Spatially Extended fMRI Signal Response to Stimulus in Non-Functionally Relevant Regions of the Human Brain: Preliminary Results

The blood-oxygenation level dependent (BOLD) haemodynamic response function (HDR) in functional magnetic resonance imaging (fMRI) is a delayed and indirect marker of brain activity. In this single case study a small BOLD response synchronised with the stimulus paradigm is found globally, i.e. in all areas outside those of expected activation in a single subject study. The nature of the global response has similar shape properties to the archetypal BOLD HDR, with an early positive signal and a late negative response typical of the negative overshoot. Fitting Poisson curves to these responses showed that voxels were potentially split into two sets: one with dominantly positive signal and the other predominantly negative. A description, quantification and mapping of the global BOLD response is provided along with a 2 × 2 classification table test to demonstrate existence with very high statistical confidence. Potential explanations of the global response are proposed in terms of 1) global HDR balancing; 2) resting state network modulation; and 3) biological systems synchronised with the stimulus cycle. Whilst these widespread and low-level patterns seem unlikely to provide additional information for determining activation in functional neuroimaging studies as conceived in the last 15 years, knowledge of their properties may assist more comprehensive accounts of brain connectivity in the future

Punishing Our Own Rascals: Great Britain, the United States, and the Right to Search During the Era of Slave Trade Suppression

This thesis examines the relationship between the United States and Great Britain during the era of slave trade suppression in the nineteenth century. Two ideals of international relations came into conflict when Great Britain’s humanitarian drive to rid the world of the international slave trade ran headlong into the United States’ claims to sovereignty under the Law of Nations. Under international maritime law a ship is the sovereign territory of the nation under whose flag it sails; the forcible boarding of a ship is tantamount to an invasion of the country itself. Britain sought to circumvent this rule in the pursuit of their humanitarian cause by negotiating bilateral treaties with all maritime powers, allowing the reciprocal right to search the vessels of every signatory, therefore nullifying that tenant of international maritime law. The United States remained a “persistent objector,” refusing to go along with the plan, despite its humanitarian purpose. British government sources and those of many historians charge that American intransigence was mainly driven by American slave interests, but records drawn from Congressional sources, the United States Department of State and the United States Navy show that the U.S. was more interested in protecting the sovereignty of ships that flew the American flag from the aggressive actions of the British Navy. The British finally gave up trying to force the Americans to adopt the right to visit and search in 1858. Four years later the United States negotiated a right to search agreement with Great Britain. When the Civil War ended the African slave trade, for the most part, came to end. American sovereignty was never compromised, but the price of that sovereignty was the hundreds of thousands of slaves who crossed the Atlantic, under the Stars and Stripes, to a life of forced labor

The Phenomenon of Exquisite Motor Control in Tic Disorders and its Pathophysiological Implications

The unifying characteristic of movement disorders is the phenotypic presentation of abnormal motor outputs, either as isolated phenomena or in association with further clinical, often neuropsychiatric, features. However, the possibility of a movement disorder also characterized by supranormal or enhanced volitional motor control has not received attention. Based on clinical observations and cases collected over a number of years, we here describe the intriguing clinical phenomenon that people with tic disorders are often able to control specific muscle contractions as part of their tic behaviors to a degree that most humans typically cannot. Examples are given in accompanying video documentation. We explore medical literature on this topic and draw analogies with early research of fine motor control physiology in healthy humans. By systematically analyzing the probable sources of this unusual capacity, and focusing on neuroscientific accounts of voluntary motor control, sensory feedback, and the role of motor learning in tic disorders, we provide a novel pathophysiological account explaining both the presence of exquisite control over motor output and that of overall tic behaviors. We finally comment on key questions for future research on the topic and provide concluding remarks on the complex movement disorder of tic behaviors

COVCOG 1: Factors Predicting Physical, Neurological and Cognitive Symptoms in Long COVID in a Community Sample. A First Publication From the COVID and Cognition Study

