Functional neuroimaging as a catalyst for integrated neuroscience.

Functional magnetic resonance imaging (fMRI) enables non-invasive access to the awake, behaving human brain. By tracking whole-brain signals across a diverse range of cognitive and behavioural states or mapping differences associated with specific traits or clinical conditions, fMRI has advanced our understanding of brain function and its links to both normal and atypical behaviour. Despite this headway, progress in human cognitive neuroscience that uses fMRI has been relatively isolated from rapid advances in other subdomains of neuroscience, which themselves are also somewhat siloed from one another. In this Perspective, we argue that fMRI is well-placed to integrate the diverse subfields of systems, cognitive, computational and clinical neuroscience. We first summarize the strengths and weaknesses of fMRI as an imaging tool, then highlight examples of studies that have successfully used fMRI in each subdomain of neuroscience. We then provide a roadmap for the future advances that will be needed to realize this integrative vision. In this way, we hope to demonstrate how fMRI can help usher in a new era of interdisciplinary coherence in neuroscience.

Lights on music cognition: A systematic and critical review of fNIRS applications and future perspectives.

Research investigating the neural processes related to music perception and production constitutes a well-established field within the cognitive neurosciences. While most neuroimaging tools have limitations in studying the complexity of musical experiences, functional Near-Infrared Spectroscopy (fNIRS) represents a promising, relatively new tool for studying music processes in both laboratory and ecological settings, which is also suitable for both typical and pathological populations across development. Here we systematically review fNIRS studies on music cognition, highlighting prospects and potentialities. We also include an overview of fNIRS basic theory, together with a brief comparison to characteristics of other neuroimaging tools. Fifty-nine studies meeting inclusion criteria (i.e., using fNIRS with music as the primary stimulus) are presented across five thematic sections. Critical discussion of methodology leads us to propose guidelines of good practices aiming for robust signal analyses and reproducibility. A continuously updated world map is proposed, including basic information from studies meeting the inclusion criteria. It provides an organized, accessible, and updatable reference database, which could serve as a catalyst for future collaborations within the community. In conclusion, fNIRS shows potential for investigating cognitive processes in music, particularly in ecological contexts and with special populations, aligning with current research priorities in music cognition.

Scanning the horizon: towards transparent and reproducible neuroimaging research.

Functional neuroimaging techniques have transformed our ability to probe the neurobiological basis of behaviour and are increasingly being applied by the wider neuroscience community. However, concerns have recently been raised that the conclusions that are drawn from some human neuroimaging studies are either spurious or not generalizable. Problems such as low statistical power, flexibility in data analysis, software errors and a lack of direct replication apply to many fields, but perhaps particularly to functional MRI. Here, we discuss these problems, outline current and suggested best practices, and describe how we think the field should evolve to produce the most meaningful and reliable answers to neuroscientific questions.

Human Positron Emission Tomography Neuroimaging.

Neuroimaging with positron emission tomography (PET) is the most powerful tool for understanding pharmacology, neurochemistry, and pathology in the living human brain. This technology combines high-resolution scanners to measure radioactivity throughout the human body with specific, targeted radioactive molecules, which allow measurements of a myriad of biological processes in vivo. While PET brain imaging has been active for almost 40 years, the pace of development for neuroimaging tools, known as radiotracers, and for quantitative analytical techniques has increased dramatically over the past decade. Accordingly, the fundamental questions that can be addressed with PET have expanded in basic neurobiology, psychiatry, neurology, and related therapeutic development. In this review, we introduce the field of human PET neuroimaging, some of its conceptual underpinnings, and motivating questions. We highlight some of the more recent advances in radiotracer development, quantitative modeling, and applications of PET to the study of the human brain.

Magnetoencephalography and the infant brain.

