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)

Research into the neural correlates of consciousness (NCCs) has blossomed, due to the advent of new and increasingly sophisticated brain research tools. Neuroimaging has uncovered a variety of brain processes that relate to conscious perception, obtained in a range of experimental paradigms. But methods such as functional magnetic resonance imaging or electroencephalography do not always afford inference on the functional role these brain processes play in conscious vision. Such empirical NCCs could reflect neural prerequisites, neural consequences, or neural substrates of (...) a conscious experience. Here, we take a closer look at the use of non-invasive brain stimulation (NIBS) techniques in this context. We discuss and review how NIBS methodology can enlighten our understanding of brain mechanisms underlying conscious vision by disentangling the empirical NCCs. (shrink)

This volume is written jointly by Witold Marciszewski, who contributed the introductory and the three subsequent chapters, and Roman Murawski who is the author of the next ones - those concerned with the 19th century and the modern inquiries into formalization, algebraization and mechanization of reasonings. Besides the authors there are other persons, as well as institutions, to whom the book owes its coming into being. The study which resulted in this volume was carried out in the Historical Section of (...) the research project _Logical Systems and Algorithms for Automatic Testing of Reasoning,_ 1986-1990, in which participated nine Polish universities; the project was coordinated by the Department of Logic, Methodology and Philosophy of Science of the Bia??l??ystok Branch of the University of Warsaw, and supported by the Ministry of Education 1987). The major part of the project was focussed on the software for computer-aided theorem proving called Mizar MSE ) due to Dr. Andrzej Trybulec. He and other colleagues deserve a grateful mention for a hands-on experience and theoretical stimulants owed to their collaboration. (shrink)

Deep brain stimulation (DBS) of the globus pallidus interna and subthalamic nucleus has restored some degree of motor control in many patients in advanced stages of Parkinson’s disease. DBS has also been used to treat dystonia, essential tremor (progressive neurological condition causing trembling), chronic pain, obsessive-compulsive disorder, Tourette’s syndrome, major depressive disorder, obesity, cerebral palsy, and the minimally conscious state. Although the underlying mechanisms of the technique are still not clear, DBS can modulate underactive or overactive neural circuits and (...) restore disrupted communication between and among groups of neurons in interacting regions of the brain. This can control and relieve many symptoms associated with a range of neurological and psychiatric disorders.But the procedures of implanting and stimulating the electrodes are brain-invasive and entail significant risks. Some patients receiving DBS have experienced intracerebral hemorrhage, infection, cognitive disturbances such as impulsive behavior, and affective disturbances such as mania. It is not known whether continuous electrical stimulation of the brain would reshape synaptic connectivity and permanently alter neural circuits in ways that may not be salutary. The risk of these effects indicates that DBS should be used only when a patient’s condition is refractory to all other interventions and when there is a high probability that the technique will benefit the patient and improve his or her quality of life. If a patient’s quality of life is poor and all other treatment options have been exhausted, then the likelihood of benefit can justify physicians’ exposing patients to some risk. The clinical and ethical significance of the risk in DBS underscores the obligation of physicians to obtain fully informed consent from patients undergoing the procedure. (shrink)

Artificial stimulation of the peripheral vestibular system has been shown to improve ownership of body parts in neurological patients, suggesting vestibular contributions to bodily self-consciousness. Here, we investigated whether galvanic vestibular stimulation interferes with the mechanisms underlying ownership, touch, and the localization of one’s own hand in healthy participants by using the “rubber hand illusion” paradigm. Our results show that left anodal GVS increases illusory ownership of the fake hand and illusory location of touch. We propose that these (...) changes are due to vestibular interference with spatial and/or temporal mechanisms of visual-tactile integration leading to an enhancement of visual capture. As only left anodal GVS lead to such changes, and based on neurological data on body part ownership, we suggest that this vestibular interference is mediated by the right temporo-parietal junction and the posterior insula. (shrink)

This article is an introduction to and advertisement of Erwin Schrödinger’s little-known real-valued wave equation, the first published time dependent Schrödinger equation. I argue that this equation is not merely a historical curiosity. Not only does it show that quantum mechanics need not be viewed as essentially complex-valued, but the real formalism also provides a deep insight into the puzzling nature of time reversal in a quantum world. It is hoped that this observation will stimulate the discovery of other areas (...) where ‘keeping it real’ will prove pedagogically or foundationally useful. (shrink)

Objective: Caloric vestibular stimulation has traditionally been used as a tool for neurological diagnosis. More recently, however, it has been applied to a range of phenomena within the cognitive neurosciences. Here, we provide an overview of such studies and review our work using CVS to investigate the neural mechanisms of a visual phenomenon - binocular rivalry. We outline the interhemispheric switch model of rivalry supported by this work and its extension to a metarivalry model of interocular-grouping phenomena. In addition, (...) studies showing a slow rate of binocular rivalry in bipolar disorder are discussed, and the relationship between this finding and the interhemispheric switch model is described. We also review the effects of CVS in various clinical contexts, explain how the technique is performed and discuss methodological issues in its application. (shrink)

