Though the realm of biology has long been under the philosophical rule of the mechanistic magisterium, recent years have seen a surprisingly steady rise in the usurping prowess of process ontology. According to its proponents, theoretical advances in the contemporary science of evo-devo have afforded that ontology a particularly powerful claim to the throne: in that increasingly empirically confirmed discipline, emergently autonomous, higher-order entities are the reigning explanantia. If we are to accept the election of evo-devo as our best conceptualisation (...) of the biological realm with metaphysical rigour, must we depose our mechanistic ontology for failing to properly “carve at the joints” of organisms? In this paper, I challenge the legitimacy of that claim: not only can the theoretical benefits offered by a process ontology be had without it, they cannot be sufficiently grounded without the metaphysical underpinning of the very mechanisms which processes purport to replace. The biological realm, I argue, remains one best understood as under the governance of mechanistic principles. (shrink)

Liquid‐liquid phase separation (LLPS) has recently emerged as a possible mechanism that enables ubiquitin‐binding shuttle proteins to facilitate the degradation of ubiquitinated substrates via distinct protein quality control (PQC) pathways. Shuttle protein LLPS is modulated by multivalent interactions among their various domains as well as heterotypic interactions with polyubiquitin chains. Here, the properties of three different shuttle proteins (hHR23B, p62, and UBQLN2) are closely examined, unifying principles for the molecular determinants of their LLPS are identified, and how LLPS is (...) connected to their functions is discussed. Evidence supporting LLPS of other shuttle proteins is also found. In this review, it is proposed that shuttle protein LLPS leads to spatiotemporal regulation of PQC activities by mediating the recruitment of PQC machinery (including proteasomes or autophagic components) to biomolecular condensates, assembly/disassembly of condensates, selective enrichment of client proteins, and extraction of ubiquitinated proteins from condensates in cells. (shrink)

Numerous studies have investigated the neuro-cognitive mechanism of learning words in isolation or in semantic contexts recently. However, emotion as an important influencing factor on novel word learning has not been fully considered in the previous studies and how emotion affect word learning and the underlying neural mechanism have not been systematically investigated. 16 participants were trained to learn novel concrete or abstract words under negative, neutral and positive contextual emotions in continuous three days, and fufilled the testing (...) tasks in day1 and day3 during fMRI scanning. We compared the brain activations in day1 and day3 aming to investigate the role of contextual emotions in learning different types of words and the corresponding neural plasticity changes. Behaviorally, the performance for the words learned in negative context was lower than the neutral and positive contexts, which indicated that the contextual emotions had significant impact on novel word learning. Correspondingly, the functional plasticity changes of the right angular (AG), bilateral insula and anterior cingulate gyrus (ACC) induced by word learning were modulated by the contextual emotions. And the insula also was sensitive to the concreteness of the learned words. More importantly, the functional plasticity changes of left inferior frontal gyrus(L IFG) and left fusiform(L FG) were interactively influenced by the contextual emotions and words’ concreteness, suggesting that the contextual emotional information had a discriminable effect on different types of words in the neural mechanism level. These results demonstrate that the emotional information in contexts is inevitable for word learning, and the role of contextual emotions in brain plasticity for learning was discussed. (shrink)

Conventional wisdom suggests mid-task rest as a potential approach to relieve the time-on-task (TOT) effect while accumulating evidence indicated that acute exercise might also effectively restore mental fatigue. However, few studies have explored the neural mechanism underlying these different break types, and the results were scattered. This study provided one of the first looks at how different types of fatigue-recovery break exerted influence on the cognitive processes by evaluating the corresponding behavioral improvement and neural response (EEG power spectral) in (...) a sustained attention task. Specifically, 19 participants performed three sessions of psychomotor vigilance tasks (PVT), with one session including a continuous 30-min PVT while the other two sessions additionally inserted a 15-min mid-task cycling and rest break, respectively. For behavioral performance, both types of break could restore objective vigilance transiently, while subjective feeling was only maintained after mid-task rest. Moreover, divergent patterns of EEG change were observed during post-break improvement. In detail, relative theta decreased and delta increased immediately after mid-task exercise, while decreased delta was found near the end of the rest-inserted task. Meanwhile, theta and delta could serve as neurological indicators to predict the reaction time change for exercise and rest intervention, respectively. In sum, our findings provided novel evidence to demonstrate divergent neural patterns following the mid-task exercise and rest intervention to counter TOT effects, which might lead to new insights into the nascent field of neuroergonomics for mental fatigue restoration. (shrink)

ABSTRACTDespite interest in exercise as a treatment for anxiety disorders the mechanism behind the anxiolytic effects of exercise is unclear. Two observations motivate the present work. First, engagement of attention control during increased working memory load can decrease anxiety. Second, exercise can improve attention control. Therefore, exercise could boost the anxiolytic effects of increased WM load via its strengthening of attention control. Anxiety was induced by threat of shock and was quantified with anxiety-potentiated startle. Thirty-five healthy volunteers participated in (...) two types of activity, exercise and control-activity. After each activity, participants completed a WM task at low- and high-load during safe and threat. Results were not consistent with the hypothesis: exercise vs. control-activity increased APS in high-load. However, this incre... (shrink)

