Transcranial magnetic stimulation can be used to mask visual stimuli, disrupting visual task performance or preventing visual awareness. While TMS masking studies generally fix stimulation intensity, we hypothesized that varying the intensity of TMS pulses in a masking paradigm might inform several ongoing debates concerning TMS disruption of vision as measured subjectively versus objectively, and pre-stimulus versus post-stimulus TMS masking. We here show that both pre-stimulus TMS pulses and post-stimulus TMS pulses could strongly mask visual stimuli. (...) We found no dissociations between TMS effects on the subjective and objective measures of vision for any masking window or intensity, ruling out the option that TMS intensity levels determine whether dissociations between subjective and objective vision are obtained. For the post-stimulus time window particularly, we suggest that these data provide new constraints for models of vision and visual awareness. Finally, our data are in line with the idea that pre-stimulus masking operates differently from conventional post-stimulus masking. (shrink)

Developmental Dyslexia significantly interferes with children’s academic, personal, social, and emotional functioning. Nevertheless, therapeutic options need to be further validated and tested in randomized controlled clinical trials. The use of transcranial direct current stimulation has been gaining ground in recent years as a new intervention option for DD. However, there are still open questions regarding the most suitable tDCS protocol for young people with DD. The current crossover study tested the effectiveness of a short and intensive tDCS protocol, including (...) the long-term effects, as well as the influence of age and neuropsychological processes at baseline on reading improvements. Twenty-four children and adolescents with DD were randomly assigned to receive active tDCS during the first slot and sham tDCS during the second slot or vice versa. Five consecutive daily sessions of left anodal/right cathodal tDCS set at 1 mA for 20 min were administered over the parieto-occipital regions. Reading measures and neuropsychological measures were collected before, immediately after, 1 week and 1 month later the treatment. Our results showed that only the active tDCS condition improved non-word reading speed immediately after and 1 month later the end of the treatment compared with baseline. In addition, the improvement in non-word reading speed was significantly correlated with age and with neuropsychological measures at baseline but only in the active tDCS condition. The current crossover study contributed to enforce previous effects of tDCS, including long-term effects, on non-word reading speed and to understand the effect of age and neuropsychological processes on reading outcomes. Our findings showed that tDCS could be a low-cost and easy-to-implement treatment option with long-term effects for children and adolescents with DD. (shrink)

Motor training to improve walking and balance function is a common aspect of rehabilitation following motor-incomplete spinal cord injury. Evidence suggests that moderate- to high-intensity exercise facilitates neuroplastic mechanisms that support motor skill acquisition and learning. Furthermore, enhancing corticospinal drive via transcranial direct current stimulation may augment the effects of motor training. In this pilot study, we investigated whether a brief moderate-intensity locomotor-related motor skill training circuit, with and without tDCS, improved walking and balance outcomes in persons (...) with MISCI. In addition, we examined potential differences between within-day and between-day effects of MST. Twenty-six adults with chronic MISCI, who had some walking ability, were enrolled in a 5-day double-blind, randomized study with a 3-day intervention period. Participants were assigned to an intensive locomotor MST circuit and concurrent application of either sham tDCS or active tDCS. The primary outcome was overground walking speed measured during the 10-meter walk test. Secondary outcomes included spatiotemporal gait characteristics, peak trailing limb angle, intralimb coordination, the Berg Balance Scale, and the Falls Efficacy Scale-International questionnaire. Analyses revealed a significant effect of the MST circuit, with improvements in walking speed, cadence, bilateral stride length, stronger limb TLA, weaker limb ACC, BBS, and FES-I observed in both the MST+tDCSsham and MST+tDCS groups. No differences in outcomes were observed between groups. Between-day change accounted for a greater percentage of the overall change in walking outcomes. In persons with MISCI, brief intensive MST involving a circuit of ballistic, cyclic locomotor-related skill activities improved walking outcomes, and selected strength and balance outcomes; however, concurrent application of tDCS did not further enhance the effects of MST.Clinical Trial Registration[ClinicalTrials.gov], identifier [NCT03237234]. (shrink)

