more frequent from 2013 to 2019. We observed increases in positively and negatively toned articles, suggesting growing polarization. While many sources discuss realistic applications of brain organoids, others suggest treatment and cures beyond the scope of the current technology. This could work to overhype the technology and disillusion patients and families by offering false hope. In the ethical narrative we observe a preoccupation with issues such as development of artificial consciousness and “humanization” of organoid-animal chimeras. Issues of regulation, ownership, and accuracy of the organoid models are rarely discussed. Conclusions Given the power that media have to inform or misinform the public, it is important this literature provides an accurate and balanced reflection of the therapeutic potential and associated ethical issues regarding brain organoid research. Our study suggests increasing polarization, coupled with misplaced and unfounded ethical concern. Given the inhibitory effects of public fear or disillusion on research funding, it is important media literature provides an accurate reflection of brain organoids. (shrink)

The aim of the present study is to examine the effect of group-play intervention on executive function in preschoolers. This group-play intervention was integrated as moderate to vigorous physical activity and cognitively loaded exercise to promote EF in preschoolers. An 8-week group-play MVPA intervention program, consisting of a series of outdoor physical and cognitively loaded games, was designed to improve preschoolers’ EF. This intervention program was implemented in group-play form, and conducted by teachers who received standardized training before the intervention. (...) Two classes of second grade preschoolers were randomly allocated to experimental and control groups. The intervention group received the intervention three times a week, while the control group exercised as usual in preschool. Before, in the middle of, and after the intervention, 10-m running, standing broad jump, throwing, body flexion, balance beam, and skip jump were assessed as tests of motor skills. In addition, three components of EF were measured separately before, in the middle of, and after the intervention: inhibitory control was assessed by using the silly sound Stroop task, working memory was tested using the empty house task, and shifting was assessed using the dimensional change card sorting task. Although both groups showed an increasing trend in terms of motor skills and EF during the intervention, the increasing amounts of the intervention group were significantly higher than the control group. The findings of the present study suggested that group-play intervention has positive effects on aspects of EF in addition to motor skills in preschoolers. (shrink)

The classical/balance controversy continued along these lines throughout the first half of the sixties. Then, at about the same time that the classical position lost its leading advocate, the balance position received striking new support from Harry Harris, and independently from Dobzhansky's former student Lewontin, and Lewontin's research partner, Jack Hubby.80 These developments served more to reorient the controversy than to end it — and the resulting “neoclassical”/balance controversy is different enough to be grist for another mill.Social (...) policy considerations no longer play a role in keeping the dispute alive. This particular respect in which the issues have changed is, as Diane Paul suggests in her contribution to this volume, as striking as any other.82 There is, however, little danger of our forgetting that this was once much more than just a narrowly technical controversy — the additional social policy issues were far too blatant.However, although blatant, they were by no means the only, or even the most important, issues. In choosing to concentrate on the social policy considerations, I do not mean to suggest that the empirical issues were irrelevant, or simple and straightforward, or otherwise uninteresting. That is by no means the case. What I have tried to show is that there was much more to the classical/balance stalemate than just the empirical underdetermination of the theoretical issues, and that the empirical issues cannot be treated adequately without taking into account the social policy considerations that were involved. Dobzhansky and Muller both appealed to the dangers of misguided social policy that might have resulted from prematurely resolving their controversy in the other's favor. They called for high empirical standards on those grounds, more than once seeking to forestall the resolution of their dispute in this way. (shrink)

This book is the result of a three-year study undertaken by a multidisciplinary working party of the Institute of Medical Ethic (UK). The group was chaired by a moral theologian, and its members included biological and ethological scientists, toxicologists, physicians, veterinary surgeons, an expert in alternatives to animal use, officers of animal welfare organizations, a Home Office Inspector, philosophers, and a lawyer. Coming from these different backgrounds, and holding a diversity of moral views, the members produced the agreed report as (...) a result of detailed and rigorous discussions. The book sets out facts about animal experiments and about animal abilities to experience pain, distress and anxiety. There is a detailed examination of the moral claims related to the benefits likely to accrue from animal research, and of strategies for weighing these benefits against the harm caused to animals, in order to decide whether particular research projects ought or ought not to proceed. This leads to consideration of the statutory and non-statutory controls which safeguard standards in such research. The final section explores a variety of philosophical arguments about the use of animals in research, and offers a philosophical justification for the Working Party's more practical conclusions. Written in clear, nontechnical language, this book is accessible to lay people as well as to scientists. It is the first such document to emerge from a meeting of people with such widely differing views on this highly controversial subject, and represents a major contribution towards informing and raising the quality of contemporary debate. The book is unique in drawing together material and ideas never before found in one volume. It will interest a broad spectrum of readers, from ethicists and animal rights advocates to scientific researchers and laboratory administrators, along with general readers concerned about this compelling issue. (shrink)

This work provides a comprehensive introduction to Asian ethics, covering Hinduism, Buddhism, Zen Buddhism, Taoism and Confucianism. Each chapter comprises historical background, essential ethical themes or topics, primary sources and more.