The biochemical mechanism by which the phytochrome family of plant sensory photoreceptors transmit perceived informational light signals downstream to transduction pathway components is undetermined. The recent sequencing of the entire genome of the cyanobacterium Synechocystis, however, has revealed a protein that has an NH2‐terminal domain with striking sequence similarity to the photosensory NH2‐terminal domain of the phytochromes, and a COOH‐terminal domain strongly related to the transmitter histidine kinase module of bacterial two‐component sensors. The Synechocystis protein is capable of autocatalytic (...) chromophore ligation and exhibits photoreversible light‐absorption changes analogous to the phytochromes, indicating its capacity to function as an informational photoreceptor. Together with earlier observations that the COOH‐terminal domains of the plant phytochromes also have sequence similarity to the histidine kinases, these data suggest that the cyanobacteria utilize photoregulated histidine kinases as a sensory system and that the plant phytochromes may be evolutionary descendants of these photoreceptors. (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)

Acceptable analyticities, i.e. contradictions or tautologies, constitute problematic evidence for the idea that language includes a deductive system. In recent discussion, two accounts have been presented in the literature to explain the available evidence. According to one of the accounts, grammatical analyticities are accessible to the system but a pragmatic strengthening repair mechanism can apply and prevent the structures from being actually interpreted as contradictions or tautologies. The proposed data, however, leaves it open whether other versions of the meaning (...) modulation operation are required. Novel evidence we present argues that a loosening version of the repair mechanism must be available. Our observation concerns acceptable lexical contradictions that cannot be rescued if only a strengthening version of the pragmatic strategy is available. (shrink)

The present study aims to delineate the working mechanism of prediction in sentence comprehension, by disentangling the influence of the facilitated general memory retrieval from the coexistent influence of the predicted language-specific semantic and/or syntactic information for the first time. The results support that prediction might influence the downstream cognitive processing in two aspects: the pre-activated information facilitates the retrieval of a matched input in memory and, the pre-activated information interacts with higher-level semantic/syntactic processing. More importantly, the present findings (...) suggest that these two types of influences seem to occur at different stages of sentence comprehension: the facilitated memory retrieval of the input modulates N400 amplitude and the latency of post-N400 late central-parietal positivity/P600, while the predicted semantic/syntactic information and/or their interactions modulate the amplitude of the late positivity. The present findings would be helpful for interpreting the underlying mechanism of observed effects in prediction studies. (shrink)

The glucocorticoid receptor belongs to an important class of transcription factors that alter the expression of target genes in response to a specific hormone signal. The glucocorticoid receptor can function at least at three levels: (1) recruitment of the general transcription machinery; (2) modulation of transcription factor action, independent of DNA binding, through direct protein‐protein interactions; and (3) modulation of chromatin structure to allow the assembly of other gene regulatory proteins and/or the general transcription machinery on the DNA. (...) This review will focus on the multifaceted nature of protein‐protein interactions involving the glucocorticoid receptor and basal transcription factors, coactivators and other transcription factors, occurring at these different levels of regulation. (shrink)

Prominent research programs dealing with the nature and mechanisms of interpersonal social coordination have emerged in cognitive science, developmental psychology and evolutionary anthropology. I argue that the mechanistic approach to explanation in contemporary philosophy of science can facilitate interdisciplinary integration and division of labor between these different disciplinary research programs. By distinguishing phenomenal models from mechanistic models and structural decomposition from functional decomposition in the process of mechanism discovery, I argue that behavioral and cognitive scientists can make interlocking contributions (...) to families of mechanism models representing a) what central forms of interpersonal social coordination consist in, b) what types of agents engage in such forms of coordination, c) what types of cognitive mechanisms give rise to such forms of coordination, d) how the operation of such mechanisms is modulated by the natural and social environments that the agents populate. Thus mechanistic philosophy of science can play a heuristic role in guiding the research strategies of scientists in different scientific disciplines in a manner that is complementary to the research strategies of scientists in other disciplines and thereby efficient from the point of view of the division of epistemic labor. (shrink)

Much contemporary debate on the nature of mechanisms centers on the issue of modulating negative causes. One type of negative causability, which I refer to as "causation by absence," appears difficult to incorporate into modern accounts of mechanistic explanation. This paper argues that a recent attempt to resolve this problem, proposed by Benjamin Barros, requires improvement as it overlooks the fact that not all absences qualify as sources of mechanism failure. I suggest that there are a number of additional (...) types of effects caused by absences that need to be incorporated to account for the diversity of causal connections in the biological sciences. Furthermore, it is argued that recognizing natural variability in mechanisms, such as attenuation, leads to some interesting line-drawing issues for contemporary philosophy of mechanisms. (shrink)

Accounts of mechanistic explanation have emphasized the importance of looking down—decomposing a mechanism into its parts and operations. Using research on visual processing as an exemplar, I illustrate how productive such research has been. But once multiple components of a mechanism have been identified, researchers also need to figure out how it is organized—they must look around and determine how to recompose the mechanism. Although researchers often begin by trying to recompose the mechanism in terms of (...) sequential operations, they frequently find that the components of a mechanism interact in complex ways involving positive and negative feedback and that the organization often exhibits highly interactive local networks linked by a few long-range connections (small-worlds organization) and power law distributions of connections. The mechanisms are themselves active systems that are perturbed by inputs but not set in motion by them. Researchers also need to look up —situate a mechanism in its context, which may be a larger mechanism that modulates its behavior. When looking down is combined with looking around and up, mechanistic research results in an integrated, multi-level perspective. (shrink)

Although applauding Pickering & Garrod's (P&G's) attempt to ground language use in the ideomotor perception-action link, which provides an of embodied social interaction, we suggest that it needs to be complemented by an additional control mechanism that modulates its operation in the service of the language users' communicative intentions. Implications for intergroup relationships and intercultural communication are discussed.