The measurement of sensory intensity has had a long history, attracting the attention of investigators from many disciplines including physiology, psychology, physics, mathematics, philosophy, and even chemistry. While there has been a continuing doubt by some that sensation has the properties necessary for measurement, experiments designed to obtain estimates of sensory intensity have found that a general rule applies: Equal stimulus ratios produce equal sensory ratios. Theories concerning the basis for this simple psychophysical rule are discussed, with emphasis (...) given to the physical correlate theory, which considers judgments of subjective magnitudes to be based upon estimates of physical dimensions that vary regularly with changes in degree of stimulation. For the most thoroughly investigated sensory scales, brightness and loudness, the physical correlate is considered to be distance. Our “tacit knowledge” of the sensory effects of changing distance plays an essential role in matching motor activities to environmental conditions and in ensuring accurate perceptual evaluations through brightness and loudness constancies. In psychophysical experiments, subjects apparently use this same tacit knowledge when required to estimate relative subjective magnitudes. The evidence related to the physical correlate theory is summarized, and it is concluded that, while under appropriate conditions we demonstrate considerable skill in evaluating environmental relationships, we are quite unable to estimate the neurophysiological nature or quantity of sensory response. A psychophysics devoted to studying conditions required for accuracy and conditions producing errors in the perception of environmental relationships would seem to be more valuable than one devoted to subjective magnitudes. (shrink)

Fourteen healthy children (13.8±2.2 years, range 10 to 16; M:F=5:9) received 30 Hz intermittent theta burst transcranial magnetic stimulation (iTBS) with a stimulation intensity of 70% of resting motor threshold (RMT) with a total of 300 (iTBS300) pulses. All volunteers were free of neurologic, psychiatric and serious medical illnesses, not taking any neuropsychiatric medications, and did not have any contraindications to Transcranial Magnetic Stimulation. Changes in the mean amplitudes of motor-evoked potentials from baseline following iTBS were (...) expressed as a ratio and assessed from 1 to 10 minutes (BLOCK1) and 1 to 30 minutes (BLOCK2) using repeated-measures analysis of variance. All 14 subjects completed iTBS300 over the dominant primary motor cortex (M1) without any clinically reported adverse events. ITBS300 produced significant M1 facilitation (F5,65=3.165, p=0.01) at BLOCK1 and trend level M1 facilitation at BLOCK2 (F10,129=1.69, p=0.089). Although iTBS300 (stimulation duration of 92 seconds at 70% RMT) delivered over M1 in typically developed children was well-tolerated and produced on average significant facilitatory changes in cortical excitability, the post-iTBS300 neurophysiologic response was variable in our small sample. ITBS300-induced changes may represent a potential neuroplastic biomarker in healthy children and those with neuro-genetic or neuro-psychiatric disorders. However, a larger sample size is needed to address safety and concerns of response variability. (shrink)

It has been well documented that the auditory system in the superior temporal cortex is responsible for processing basic auditory sound features, such as sound frequency and intensity, while the prefrontal cortex is involved in higher-order auditory functions, such as language processing and auditory episodic memory. The temporal auditory cortex has vast forward anatomical projections to the prefrontal auditory cortex, connecting with the lateral, medial, and orbital parts of the prefrontal cortex. The connections between the auditory cortex and the (...) prefrontal cortex thus help in localizing, recognizing, and comprehending external auditory inputs. In addition, the medial prefrontal cortex (MPFC) is believed to be a core region of episodic memory retrieval and is one of the most important regions in the default mode network (DMN). However, previous neural evidence with regard to the comparison between basic auditory processing and auditory episodic memory retrieval mainly comes from fMRI studies. The specific neural networks and the corresponding critical frequency bands of neuronal oscillations underlying the two auditory functions remain unclear. In the present study, we reported results of direct cortical stimulations during stereo-electro-encephalography (SEEG) recording in a patient with drug-resistant epilepsy. Electrodes covered the superior temporal gyrus, the operculum and the insula cortex of bilateral hemispheres, the prefrontal cortex, the parietal lobe, the anterior and middle cingulate cortex, and the amygdala of the left hemisphere. Two types of auditory hallucinations were evoked with direct cortical stimulations, which were consistent with the habitual seizures. The noise hallucinations, i.e., “I could hear buzzing noises in my head,” were evoked with the stimulation of the superior temporal gyrus. The episodic memory hallucinations “I could hear a young woman who was dressed in a red skirt saying: What is the matter with you?,” were evoked with the stimulation of MPFC. The patient described how she had met this young woman when she was young and that the woman said the same sentence to her. Furthermore, by analyzing the high gamma power (HGP) induced by direct electrical stimulation, two dissociable neural networks underlying the two types of auditory hallucinations were localized. Taken together, the present results confirm the hierarchical processing of auditory information by showing the different involvements of the primary auditory cortex vs. the prefrontal cortex in the two types of auditory hallucinations. (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)