There is preliminary evidence, from case reports and investigational studies, to suggest that Deep Brain Stimulation could be used to treat some patients with Anorexia Nervosa. Although this research is at an early stage, the invasive nature of the intervention and the vulnerability of the potential patients are such that anticipatory ethical analysis is warranted. In this paper, we first show how different treatment mechanisms raise different philosophical and ethical questions. We distinguish three potential mechanisms alluded to in the (...) neuroscientific literature, relating to desire, control, and emotion, respectively. We explain why the precise nature of the mechanism has important implications for the patient’s autonomy and personal identity. In the second part of the paper, we consider practical dimensions of offering DBS to patients with AN in certain cases. We first discuss some limited circumstances where the mere offering of the intervention might be perceived as exerting a degree of coercive pressure that could serve to undermine the validity of the patient’s consent. Finally, we consider the implications of potential effects of DBS for the authenticity of the patient’s choice to continue using stimulation to ameliorate their condition. (shrink)

Deep brain stimulation of the subthalamic nucleus is an effective treatment for the motor symptoms of movement disorders including Parkinson's Disease. Despite its therapeutic benefits, STN-DBS has been associated with adverse effects on mood and cognition. Specifically, apathy, which is defined as a loss of motivation, has been reported to emerge or to worsen following STN-DBS. However, it is often challenging to disentangle the effects of STN-DBSper sefrom concurrent reduction of dopamine replacement therapy, from underlying PD pathology or from (...) disease progression. To this end, pre-clinical models allow for the dissociation of each of these factors, and to establish neural substrates underlying the emergence of motivational symptoms following STN-DBS. Here, we performed a systematic analysis of rodent studies assessing the effects of STN-DBS on reward seeking, reward motivation and reward consumption across a variety of behavioral paradigms. We find that STN-DBS decreases reward seeking in the majority of experiments, and we outline how design of the behavioral task and DBS parameters can influence experimental outcomes. While an early hypothesis posited that DBS acts as a “functional lesion,” an analysis of lesions and inhibition of the STN revealed no consistent pattern on reward-related behavior. Thus, we discuss alternative mechanisms that could contribute to the amotivational effects of STN-DBS. We also argue that optogenetic-assisted circuit dissection could yield important insight into the effects of the STN on motivated behavior in health and disease. Understanding the mechanisms underlying the effects of STN-DBS on motivated behavior-will be critical for optimizing the clinical application of STN-DBS. (shrink)

We recently demonstrated, by means of short latency afferent inhibition (SAI), that before an imagined movement, during the reaction time (RT), SAI decreases only in the movement-related muscle (sensorimotor modulation) and that a correlation exists between sensorimotor modulation and motor imagery (MI) ability. Excitatory anodal transcranial direct current stimulation (a-tDCS) on M1 could enhance the MI outcome; however, mechanisms of action are not completely known. Here, we assessed if a-tDCS on M1 prior to an MI task could affect sensorimotor (...) modulation. Participants imagined abducting the index or little finger in response to an acoustic signal. SAI was evaluated from the first dorsal interosseus after the “go” signal, before the expected electromyographic (EMG) activity. Participants received 20-min 1.5 mA a-tDCS or sham-tDCS on M1 on two different days, in random order. Results showed that a-tDCS on M1 increases the sensorimotor modulation consisting of a weakening of SAI after the Go signal with respect to sham-tDCS, in the movement-related muscle right before the beginning of MI. These results suggest that a-tDCS on M1 further potentiate those circuits responsible for sensorimotor modulation in the RT phase of MI. Increased sensorimotor modulation during MI may be one of the mechanisms involved in MI improvement after a-tDCS over M1. (shrink)

BackgroundFreezing of gait is a disabling burden for Parkinson’s disease patients with poor response to conventional therapies. Combined deep brain stimulation of the subthalamic nucleus and substantia nigra moved into focus as a potential therapeutic option to treat the parkinsonian gait disorder and refractory FoG. The mechanisms of action of DBS within the cortical-subcortical-basal ganglia network on gait, particularly at the cortical level, remain unclear.MethodsTwelve patients with idiopathic PD and chronically-implanted DBS electrodes were assessed on their regular dopaminergic medication (...) in a standardized stepping in place paradigm. Patients executed the task with DBS switched off, conventional STN DBS and combined STN+SN DBS and were compared to healthy matched controls. Simultaneous high-density EEG and kinematic measurements were recorded during resting-state, effective stepping, and freezing episodes.ResultsClinically, STN+SN DBS was superior to conventional STN DBS in improving temporal stepping variability of the more affected leg. During resting-state and effective stepping, the cortical activity of PD patients in STIM OFF was characterized by excessive over-synchronization in the theta, alpha, and high-beta band compared to healthy controls. Both active DBS settings similarly decreased resting-state alpha power and reduced pathologically enhanced high-beta activity during resting-state and effective stepping compared to STIM OFF. Freezing episodes during STN DBS and STN+SN DBS showed spectrally and spatially distinct cortical activity patterns when compared to effective stepping. During STN DBS, FoG was associated with an increase in cortical alpha and low-beta activity over central cortical areas, while with STN+SN DBS, an increase in high-beta was prominent over more frontal areas.ConclusionsSTN+SN DBS improved temporal aspects of parkinsonian gait impairment compared to conventional STN DBS and differentially affected cortical oscillatory patterns during regular locomotion and freezing suggesting a potential modulatory effect on dysfunctional cortical-subcortical communication in PD. (shrink)