Inception module is one of the most used variants in convolutional neural networks. It has a large portfolio of success cases in computer vision. In the past years, diverse inception flavours, differing in the number of branches, the size and the number of the kernels, have appeared in the scientific literature. They are proposed based on the expertise of the practitioners without any optimization process. In this work, an implementation of population-based incremental learning is proposed for automatic optimization of the (...) hyperparameters of the inception module. This hyperparameters optimization undertakes classification of the MNIST database of handwritten digit images. This problem is widely used as a benchmark in classification, and therefore, the learned best configurations for the Inception module will be of wide use in the deep learning community. In order to reduce the carbon footprint of the optimization process, policies for reducing the redundant evaluations have been undertaken. As a consequence of this work, an evaluation of configurations of the inception module and a mechanism for optimizing hyperparameters in deep learning architectures are stated. (shrink)

Recent studies suggest that the tetracycline antibiotic minocycline, or its cousins, hold therapeutic potential for affective and psychotic disorders. This is proposed on the basis of a direct effect on microglia‐mediated frontocortical synaptic pruning (FSP) during adolescence, perhaps in genetically susceptible individuals harboring risk alleles in the complement component cascade that is involved in this normal process of CNS circuit refinement. In reviewing this field, it is argued that minocycline is actually probing and modulating a deeply evolved and intricate system (...) wherein psychosocial stimuli sculpt the circuitry of the “social brain” underlying adult behavior and personality. Furthermore, this system can generate psychiatric morbidity that is not dependent on genetic variation. This view has important ramifications for understanding “pathologies” of human social behavior and cognition as well as providing long‐sought potential mechanistic links between social experience and susceptibility to mental and physical disease. (shrink)

The master-module theory of consciousness is considered in the light of experimental evidence that has emerged since the model was first published. It is found that these new results tend to strengthen the original hypothesis. It is also argued that the master module is involved in generation of the schemata previously postulated to be associated with consciousness . The recent discovery of attention-related activity in the thalamic intralaminar nuclei is taken to indicate that these structures constitute an important part of (...) the feedback loop which the theory conjectured to mediate thought. The theory is shown to lead to a remarkably simple rationalization of the cerebral cortex, and it offers explanations of attention, binocular rivalry and qualia. It also makes the surprising prediction that Broca's area might not exclusively serve speech. (shrink)

Although the induction of a hypnotic state does not seem necessary for suggestive modulation of the Stroop effect, this important phenomenon has seemed to be dependent on the subject’s level of hypnotic suggestibility. Raz and Campbell’s study indicates that suggestion can modulate the Stroop effect substantially in very low suggestible subjects, as well as in those who are highly suggestible. This finding casts doubt on the presumed mechanism by which suggestive modulation is brought about. Research aimed at (...) uncovering the means by which low suggestible individuals are able to modulate the Stroop effect would be welcome, as would assessment of this effect in moderately suggestible people. (shrink)

Different anesthetics are known to modulate different types of membrane-bound receptors. Their common mechanism of action is expected to alter the mechanism for consciousness. Consciousness is hypothesized as the integral of all the units of internal sensations induced by reactivation of inter-postsynaptic membrane functional LINKs during mechanisms that lead to oscillating potentials. The thermodynamics of the spontaneous lateral curvature of lipid membranes induced by lipophilic anesthetics can lead to the formation of non-specific inter-postsynaptic membrane functional LINKs by different (...) mechanisms. These include direct membrane contact by excluding the inter-membrane hydrophilic region and readily reversible partial membrane hemifusion. The constant reorganization of the lipid membranes at the lateral edges of the postsynaptic terminals (dendritic spines) resulting from AMPA receptor-subunit vesicle exocytosis and endocytosis can favor the effect of anesthetic molecules on lipid membranes at this location. Induction of a large number of non-specific LINKs can alter the conformation of the integral of the units of internal sensations that maintain consciousness. Anesthetic requirement is reduced in the presence of dopamine that causes enlargement of dendritic spines. Externally applied pressure can transduce from the middle ear through the perilymph, cerebrospinal fluid, and the recently discovered glymphatic pathway to the extracellular matrix space, and finally to the paravenular space. The pressure gradient reduce solubility and displace anesthetic molecules from the membranes into the paravenular space, explaining the pressure reversal of anesthesia. Changes in membrane composition and the conversion of membrane hemifusion to fusion due to defects in the checkpoint mechanisms can lead to cytoplasmic content mixing between neurons and cause neurodegenerative changes. The common mechanism of anesthetics presented here can operate along with the known specific actions of different anesthetics. (shrink)