Magnetoencephalography (MEG) is a non-invasive neuroimaging technique that provides whole-head measures of neural activity with millisecond temporal resolution. Over the last three decades, MEG has been used for assessing brain activity, most commonly in adults. MEG has been used less often to examine neural function during early development, in large part due to the fact that infant whole-head MEG systems have only recently been developed. In this review, an overview of infant MEG studies is provided, focusing on the period from birth to three years. The advantages of MEG for measuring neural activity in infants are highlighted (See Box 1), including the ability to assess activity in brain (source) space rather than sensor space, thus allowing direct assessment of neural generator activity. Recent advances in MEG hardware and source analysis are also discussed. As the review indicates, efforts in this area demonstrate that MEG is a promising technology for studying the infant brain. As a noninvasive technology, with emerging hardware providing the necessary sensitivity, an expected deliverable is the capability for longitudinal infant MEG studies evaluating the developmental trajectory (maturation) of neural activity. It is expected that departures from neuro-typical trajectories will offer early detection and prognosis insights in infants and toddlers at-risk for neurodevelopmental disorders, thus paving the way for early targeted interventions.

MRI and MRS of the human brain at magnetic fields of 14T to 20T: Technical feasibility, safety, and neuroscience horizons.

The three goals of this paper are: 1) to evaluate the improvements in technology for increasing magnetic flux density (magnetic field) to 14T in the next few years and eventually to 20T; 2) to highlight neuroscience opportunities enabled by these advances; and, 3) to evaluate the physiological and biophysical effects associated with MRI at very high performance levels. Substantial recent advances in magnet technology including superconductor developments enable neuroscience goals that are not obtainable at contemporary magnetic fields. Ten areas of brain neuroscience include potential improvements in resolution for functional MRI(BOLD), diffusion weighted MRI, tractography, susceptibility weighted MR, neuronal architecture patterns related to human behavior, proton spectroscopy of small brain biochemicals, chemical exchange saturation transfer (CEST), dynamic contrast enhanced MRI, brain energy metabolism using 13C, 17O, and 31P; and brain electrolyte physiology using 23Na, 35Cl, and 39K. Physiological phenomena and safety aspects include: absorbed RF power, acoustic sound pressure levels, induced electric fields, Lorentz forces, magnetohydrodynamic forces, and biophysical phenomena in cells and tissues. Where feasible, effects are quantified for magnetic fields beyond 7T with the conclusion that there are no foreseen barriers either in the technical or human safety aspects of brain MRI and MRS at fields up to 20T. This conclusion is conditioned on results of recommended experiments to verify the predicted level of physiological effects beyond 9.4T. This technology is predicted to enable quantification of biochemical components of the functioning brain not detectable heretofore.

Recent neuroimaging advances in the study of primary headaches.

Neuroimaging techniques can be used to investigate both functional and structural features of the brain in patients who have primary headache disorders such as migraine or cluster headache. Improved treatments are needed for both, and this goal will likely be facilitated by a better understanding of the underlying biology. Functional imaging studies have identified regions active during attacks, as well as abnormalities that are present during the interictal period. Volumetric, surface-based morphometric, and tractography studies have revealed structural changes, although whether these represent a cause or effect of the condition remains to be determined. The development of new techniques and modalities promises to yield additional insights in the future. This article aims to review the major findings and most recent advances in neuroimaging of migraine and cluster headache.

[Frontiers in Live Bone Imaging Researches. In vivo imaging of neuron and glia].

Glial cells originate the Greek word'glue'had traditionally been only thought as supporting cells for neurons. Because glial cells are electrically non-excitable, neuroscience researchers have focused on elucidation of excitable cell properties, neuron. Recent advanced optical methods lead us to observe glial structure, motility and their function in normal physiological conditions. These approaches let us to know that they are not just the supporting cells for neuron but could receive signal from neurons through receptors for neurotransmitters and to regulate neuronal functions, thus modulating behavior phenotype. Such studies also suggest that glial cells are highly dynamic and actively maintain brain homeostasis. Here, we review physiological function of glial cells through a new perspective clarified by innovations of imaging technology including two-photon microscope.

Neuroimaging: beginning to appreciate its complexities.

For over a century, scientists have sought to see through the protective shield of the human skull and into the living brain. Today, an array of technologies allows researchers and clinicians to create astonishingly detailed images of our brain's structure as well as colorful depictions of the electrical and physiological changes that occur within it when we see, hear, think and feel. These technologies-and the images they generate-are an increasingly important tool in medicine and science. Given the role that neuroimaging technologies now play in biomedical research, both neuroscientists and nonexperts should aim to be as clear as possible about how neuroimages are made and what they can-and cannot-tell us. Add to this that neuroimages have begun to be used in courtrooms at both the determination of guilt and sentencing stages, that they are being employed by marketers to refine advertisements and develop new products, that they are being sold to consumers for the diagnosis of mental disorders and for the detection of lies, and that they are being employed in arguments about the nature (or absence) of powerful concepts like free will and personhood, and the need for citizens to have a basic understanding of how this technology works and what it can and cannot tell us becomes even more pressing.