Background: Eye movement desensitization and reprocessing [EMDR] is an innovative, evidence-based and effective psychotherapy for post-traumatic stress disorder [PTSD]. As with other psychotherapies, the effectiveness of EMDR contrasts with a limited knowledge of its underlying mechanism of action. In its relatively short life as a therapeutic option, EMDR has not been without controversy, in particular regarding the role of the bilateral stimulation as an active component of the therapy. The high prevalence of EMDR in clinical practice and the dramatic (...) increase in EMDR research in recent years, with more than 26 randomized controlled trials published to date, highlight the need for a better understanding of its mechanism of action. Methods: We conducted a thorough systematic search of studies published until October 2017, using PubMed, ScienceDirect, Web of Knowledge and Scopus databases that examined the mechanism of action of EMDR or provided conclusions within the framework of current theoretical models of EMDR functioning. Results: Seventy-five studies were selected for review and classified into three overarching models; (i) psychological models (ii) psychophysiological models and (iii) neurobiological models. The evidence available from each study was analysed and discussed. Results demonstrated a reasonable empirical support for the working memory hypothesis and for the physiological changes associated with successful EMDR therapy. Recently, more sophisticated structural and functional neuroimaging studies using high resolution structural and temporal techniques are starting to provide preliminary evidence into the neuronal correlates before, during and after EMDR therapy. Discussion: Despite the increasing number of studies that published in recent years, the research into the mechanisms underlying EDMR therapy are still in its infancy. Studies in well-defined clinical and non-clinical populations, larger sample sizes and tighter methodological control are further needed in order to establish firm conclusions. (shrink)

Neuromodulatory effects of non-invasive brain stimulation (NIBS) have been extensively studied in chronic pain. A hypothetic mechanism of action would be to prevent or revert the ongoing maladaptive plasticity within the pain matrix. In this review, the authors discuss the mechanisms underlying the development of an abnormal plasticity in patients with chronic pain and the putative mechanisms of NIBS in modulating synaptic plasticity in neuropathic pain conditions.

Selective accessibility mechanisms indicate that anchoring effects are results of selective retrieval of working memory. Neuroimaging studies have revealed that the right dorsolateral prefrontal cortex (DLPFC) is closely related to memory retrieval and performance. However, no research has investigated the effect of changing the cortical excitability in right DLPFC on anchoring effects. Transcranial direct current stimulation (tDCS) can modulate the excitability of the human cerebral cortex, while anodal and cathodal tDCS are postulated to increase or decrease cortical activity, respectively. (...) In this study, we used tDCS to investigate whether effects of increased or decreased right DLPFC excitability influence anchoring effects in willingness to pay (WTP) experiments. Ninety participants were first randomly assigned to receive either anodal, cathodal, or sham stimulation of 15 minutes, then they performed a valuation task regarding WTP. The results showed that anchoring effects were negatively related to activities of right DLPFC: the anodal stimulation diminished anchoring effects while the cathodal stimulation increased anchoring effects. These outcomes provide one of the first instances of neural evidence for the role of the right DLPFC in anchoring effects and support psychological explanations of the selective accessibility mechanisms and cognitive sets. (shrink)

IntroductionTranscranial direct current stimulation is a noninvasive brain stimulation technique that applied to modulate brain activity and enhance motor recovery. However, the neurobiological substrates underlying the effects of tDCS on brain function remain poorly understood. This study aimed to investigate the central mechanisms of tDCS on improving the athletic performance of male rowing athletes.MethodsTwelve right-handed male professional rowing athletes received tDCS over the left primary motor cortex while undergoing regular training. The resting-state functional magnetic resonance imaging data were (...) acquired before and after tDCS. Measures of amplitude of low-frequency fluctuation and regional homogeneity were calculated and compared between baseline and follow-up, as well as topological measures including global and local efficiency of functional brain networks constructed by graph theoretical analysis.ResultsMale rowing athletes showed increased isokinetic muscle strength of the left knee and left shoulder after tDCS. Increased ALFF values were found in the right precentral gyrus of male rowing athletes after tDCS when compared with those before tDCS. In addition, male rowing athletes showed increased ReHo values in the left paracentral lobule following tDCS. Moreover, increased nodal global efficiency was identified in the left inferior frontal gyrus of male rowing athletes after tDCS.ConclusionThe findings suggested that simultaneous tDCS-induced excitation over the primary motor cortex might potentially improve the overall athletic performance in male rowing athletes through the right precentral gyrus and left paracentral lobule, as well as left inferior frontal gyrus. (shrink)