Introduction Deep brain stimulation (DBS) is approved under a humanitarian device exemption to manage treatment-resistant obsessive-compulsive disorder (TR-OCD) in adults. It is possible that DBS may be trialed or used clinically off-label in children and adolescents with TR-OCD in the future. DBS is already used to manage treatment-resistant childhood dystonia. Evidence suggests it is a safe and effective intervention for certain types of dystonia. Important questions remain unanswered about the use of DBS in children and adolescents with TR-OCD, including (...) whether mental health clinicians would refer pediatric patients for DBS, and who would be a good candidate for DBS.Objectives To explore mental health clinicians’ views on what clinical and psychosocial factors they would consider when determining which children with OCD would be good DBS candidates.Materials and Methods In depth, semi-structured interviews were conducted with n = 25 mental health clinicians who treat pediatric patients with OCD. The interviews were transcribed, coded, and analyzed using thematic content analysis. Three questions focused on key, clinical, and psychosocial factors for assessing candidacy were analyzed to explore respondent views on candidacy factors. Our analysis details nine overarching themes expressed by clinicians, namely the patient’s previous OCD treatment, OCD severity, motivation to commit to treatment, presence of comorbid conditions, family environment, education on DBS, quality of life, accessibility to treatment, and patient age and maturity.Conclusions Clinicians generally saw considering DBS treatment in youth as a last resort and only for very specific cases. DBS referral was predominantly viewed as acceptable for children with severe TR-OCD who have undertaken intensive, appropriate treatment without success, whose OCD has significantly reduced their quality of life, and who exhibit strong motivation to continue treatment given the right environment. Appropriate safeguards, eligibility criteria, and procedures should be discussed and identified before DBS for childhood TR-OCD becomes practice. (shrink)

BackgroundConventionally, transcranial direct current stimulation (tDCS) aims to focalize the current reaching the target region-of-interest (ROI). The focality can be quantified by the dose-target-determination-index (DTDI). Despite having a uniform tDCS setup, some individuals receive focal stimulation (high DTDI) while others show reduced focality (“non-focal”). The volume of cerebrospinal fluid (CSF), gray matter (GM), and white matter (WM) underlying each ROI govern the tDCS current distribution inside the brain, thereby regulating focality.AimTo determine the regional volume parameters that differentiate the (...) focal and non-focal groups.MethodsT1-weighted images of the brain from 300 age-sex matched adults were divided into three equal groups- (a) Young (20 ≤ × < 40 years), (b) Middle (40 ≤ × < 60 years), and (c) Older (60 ≤ × < 80 years). For each group, inter and intra-hemispheric montages with electrodes at (1) F3 and right supraorbital region (F3-RSO), and (2) CP5 and Cz (CP5-Cz) were simulated, targeting the left- Dorsolateral Prefrontal Cortex (DLPFC) and -Inferior Parietal Lobule (IPL), respectively. Both montages were simulated for two current doses (1 and 2 mA). For each individual head simulated for a tDCS configuration (montage and dose), the current density at each region-of-interest (ROI) and their DTDI were calculated. The individuals were categorized into two groups- (1) Focal (DTDI ≥ 0.75), and (2) Non-focal (DTDI < 0.75). The regional volume of CSF, GM, and WM of all the ROIs was determined. For each tDCS configuration and ROI, three 3-way analysis of variance was performed considering- (i) GM, (ii) WM, and (iii) CSF as the dependent variable (DV). The age group, sex, and focality group were the between-subject factors. For a given ROI, if any of the 3 DV’s showed a significant main effect or interaction involving the focality group, then that ROI was classified as a “focal ROI.”ResultsRegional CSF was the principal determinant of focality. For interhemispheric F3-RSO montage, interaction effect (p < 0.05) of age and focality was observed at Left Caudate Nucleus, with the focal group exhibiting higher CSF volume. The CSF volume of focal ROI correlated positively (r ∼ 0.16, p < 0.05) with the current density at the target ROI (DLPFC). For intrahemispheric CP5-Cz montage, a significant (p < 0.05) main effect was observed at the left pre- and post-central gyrus, with the focal group showing lower CSF volume. The CSF volume correlated negatively (r ∼ –0.16, p < 0.05) with current density at left IPL. The results were consistent for both current doses.ConclusionThe CSF channels the flow of tDCS current between electrodes with focal ROIs acting like reservoirs of current. The position of focal ROI in the channel determines the stimulation intensity at the target ROI. For focal stimulation in interhemispheric F3-RSO, the proximity of focal ROI reserves the current density at the target ROI (DLPFC). In contrast, for intrahemispheric montage (CP5-Cz), the far-end location of focal ROI reduces the current density at the target (IPL). (shrink)