Functional neuroimaging: technical, logical, and social perspectives.

Neuroscientists have long sought to study the dynamic activity of the human brain-what's happening in the brain, that is, while people are thinking, feeling, and acting. Ideally, an inside look at brain function would simultaneously and continuously measure the biochemical state of every cell in the central nervous system. While such a miraculous method is science fiction, a century of progress in neuroimaging technologies has made such simultaneous and continuous measurement a plausible fiction. Despite this progress, practitioners of modern neuroimaging struggle with two kinds of limitations: those that attend the particular neuroimaging methods we have today and those that would limit any method of imaging neural activity, no matter how powerful. In this essay, I consider the liabilities and potential of techniques that measure human brain activity. I am concerned here only with methods that measure relevant physiologic states of the central nervous system and relate those measures to particular mental states. I will consider in particular the preeminent method of functional neuroimaging: BOLD fMRI. While there are several practical limits on the biological information that current technologies can measure, these limits-as important as they are-are minor in comparison to the fundamental logical restraints on the conclusions that can be drawn from brain imaging studies.

Functional neuroimaging and psychology: what have you done for me lately?

Functional imaging has become a primary tool in the study of human psychology but is not without its detractors. Although cognitive neuroscientists have made great strides in understanding the neural instantiation of countless cognitive processes, commentators have sometimes argued that functional imaging provides little or no utility for psychologists. And indeed, myriad studies over the last quarter century have employed the technique of brain mapping-identifying the neural correlates of various psychological phenomena-in ways that bear minimally on psychological theory. How can brain mapping be made more relevant to behavioral scientists broadly? Here, we describe three trends that increase precisely this relevance: (i) the use of neuroimaging data to adjudicate between competing psychological theories through forward inference, (ii) isolating neural markers of information processing steps to better understand complex tasks and psychological phenomena through probabilistic reverse inference, and (iii) using brain activity to predict subsequent behavior. Critically, these new approaches build on the extensive tradition of brain mapping, suggesting that efforts in this area-although not initially maximally relevant to psychology-can indeed be used in ways that constrain and advance psychological theory.

Neuroimaging of resilience to stress: current state of affairs.

Resilience is defined as a dynamic, multidimensional process encompassing positive adaptation within the context of significant adversity. The complex nature of this construct makes it a difficult topic to study in neuroimaging research; however, in this article, we propose ways to operationalize resilience. The limited amount of structural and functional neuroimaging studies specifically designed to examine resilience have mainly focused on investigating alterations in regions of the brain involved in emotion and stress regulation circuitry. In the future, neuroimaging of resilience is expected to benefit from functional and structural connectivity approaches and the use of novel imaging task paradigms.

Recent advances in the brain imaging of social anxiety disorder.

Social anxiety disorder (SAD) is one of the most common and disabling anxiety disorders, yet much remains to be learned about its psychobiology. Although functional imaging has emphasized the role of the amygdala and other limbic structures in the neurobiology of SAD, structural and connectivity imaging techniques have emphasized the possibility of abnormalities in other regions and in whole-brain networks. The involvement of a broad range of networks in SAD is consistent with current understandings of the neuroanatomy of emotion and of social processing.

Imaging preictal hemodynamic changes in neocortical epilepsy.

OBJECT: The ability to predict seizure occurrence is extremely important to trigger abortive therapies and to warn patients and their caregivers. Optical imaging of hemodynamic parameters such as blood flow, blood volume, and tissue and hemoglobin oxygenation has already been shown to successfully localize epileptic events with high spatial and temporal resolution. The ability to actually predict seizure occurrence using hemodynamic parameters is less well explored. METHODS: In this article, the authors critically review data from the literature on neocortical epilepsy and optical imaging, and they discuss the preictal hemodynamic changes and their application in neurosurgery. RESULTS: Recent optical mapping studies have demonstrated preictal hemodynamic changes in both human and animal neocortex. CONCLUSIONS: Optical measurements of blood flow and oxygenation may become increasingly important for predicting and localizing epileptic events. The ability to successfully predict ictal onsets may be useful to trigger closed-loop abortive therapies.

