The Selective Preservation of Phonological Reading

Chapter 4 began with the programme of understanding dyslexic difficulties using a multiple-route model of the normal reading process. On this programme, the selective impairment of any individual route would correspond to a form of central dyslexia. However, the one candidate reading disorder considered, surface dyslexia, has proved a disappointment. Far from consisting of a selective impairment of the semantic reading route, in its best known form, it seems to consist of compensatory behaviour for an underlying peripheral dyslexic difficulty.

Can an improvement be obtained using the dissociation approach? Can one adapt the method of defining syndromes by dissociations in order to lessen the probability that the dissociation reflects only the operation of a compensatory procedure? One approach is to insist that the better performed task is not merely ‘better’ than the poorly performed task, but also normal or nearly so on any relevant measure. In the terminology to be developed in chapter 10, this dissociation is a ‘classical’ or near-classical one. In this case, it would be unlikely to arise as a result of the operation of a laborious compensatory strategy. Having made this distinction, I will, however, immediately relax it. The critical aspects that distinguish the use of, say, a normal phonological reading procedure – if somewhat impaired – from the compensatory strategies discussed in chapter 4 are the speed and fluency of reading.

The Syndrome

To isolate a new functional syndrome that does not have its characteristics mapped out by previous studies is a difficult and delicate process. The investigator has to be sensitive to the presence of a novel dissociation, itself a far from straightforward matter. Then a set of simpler and duller explanations in terms of syndromes that are already known have to be assessed. Only if they can be adequately rejected has a putative functional syndrome been isolated and only then can one begin to consider its theoretical implications. In this chapter, I am going to illustrate the process by considering a single syndrome – the short-term memory syndrome – from both a clinical and a theoretical perspective.

It is in clinical practice that new syndromes are detected. An unexpected result on a particular test is noticed and explored. In the present case, the unexpected result occurred on the Wechsler IQ battery. Many clinicians begin their assessment of a patient by using Wechsler subtests, not primarily to obtain an estimate of IQ but to see if any particular pattern of scores occurs across the different subtests (e.g. McFie, 1975; Lezak, 1976). In the late 1960s, Elizabeth Warrington was using this procedure to assess a patient, KF, who had sustained a severe head injury. He had a very low score on the Digit Span subtest, with performance on other subtests being relatively normal (Table 3.1) Obviously, no theoretical inferences can be made unless the deficit is reliable.

Introduction

The last few chapters have shown the cognitive neuropsychology approach to be applicable to a number of different topics. Yet the areas treated have actually covered a fairly narrow range by comparison with those that are conventionally included in, say, either clinical neuropsychology or cognitive psychology. The topics discussed so far have all been aspects of language. In later chapters, the approach will be applied much more widely by considering areas where the method provides fascinating glimpses into relatively unexplored terrain. In general, though, these areas are not too helpful for an overall assessment of the solidity of the cognitive neuropsychology methodology. One area outside language – visual perception –does contain a set of interesting and solid neuropsychological studies, and the inferences drawn from these investigations can be compared with those derived from completely different disciplines.

This area is important to consider for another reason. So far, it has been argued that the only effective methodology in cognitive neuropsychology is the single-case study. Group studies, it has been suggested, particularly in chapter 7, are not an effective source of evidence. This view is too extreme. Indeed, some of the more interesting studies on disorders of visual perception have been group studies, although of a type somewhat different from those discussed in chapter 7.

Why the Acquired Dyslexias?

In this chapter and the next, I consider whether the cognitive neuropsychology research programme is working at a level more complex than a single functional syndrome. Can the approach provide information about the organisation of a group of subsystems, and not just about the functioning of a single one? If each potential subsystem could be shown to be damaged by a pure syndrome specific to it, the power and plausibility of the approach would be greatly increased.

What domain should one choose to explore in detail in order to assess whether the breakdown of related functions in different patients is caused by damage to different components of a modular organisation? It might seem natural to take a domain like language or object perception, in which any such modular organisation would have been honed by evolution. Instead, I am going to consider the breakdown of reading, a skill that is specific not only to one species, but also to what is, from an evolutionary perspective, a tiny time period. A prerequisite for taking such a domain as a prototype is that contrary to one of Fodor's (1983) assumptions, the human modular structure must be affected by the experience of the organism, with respect to not only the operation of individual subsystems, but also the organisation of the functional architecture itself.

There are a number of reasons for choosing the reading system and the syndromes that occur when it is damaged – the acquired dyslexias.

Classical Views on Frontal Lobe Function

Initiation of an action sequence can occur in an unintended fashion. This is well shown by the existence of certain types of action lapses called ‘capture errors’ (Reason, 1979; Norman, 1981), as, for instance, William James's (1890) famous example of going upstairs to change and discovering himself in bed. Such errors tend to occur when one is preoccupied with some other line of thought, as Reason (1984) has shown. Action initiation is occurring in parallel with some other activity. Unintended actions do not, though, occur only when they are inappropriate. They can be both appropriate and unmonitored. This fits with the suggestion made early in chapter 13 that the control of which subsystems will be devoted to what task is often carried out in a decentralised fashion.

