The question, “Will science remain human?” expresses a worry that deep learning algorithms will replace scientists in making crucial judgments of classification and inference and that something crucial will be lost if that happens. Ever since the introduction of telescopes and microscopes humans have relied on technologies to “extend” beyond human sensory perception in acquiring scientific knowledge. In this paper I explore whether the ways in which new learning technologies “extend” beyond human cognitive aspects of science can be treated instrumentally. (...) I will consider the norms for determining the reliability of a detection instrument, nuclear magnetic resonance spectroscopy, in predicting models of protein atomic structure. Do the same norms that apply in that case be used to judge the reliability of Artificial Intelligence deep learning algorithms? (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)

In the 1940s and 1950s, nuclear magnetic resonance , one of the most important analytical techniques in chemistry, grew to maturity in the intermediate research field of chemical physics. Chemists and physicists adapted the new technology to the experimental culture of molecular spectroscopy which was based on a pragmatic experimental style. In molecular spectroscopy, the purpose of experiments was the establishment of methods that suited both the physicists' quest for precision and theoretical model building and the (...) chemists' longing for empirical data and understanding of structural formulae and reaction courses. In this process, an experimental style emerged that can be characterized as reliance on self‐built instrumentation, theoretical foundation in quantum mechanics, and proof of utility in the solution of structural and dynamical questions. This article focuses on the early development of NMR at Harvard University, with particular emphasis on the contributions of the first chemist working in the field of NMR, Herbert S. Gutowsky. (shrink)

WHO II low grade glioma evolves inevitably to anaplastic transformation. Magnetic resonance imaging is a good non-invasive way to watch it, by hemodynamic and metabolic modifications, thanks to multinuclear spectroscopy 1H/31P. In this work we study a multi-scale minimal model of hemodynamics and metabolism applied to the study of gliomas. This mathematical analysis leads us to a fast-slow system. The control of the position of the stationary point brings to the concept of domain of viability. Starting from (...) this system, the equations bring to light the parameters that push glioma cells out of their domain of viability. Four fundamental factors are highlighted. The first two are cerebral blood flow and the rate of lactate transport through monocarboxylate transporters, which must be reduced in order to push glioma out of its domain of viability. Another factor is the intra arterial lactate, which must be increased. The last factor is pH, indeed a decrease of intra cellular pH could interfere with glioma growth. These reflections suggest that these four parameters could lead to new therapeutic strategies for the management of low grade gliomas. (shrink)

Training under high interference conditions through interleaved practice results in performance suppression during training but enhances long-term performance relative to repetitive practice involving low interference. Previous neuroimaging work addressing this contextual interference effect of motor learning has relied heavily on the blood-oxygen-level-dependent response using functional magnetic resonance imaging methodology resulting in mixed reports of prefrontal cortex recruitment under IP and RP conditions. We sought to clarify these equivocal findings by imaging bilateral PFC recruitment using functional near-infrared spectroscopy (...) while discrete key pressing sequences were trained under IP and RP schedules and subsequently tested following a 24-h delay. An advantage of fNIRS over the fMRI BOLD response is that the former measures oxygenated and deoxygenated hemoglobin changes independently allowing for assessment of cortical hemodynamics even when there is neurovascular decoupling. Despite slower sequence performance durations under IP, bilateral PFC oxygenated and deoxygenated hemoglobin values did not differ between practice conditions. During test, however, slower performance from those previously trained under RP coincided with hemispheric asymmetry in PFC recruitment. Specifically, following RP, test deoxygenated hemoglobin values were significantly lower in the right PFC. The present findings contrast with previous behavioral demonstrations of increased cognitive demand under IP to illustrate a more complex involvement of the PFC in the contextual interference effect. IP and RP incur similar levels of bilateral PFC recruitment, but the processes underlying the recruitment are dissimilar. PFC recruitment during IP supports action reconstruction and memory elaboration while RP relies on PFC recruitment to maintain task variation information in working memory from trial to trial. While PFC recruitment under RP serves to enhance immediate performance, it does not support long-term performance. (shrink)

