Under the Mind's Hood: What We Have Learned by Watching the Brain at Work.

Imagine you were asked to investigate the workings of an engine, but to do so without ever opening the hood. Now imagine the engine fueled the human mind. This is the challenge faced by cognitive neuroscientists worldwide aiming to understand the neural bases of our psychological functions. Luckily, human ingenuity comes to the rescue. Around the same time as the Society for Neuroscience was being established in the 1960s, the first tools for measuring the human brain at work were becoming available. Noninvasive human brain imaging and neurophysiology have continued developing at a relentless pace ever since. In this 50 year anniversary, we reflect on how these methods have been changing our understanding of how brain supports mind.

From the wax cast of brain ventricles (1508-9) by Leonardo da Vinci to air cast ventriculography (1918) by Walter E. Dandy.

The mold of the human cerebral ventricles produced in 1918 by Walter E. Dandy had an experimental precedent, a wax cast of ox ventricles made four hundred years earlier (1508-9) by Leonardo da Vinci (1452-1519). This paper is an homage to the epitome of Renaissance and polymath Leonard da Vinci, as well as to Walter Edward Dandy (1886-1946) who developed the ventriculography (1918) and pneumoencephalography (1919) techniques. Pneumoencephalography was applied broadly up to the late 1970s, when it was replaced by less invasive and more accurate neuroimaging techniques.

Insights into the Past and Future of Atlantoaxial Stabilization Techniques.

Over the past century, atlantoaxial stabilization techniques have improved considerably. To our knowledge there has been a scarcity of articles published that focus specifically on the history of atlantoaxial stabilization. Examining the history of instrumentation allows us to evaluate the impact of early influences on current modern stabilization techniques. It also provides inspiration to further develop the techniques and prevents repetition of mistakes. This paper reviews the evolution of C1-C2 instrumentation techniques over time and provides insights into the future of these practices.We did an extensive literature search in PubMed, Embase and Google Scholar, using the following search terms: 'medical history', 'atlantoaxial', 'C1/C2', 'stabilization', 'instrumentation', 'fusion', 'arthrodesis', 'grafting', 'neuroimaging', 'biomechanical testing', 'anatomical considerations' and 'future'.Many different entry zones have been tested, as well as different constructs, from initial attempts with use of silk threads to use of hooks and rod-wire techniques, and handling of bone grafts, which eventually led to the development of the advanced screw-rod constructs that are currently in use. Much of this evolution is attributable to advancements in neuroimaging, a wide range of new materials available and an improvement in biomechanical understanding in relation to anatomical structures.

Imaging at ultrahigh magnetic fields: History, challenges, and solutions.

Following early efforts in applying nuclear magnetic resonance (NMR) spectroscopy to study biological processes in intact systems, and particularly since the introduction of 4 T human scanners circa 1990, rapid progress was made in imaging and spectroscopy studies of humans at 4 T and animal models at 9.4 T, leading to the introduction of 7 T and higher magnetic fields for human investigation at about the turn of the century. Work conducted on these platforms has provided numerous technological solutions to challenges posed at these ultrahigh fields, and demonstrated the existence of significant advantages in signal-to-noise ratio and biological information content. Primary difference from lower fields is the deviation from the near field regime at the radiofrequencies (RF) corresponding to hydrogen resonance conditions. At such ultrahigh fields, the RF is characterized by attenuated traveling waves in the human body, which leads to image non-uniformities for a given sample-coil configuration because of destructive and constructive interferences. These non-uniformities were initially considered detrimental to progress of imaging at high field strengths. However, they are advantageous for parallel imaging in signal reception and transmission, two critical technologies that account, to a large extend, for the success of ultrahigh fields. With these technologies and improvements in instrumentation and imaging methods, today ultrahigh fields have provided unprecedented gains in imaging of brain function and anatomy, and started to make inroads into investigation of the human torso and extremities. As extensive as they are, these gains still constitute a prelude to what is to come given the increasingly larger effort committed to ultrahigh field research and development of ever better instrumentation and techniques.