Although the promyelocytic leukemia (PML) protein is renowned for regulating a wide range of cellular processes and as an essential component of PML nuclear bodies (PML‐NBs), the mechanisms through which it exerts its broad physiological impact are far from fully elucidated. Here, we review recent studies supporting an emerging view that PML's pleiotropic effects derive, at least partially, from its role in regulating histone H3.3 chromatin assembly, a critical epigenetic mechanism. These studies suggest that PML maintains heterochromatin organization by (...) restraining H3.3 incorporation. Examination of PML's contribution to H3.3 chromatin assembly in the context of the cell cycle and PML‐NB assembly suggests that PML represses heterochromatic H3.3 deposition during S phase and that transcription and SUMOylation regulate PML's recruitment to heterochromatin. Elucidating PML’ s contributions to H3.3‐mediated epigenetic regulation will provide insight into PML's expansive influence on cellular physiology and open new avenues for studying oncogenesis linked to PML malfunction. (shrink)

At present, person reidentification based on attention mechanism has attracted many scholars’ interests. Although attention module can improve the representation ability and reidentification accuracy of Re-ID model to a certain extent, it depends on the coupling of attention module and original network. In this paper, a person reidentification model that combines multiple attentions and multiscale residuals is proposed. The model introduces combined attention fusion module and multiscale residual fusion module in the backbone network ResNet 50 to enhance the feature (...) flow between residual blocks and better fuse multiscale features. Furthermore, a global branch and a local branch are designed and applied to enhance the channel aggregation and position perception ability of the network by utilizing the dual ensemble attention module, as along as the fine-grained feature expression is obtained by using multiproportion block and reorganization. Thus, the global and local features are enhanced. The experimental results on Market-1501 dataset and DukeMTMC-reID dataset show that the indexes of the presented model, especially Rank-1 accuracy, reach 96.20% and 89.59%, respectively, which can be considered as a progress in Re-ID. (shrink)

Histone H3.3 turnover displays distinct dynamics at various genomic elements such as promoters, enhancers, gene bodies, and heterochromatic regions, suggesting that it is differentially regulated according to chromatin context. Incorporation of variant histones into chromatin provides a mechanism to modulate chromatin states in addition to histone modifications. The replication‐independent deposition and replacement of histone variant H3.3, i.e. H3.3 turnover, is mainly associated with transcriptional activity. H3.3 or H3.3‐like histone turnover has been studied in various organisms from yeast to mammals. (...) Here, we review the recent progress on this topic. The diversified turnover profiles of H3.3, and their corresponding underlying mechanisms, may reflect distinct requirements for chromatin accessibility in different biological events. (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)

Understanding spoken words involves a rapid mapping from speech to conceptual representations. One distributed feature-based conceptual account assumes that the statistical characteristics of concepts’ features—the number of concepts they occur in and likelihood of co-occurrence —determine conceptual activation. To test these claims, we investigated the role of distinctiveness/sharedness and correlational strength in speech-to-meaning mapping, using a lexical decision task and computational simulations. Responses were faster for concepts with higher sharedness, suggesting that shared features are facilitatory in tasks like lexical decision (...) that require access to them. Correlational strength facilitated responses for slower participants, suggesting a time-sensitive co-occurrence-driven settling mechanism. The computational simulation showed similar effects, with early effects of shared features and later effects of correlational strength. These results support a general-to-specific account of conceptual processing, whereby early activation of shared features is followed by the gradual emergence of a specific target representation. (shrink)

Jane is calmly strolling through the forest one lovely day. Suddenly, a large spider drops in front of her face. She immediately freezes; her heart races; her hands tremble; her face broadcasts “fear.” She screams and runs away. Both before and after, she concedes that spiders in this forest are harmless.Jane's reaction to the spider contrasts greatly with the way she normally reacts to events. Normally, or so the story goes, Jane weighs her options thoughtfully, choosing a course of action (...) consistent with her beliefs and with the greatest benefit. Indeed, her reaction to the spider contrasts so greatly with calm, rational, deliberate, belief-consistent action that traditional folk psychology supposed two different kinds of mechanism are at work: animal-like emotion versus human reason. Her emotion explains her reaction to the spider. Her emotion made her do it. (shrink)

This paper sets forward a novel theory of temporal binding, a mechanism that integrates the temporal properties of sensory features into coherent perceptual experiences. Specifying a theory of temporal binding remains a widespread problem. The popular ‘brain time theory’ suggests that the temporal content of perceptual experiences is determined by when sensory features complete processing. However, this theory struggles to explain how perceptual experiences can accurately reflect the relative timing of sensory features processed at discrepant times. In contrast, ‘event (...) time theories’ suggest that the temporal content of perceptual experiences reflects the relative event time of external sensory features and that the brain accommodates differential processing times. We can formulate retrodictive and predictive versions of this theory. Retrodictive event time theories propose that we accommodate desynchronised processing retrodictively. Predictive event time theories propose that we accommodate desynchronised processing by predictively modelling the event time of sensory features. I argue that both views have strengths and weaknesses. This paper proposes a new hybrid theory that integrates these theories to accommodate these weaknesses. Firstly, I argue how retrodictions and predictions can interact in mutually beneficial ways to ensure speedy and accurate temporal binding. Secondly, I propose how attention plays a central role in flexibly selecting which contents get to be temporally bound. This theory can explain how prediction and retrodiction differentially affect temporal binding and, in turn, proposes a new way to understand temporal binding and has implications for how we should understand conscious experiences. (shrink)

I applaud Huang & Bargh's theory that places goals at the center of cognition, and I discuss two ingredients missing from that theory. First, I argue that the brains of organisms much simpler than those of humans are already configured for goal achievement in situated interactions. Second, I propose a mechanistic view of the “reconfiguration principle” that links the theory with current views in computational neuroscience.