Advances in myelin imaging with potential clinical application to pediatric imaging.

White matter development and myelination are critical processes in neurodevelopment. Myelinated white matter facilitates the rapid and coordinated brain messaging required for higher-order cognitive and behavioral processing. Whereas several neurological disorders such as multiple sclerosis are associated with gross white matter damage and demyelination, other disorders such as epilepsy may involve altered myelination in the efferent or afferent white matter pathways adjoining epileptic foci. Current MRI techniques including T1 weighting, T2 weighting, FLAIR, diffusion tensor imaging, and MR spectroscopy permit visualization of gross white matter abnormalities and evaluation of underlying white matter fiber architecture and integrity, but they provide only qualitative information regarding myelin content. Quantification of these myelin changes could provide new insight into disease severity and prognosis, reveal information regarding spatial location of foci or lesions and the associated affected neural systems, and create a metric to evaluate treatment efficacy. Multicomponent analysis of T1 and T2 relaxation data, or multicomponent relaxometry (MCR), is a quantitative imaging technique that is sensitive and specific to myelin content alteration. In the past, MCR has been associated with lengthy imaging times, but a new, faster MCR technique (mcDESPOT) has made quantitative analysis of myelin content more accessible for clinical research applications. The authors briefly summarize traditional white matter imaging techniques, describe MCR and mcDESPOT, and discuss current and future clinical applications of MCR, with a particular focus on pediatric epilepsy.

Brain imaging in fibromyalgia.

Fibromyalgia is a primary brain disorder or a result of peripheral dysfunctions inducing brain alterations, with underlying mechanisms that partially overlap with other painful conditions. Although there are methodologic variations, neuroimaging studies propose neural correlations to clinical findings of abnormal pain modulation in fibromyalgia. Growing evidences of specific differences of brain activations in resting states and pain-evoked conditions confirm clinical hyperalgesia and impaired inhibitory descending systems, and also demonstrate cognitive-affective influences on painful experiences, leading to augmented pain-processing. Functional data of neural activation abnormalities parallel structural findings of gray matter atrophy, alterations of intrinsic connectivity networks, and variations in metabolites levels along multiple pathways. Data from positron-emission tomography, single-photon-emission-computed tomography, blood-oxygen-level-dependent, voxel-based morphometry, diffusion tensor imaging, default mode network analysis, and spectroscopy enable the understanding of fibromyalgia pathophysiology, and favor the future establishment of more tailored treatments.

The challenge of non-ergodicity in network neuroscience.

Ergodicity can be assumed when the structure of data is consistent across individuals and time. Neural network approaches do not frequently test for ergodicity in data which holds important consequences for data integration and intepretation. To demonstrate this problem, we present several network models in healthy and clinical samples where there exists considerable heterogeneity across individuals. We offer suggestions for the analysis, interpretation, and reporting of neural network data. The goal is to arrive at an understanding of the sources of non-ergodicity and approaches for valid network modeling in neuroscience.

Brain aging mechanisms with mechanical manifestations.

Brain aging is a complex process that affects everything from the subcellular to the organ level, begins early in life, and accelerates with age. Morphologically, brain aging is primarily characterized by brain volume loss, cortical thinning, white matter degradation, loss of gyrification, and ventricular enlargement. Pathophysiologically, brain aging is associated with neuron cell shrinking, dendritic degeneration, demyelination, small vessel disease, metabolic slowing, microglial activation, and the formation of white matter lesions. In recent years, the mechanics community has demonstrated increasing interest in modeling the brain's (bio)mechanical behavior and uses constitutive modeling to predict shape changes of anatomically accurate finite element brain models in health and disease. Here, we pursue two objectives. First, we review existing imaging-based data on white and gray matter atrophy rates and organ-level aging patterns. This data is required to calibrate and validate constitutive brain models. Second, we review the most critical cell- and tissue-level aging mechanisms that drive white and gray matter changes. We focuse on aging mechanisms that ultimately manifest as organ-level shape changes based on the idea that the integration of imaging and mechanical modeling may help identify the tipping point when normal aging ends and pathological neurodegeneration begins.