Shrinking resources and the increasing complexity of clinical decisions are stimulating research in knowledge-intensive computer applications for the delivery of social services. The expected benefits of knowledge-intensive applications such as expert systems include improvement in both the quality and the consistency of service delivery, augmentation of institutional memory, and reduced labour costs through greater reliance on paraprofessionals. This paper analyses the likely impacts of knowledge-intensive systems on social service organisations, drawing on trends in related service-delivery fields, and on known impacts (...) of computer applications in organisations. A structural change may be anticipated: decision making and planning functions will shift increasingly from social service professionals to administrators. (shrink)

This book is an in-depth exploration of the nature of sensations and how they are affected by different types of stimuli. The author, Harold Griffing, presents a detailed analysis of the ways in which pressure and impact can influence sensations, and offers insights into how these findings can be applied in a variety of contexts. This work has been selected by scholars as being culturally important, and is part of the knowledge base of civilization as we know it. This work (...) is in the "public domain in the United States of America, and possibly other nations. Within the United States, you may freely copy and distribute this work, as no entity (individual or corporate) has a copyright on the body of the work. Scholars believe, and we concur, that this work is important enough to be preserved, reproduced, and made generally available to the public. We appreciate your support of the preservation process, and thank you for being an important part of keeping this knowledge alive and relevant. (shrink)

Transcranial magnetic stimulation studies have demonstrated increased cortical facilitation and reduced inhibition following aerobic exercise, even when examining motor regions separate to the exercised muscle group. These changes in brain physiology following exercise may create favorable conditions for adaptive plasticity and motor learning. One candidate mechanism behind these benefits is the increase in brain-derived neurotropic factor observed following exercise, which can be quantified from a venous blood draw. The aim of this study was to investigate changes in motor cortex (...) excitability and inhibition of the upper limb, and circulating BDNF, following high-intensity interval training on a stationary bicycle. Nineteen sedentary adults participated in a randomized crossover design study involving a single bout of high-intensity interval cycling for 20 min or seated rest. Venous blood samples were collected, and transcranial magnetic stimulation was used to stimulate the extensor carpi radialis, where motor evoked potentials were recorded pre- and post-condition. Following exercise, there was a significant increase in corticospinal excitability measured at 120% of resting motor threshold and a reduction in short-interval cortical inhibition. There was a non-significant 23.6% increase in BDNF levels. Collectively, these results reflect a net reduction in gamma aminobutyric acid ergic synaptic transmission and increased glutamatergic facilitation, resulting in increased corticospinal excitability. This study supports the notion that acute high-intensity exercise provides a potent stimulus for inducing cortical neuroplasticity, which may support enhanced motor learning. (shrink)