The theory of psychosis and autism as diametrical disorders offers a tractable and testable view of normal and abnormal human cognitive variation as a function of opposing traits grouped by their selection for maternal and paternal reproductive fitness. The theory could be usefully rooted and developed with reference to the lower-level perceptual and attentional phenomena from which social cognitive modules are developmentally refined.

Atran's putative module for folk biology is evaluated with respect to evidence from patients showing category-specific impairments for living kinds. Existing neuropsychological evidence provides no support for the primacy of categorization at the generic species level. We outline reasons for this and emphasize that such claims should be tested using inductive reasoning tasks.

Despite the progress made in studying the observable exteriors of conscious processes, which are reflected in the neural correlates of consciousness (NCC), there are still no satisfactory answers to two closely related core questions. These are the question of the origin of the subjective, phenomenal aspects of consciousness, and the question of the causal mechanisms underlying the generation of specific phenomenal states. In this article, we address these questions using a novel variant of cosmopsychism, a holistic form of panpsychism relying (...) on the central idea that the universe is imbued with a ubiquitous field of consciousness (UFC). This field is understood as a foundational dual-aspect component of the cosmos, the extrinsic appearance of which is physical in nature and the intrinsic manifestation of which is phenomenological in nature. We argue that this approach brings a new perspective into play, according to which the organizational characteristics of the NCC are indicative of the brain’s interaction with and modulation of the UFC. Key insights from modern physics suggest that the modulation mechanism is identical with the fundamental mechanism underlying quantum systems, resulting in the conclusion that a coherently oscillating neural cell assembly acquires phenomenal properties by tapping into the universal pool of phenomenal nuances predetermined by the UFC, or more specifically, by entering into a temporary liaison with the UFC and extracting a subset of phenomenal tones from the phenomenal color palette inherent in the basic structure of the UFC. This hypothesis is supported by a substantial body of empirical evidence. (shrink)

We report results of a study that utilizes a BCI to drive an interactive interface countermeasure that allows users to self-regulate sustained attention while performing an ecologically valid, long-duration business logistics task. An engagement index derived from EEG signals was used to drive the BCI while fNIRS measured hemodynamic activity for the duration of the task. Participants ( n = 30) were split into three groups (1) no countermeasures (NOCM), (2) continuous countermeasures (CCM), and (3) event synchronized, level-dependent countermeasures (ECM). (...) We hypothesized that the ability to self-regulate sustained attention through a neurofeedback mechanism would result in greater task engagement, decreased error rate and improved task performance. Data were analyzed by wavelet coherence analysis, statistical analysis, performance metrics and self-assessed cognitive workload via RAW-TLX. We found that when the BCI was used to deliver continuous interface countermeasures (CCM), task performance was moderately enhanced in terms of total 14,785 (σ = 423) and estimated missed sales 7.46% (σ = 1.76) when compared to the NOCM 14,529 (σ = 510), 9.79% (σ = 2.75), and the ECM 14,180 (σ = 875), 9.62% (σ = 4.91) groups. An “actions per minute” (APM) metric was used to determine interface interaction activity which showed that overall the CCM and ECM groups had a higher APM of 3.460 ( SE = 0.140) and 3.317 ( SE = 0.139) respectively when compared with the NOCM group 2.65 ( SE = 0.097). Statistical analysis showed a significant difference between ECM - NOCM and CCM - NOCM ( p p. (shrink)

Our understanding of body ownership largely relies on the Rubber Hand Illusion (RHI) paradigm where synchronous stroking of the real and fake hands leads to an illusion of ownership of RH provided its physical, anatomical, and spatial plausibility. Self-attribution of a fake hand also occurs during visuomotor synchrony, when the visual feedback of self-initiated movements follows the trajectory of the instantiated motor command. In both cases, the experience of ownership is established through bottom-up integration and top-down prediction of multisensory (proximodistal) (...) cues within the peripersonal space. It seems, however, that depending on whether the signals are externally or self-generated, top-down expectation signals are qualitatively different. On the one hand, in RHI, the sensory correlations are modulated by empirically induced priors about the internal model of the body. On the other hand, in mRHI, body ownership is actively shaped by processes allowing for continuous comparison between the actual and predicted sensory consequences of the actions. Ample research demonstrates that the differential processing of the predicted and the actual reafferent information is addressed by the central nervous system via an internal Forward Model (FM). Indeed, results from mRHI suggest that in action-contexts mechanism underlying body ownership could be similar to the FM. Crucially FMs integrate across all sensory input including not only proximodistal (visuomotor) but also purely distal sensory signals (visuoauditory). Thus if body ownership results from a consistency of FM, it would be affected by the (in)congruency of purely distal signals provided that they inform about the action-consequences relevant to the task. Here we explicitly address this question. To test our hypothesis, we devise an embodied VR-based task where action outcomes were signaled by distinct auditory cues. By manipulating the cues with respect to their spatial, temporal and semantic congruency, we show that purely distal feedback violating predictions about action outcomes compromises both body ownership and performance. These results demonstrate that body ownership is influenced by cues which not only pertain to the body itself but also those arising outside of the body, and suggest that in goal-oriented tasks body ownership might result from the consistency of forward models. (shrink)