Novel forms of matter, such as states made of gluons (glueballs), multiquark mesons or baryons and hybrid mesons are predicted by low energy QCD, for which several candidates have recently been identified. Searching for such exotic states of matter and studying their production and decay properties in detail has become a flourishing field at the experimental facilities now available or being built - e.g. BESIII in Beijing, BELLE II at SuperKEKB, GlueX at Jefferson Lab, PANDA at FAIR, J-PARC and in (...) the upgraded LHC experiments, in particular LHCb. A modern primer in the field is required so as to both revive and update the teaching of a new generation of researchers in the field of QCD. These lectures on hadron spectroscopy are intended for Master and PhD students and have been originally developed for a course delivered at the Stefan Meyer Institute of the Austrian Academy of Sciences. They are phenomenologically oriented and intended as complementary material for basic courses in particle and nuclear physics. The book describes the spectra of light and heavy mesons and baryons, and introduces the fundamental properties based on symmetries. Further, it derives multiplet structures, mixing angle, decay coupling constants, magnetic moments of baryons, and predictions for multiquark states and compares these with suitable experimental data. Basic methods of calculating decay angular distributions and determining masses and widths of resonances are also presented. The appendices provide students and newcomers to the field with the necessary background information, and include a set of problems and solutions. (shrink)

Executive function is essential to child development, with associated skills beginning to emerge in the first few years of life and continuing to develop into adolescence and adulthood. The prefrontal cortex, which follows a neurodevelopmental timeline similar to EF, plays an important role in the development of EF. However, limited research has examined prefrontal function in young children due to limitations of currently available neuroimaging techniques such as functional resonance magnetic imaging. The current study developed and applied a (...) multimodal Go/NoGo task to examine the EF component of inhibitory control in children 4–10 years of age. Cortical activity was measured using a non-invasive and child-friendly neuroimaging technique – functional near-infrared spectroscopy. Children’s response accuracy and reaction times were captured during the fNIRS session and compared with responses obtained using the standardized assessments from NIH Toolbox cognition battery. Results showed significant correlations between the behavioral measures during the fNIRS session and the standardized EF assessments, in line with our expectations. Results from fNIRS measures demonstrated a significant, age-independent effect of inhibitory control in the right PFC, and an age-dependent effect in the left orbitofrontal cortex, consistent with results in previous studies using fNIRS and fMRI. Thus, the new task designed for fNIRS was suitable for examining IC in young children, and results showed that fNIRS measures can reveal prefrontal IC function. (shrink)

Hippocampal neurogenesis has been implicated in the pathogenesis of and recovery from depression. However, most of the underlying studies were endpoint investigations in experimental animals yielding conflicting results, and it has been under debate to which extent these results could be transferred to human patients. Now, researchers have developed a powerful new tool to address these questions by a non‐invasive method in humans and animals in vivo, using magnetic resonance spectroscopy to detect a biomarker for proliferating progenitor (...) cells that give rise to new neurons.1 This makes it possible to study the role of neural progenitor cells in a wide variety of human brain disorders. BioEssays 30:806–810, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

White matter tracts are known to be susceptible to injury following concussion. The objective of this study was to determine whether contact play in sport could alter white matter metabolite levels in female varsity athletes independent of changes induced by long-term exercise. Metabolite levels were measured by single voxel proton magnetic resonance spectroscopy in the prefrontal white matter at the beginning and end of season in contact and non-contact varsity athletes. Sedentary women were scanned once, at a (...) time equivalent to the Off-Season time point. Metabolite levels in non-contact athletes did not change over a season of play, or differ from age matched sedentary women except that non-contact athletes had a slightly lower myo-inositol level. The contact athletes had lower levels of myo-inositol and glutamate, and higher levels of glutamine compared to both sedentary women and non-contact athletes. Lower levels of myo-inositol in non-contact athletes compared to sedentary women indicates long-term exercise may alter glial cell profiles in these athletes. The metabolite differences observed between contact and non-contact athletes suggest that non-contact athletes should not be used as controls in studies of concussion in high-impact sports because repetitive impacts from physical contact can alter white matter metabolite level profiles. It is imperative to use athletes engaged in the same contact sport as controls to ensure a matched metabolite profile at baseline. (shrink)

This book reflects on the significant and highly original scientific contributions of Hans Primas. A professor of chemistry at ETH Zurich from 1962 to 1995, Primas continued his research activities until his death in 2014. Over these 50 years and more, he worked on the foundations of nuclear magnetic resonance spectroscopy, contributed to a number of significant issues in theoretical chemistry, helped to clarify central topics in quantum theory and the philosophy of physics, suggested innovative ways of (...) addressing interlevel relations in the philosophy of science, and introduced cutting-edge approaches in the flourishing young field of scientific studies of consciousness. His work in these areas of research and its continuing impact is described by noted experts, colleagues, and collaborators of Primas. All authors contextualize their contributions to facilitate the mutual dialog between these fields. (shrink)

