A Theory of the Basal Ganglia and Their Disorders PDF

Preface

The basal ganglion, to adapt a phrase of Churchill's, is "a riddle wrapped in a mystery inside an enigma." These structures are a minefi eld for theoreticians of brain function, for several reasons. First, there are a number of different nuclear structures within the basal ganglia, each with different roles, but all collaborating in the overall dynamics of the basal ganglia. In this respect, the basal ganglia are more complicated than the much larger cerebral cortex, which, despite its formidable complexity, has a degree of overall uniformity. Second, most of the neurons in most of these component nuclei are inhibitory. As a result, in the interaction between the different nuclei, there are endless possibilities for reversals of the mathematical sign of infl uence, and the number of such reversals is a matter of debate. Consequently, there are many alternative suggestions of how the various nuclei might actually operate together. Third, the fundamentals of anatomy and physiology of the basal ganglia are best known to basic scientists. However, some of the key facts for understanding them are clinical facts best known to a different group of researchers, those with everyday experience of assessing and treating disorders of the basal ganglia in human patients. In addition, some of those essential clinical facts are in the fi eld of neurology and some in the fi eld of psychiatry. In the nineteenth century, these two branches of medicine were part of a unifi ed discipline concerned with "nervous and mental disorders." Since then, in many countries, the two disciplines have diverged. While medical traditions in some countries have preserved the two specialties as part of a unifi ed discipline, in many parts of the world, psychiatry and neurology have, for many years, developed along different lines, and have built up differing traditions, with inevitable barriers to communication between the two. In the present work, I (with no qualifi cations in either of these medical specialties, but a background in the overall theory of the mammalian forebrain) attempt to resolve the riddle of the basal ganglia, and to place the essential clinical facts from both neurology and psychiatry within the framework formulated for normal operations of the basal ganglia.

This monograph has two parts, the fi rst dealing with the basic framework in which normal functions of the basal ganglia can be understood and the second focusing on major disorders of the basal ganglia. In fact, the division between normal and abnormal operation of the basal ganglia is not followed through in a strict fashion: Some clinical facts (e.g., about Huntington's disease) are important in developing ideas about the basic framework; and some basic facts about the normal organization of the basal ganglia (e.g., the role of the striatal cholinergic neurons) are not essential in formulating the basic framework, but are more relevant in the context of disorders of basal ganglia. Moreover, the reader should not expect that all disorders arising in the basal ganglia are analyzed in Part II. The aim of this part is to explain, as far as possible, symptoms and related clinical facts in terms of underlying pathology and pathophysiology (i.e., cell loss or changes in fi ring frequency in cell groups). With this as the aim, disorders of the basal ganglia are included only when there are already clear ideas about the underlying neuropathology or pathophysiology.

Sometimes these ideas are already well established, while at other times the argument is based on plausible proposals, which are still under evaluation. Theories stand or fall by what they predict. Therefore, in the synopses of both Parts I and II, specifi c mention is made of the predictions following from the theory presented here, as well as signifi cant points that are not yet dealt with by the theory.

Chapter 9 discusses psychosis. There is one aspect of this chapter, which I feel I should explain here to avoid possible misunderstandings. My particular interest in this topic goes back 40 years, when, as a young man, I experienced two fl orid psychotic breakdowns. I have very clear memories of this time, especially of the second of these episodes. The story of this period of my life was put in writing in the 1970s, and the account was eventually published quite recently. As someone who had already embarked on neuroscience research, these episodes provided me with strong motivation to understand, and a rich source of fi rst-hand experience upon which to draw. This led, in the mid-1970s, to my fi rst attempts at scientifi c formulation of the abnormalities of information processing in psychosis, and, by 1981, to ideas about dopamine-mediated synaptic plasticity in the striatum. In a broader perspective, these experiences have opened up the whole fi eld of the dynamic operations of the basal ganglia (dealt with here), as well as wider issues about the nature of the disorder called schizophrenia. Those experiences were the real origin of the present work. A number of my previous papers have wrestled with aspects of the functions of the basal ganglia, but have never had a sense of completion. The present book might just have achieved this.