Cells can change their function by rapidly modulating the levels of certain proteins at the plasma membrane. This rapid modulation is achieved by using a specialised trafficking process called constitutive cycling. The constitutive cycling of a variety of transmembrane proteins such as receptors, channels and transporters has recently been directly demonstrated in a wide range of cell types. This regulation is thought to underlie important biological phenomena such as learning and memory, gastric acid secretion and water and blood glucose (...) homeostasis. This review discusses the molecular mechanisms of constitutive cycling, its regulation by extracellular agents such as hormones and its misregulation in disease states. BioEssays 25:39–46, 2003. © 2002 Wiley Periodicals, Inc. (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)

Behrendt & Young's (B&Y's) theory offers a potentially important perspective on the neurobiology of schizophrenia, but it remains incomplete. In addition to bottom-up contributions, such as those associated with disturbances in sensory constraints on cognitive processes, a comprehensive model requires the integration of the consequences of abnormal top-down modulation of input processing for the evolution of “underconstrained” perceptions. Dysfunctional cholinergic modulation of input functions represents a necessary mechanism for the generation of false perceptions.

Previous research has indicated that frontal midline theta reflects a domain-general cognitive control mechanism of the prefrontal cortex. Brain imaging studies have shown that the inhibition of implicit stereotypes was dependent on this domain-general cognitive control mechanism. Based on this knowledge, the present study investigated the neural oscillatory correlates of implicit gender stereotype control in an extrinsic affective Simon task using electrophysiological methods. Participants in this task conducted verification to white gender names and colored gender traits, and their (...) behavioral response and electroencephalogram were recorded during their performances. As predicted, stereotype-inconsistent trials resulted in reduced response accuracies and slower response times than stereotype-consistent trials. For the event-related potential results, the enhanced performance of stereotype-inconsistent trials was accompanied by an enhanced N400 amplitude but an attenuated late positive potential amplitude. In contrast, early attentional components such as P2 and N2 as well as their amplitudes were impacted by the experimental manipulations and individual differences in gender factors. In addition, based on time–frequency analysis, we found that the enhanced performance of stereotype-inconsistent trials was also accompanied by an event-related synchronization on the frontal theta oscillation. This frontal theta appeared at a late processing stage and persisted across a time window from N400 to late positive potential. Additionally, this enhanced frontal theta effect was not modulated by the experimental manipulations and individual differences in gender factors. Based on these findings, the feature of frontal theta oscillation in the implicit gender stereotype control process was discussed. (shrink)

Oxygen is a key regulator of both development and homeostasis and a promising candidate to bridge the influence of the environment and the evolution of new traits. To clarify the various ways in which oxygen may modulate embryogenesis, its effects are reviewed at distinct organizational levels. First, the role of pathways that sense dioxygen levels and reactive oxygen species are reviewed. Then, the effects of microenvironmental oxygen on metabolism, stemness, and differentiation throughout embryogenesis are discussed. Last, the interplay between ecology (...) and development are reexamined with a focus on the evolution of tetrapods, including during the emergence of a novel mechanism that shapes amniote limbs—interdigital cell death. Both genetic and environmental components work together during the formation of organisms, highlighting the importance of a multidisciplinary approach for understanding the evolution of new traits. (shrink)

The effects of striatal dopamine (DA) on behavior have been widely investigated over the past decades, with “phasic” burst firings considered as the key expression of a reward prediction error responsible for reinforcement learning. Less well studied is “tonic” DA, where putative functions include the idea that it is a regulator of vigor, incentive salience, disposition to exert an effort and a modulator of approach strategies. We present a model combining tonic and phasic DA to show how different outflows triggered (...) by either intrinsically or extrinsically motivating stimuli dynamically affect the basal ganglia by impacting on a selection process this system performs on its cortical input. The model, which has been tested on the simulated humanoid robot iCub interacting with a mechatronic board, shows the putative functions ascribed to DA emerging from the combination of a standard computational mechanism coupled to a differential sensitivity to the presence of DA across the striatum. (shrink)

The majority of G protein-coupled receptors (GPCRs) self-assemble in the form dimeric/oligomeric complexes along the plasma membrane. Due to the molecular interactions they participate, GPCRs can potentially provide the framework for discriminating a wide variety of intercellular signals, as based on some kind of combinatorial receptor codes. GPCRs can in fact transduce signals from the external milieu by modifying the activity of such intracellular proteins as adenylyl cyclases, phospholipases and ion channels via interactions with specific G-proteins. However, in spite of (...) the number of cell functions they can actually control, both GPCRs and their associated signal transduction pathways are extremely well conserved, for only a few alleles with null or minor functional alterations have so far been found. This would seem to suggest that, beside a mechanism for DNA repairing, there must be another level of quality control that may help maintaining GPCRs rather stable throughout evolution. We propose here receptor oligomerization to be a basic molecular mechanism controlling GPCRs redundancy in many different cell types, and the plasma membrane as the first hierarchical cell structure at which selective categorical sensing may occur. Categorical sensing can be seen as the cellular capacity for identifying and ordering complex patterns of mixed signals out of a contextual matrix, i.e., the recognition of meaningful patterns out of ubiquitous signals. In this context, redundancy and degeneracy may appear as the required feature to integrate the cell system into functional units of progressively higher hierarchical levels. (shrink)