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

Following coma, some patients will recover wakefulness without signs of consciousness (only showing reflex movements, i.e., the vegetative state) or may show non-reflex movements but remain without functional communication (i.e., the minimally conscious state). Currently, there remains a high rate of misdiagnosis of the vegetative state (Schnakers et. al. BMC Neurol, 9:35, 8) and the clinical and electrophysiological markers of outcome from the vegetative and minimally conscious states remain unsatisfactory. This should incite clinicians to use multimodal assessment to detect objective (...) signs of consciousness and validate para-clinical prognostic markers in these challenging patients. This review will focus on advanced magnetic resonance imaging (MRI) techniques such as magnetic resonance spectroscopy, diffusion tensor imaging, and functional MRI (fMRI studies in both “activation” and “resting state” conditions) that were recently introduced in the assessment of patients with.. (shrink)

The paper illustrates how organic chemists dramatically altered their practices in the middle part of the twentieth century through the adoption of analytical instrumentation - such as ultraviolet and infrared absorption spectroscopy and nuclear magnetic resonance spectroscopy - through which the difficult process of structure determination for small molecules became routine. Changes in practice were manifested in two ways: in the use of these instruments in the development of 'rule-based' theories; and in an increased focus on (...) synthesis, at the expense of chemical analysis. These rule-based theories took the form of generalizations relating structure to chemical and physical properties, as measured by instrumentation. This 'Instrumental Revolution' in organic chemistry was two-fold: encompassing an embrace of new tools that provided unprecedented access to structures, and a new way of thinking about molecules and their reactivity in terms of shape and structure. These practices suggest the possibility of a change in the ontological status of chemical structures, brought about by the regular use of instruments. The career of Robert Burns Woodward (1917-1979) provides the central historical examples for the paper. Woodward was an organic chemist at Harvard from 1937 until the time of his death. In 1965, he won the Nobel Prize in Chemistry. (shrink)

The term ‘locked-in’ syndrome (LIS) describes a medical condition in which persons concerned are severely paralyzed and at the same time fully conscious and awake. The resulting anarthria makes it impossible for these patients to naturally communicate, which results in diagnostic as well as serious practical and ethical problems. Therefore, developing alternative, muscle-independent communication means is of prime importance. Such communication means can be realized via brain–computer interfaces (BCIs) circumventing the muscular system by using brain signals associated with preserved cognitive, (...) sensory, and emotional brain functions. Primarily, BCIs based on electrophysiological measures have been developed and applied with remarkable success. Recently, also blood flow–based neuroimaging methods, such as functional magnetic resonance imaging (fMRI) and functional near-infrared spectroscopy (fNIRS), have been explored in this context. After reviewing recent literature on the development of especially hemodynamically based BCIs, we introduce a highly reliable and easy-to-apply communication procedure that enables untrained participants to motor-independently and relatively effortlessly answer multiple-choice questions based on intentionally generated single-trial fMRI signals that can be decoded online. Our technique takes advantage of the participants’ capability to voluntarily influence certain spatio-temporal aspects of the blood oxygenation level–dependent (BOLD) signal: source location (by using different mental tasks), signal onset and offset. We show that healthy participants are capable of hemodynamically encoding at least four distinct information units on a single-trial level without extensive pretraining and with little effort. Moreover, realtime data analysis based on simple multi-filter correlations allows for automated answer decoding with a high accuracy (94.9%) demonstrating the robustness of the presented method.. (shrink)

euroscience of Rule-Guided Behavior brings together, for the first time, the experiments and theories that have created the new science of rules. Rules are central to human behavior, but until now the field of neuroscience lacked a synthetic approach to understanding them. How are rules learned, retrieved from memory, maintained in consciousness and implemented? How are they used to solve problems and select among actions and activities? How are the various levels of rules represented in the brain, ranging from simple (...) conditional ones if a traffic light turns red, then stop to rules and strategies of such sophistication that they defy description? And how do brain regions interact to produce rule-guided behavior? These are among the most fundamental questions facing neuroscience, but until recently there was relatively little progress in answering them. It was difficult to probe brain mechanisms in humans, and expert opinion held that animals lacked the capacity for such high-level behavior. However, rapid progress in neuroimaging technology has allowed investigators to explore brain mechanisms in humans, while increasingly sophisticated behavioral methods have revealed that animals can and do use high-level rules to control their behavior. The resulting explosion of information has led to a new science of rules, but it has also produced a plethora of overlapping ideas and terminology and a field sorely in need of synthesis. In this book, Silvia Bunge and Jonathan Wallis bring together the worlds leading cognitive and systems neuroscientists to explain the most recent research on rule-guided behavior. Their work covers a wide range of disciplines and methods, including neuropsychology, functional magnetic resonance imaging, neurophysiology, electroencephalography, neuropharmacology, near-infrared spectroscopy, and transcranial magnetic stimulation. This unprecedented synthesis is a must-read for anyone interested in how complex behavior is controlled and organized by the brain. (shrink)