Historical Trends in the Diagnosis of Peduncular Hallucinosis.

BACKGROUND: Peduncular hallucinosis (PH) describes the clinical syndrome of vivid, dream-like visual hallucinations that intrude on normal wakefulness. Additional clinical deficits, especially ophthalmoparesis, have historically been an important part of the diagnosis and localization of this syndrome. We examined how modern neuroimaging has impacted the diagnosis of PH. METHODS: We reviewed all available cases of PH, including 3 of ours and all previously reported in the literature. We determined whether other eye movement abnormalities were part of the clinical presentation and whether a neuroimaging study was performed to make the diagnosis. RESULTS: A total of 85 cases were identified and evaluated. Eye movement abnormalities were present in 12/15 (80%) without a neuroimaging study but in only 24/70 (34%) of cases in which a neuroimaging study was performed (P = 0.001). CONCLUSIONS: Although eye movement abnormalities historically have been considered a key localizing clinical feature supporting the diagnosis of PH, we found that in the era of modern neuroimaging, co-occurring eye movement abnormalities are far less frequent and are not a requisite feature of the diagnosis.

Fifty Years of Prefrontal Cortex Research: Impact on Assessment.

Our knowledge of the functions of the prefrontal cortex, often called executive, supervisory, or control, has been transformed over the past 50 years. After operationally defining terms for clarification, we review the impact of advances in functional, structural, and theoretical levels of understanding upon neuropsychological assessment practice as a means of identifying 11 principles/challenges relating to assessment of executive function. Three of these were already known 50 years ago, and 8 have been confirmed or emerged since. Key themes over this period have been the emergence of the use of naturalistic tests to address issues of "ecological validity"; discovery of the complexity of the frontal lobe control system; invention of new tests for clinical use; development of key theoretical frameworks that address the issue of the role of prefrontal cortex systems in the organization of human cognition; the move toward considering brain systems rather than brain regions; the advent of functional neuroimaging, and its emerging integration into clinical practice. Despite these huge advances, however, practicing neuropsychologists are still desperately in need of new ways of measuring executive function. We discuss pathways by which this might happen, including decoupling the two levels of explanation (information processing; brain structure) and integrating very recent technological advances into the neuropsychologist's toolbox. (JINS, 2017, 23, 755-767).

Weighing brain activity with the balance: Angelo Mosso's original manuscripts come to light.

Neuroimaging techniques, such as positron emission tomography and functional magnetic resonance imaging are essential tools for the analysis of organized neural systems in working and resting states, both in physiological and pathological conditions. They provide evidence of coupled metabolic and cerebral local blood flow changes that strictly depend upon cellular activity. In 1890, Charles Smart Roy and Charles Scott Sherrington suggested a link between brain circulation and metabolism. In the same year William James, in his introduction of the concept of brain blood flow variations during mental activities, briefly reported the studies of the Italian physiologist Angelo Mosso, a multifaceted researcher interested in the human circulatory system. James focused on Mosso's recordings of brain pulsations in patients with skull breaches, and in the process only briefly referred to another invention of Mosso's, the 'human circulation balance', which could non-invasively measure the redistribution of blood during emotional and intellectual activity. However, the details and precise workings of this instrument and the experiments Mosso performed with it have remained largely unknown. Having found Mosso's original manuscripts in the archives, we remind the scientific community of his experiments with the 'human circulation balance' and of his establishment of the conceptual basis of non-invasive functional neuroimaging techniques. Mosso unearthed and investigated several critical variables that are still relevant in modern neuroimaging such as the 'signal-to-noise ratio', the appropriate choice of the experimental paradigm and the need for the simultaneous recording of differing physiological parameters.

The Alzheimer's Disease Neuroimaging Initiative informatics core: A decade in review.

The Informatics Core of the Alzheimer's Disease Neuroimaging Initiative has coordinated data integration and dissemination for a continually growing and complex data set in which both data contributors and recipients span institutions, scientific disciplines, and geographic boundaries. This article provides an update on the accomplishments and future plans.

Alzheimer's Disease Neuroimaging Initiative 2 Clinical Core: Progress and plans.