Arthrogryposis multiplex congenita (AMC) is a heterogeneous syndrome where multiple joints have reduced range of motion due to contracture formation prior to birth. A common cause of AMC is reduced embryonic movement in utero. This reduction in embryonic movement can perturb molecular mechanisms and signaling pathways involved in the formation of joints during development. The absence of mechanical stimuli can impair joint cavitation, resulting in joint fusion, and ultimately eliminate function. In turn, mechanical stimuli are critical for proper (...) joint formation during development and for mitigating AMC. Studies in experimental animal models have provided a greater understanding on the molecular pathophysiology of congenital contracture formation as a consequence of embryonic immobilization. Elucidation of how the mechanical signaling environment is transduced to initiate a biological response will be necessary to gain a deeper understanding of how mechanical stimuli are intertwined in the molecular regulation of joint development. (shrink)

Advocates of moral enhancement through pharmacological, genetic, or other direct interventions sometimes explicitly argue, or assume without argument, that traditional moral education and development is insufficient to bring about moral enhancement. Traditional moral education grounded in a Kohlbergian theory of moral development is indeed unsuitable for that task; however, the psychology of moral development and education has come a long way since then. Recent studies support the view that moral cognition is a higher-order process, unified at a functional level, and (...) that a specific moral faculty does not exist. It is more likely that moral cognition involves a number of different mechanisms, each connected to other cognitive and affective processes. Taking this evidence into account, we propose a novel, empirically informed approach to moral development and education, in children and adults, which is based on a cognitive-affective approach to moral dispositions. This is an interpretative approach that derives from the cognitive-affective personality system (Mischel and Shoda, 1995). This conception individuates moral dispositions by reference to the cognitive and affective processes that realise them. Conceived of in this way, moral dispositions influence an agent's behaviour when they interact with situational factors, such as mood or social context. Understanding moral dispositions in this way lays the groundwork for proposing a range of indirect methods of moral enhancement, techniques that promise similar results as direct interventions whilst posing fewer risks. (shrink)

Contemplative practices, such as meditation and yoga, are increasingly popular among the general public and as topics of research. Beneficial effects associated with these practices have been found on physical health, mental health, and cognitive performance. However, studies and theories that clarify the underlying mechanisms are lacking or scarce. This theoretical review aims to address and compensate this scarcity. We will show that various contemplative activities have in common that breathing is regulated or attentively guided. This respiratory discipline in turn (...) could parsimoniously explain the physical and mental benefits of contemplative activities through changes in autonomic balance. We propose a neurophysiological model that explains how these specific respiration styles could operate, by phasically and tonically stimulating the vagal nerve: respiratory vagal nerve stimulation. The vagal nerve, as a proponent of the parasympathetic nervous system, is the prime candidate in explaining the effects of contemplative practices on health, mental health, and cognition. We will discuss implications and limitations of our model. (shrink)

Single-pulse and repetitive transcranial magnetic stimulation are used in clinical practice for diagnostic and therapeutic purposes. However, rTMS-based therapies that lead to a significant and sustained reduction in neuropsychiatric symptoms remain scarce. While it is generally accepted that the stimulation frequency plays a crucial role in producing the therapeutic effects of rTMS, less attention has been dedicated to determining the role of the electric field strength. Conventional threshold-based intensity selection approaches, such as the resting motor threshold, produce variable (...) stimulation intensities and electric fields across participants and cortical regions. Insufficient standardization of electric field strength may contribute to the variability of rTMS effects and thus therapeutic success. Computational approaches that can prospectively optimize the electric field and standardize it across patients and cortical targets may overcome some of these limitations. Here, we discuss these approaches and propose that electric field standardization will be instrumental for translational science frameworks aimed at deciphering the subcellular, cellular, and network mechanisms of rTMS. Advances in understanding these mechanisms will be important for optimizing rTMS-based therapies in psychiatry. (shrink)

ObjectiveThe effects and possible mechanisms of cerebellar high-frequency repetitive transcranial magnetic stimulation on swallowing-related neural networks were studied using resting-state functional magnetic resonance imaging.MethodA total of 23 healthy volunteers were recruited, and 19 healthy volunteers were finally included for the statistical analysis. Before stimulation, the cerebellar hemisphere dominant for swallowing was determined by the single-pulse TMS. The cerebellar representation of the suprahyoid muscles of this hemisphere was selected as the target for stimulation with 10 Hz rTMS, 100% (...) resting motor threshold, and 250 pulses, with every 1 s of stimulation followed by an interval of 9 s. The motor evoked potential amplitude of the suprahyoid muscles in the bilateral cerebral cortex was measured before and after stimulation to evaluate the cortical excitability. Forty-eight hours after elution, rTMS was reapplied on the dominant cerebellar representation of the suprahyoid muscles with the same stimulation parameters. Rs-fMRI was performed before and after stimulation to observe the changes in amplitude of low-frequency fluctuation and regional homology at 0.01–0.08 Hz, 0.01–0.027 Hz, and 0.027–0.073 Hz.ResultsAfter cerebellar high-frequency rTMS, MEP recorded from swallowing-related bilateral cerebral cortex was increased. The results of rs-fMRI showed that at 0.01–0.08 Hz, ALFF was increased at the pons, right cerebellum, and medulla and decreased at the left temporal lobe, and ReHo was decreased at the left insular lobe, right temporal lobe, and corpus callosum. At 0.01–0.027 Hz, ALFF was decreased at the left temporal lobe, and ReHo was decreased at the right temporal lobe, left putamen, and left supplementary motor area.ConclusionRepetitive transcranial magnetic stimulation of the swallowing cortex in the dominant cerebellar hemisphere increased the bilateral cerebral swallowing cortex excitability and enhanced pontine, bulbar, and cerebellar spontaneous neural activity, suggesting that unilateral high-frequency stimulation of the cerebellum can excite both brainstem and cortical swallowing centers. These findings all provide favorable support for the application of cerebellar rTMS in the clinical practice. (shrink)