Background: Maximum safe resection of infiltrative brain tumors in eloquent area is the primary objective in surgical neuro-oncology. This goal can be achieved with direct electrical stimulation to perform a functional mapping of the brain in patients awake intraoperatively. When awake surgery is not possible, we propose a pipeline procedure that combines advanced techniques aiming at performing a dissection that respects the anatomo-functional connectivity of the peritumoral region. This procedure can benefit from intraoperative monitoring with computerized tomography scan and brain (...) shift correction. Associated with this intraoperative monitoring, the additional value of preoperative investigation combining brain mapping by navigated transcranial magnetic stimulation with various neuroimaging modalities has not yet been reported.Case Report: A 42-year-old left-handed man had increased intracranial pressure, left hand muscle deficit, and dysarthria, related to an infiltrative tumor of the right frontal lobe with large mass effect and circumscribed contrast enhancement in motor and premotor cortical areas. Spectroscopy profile and intratumoral calcifications on CT-scan suggested an WHO grade III glioma, later confirmed by histology. The aforementioned surgical procedure was considered, since standard awake surgery was not appropriate for this patient. In preoperative time, nTMS mapping of motor function was performed, combined with magnetic resonance imaging -based tractography reconstruction of 6 neural tracts and resting-state functional MRI connectivity of sensorimotor and language networks. In intraoperative time, DES mapping was performed with motor evoked response recording and tumor resection was optimized using non-rigid image transformation of the preoperative data to iCT data. Image guidance was updated with correction for brain shift and tissue deformation using biomechanical modeling taking into account brain elastic properties. This correction was done at crucial surgical steps, i.e., when tumor bulged through the craniotomy after dura mater opening and when approaching the presumed eloquent brain regions. This procedure allowed a total resection of the tumor region with contrast enhancement as well as a complete regression of IICP and dysarthria. Hand paresis remained stable with no additional deficit. Postoperative nTMS mapping confirmed the good functional outcome.Conclusion: This case report and technical note highlights the value of preoperative functional evaluation by nTMS updated intraoperatively with correction of brain deformation by iCT. This multimodal approach may become the optimized technique of reference for patients with brain tumors in eloquent areas that are unsuitable for awake brain surgery. (shrink)

The blood oxygen level dependent effect that provides the contrast in functional magnetic resonance imaging has been demonstrated to affect the linewidth of spectral peaks as measured with magnetic resonance spectroscopy and through this, may be used as an indirect measure of cerebral blood flow related to neural activity. By acquiring MR-spectra interleaved with frames without water suppression, it may be possible to image the BOLD effect and associated metabolic changes simultaneously through changes in the (...) linewidth of the unsuppressed water peak. The purpose of this study was to implement this approach with the MEGA-PRESS sequence, widely considered to be the standard sequence for quantitative measurement of GABA at field strengths of 3 T and lower, to observe how changes in both glutamate and GABA levels may relate to changes due to the BOLD effect. MR-spectra and fMRI were acquired from the occipital cortex of 20 healthy participants whilst undergoing intrascanner visual stimulation in the form of a red and black radial checkerboard, alternating at 8 Hz, in 90 s blocks comprising 30 s of visual stimulation followed by 60 s of rest. Results show very strong agreement between the changes in the linewidth of the unsuppressed water signal and the canonical haemodynamic response function as well as a strong, negative, but not statistically significant, correlation with the Glx signal as measured from the OFF spectra in MEGA-PRESS pairs. Findings from this experiment suggest that the unsuppressed water signal provides a reliable measure of the BOLD effect and that correlations with associated changes in GABA and Glx levels may also be measured. However, discrepancies between metabolite levels as measured from the difference and OFF spectra raise questions regarding the reliability of the respective methods. (shrink)