INTRODUCTION: This article reviews the current status of the Clinical Core of the Alzheimer's Disease Neuroimaging Initiative (ADNI), and summarizes planning for the next stage of the project. METHODS: Clinical Core activities and plans were synthesized based on discussions among the Core leaders and external advisors. RESULTS: The longitudinal data in ADNI-2 provide natural history data on a clinical trials population and continue to inform refinement and standardization of assessments, models of trajectories, and clinical trial methods that have been extended into sporadic preclinical Alzheimer's disease (AD). DISCUSSION: Plans for the next phase of the ADNI project include maintaining longitudinal follow-up of the normal and mild cognitive impairment cohorts, augmenting specific clinical cohorts, and incorporating novel computerized cognitive assessments and patient-reported outcomes. A major hypothesis is that AD represents a gradually progressive disease that can be identified precisely in its long presymptomatic phase, during which intervention with potentially disease-modifying agents may be most useful.

History and evolution of brain tumor imaging: insights through radiology.

This review recounts the history of brain tumor diagnosis from antiquity to the present and, indirectly, the history of neuroradiology. Imaging of the brain has from the beginning held an enormous interest because of the inherent difficulty of this endeavor due to the presence of the skull. Because of this, most techniques when newly developed have always been used in neuroradiology and, although some have proved to be inappropriate for this purpose, many were easily incorporated into the specialty. The first major advance in modern neuroimaging was contrast agent-enhanced computed tomography, which permitted accurate anatomic localization of brain tumors and, by virtue of contrast enhancement, malignant ones. The most important advances in neuroimaging occurred with the development of magnetic resonance imaging and diffusion-weighted sequences that allowed an indirect estimation of tumor cellularity; this was further refined by the development of perfusion and permeability mapping. From its beginnings with indirect and purely anatomic imaging techniques, neuroradiology now uses a combination of anatomic and physiologic techniques that will play a critical role in biologic tumor imaging and radiologic genomics.

The history of the future of the Bayesian brain.

The slight perversion of the original title of this piece (The Future of the Bayesian Brain) reflects my attempt to write prospectively about 'Science and Stories' over the past 20 years. I will meet this challenge by dealing with the future and then turning to its history. The future of the Bayesian brain (in neuroimaging) is clear: it is the application of dynamic causal modeling to understand how the brain conforms to the free energy principle. In this context, the Bayesian brain is a corollary of the free energy principle, which says that any self organizing system (like a brain or neuroimaging community) must maximize the evidence for its own existence, which means it must minimize its free energy using a model of its world. Dynamic causal modeling involves finding models of the brain that have the greatest evidence or the lowest free energy. In short, the future of imaging neuroscience is to refine models of the brain to minimize free energy, where the brain refines models of the world to minimize free energy. This endeavor itself minimizes free energy because our community is itself a self organizing system. I cannot imagine an alternative future that has the same beautiful self consistency as mine. Having dispensed with the future, we can now focus on the past, which is much more interesting:

Tracing the route to path analysis in neuroimaging.

This article provides a personal perspective of the adoption of path analysis (structural equation modeling) to neuroimaging. The paper covers the motivation stemming from the need to merge functional measures with neuroanatomy and early innovations in its application. The use of path analysis as a means to test directional hypotheses about networks is presented along with the development of the complementary method, partial least squares. A method is useful when it provides insights that were previously inaccessible, and reflecting this, the paper concludes with a synopsis of the theoretical developments that arose for the routine use of methods like path analysis.

The future of the human connectome.

The opportunity to explore the human connectome using cutting-edge neuroimaging methods has elicited widespread interest. How far will the field be able to progress in deciphering long-distance connectivity patterns and in relating differences in connectivity to phenotypic characteristics in health and disease? We discuss the daunting nature of this challenge in relation to specific complexities of brain circuitry and known limitations of in vivo imaging methods. We also discuss the excellent prospects for continuing improvements in data acquisition and analysis. Accordingly, we are optimistic that major insights will emerge from human connectomics in the coming decade.