The proteins encoded by the ras proto‐oncogenes play critical roles in normal cellular growth, differentiation and development in addition to their potential for malignant transformation. Several proteins that are involved in the control of the activity of p21ras have now been characterised. p120GAP stimulates the GTPase activity of p21ras and hence acts as a negative regulator of ras proteins. It may be controlled by tyrosine phosphorylation or association with tyrosine phosphorylated proteins. The neurofibromatosis type 1 (NF 1) gene also encodes (...) a potential GTPase activating protein which is likely to be subject to a different control mechanism. Guanosine nucleotide exchange factors for p21ras have now been identified: these may be positive regulators of ras protein function. It appears that p21ras is subject to rapid regulation by several distinct mechanisms which are likely to vary in different cell types; the ras proteins are thereby able to act as very sensitive cellular monitors of the extracellular environment. (shrink)

Cranial electrotherapy stimulation is a neuromodulation tool used for treating several clinical disorders, including insomnia, anxiety, and depression. More recently, a limited number of studies have examined CES for altering affect, physiology, and behavior in healthy, non-clinical samples. The physiological, neurochemical, and metabolic mechanisms underlying CES effects are currently unknown. Computational modeling suggests that electrical current administered with CES at the earlobes can reach cortical and subcortical regions at very low intensities associated with subthreshold neuromodulatory effects, and studies using (...) electroencephalography and functional magnetic resonance imaging show some effects on alpha band EEG activity, and modulation of the default mode network during CES administration. One theory suggests that CES modulates brain stem, limbic, and cortical regions and increases relative parasympathetic to sympathetic drive in the autonomic nervous system. There is no direct evidence supporting this theory, but one of its assumptions is that CES may induce its effects by stimulating afferent projections of the vagus nerve, which provides parasympathetic signals to the cardiorespiratory and digestive systems. In our critical review of studies using CES in clinical and non-clinical populations, we found severe methodological concerns, including potential conflicts of interest, risk of methodological and analytic biases, issues with sham credibility, lack of blinding, and a severe heterogeneity of CES parameters selected and employed across scientists, laboratories, institutions, and studies. These limitations make it difficult to derive consistent or compelling insights from the extant literature, tempering enthusiasm for CES and its potential to alter nervous system activity or behavior in meaningful or reliable ways. The lack of compelling evidence also motivates well-designed and relatively high-powered experiments to assess how CES might modulate the physiological, affective, and cognitive responses to stress. Establishing reliable empirical links between CES administration and human performance is critical for supporting its prospective use during occupational training, operations, or recovery, ensuring reliability and robustness of effects, characterizing if, when, and in whom such effects might arise, and ensuring that any benefits of CES outweigh the risks of adverse events. (shrink)

Rebound effects on the consumer level occur when consumers’ realized greenhouse gas emission savings caused by behaviors that might be beneficial to the environment are lower than their potential greenhouse gas emission savings because the savings are offset by behavioral adjustments. While previous literature mainly studied the economic mechanisms of such rebound effects, research has largely neglected the moral-psychological mechanisms. A comprehensive conceptualization of rebound effects on the consumer level can help fill this void and stimulate more empirical research in (...) this relevant area. To this end, the paper introduces three focal dimensions of rebound effects on the consumer level: mechanism of rebound effects, product category, and consumption context. Based on this conceptualization, and integrating assumptions from the theory of moral licensing, the theory of categorization, and the construal level theory, this paper further refines the conceptualization of the moral component as an explanatory factor for rebound effects and highlights that the moral-psychological mechanisms of indirect rebound effects are more complex and diverse than the economic mechanisms. The paper outlines promising directions for future studies considering the different quantification and characteristics of economic and moral currencies that explain rebound effects on the consumer level and the strategic categorization of products and consumption contexts. (shrink)