The whale optimization algorithm is a powerful swarm intelligence method which has been widely used in various fields such as parameter identification of solar cells and PV modules. In order to better balance the exploration and exploitation of WOA, we propose a novel modified WOA in which both the mutation strategy based on Levy flight and a local search mechanism of pattern search are introduced. On the one hand, Levy flight can make the algorithm get rid of the local (...) optimum and avoid stagnation; thus, it is able to prevent the algorithm from losing diversity and to increase the global search capability. On the other hand, pattern search, a direct search method, has not only high convergence rate but also good stability, which can boost the local optimization ability of the WOA. Therefore, the combination of these two mechanisms can greatly improve the capability of WOA to obtain the best solution. In addition, MWOA may be employed to estimate parameters in single diode model, double diode model, and PV modules and to identify unknown parameters of two different types of PV modules under diverse light irradiance and temperature conditions. The analytical results demonstrate the validity and the practicality of MWOA for estimating parameters of solar cells and PV modules. (shrink)

Selective attention depends on goal-directed and stimulus-driven modulatory factors, each relayed by different brain rhythms. Under certain circumstances, stress-related states can change the balance between goal-directed and stimulus-driven factors. However, the neuronal mechanisms underlying these changes remain unclear. In this study, we explored how psychosocial stress can modulate brain rhythms during an attentional task and a task-free period. We recorded the EEG and ECG activity of 42 healthy participants subjected to either the Trier Social Stress Test, a controlled procedure to (...) induce stress, or a comparable control protocol, flanked by an attentional task, a 90 s of task-free period and a state of anxiety questionnaire. We observed that psychosocial stress induced an increase in heart rate, self-reported anxiety, and alpha power synchronization. Also, psychosocial stress evoked a relative beta power increase during correct trials of the attentional task, which correlates positively with anxiety and heart rate increase, and inversely with attentional accuracy. These results suggest that psychosocial stress affects performance by redirecting attentional resources toward internal threat-related thoughts. An increment of endogenous top-down modulation reflected an increased beta-band activity that may serve as a compensatory mechanism to redirect attentional resources toward the ongoing task. The data obtained here may contribute to designing new ways of clinical management of the human stress response in the future and could help to minimize the damaging effects of persistent stressful experiences. (shrink)

RNAs have emerged as a major target for diagnostics and therapeutics approaches. Regulatory nonprotein‐coding RNAs (ncRNAs) in particular display remarkable versatility. They can fold into complex structures and interact with proteins, DNA, and other RNAs, thus modulating activity, localization, or interactome of multi‐protein complexes. Thus, ncRNAs confer regulatory plasticity and represent a new layer of regulatory control. Interestingly, long noncoding RNAs (lncRNAs) tend to acquire complex secondary and tertiary structures and their function—in many cases—is dependent on structural conservation rather than (...) primary sequence conservation.Whereas for many proteins, structure and its associated function are closely connected, for lncRNAs, the structural domains that determine functionality and its interactome are still not well understood. Numerous approaches for analyzing the structural configuration of lncRNAs have been developed recently. Here, will provide an overview of major experimental approaches used in the field, and discuss the potential benefit of using combinatorial strategies to analyze lncRNA modes of action based on structural information. (shrink)

Recently, we found that the Pseudomonas aeruginosa type II secreted protease IV functions as a unique Arabidopsis innate immunity elicitor. The protease IV‐activated pathway involves G protein signaling and raises the question of how protease elicitation leads to the activation of G protein‐mediated signaling, because plants do not appear to have metazoan‐like G protein‐coupled receptors. Importantly, our data suggest that Arabidopsis has evolved a mechanism to detect the proteolytic activity of a pathogen‐encoded protease, supporting the host‐pathogen arms race model. (...) In the case of opportunistic multi‐host pathogens like P. aeruginosa, however, it is not plausible that P. aeruginosa is simultaneously co‐evolving in a gene‐for‐gene manner with all of its potential hosts, which include plants, nematodes, insects, and mammals. This prompts us to ask what is the driving force for co‐evolution of defense response in Arabidopsis and pathogenesis of P. aeruginosa, which might not have been subject to iterative cycles of evolutionary selections. (shrink)

Temporal binding via 40-Hz synchronization of neuronal discharges in sensory cortices has been hypothesized to be a necessary condition for the rapid selection of perceptually relevant information for further processing in working memory. Binocular rivalry experiments have shown that late stage visual processing associated with the recognition of a stimulus object is highly correlated with discharge rates in inferotemporal cortex. The hippocampus is the primary recipient of inferotemporal outputs and is known to be the substrate for the consolidation of working (...) memories to long-term, episodic memories. The prefrontal cortex, on the other hand, is widely thought to mediate working memory processes, per se. This article reviews accumulated evidence for the role of a subcortical matrix in linking frontal and hippocampal systems to select and ''stream'' conscious episodes across time (hundreds of milliseconds to several seconds). ''Streaming'' is hypothesized to be mediated by the selective gating of reentrant flows of information between these cortical systems and the subcortical matrix. The physiological mechanism proposed for this temporally extended form of binding is synchronous oscillations in the slower EEG spectrum (< 8 Hz). (shrink)