What makes some firms more innovative than others and what determines the source of these innovations are questions that are still not adequately answered due to the complex, often esoteric, nature of the innovation process. This paper considers the effect of one externally oriented strategy (extent of formal inter-organizational linkages) and one internally oriented strategy (degree of knowledge intensity) on overall levels of innovativeness and the source of these innovations. Using data collected from firms operating in the bioscience-technology industries (...) in both New York and Utah, our results suggest that both of these strategies have a significant effect upon innovation levels and the source of innovation (internally versus externally stimulated). Interestingly, there were few firms that undertook both of these strategies simultaneously and thus the proposed interaction effect where increased absorptive capacity (on the basis of knowledge intensity) would make external linkages even more valuable could not be discerned. (shrink)

Previous research has demonstrated that regular exercise modulates motor cortical plasticity and cognitive function, but the influence of short-term high-intensity interval training remains unclear. In the present study, the effect of short-term HIIT on neuroplasticity and executive function was assessed in 32 sedentary females. Half of the participants undertook 2 weeks of HIIT. Paired-pulse transcranial magnetic stimulation was used to measure motor cortical plasticity via short intracortical inhibition and intracortical facilitation. We further adapted the Stroop task using functional (...) near-infrared spectroscopy to evaluate executive function in the participants. The results indicated that, compared with the control group, the HIIT group exhibited decreased ICF. In the Stroop task, the HIIT group displayed greater activation in the left dorsolateral prefrontal cortex and left orbitofrontal cortex even though no significant difference in task performance was observed. These findings indicate that short-term HIIT may modulate motor cortical plasticity and executive function at the neural level. (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)

Cranial electrical stimulation has been applied at various current levels in both adults and children with neurological conditions with seemingly promising but somewhat inconsistent results. Stimulation-induced spatial electric fields within a specific brain region are likely a significant contributing factor for the biological effects. Although several simulation models have been used to predict EF distributions in the brain, these models actually have not been validated by in vivo CES-induced EF measurements in the live human brain. This study directly (...) measured the CES-induced voltage changes with implanted stereotactic-electroencephalographic electrodes in twenty-one epilepsy participants and then compared these measured values with the simulated ones obtained from the personalized models. In addition, we further investigated the influence of stimulation frequency, intensity, electrode montage and age on EFs in parts of participants. We found both measured voltages and EFs obtained in vivo are highly correlated with the predicted ones in our cohort. In white matter and gray matter, the measured voltages linearly increased when the stimulation intensity increased from 5 to 500 μA but showed no significant changes with changing stimulation frequency from 0.5 to 200 Hz. Electrode montage, but not age, significantly affects the distribution of the EFs. Our in vivo measurements demonstrate that the individualized simulation model can reliably predict the CES-induced EFs in both adults and children. It also confirms that the CES-induced EFs highly depend on the electrode montages and individual anatomical features. (shrink)

Transvertebral magnetic stimulation (TVMS) of the human lumbar spinal cord can evoke bilateral rhythmic leg movements, as in walking, supposedly through the activation of spinal locomotor neural circuitry. However, an appropriate stimulus intensity that can effectively drive the human spinal locomotor circuitry to evoke walking-like movements has not been determined. To address this issue, TVMS was delivered over an intervertebral space of the lumbar cord (L1–L3) at different stimulus intensities (10–70% of maximum stimulator output) in healthy human adults. (...) In a stimulus intensity-dependent manner, TVMS evoked two major patterns of rhythmic leg movements in which the left-right movement cycles were coordinated with different phase relationships: hopping-like movements, in which both legs moved in the same direction in phase, and walking-like movements, in which both legs moved alternatively in anti-phase; uncategorized movements were also observed which could not be categorized as either movement type. Even at the same stimulation site, the stimulus-evoked rhythmic movements changed from hopping-like movements to walking-like movements as stimulus intensity was increased. Different leg muscle activation patterns were engaged in the induction of the hopping- and walking-like movements. The magnitude of the evoked hopping- and walking-like movements was positively correlated with stimulus intensity. The human spinal neural circuitry required a higher intensity of magnetic stimulation to produce walking-like leg movements than to produce hopping-like movements. These results suggest that TVMS activates distinct neural modules in the human spinal cord to generate hopping- and walking-like movements. (shrink)