ObjectiveThis systematic review aims to analyze existing literature of the effects of transcranial direct current stimulation (tDCS) on motor skills learning of healthy adults and discuss the underlying neurophysiological mechanism that influences motor skills learning.MethodsThis systematic review has followed the recommendations of the Preferred Reporting Items for Systematic reviews and Meta-Analyses. The PubMed, EBSCO, and Web of Science databases were systematically searched for relevant studies that were published from database inception to May 2022. Studies were included based on the (...) Participants, Intervention, Comparison, Outcomes, and Setting inclusion strategy. The risk of bias was evaluated by using the Review manager 5.4 tool. The quality of each study was assessed with the Physiotherapy Evidence Database (PEDro) scale.ResultsThe electronic search produced 142 studies. Only 11 studies were included after filtering. These studies performed well in terms of distribution, blinding availability and selective reporting. They reported that tDCS significantly improved motor skills learning. The main outcomes measure were the improvement of the motor sequence tasks and specific motor skills. Nine studies showed that tDCS interventions reduced reaction time to complete motor sequence tasks in healthy adults and two studies showed that tDCS interventions improved golf putting task performance.ConclusionThe included studies showed that tDCS can help healthy adults to improve the motor skills learning by activating different brain regions, such as the primary motor cortex, left dorsolateral prefrontal cortex and right cerebellum. However, the number of included studies was limited, and the sample sizes were small. Therefore, more studies are urgently needed to validate the results of current studies and further explore the underlying neurophysiological mechanisms of tDCS in the future. (shrink)

Mechanical stimulation has a critical role in the development and maintenance of the skeleton. This function requires the perception of extracellular stimuli as well as their conversion into intracellular biochemical responses. This process is called mechanotransduction and is mediated by a plethora of molecular events that regulate bone metabolism. Indeed, mechanoreceptors, such as integrins, G protein‐coupled receptors, receptor protein tyrosine kinases, and stretch‐activated Ca2+ channels, together with their downstream effectors coordinate the transmission of load‐induced signals to the nucleus (...) and the expression of bone‐related genes. During the past decade, scientists have gained increasing insight into the molecular networks implicated in bone mechanotransduction. In the present paper, we consider the major signaling cascades and transcription factors that control bone and cartilage mechanobiology and discuss the influence of the mechanical microenvironment on the determination of skeletal morphology. (shrink)

Deep brain stimulation of the subthalamic nucleus is a clinically effective tool for treating medically refractory Parkinson’s disease, but its neural mechanisms remain debated. Previous work has demonstrated that STN DBS results in evoked potentials in the primary motor cortex, suggesting that modulation of cortical physiology may be involved in its therapeutic effects. Due to technical challenges presented by high-amplitude DBS artifacts, these EPs are often measured in response to low-frequency stimulation, which is generally ineffective at PD symptom (...) management. This study aims to characterize STN-to-cortex EPs seen during clinically relevant high-frequency STN DBS for PD. Intraoperatively, we applied STN DBS to 6 PD patients while recording electrocorticography from an electrode strip over the ipsilateral central sulcus. Using recently published techniques, we removed large stimulation artifacts to enable quantification of STN-to-cortex EPs. Two cortical EPs were observed – one synchronized with DBS onset and persisting during ongoing stimulation, and one immediately following DBS offset, here termed the “start” and the “end” EPs respectively. The start EP is, to our knowledge, the first long-latency cortical EP reported during ongoing high-frequency DBS. The start and end EPs differ in magnitude and latency, and the end, but not the start, EP magnitude has a significant relationship to ongoing high gamma power during the EP. These contrasts may suggest mechanistic or circuit differences in EP production during the two time periods. This represents a potential framework for relating DBS clinical efficacy to the effects of a variety of stimulation parameters on EPs. (shrink)

Neurophysiological studies in humans employing magneto- and electro- encephalography increasingly suggest that oscillatory rhythmic activity of the brain may be a core mechanism for binding sensory information across space, time, and object features to generate a unified perceptual representation. To distinguish whether oscillatory activity is causally related to binding processes or whether, on the contrary, it is a mere epiphenomenon, one possibility is to employ neuromodulatory techniques such as transcranial alternating current stimulation. tACS has seen a rising interest due (...) to its ability to modulate brain oscillations in a frequency-dependent manner. In the present review, we critically summarize current tACS evidence for a causal role of oscillatory activity in spatial, temporal, and feature binding in the context of visual perception. For temporal binding, the emerging picture supports a causal link with the power and the frequency of occipital alpha rhythms ; however, there is no consistent evidence on the causal role of the phase of occipital tACS. For feature binding, the only study available showed a modulation by occipital alpha tACS. The majority of studies that successfully modulated oscillatory activity and behavioral performance in spatial binding targeted parietal areas, with the main rhythms causally linked being the theta and beta frequency bands. On the other hand, spatio-temporal binding has been directly modulated by parieto-occipital gamma and alpha tACS, suggesting a potential role of cross-frequency coupling when binding across space and time. Nonetheless, negative or partial results have also been observed, suggesting methodological limitations that should be addressed in future research. Overall, the emerging picture seems to support a causal role of brain oscillations in binding processes and, consequently, a certain degree of plasticity for shaping binding mechanisms in visual perception, which, if proved to have long lasting effects, can find applications in different clinical populations. (shrink)