The transcription factor NF‐κB (p65/p50) plays a central role in the coordination of cellular responses by activating the transcription of numerous target genes. The precise role of the dynamics of NF‐κB signalling in regulating gene expression is still an open question. Here, we show that besides external stimulation intracellular parameters can influence the dynamics of NF‐κB. By applying mathematical modelling and bifurcation analyses, we show that NF‐κB is capable of exhibiting different types of dynamics in response to the same stimulus. (...) We identified the total NF‐κB concentration and the IκBα transcription rate constant as two critical parameters that modulate the dynamics and the fold change of NF‐κB. Both parameters might vary as a result of cell‐to‐cell variability. The regulation of the IκBα transcription rate constant, e.g. by co‐factors, provides the possibility of regulating the NF‐κB dynamics by crosstalk. (shrink)

In a recent paper, Kaplan (Synthese 183:339–373, 2011) takes up the task of extending Craver’s (Explaining the brain, 2007) mechanistic account of explanation in neuroscience to the new territory of computational neuroscience. He presents the model to mechanism mapping (3M) criterion as a condition for a model’s explanatory adequacy. This mechanistic approach is intended to replace earlier accounts which posited a level of computational analysis conceived as distinct and autonomous from underlying mechanistic details. In this paper I discuss work (...) in computational neuroscience that creates difficulties for the mechanist project. Carandini and Heeger (Nat Rev Neurosci 13:51–62, 2012) propose that many neural response properties can be understood in terms of canonical neural computations. These are “standard computational modules that apply the same fundamental operations in a variety of contexts.” Importantly, these computations can have numerous biophysical realisations, and so straightforward examination of the mechanisms underlying these computations carries little explanatory weight. Through a comparison between this modelling approach and minimal models in other branches of science, I argue that computational neuroscience frequently employs a distinct explanatory style, namely, efficient coding explanation. Such explanations cannot be assimilated into the mechanistic framework but do bear interesting similarities with evolutionary and optimality explanations elsewhere in biology. (shrink)

This work is mainly concerned with the notion of hierarchical modularity and its use in explaining structure and dynamical behavior of complex systems by means of hierarchical modular models, as well as with a concept of my proposal, antimodularity, tied to the possibility of the algorithmic detection of hierarchical modularity. Specifically, I highlight the pragmatic bearing of hierarchical modularity on the possibility of scientific explanation of complex systems, that is, systems which, according to a chosen basic description, can be considered (...) as composed of elementary, discrete, interrelated parts. I stress that hierarchical modularity is also required by the experimentation aimed to discover the structure of such systems. Algorithmic detection of hierarchical modularity turns out to be a task plagued by the demonstrated computational intractability of the search for the best hierarchical modular description, and by the high computational expensiveness of even approximated detection methods. Antimodularity consists in the lack of a modular description fitting the needs of the observer, a lack due either to absence of modularity in the system’s chosen basic description, or to the impossibility, due to the excessive size of the system under assessment in relation to the computational cost of algorithmic methods, to algorithmically produce a valid hierarchical description. I stress that modularity and antimodularity depend on the pragmatic choice of a given basic description of the system, a choice made by the observer based on explanatory goals. I show how antimodularity hinders the possibility of applying at least three well-known types of explanation: mechanistic, deductive-nomological and computational. A fourth type, topological explanation, remains unaffected. I then assess the presence of modularity in biological systems, and evaluate the possible consequences, and the likelihood, of incurring in antimodularity in biology and other sciences, concluding that this eventuality is quite likely, at least in systems biology. I finally indulge in some metaphysical and historical speculations: metaphysically, antimodularity seems to suggest a possible position according to which natural kinds are detected modules, and as such, due to the computational hardness of the detection of the best hierarchical modular description, they are unlikely to be the best possible way to describe the world, because the modularity of natural kinds quite probably does not reflect the best possible modularity of the world. From an historical point of view, the growing use of computational methods for modularity detection or simulation of complex systems, especially in certain areas of scientific research, hints at the envisioning of a multiplicity of emerging scientific disciplines guided by a self- sustained, growing production of possibly human-unintelligible explanations. This, I suggest, would constitute an historical change in science, which, if has not already occurred, could well be on the verge of happening. (shrink)

Extant contextualist theories have relied on the mechanism of pragmatically driven modulation to explain the way non-indexical expressions take on different interpretations in different contexts. In this paper I argue that a modulation-based contextualist semantics is untenable with respect to non-ambiguous expressions whose invariant meaning fails to determine a unique literal interpretation, such as ‘lawyer’ ‘musician’ ‘book’ and ‘game’. The invariant meaning of such an expression corresponds to a range of closely related and equally basic interpretations, none (...) of which can be distinguished as the literal interpretation. Moreover, what counts as a literal interpretation as opposed to a non-literal one is arguably vague. The nonuniqueness of the literal interpretation and the vagueness in the literal/non-literal divide doubly challenge a modulation-based semantics, for modulation is supposed to operate on a unique literal interpretation to generate a clearly non-literal interpretation. Lastly I contend that non-ambiguous expressions which lack determinate literal interpretation are amenable to a Radical Contextualist semantics, according to which the invariant meaning of such an expression directs its interpretation to congruent background information in context. Thereby, these expressions exhibit semantically driven context sensitivity without displaying indexicality. (shrink)