Chronic migraine is a difficult disease to diagnose, and its pathophysiology remains undefined. Its symptoms affect the quality of life and daily living tasks of the affected person, leading to momentary disability. This is a pilot, randomized, controlled, double-blind clinical trial study with female patients between 18 and 65 years old with chronic migraine. The patients underwent twelve mindfulness sessions paired with anodal transcranial direct-current stimulation over the left dorsolateral prefrontal cortex, with current intensity of 2 mA applied (...) for 20 min, three times a week for 4 weeks. In addition, 20 min of mindfulness home practices were performed by guided meditation audio files. A total of 30 participants were evaluated after the treatment, and these were subdivided into two groups—active tDCS and sham tDCS, both set to mindfulness practice. The FFMQ-BR, MIDAS, and HIT-6 questionnaires were used to evaluate the outcomes. After the treatment, the active mindfulness and tDCS group showed better results in all outcomes. The sham group also showed improvements, but with smaller effect sizes compared to the active group. The only significant difference in the intergroup analysis was the outcome evaluated by HIT-6 in the post treatment result. Our results provide the first therapeutic evidence of mindfulness practices associated with left DLPFC anodal tDCS with a consequent increase in the level of full attention and analgesic benefits in the clinical symptoms of patients with chronic migraine. (shrink)

Doctors and nurses at the neonatal intensive-care unit at The University Hospital, Rigshospitalet, in Copenhagen, Denmark regularly find themselves in ethically challenging and potentially distressing situations concerning the life of ill newborn babies. In collaboration with the neonatal intensive-care unit, my project was to develop a method that could stimulate systematically dialogical moral inquiry within everyday clinical practice. My four months of ethnographic fieldwork at the neonatal intensive-care unit generated four fundamental themes that make up the scaffold of the developed (...) model for ethical deliberation and decision making. The model is a reflective tool to be used by health care professionals in situ. It provides a structured and a systematic framework for dialogue that can clarify the obscurities of a case and give argumentative support for ethical decisions. This article explains how the 4C model was developed and whereof it consists. (shrink)

To cause pain, it is not enough to deliver a dose of noxious stimulation. Pain requires the interaction of sensory processing, emotion, and cognition. In this paper, I focus on the role of cognition in the felt intensity of pain. I provide evidence for the cognitive modulation of pain. In particular, I show that attention and expectation can influence the experience of pain intensity. I also consider the mechanisms that underlie the cognitive effects on pain. I show (...) that all the proposed mechanisms of pain modulation affirm the view that cognition impacts the sensory and discriminative aspects of pain. I conclude that pain perception is a cognitively penetrated phenomenon. (shrink)

Climate change has caused serious threats to global economic development and human well-being, and green finance is a new way to achieve ecological, economic, and social sustainable development, and it also has important theoretical significance and policy value. This study firstly aims to study the impact of green finance on regional carbon intensity. Then, it aims to determine the moderating effect of capital stock per capita on the relationship between green finance and carbon intensity based on moderating effect (...) model as well as to investigate the threshold effect of capital stock per capita on the relationship between green finance and carbon intensity based on threshold effect model. The main conclusions are as follows: Every 1% increase in green finance will lead to a 2% decrease in carbon intensity, and the inhibition of green finance on carbon intensity is most obvious in northeast and east China. The capital stock per capita has a significant moderating effect, which could enhance the restraining effect of green financial development on carbon intensity, and this moderating effect is most obvious in northeast China. The capital stock per capita has a threshold effect in the process of green finance development to suppress carbon intensity. The higher the capital stock per capita, the stronger the inhibition effect of green finance development on carbon intensity. Therefore, in the process of capital accumulation, attention should be paid to improve the relevant legal system and policy guarantee, optimization of financial structure, and stimulation of the capital allocation effect of green finance. Simultaneously, in order to strengthen the inhibitory effect of green finance on carbon intensity, differentiated green finance development policies should be formulated based on factor endowment structure and comparative advantages of different regions. (shrink)