This mini-review provides a detailed outline of studies that have used multimodal approaches in non-invasive brain stimulation to investigate the pathophysiology of the three common movement disorders, namely, essential tremor, Parkinson’s disease, and dystonia. Using specific search terms and filters in the PubMed®database, we finally shortlisted 27 studies in total that were relevant to this review. While two-thirds (Brittain et al., 2013) of these studies were performed on Parkinson’s disease patients, we could find only three studies that were conducted (...) in patients with essential tremor. We clearly show that although multimodal non-invasive brain stimulation holds immense potential in unraveling the physiological mechanisms that are disrupted in movement disorders, the technical challenges and pitfalls of combining these methods may hinder their widespread application by movement disorder specialists. A multidisciplinary team with clinical and technical expertise may be crucial in reaping the fullest benefits from such novel multimodal approaches. (shrink)

This book presents the deterministic view of quantum mechanics developed by Nobel Laureate Gerard 't Hooft. Dissatisfied with the uncomfortable gaps in the way conventional quantum mechanics meshes with the classical world, 't Hooft has revived the old hidden variable ideas, but now in a much more systematic way than usual. In this, quantum mechanics is viewed as a tool rather than a theory. The book presents examples of models that are classical in essence, but can be analysed by the (...) use of quantum techniques, and argues that even the Standard Model, together with gravitational interactions, might be viewed as a quantum mechanical approach to analysing a system that could be classical at its core. He shows how this approach, even though it is based on hidden variables, can be plausibly reconciled with Bell's theorem, and how the usual objections voiced against the idea of 'superdeterminism' can be overcome, at least in principle. This framework elegantly explains - and automatically cures - the problems of the wave function collapse and the measurement problem. Even the existence of an "arrow of time" can perhaps be explained in a more elegant way than usual. As well as reviewing the author's earlier work in the field, the book also contains many new observations and calculations. It provides stimulating reading for all physicists working on the foundations of quantum theory. (shrink)

The risk of cigarette smoking plays a pivotal role in increasing the incidence rates of lung cancer. This paper sheds new light on modeling the impact of cigarette smoking on lung cancer evolution, especially genetic instability and the number of gene mutations in the genome of stem cells. To handle this issue, we have set up stochastic multi-stage models to fit the data set of the probabilities of current and former smokers from the Nurses’ Health Study cohort of females and (...) the Health Professionals Follow up Study cohort of men. Throughout this paper, we consider both mutation rates and clonal expansion rates as parameters in each compartment. For current and former smokers, three-driver mutations are most likely to take place in the progression of lung cancer under smoking risk. For current smokers, our findings reveal that two to sixteen gene mutations are required to obtain a cancerous cell among men and women in US. Moreover, two to six cancer-mutations are available in the pathway to lung cancer among former smokers who have quit smoking for more than ten years for both male and female patients. This highlights that cigarette smoking stimulates the number of driver mutations during lung tumorigenesis in both sexes. It is very crucial to examine the role of cigarette smoking in determining whether genomic instability is an early stage or late stage in the process of lung carcinogenesis. (shrink)

Non-invasive brain stimulation promises innovative experimental possibilities for psychology and neurosci- ence as well as new therapeutic and palliative measures in medicine. Because of its good risk–benefit ratio, non-invasiveness and reversibility as well as its low effort and cost it has good chances of becoming a wide- spread tool in science, medicine and even in lay use. While most issues in medical and research ethics such as informed consent, safety, and potential for misuse can be handled with manageable effort, (...) the real promise of brain stimulation does raise one prominent moral worry: it may lay the foundation of reliable, precise and stable manipulations of the mind. This article addresses this worry and concludes that it is not the possibility of manipulation, but the shift in our understanding of our mind which stands in need of careful consideration. (shrink)

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

The non-invasive stimulation techniques are already recognized as technology that allows neuroenhancement, specifically the Transcranial Magnetic Stimulation can be applied following potentiation protocols in order to enhance both cognitive and motor systems. Hand in hand with this capacity arises the ethical problem of its application. The objective of this contribution is to describe and discuss what ethical aspects have been established in relation to this current phenomenon. Thus, we will first describe the mechanisms and results of non-invasive technology (...) in relation to neuroenhancement, focusing on TMS enhancing protocols. Next, we will make a brief historical review of the ethical aspects established around the application of TMS and its ability to result in neuroenhancement. Finally, we will discuss the ethical aspects that have been described and new debates that arise from the previous ones, concluding in an expanded vision of addressing the discussion. (shrink)

Endothelial cells, when cultured on gelled basement membrane matrix exert forces of tension through which they deform the matrix and at the same time they aggregate into clusters. The cells eventually form a network of cord-like structures connecting cell aggregates. In this network, almost all of the matrix has been pulled underneath the cell cords and cell clusters. This phenomenon has been proposed as a possible model for the growth and development of planar vascular systems in vitro. Our hypothesis is (...) that the matrix is reorganized and the cellular networks form as a result of traction forces exerted by the cells on the matrix and the latter's elasticity. We construct and analyze a mathematical model based on this hypothesis and examine conditions necessary for the formation of the pattern. We show cell migration is not necessary for pattern formation and that isotropic, strain-stimulated traction is sufficient to form the observed patterns. (shrink)

