Fatigue is ubiquitous and falls within the purview of several specialties, including neurology, psychiatry, neuropsychology, endocrinology, rheumatology, and immunology. As Simon Wessely points out in the Foreword of Fatigue as a Window to the Brain, fatigue has been virtually overlooked as an area of scientific study, because it is difficult to measure and, as a symptom, rarely aids in differential diagnosis. John DeLuca's edited book is part of the Issues in Clinical and Cognitive Neuropsychology series edited by Jordan Grafman. This is an ambitious book that examines the multidimensional and multifactorial nature of the neurobiology of central fatigue. This book advances the reader's understanding of the neural mechanisms of fatigue through review and integration of empirical data on fatigue and its cognitive correlates in neurological, medical, and psychiatric disorders.
Section I includes three chapters and lays the foundation for the remainder of the book through a discussion of the nature of fatigue, its assessment, and the relationship between fatigue and cognition. Chapter 1 addresses the nature, history, and epidemiology of fatigue from neurasthenia through Epstein-Barr virus to chronic fatigue syndrome, and persuasively indicates the need for a biopsychosocial approach. Chapter 2 sheds light on the historically murky topic of the assessment of fatigue by dividing it into (1) a subjective physical or mental experience or (2) a measurable performance decrement. Subjective fatigue is measured with self-report questionnaires that can be limited by response or recall bias as well as mood issues, whereas physical or cognitive performance decrement can be measured objectively by examining error rates and declines on cognitive or physical performance such as reduced muscle strength after physical exertion or sleep deprivation. This chapter provides a comprehensive review of fatigue scales that is useful for clinicians and researchers. Chapter 3 provides an excellent review of empirical studies of experimentally induced cognitive fatigue after prolonged time on task, sustained mental effort, and mental and physical exertion. This enlightening discussion of empirical research gives the reader perspective on the scientific study of fatigue, the cognitive domains it affects, and possible brain mechanisms.
Section II includes chapters on fatigue in various neurological conditions, including multiple sclerosis, stroke, traumatic brain injury, and other conditions (dementia, post-Lyme encephalopathy, and Parkinson's disease). This presentation of research is particularly cogent with discussion of central mechanisms, cytokines, hypothalamic-pituitary-adrenal axis and endocrine mechanisms, and the role of the reticular activating and striatocortical systems in fatigue after brain injury. Several chapters include sections in which results of functional neuroimaging studies are reviewed to provide insight into the neural correlates of fatigue in specific disease states. Functional magnetic resonance imaging (fMRI) studies of pathologic populations such as individuals with chronic fatigue syndrome or traumatic brain injury often show increased and more dispersed cerebral activation relative to healthy controls, suggesting that recruitment of additional brain regions may be needed to perform the studied task. However, the opposite pattern is seen in comparisons between healthy individuals and patients with multiple sclerosis: hypometabolism and reduced functional activation in frontal cortex and basal ganglia on fMRI were observed in multiple sclerosis patients during a simple motor task The existence of these inconsistencies highlights the conclusion that we are in the infancy of our use of neuroimaging methods to study of fatigue.
Section III addresses fatigue in various psychiatric conditions. It begins with an interesting chapter on the history of the diagnosis of fatigue in psychiatry along with a discussion of its psychiatric treatment. Chapters follow on fatigue in specific psychiatric disorders including chronic fatigue syndrome (which the authors acknowledge may be considered either a psychiatric or a neurological condition), depression, and somatization. These chapters nicely discuss the interplay between psychological and physiological factors that may contribute to fatigue.
Section IV is composed of chapters on fatigue associated with general medical conditions, including human immunodeficiency virus, cardiovascular disease, systemic lupus erythematosus, and breast cancer. The cancer chapter includes comparisons of fatigue associated with radiotherapy, chemotherapy, and autologous bone marrow transplantation, as well as considering the puzzling finding that chronic fatigue continues long after systemic therapy has been completed. This section also includes well-written chapters on the relationship between sleep and psychoneuroimmunology with an illuminating discussion of how the brain and immune system interact through proinflammatory cytokines. Although a single chapter, Section V is particularly useful clinically in that it discusses the treatment of fatigue through cognitive behavioral therapy, graded exercise, and pharmacotherapy.
The book culminates with a summary chapter in Section VI in which fatigue is separated into primary mechanisms (biological/neural) and secondary mechanisms (general), including deconditioning, depression, stress, medication, and sleep habits. This distinction is complex and appears somewhat artificial at times, however, as secondary mechanisms such as depression or stress may lead to mechanisms considered primary such as physiologic changes in neurotransmitters or hypothalamic-pituitary-adrenal axis abnormalities.
Fatigue as a Window to the Brain is unique in that fatigue is examined not only in various conditions but also from the vantage points of different disciplines with different methods of study. At first blush, fatigue as a general concept seems a challenging area for scientific inquiry because of its complexity and multifactorial nature. However, through its incisive definitions, presentation of empirical methods of study, and integration of available knowledge across disciplines, this book advances the scientific study of fatigue and provides compelling evidence that brain mechanisms underlie many of its aspects. Moreover, despite the findings presented that subjective fatigue associated with chronic physical illnesses does not correlate highly with disease severity, physical performance, or performance on neuropsychological tests, the book succeeds in using fatigue to elucidate how the brain functions.