This paper focuses on the patient's perspective and the philosophical underpinnings that support what might be considered optimal for the future design of the intensive care unit (ICU) patient room. It also addresses the question of whether the aspects that support at‐homeness are applicable to ICU patient rooms. The concept of “at‐homeness” in ICUs is strongly related to privacy and control of space and territory. This study investigates whether the sense of at‐homeness can be created in an ICU, when one (...) or more patients share a room. From an interdisciplinary perspective, we critically reflect on various aspects associated with conflicts surrounding the use of ICU patient rooms. Thus, from an architectural and a caring perspective, the significance of space and personal territory in ICU patient rooms is emphasized. Recommendations for further research are suggested. In conclusion, privacy and control are deemed to be essential factors in the stimulation of recovery processes and the promotion of well‐being in situations involving severe illness or life‐threatening conditions. (shrink)

Delineation of the subthalamic nuclei on MRI is critical for deep brain stimulation surgery in patients with Parkinson’s disease. We propose this retrospective cohort study for quantitative analysis of MR signal-to-noise ratio, contrast, and signal difference-to-noise ratio of the STN on pre-operative three-dimensional stereotactic MRI in patients with medication-refractory PD. Forty-five consecutive patients with medication-refractory PD who underwent STN-DBS surgery in our hospital from January 2018 to June 2021 were included in this study. All patients had whole-brain 3D MRI, (...) including T2-weighted imaging, T2-weighted fluid-attenuated inversion recovery, and susceptibility-weighted imaging, at 3.0 T scanner for stereotactic navigation. The signal intensities of the STN, corona radiata, and background noise were obtained after placing regions of interest on corresponding structures. Quantitative comparisons of SNR, contrast, and SDNR of the STN between MR pulse sequences, including the T2WI, FLAIR, and SWI. Subgroup analysis regarding patients’ sex, age, and duration of treatment. We used one-way repeated measures analysis of variance for quantitative comparisons of SNR, contrast, and SDNR of the STN between different MR pulse sequences, and we also used the dependent t-test for the post hoc tests. In addition, we used Mann–Whitney U test for subgroup analyses. Both the contrast and SDNR were highest on FLAIR. The SNR was highest on SWI, and both the SNR and SDNR were lowest on T2WI. Subgroup analyses demonstrated significantly lower SDNR on SWI for patients receiving medication treatment for ≥13 years. In conclusion, on 3D stereotactic MRI of medication-refractory PD patients, the contrast and SDNR for the STN are highest on FLAIR, suggesting the optimal delineation of STN on FLAIR. (shrink)

Background: The Parkinsonian [i.e., Parkinson's disease ] gait disorder represents a therapeutical challenge with residual symptoms despite the use of deep brain stimulation of the subthalamic nucleus and medical and rehabilitative strategies. The aim of this study was to assess the effect of different DBS modes as combined stimulation of the STN and substantia nigra and environmental rehabilitative factors as footwear on gait kinematics.Methods: This single-center, randomized, double-blind, crossover clinical trial assessed shod and unshod gait in patients with (...) PD with medication in different DBS conditions during different gait tasks and compared gait characteristics to healthy controls. Notably, 15 patients participated in the study, and 11 patients were analyzed after a dropout of four patients due to DBS-induced side effects.Results: Gait was modulated by both factors, namely, footwear and DBS mode, in patients with PD. Footwear impacted gait characteristics in patients with PD similarly to controls with longer step length, lower cadence, and shorter single-support time. Interestingly, DBS exerted specific effects depending on gait tasks with increased cognitive load. STN+SN DBS was the most efficient DBS mode compared to STIM OFF and STN DBS with intense effects as step length increment during dual task.Conclusion: The PD gait disorder is a multifactorial symptom, impacted by environmental factors as footwear and modulated by DBS. DBS effects on gait were specific depending on the gait task, with the most obvious effects with STN+SN DBS during gait with increased cognitive load. (shrink)

Ein Leitmotiv der medizinethischen Auseinandersetzung mit der tiefen Hirnstimulation (THS) ist die Beschäftigung mit Fragen personaler Identität. Da es sich bei personaler Identität auch um ein Problem der theoretischen Philosophie handelt, wird in diesem Aufsatz nicht nur die praktische Frage nach der ethischen Legitimation der THS durch informierte Einwilligung gestellt und ein modifiziertes Legitimationskriterium für wesensändernde THS erarbeitet. Vielmehr wird zunächst versucht, das Problem, um das es in der Debatte um THS und personaler Identität geht, besser zu verstehen.