The ability to learn sequential contingencies of actions for predicting future outcomes is indispensable for flexible behavior in many daily decision-making contexts. It remains open whether such ability may be enhanced by transcranial direct current stimulation. The present study combined tDCS with functional near-infrared spectroscopy to investigate potential tDCS-induced effects on sequential decision-making and the neural mechanisms underlying such modulations. Offline tDCS and sham stimulation were applied over the left and right dorsolateral prefrontal cortex in young male adults (...) in a double-blind between-subject design using a three-state Markov decision task. The results showed an enhanced dlPFC hemodynamic response during the acquisition of sequential state transitions that is consistent with the findings from a previous functional magnetic resonance imaging study; a tDCS-induced increase of the hemodynamic response in the dlPFC, but without accompanying performance-enhancing effects at the behavioral level; and a greater tDCS-induced upregulation of hemodynamic responses in the delayed reward condition that seems to be associated with faster decision speed. Taken together, these findings provide empirical evidence for fNIRS as a suitable method for investigating hemodynamic correlates of sequential decision-making as well as functional brain correlates underlying tDCS-induced modulation. Future research with larger sample sizes for carrying out subgroup analysis is necessary in order to decipher interindividual differences in tDCS-induced effects on sequential decision-making process at the behavioral and brain levels. (shrink)

Transcranial alternating current stimulation and neurofeedback are two different types of non-invasive neuromodulation techniques, which can modulate brain activity and improve brain functioning. In this review, we compared the current state of knowledge related to the mechanisms of tACS and NFB and their effects on electroencephalogram activity and on aftereffects, including the duration of their persistence and potential behavioral benefits. Since alpha bandwidth has been broadly studied in NFB and in tACS research, the studies of NFB and tACS in (...) modulating alpha bandwidth were selected for comparing the online and offline effects of these two neuromodulation techniques. The factors responsible for variability in the responsiveness of the modulated EEG activity by tACS and NFB were analyzed and compared too. Based on the current literature related to tACS and NFB, it can be concluded that tACS and NFB differ a lot in the mechanisms responsible for their effects on an online EEG activity but they possibly share the common universal mechanisms responsible for the induction of aftereffects in the targeted stimulated EEG band, namely Hebbian and homeostatic plasticity. Many studies of both neuromodulation techniques report the aftereffects connected to the behavioral benefits. The duration of persistence of aftereffects for NFB and tACS is comparable. In relation to the factors influencing responsiveness to tACS and NFB, significantly more types of factors were analyzed in the NFB studies compared to the tACS studies. Several common factors for both tACS and NFB have been already investigated. Based on these outcomes, we propose several new research directions regarding tACS and NFB. (shrink)

Recent advances in second-person neuroscience have allowed the underlying neural mechanisms involved in teaching-learning interactions to be better understood. Teaching is not merely a one-way transfer of information from teacher to student; it is a complex interaction that requires metacognitive and mentalizing skills to understand others’ intentions and integrate information regarding oneself and others. Physiotherapy involving therapists instructing patients on how to improve their motor skills is a clinical field in which teaching-learning interactions play a central role. Accumulating evidence suggests (...) that non-invasive brain stimulation modulates cognitive functions; however, NIBS approaches to teaching-learning interactions are yet to be utilized in rehabilitation. In this review, I evaluate the present research into NIBS and its role in enhancing metacognitive and mentalizing abilities; I then review hyperscanning studies of teaching-learning interactions and explore the potential clinical applications of NIBS in rehabilitation. Dual-brain stimulation using NIBS has been developed based on findings of brain-to-brain synchrony in hyperscanning studies, and it is delivered simultaneously to two individuals to increase inter-brain synchronized oscillations at the stimulated frequency. Artificial induction of brain-to-brain synchrony has the potential to promote instruction-based learning. The brain-to-brain interface, which induces inter-brain synchronization by adjusting the patient’s brain activity, using NIBS, to the therapist’s brain activity, could have a positive effect on both therapist-patient interactions and rehabilitation outcomes. NIBS based on second-person neuroscience has the potential to serve as a useful addition to the current neuroscientific methods used in complementary interventions for rehabilitation. (shrink)

Closed-loop transcutaneous auricular vagal nerve stimulation was officially proposed in 2020. This work firstly reviewed two existing CL-taVNS forms: motor-activated auricular vagus nerve stimulation and respiratory-gated auricular vagal afferent nerve stimulation, and then proposed three future CL-taVNS systems: electroencephalography -gated CL-taVNS, electrocardiography -gated CL-taVNS, and subcutaneous humoral signals -gated CL-taVNS. We also highlighted the mechanisms, targets, technical issues, and patterns of CL-taVNS. By reviewing, proposing, and highlighting, this work might draw a preliminary blueprint for the development of (...) CL-taVNS. (shrink)