Since its first emergence in December 2019, coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has evolved into a global pandemic. Whilst often considered a respiratory disease, a large proportion of COVID-19 patients report neurological symptoms, and there is accumulating evidence for neural damage in some individuals, with recent studies suggesting loss of gray matter in multiple regions, particularly in the left hemisphere. There are a number of mechanisms by which COVID-19 infection may lead to neurological symptoms and structural and functional changes in the brain, and it is reasonable to expect that many of these may translate into cognitive problems. Indeed, cognitive problems are one of the most commonly reported symptoms in those experiencing “Long COVID”—the chronic illness following COVID-19 infection that affects between 10 and 25% of patients. The COVID and Cognition Study is a part cross-sectional, part longitudinal, study documenting and aiming to understand the cognitive problems in Long COVID. In this first paper from the study, we document the characteristics of our sample of 181 individuals who had experienced COVID-19 infection, and 185 who had not. We explore which factors may be predictive of ongoing symptoms and their severity, as well as conducting an in-depth analysis of symptom profiles. Finally, we explore which factors predict the presence and severity of cognitive symptoms, both throughout the ongoing illness and at the time of testing. The main finding from this first analysis is that that severity of initial illness is a significant predictor of the presence and severity of ongoing symptoms, and that some symptoms during the initial illness—particularly limb weakness—may be more common in those that have more severe ongoing symptoms. Symptom profiles can be well described in terms of 5 or 6 factors, reflecting the variety of this highly heterogenous condition experienced by the individual. Specifically, we found that neurological/psychiatric and fatigue/mixed symptoms during the initial illness, and that neurological, gastrointestinal, and cardiopulmonary/fatigue symptoms during the ongoing illness, predicted experience of cognitive symptoms.</jats:p

Pneumococcal conjugate vaccines and otitis media.

Peer Reviewe

A method for determining venous contribution to BOLD contrast sensory activation

While BOLD contrast reflects haemodynamic changes within capillaries serving neural tissue, it also has a venous component. Studies that have determined the relation of large blood vessels to the activation map indicate that veins are the source of the largest response, and the most delayed in time. It would be informative if the location of these large veins could be extracted from the properties of the functional responses, since vessels are not visible in BOLD contrast images. The present study describes a method for investigating whether measures taken from the functional response can reliably predict vein location, or at least be useful in down-weighting the venous contribution to the activation response, and illustrates this method using data from one subject. We combined fMRI at 3 Tesla with high-resolution anatomical imaging and MR venography to test whether the intrinsic properties of activation time courses corresponded to tissue type. Measures were taken from a gamma fit to the functional response. Mean magnitude showed a significant effect of tissue type (P veins ≈ grey matter > white matter. Mean delays displayed the same ranking across tissue types (P grey matter. However, measures for all tissue types were distributed across an overlapping range. A logistic regression model correctly discriminated 72% of the veins from grey matter in the absence of independent information of macroscopic vessels (ROC=0.72). Whilst tissue classification was not perfect for this subject, weighting the T contrast by the predicted probabilities materially reduced the venous component to the activation map

COVCOG 2: Cognitive and Memory Deficits in Long COVID: A Second Publication From the COVID and Cognition Study.

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been often characterized as a respiratory disease. However, it is increasingly being understood as an infection that impacts multiple systems, and many patients report neurological symptoms. Indeed, there is accumulating evidence for neural damage in some individuals, with recent studies suggesting loss of gray matter in multiple regions, particularly in the left hemisphere. There are several mechanisms by which the COVID-19 infection may lead to neurological symptoms and structural and functional changes in the brain, and cognitive problems are one of the most commonly reported symptoms in those experiencing Long COVID - the chronic illness following the COVID-19 infection that affects between 10 and 25% of patients. However, there is yet little research testing cognition in Long COVID. The COVID and Cognition Study is a cross-sectional/longitudinal study aiming to understand cognitive problems in Long COVID. The first paper from the study explored the characteristics of our sample of 181 individuals who had experienced the COVID-19 infection, and 185 who had not, and the factors that predicted ongoing symptoms and self-reported cognitive deficits. In this second paper from the study, we assess this sample on tests of memory, language, and executive function. We hypothesize that performance on "objective" cognitive tests will reflect self-reported cognitive symptoms. We further hypothesize that some symptom profiles may be more predictive of cognitive performance than others, perhaps giving some information about the mechanism. We found a consistent pattern of memory deficits in those that had experienced the COVID-19 infection, with deficits increasing with the severity of self-reported ongoing symptoms. Fatigue/Mixed symptoms during the initial illness and ongoing neurological symptoms were predictive of cognitive performance

Hearing in Adults: A Digital Reprint of the Main Report From the MRC National Study of Hearing.

The 1011-page book, Hearing in Adults, published in 1995, contains the fullest report of the United Kingdom’s Medical Research Council National Study of Hearing. It was designed to determine the prevalence and distribution in Great Britain of audiometrically measured hearing loss as a function of age, gender, occupation, and noise exposure. The study’s size, quality, and breadth made it unique when it was done in the 1980s. These qualities remain, and its data are still the primary U.K. source for the prevalence of auditory problems. However, only 550 copies were printed, and the book is essentially unobtainable today. We describe here a fully searchable, open-access, digital (PDF) “reprinting” of Hearing in Adults, summarizing the study’s design and the book’s contents, together with a brief commentary in the light of subsequent developments