Airway mucin secretion is important pathophysiologically and as a model of polarized epithelial regulated exocytosis. We find the trafficking protein, SNAP23, selectively expressed in secretory cells compared with ciliated and basal cells of airway epithelium by immunohistochemistry and FACS, suggesting that SNAP23 functions in regulated but not constitutive epithelial secretion. Heterozygous SNAP23 deletant mutant mice show spontaneous accumulation of intracellular mucin, indicating a defect in baseline secretion. However mucins are released from perfused tracheas of mutant and wild-type mice at the (...) same rate, suggesting that increased intracellular stores balance reduced release efficiency to yield a fully compensated baseline steady state. In contrast, acute stimulated release of intracellular mucin from mutant mice is impaired whether measured by a static imaging assay 5 min after exposure to the secretagogue ATP or by kinetic analysis of mucins released from perfused tracheas during the first 10 min of ATP exposure. Together, these data indicate that increased intracellular stores cannot fully compensate for the defect in release efficiency during intense stimulation. The lungs of mutant mice develop normally and clear bacteria and instilled polystyrene beads comparable to WT mice, consistent with these functions depending on baseline secretion that is fully compensated. (shrink)

GraphicalThirty healthy participants received 60 trials of intermittent SO tACS at an intensity of 2 mA. Motor cortical excitability was assessed using TMS-induced MEPs acquired across different oscillatory phases during and outlasting tACS, as well as at the start and end of the stimulation session. Mean MEP amplitude increased by ∼41% from pre- to post-tACS ; however, MEP amplitudes were not modulated with respect to the tACS phase.Converging evidence suggests that transcranial alternating current stimulation may entrain endogenous (...) neural oscillations to match the frequency and phase of the exogenously applied current and this entrainment may outlast the stimulation. However, observing entrainment in the electroencephalograph during stimulation is extremely difficult due to the presence of complex tACS artifacts. The present study assessed entrainment to slow oscillatory tACS by measuring motor cortical excitability across different oscillatory phases during and outlasting stimulation. 30 healthy participants received 60 trials of intermittent SO tACS at an intensity of 2 mA peak-to-peak. Motor cortical excitability was assessed using transcranial magnetic stimulation of the hand region of the primary motor cortex to induce motor evoked potentials in the contralateral thumb. MEPs were acquired at four time-points within each trial – early online, late online, early offline, and late offline – as well as at the start and end of the overall stimulation period. A significant increase in MEP amplitude was observed from pre- to post-tACS and from the first to the last tACS block. However, no phase-dependent modulation of excitability was observed. Therefore, although SO tACS had a facilitatory effect on motor cortical excitability that outlasted stimulation, there was no evidence supporting entrainment of endogenous oscillations as the underlying mechanism. (shrink)

The European Clinical Trials Directive was issued in 2001 and aimed to simplify and harmonise the regulatory framework of clinical trials throughout Europe, thus stimulating European research. However, significant complexity and inconsistency remains due to disparate interpretation by EU member states. Critical care research has been particularly impacted due to variable and often restrictive consenting procedures for incapacitated subjects, with some countries requiring a court-appointed representative, while others recognise consent from family members and occasionally professional representatives. Furthermore, the absence of (...) a waiver of consent threatened to put an end to emergency research in Europe and was met with varied responses. Approval procedures by ethics committees are equally inconsistent, particularly those relating to provision of a single opinion for multi-centre trials. Although evidence is somewhat mixed, this complexity as well as a general increase in administrative and financial burden following the Directive has been shown to cause a reduction in clinical trial activity in Europe, particularly academic trials. We aim to clarify some of these inconsistent procedures, particularly those relating to informed consent of incapacitated subjects, as well as discussing some general weaknesses and possible improvements of the Directive ahead of its planned revision in 2011. (shrink)