Actions such as these can be contrasted with ones that are preceded by ‘an additional conscious element in the shape of a fiat, mandate or expressed consent’, to quote William James (1890). When we decide or choose or intend or concentrate or prepare, decentralised control of the operation of particular subsystems does not appear to be the sole principle operating. How does the control of either of these types of action relate to the discussions on congitive control at the beginning of chapter 13? Such phenomenological contrasts by themselves provide only a very shaky basis for theorising.

On Modularity

If Lashley's (1929) idea of mass action were valid, then neuropsychology would be of little relevance for understanding normal function. Any form of neurological damage would deplete by a greater or lesser degree the available amount of some general resource, say the mythical g. Knowing which tasks a patient could or could not perform would enable us to partition tasks on a difficulty scale. It would tell us little, if anything, about how the system operated.

If one considers the design principles that might underlie cognitive systems, a rough contrast can be drawn between systems based on equipotentiality (e.g., those that follow principles such as mass action) and more modular ones. At a metatheo-retical level, some form of the ‘modularity’ thesis is probably the most widely accepted position in the philosophy of psychology today (e.g. Chomsky, 1980; Morton, 1981; Marr, 1982; Fodor, 1983). Over the past 30 years, the arguments for the position have become increasingly compelling and diverse; they are of a number of different types: computational, linguistic, physiological, and psychological.

The most basic argument is the computational one, which we owe to Simon (1969) and Marr (1976). In Marr's words.

The Amnesic Syndrome

Twenty-five years ago, human memory was a self-contained topic. It had its own laws, its own empirical paradigms, its chain of father figures leading back to Ebbinghaus. Yet in the past 15 years, memory research has been increasingly integrated with other areas of psychology. Short-term memory has almost hived off into perception and language. Semantic memory is now approached from the perspective of general models of cognition. Recently, links have been developed with attention (e.g. Hasher & Zacks, 1979). Before the mid-1970s, research on amnesia had much the same type of isolation as memory itself had had 15 years before. Admittedly, some ideas from the study of normal memory were beginning to be influential, such as ‘levels of processing’, and the phenomena being discussed were of much greater intrinsic interest than the interference paradigms of traditional memory research on normal subjects. Yet amnesia research was still very much a closed world, with debates couched in the conceptual terms of the 1950s. Moreover, there were fierce empirical disputes in the field about whether key results arose from artefacts.

Since the mid-1970s, there has been a great change. As was discussed in chapter 2, the disputes over replication have, to a considerable extent, been resolved. It is now widely accepted that many patients with severe memory disorders have additional damage to other processing systems, which can lead to the existence of observed associations between memory and non-memory disorders that may be functionally misleading.

Introduction

Vertebrates produce a variety of molecules that are important in controlling and regulating the life processes. Initially, a clear distinction was made between the peptide hormones produced by the endocrine system, and the other major class of regulatory substances, the neurotransmitters, produced by the nervous system. Emphasis was placed on the contrasts between these two types of molecules, and comparisons were made of the differences in the sites of production, methods of release, transportation within the body and the duration of action. On the basis of these comparisons the endocrine and nervous systems were considered to be completely different.

Gradually, however, these two systems have come to be seen as the extremes in a wide spectrum of control mechanisms over biological processes. In between, we have a subtle arrangement and interplay of molecules which cannot, usefully, be categorised as either hormonal or nervous.

A major factor in the shift away from this traditional and separatist view of biological control systems is the finding that the brain produces a great variety of peptides. Indeed, the term ‘endocrine brain’ has been coined (Motta 1980). The discovery of the peptide hormones of the hypothalamus, firstly oxytocin and vasopressin and shortly afterwards the releasing hormones, provided the first clear evidence that certain neurones were peptidergic. Subsequently the phenomenon of neurosecretion has been studied in a wide range of vertebrates and invertebrates.

Nerve cells use various chemical messengers, including acetylcholine, monoamines, amino acids and neuropeptides. In the past 10 years it has become clear that there is a great molecular diversity of such messengers particularly amongst the amino acids. However, the molecular diversity of neuropeptides exceeds by far that of the amino acids. There is now evidence that in one animal species as many as 100-200 different peptide molecules may serve as neuronal messengers (Kandel 1983; Nieuwenhuys 1985; Joosse 1986).

Neuropeptides occur in nervous systems of all animals, even in the most simple such as coelenterates (Schaller et al. 1984). For many years neuronal peptides were thought to have only a neuroendocrine role. The present view however is that, in addition to their role as neurohormones, they may act as typical synaptic neurotransmitters and as paracrine or neurocrine regulators at non-synaptic sites (Buma & Roubos 1985; Nieuwenhuys 1985).

Immunocytochemical and biochemical studies provide substantial evidence that structurally related peptides are found in many different phyla. Well-known examples are insulin-like peptides and FMRFamide. An important consequence of these findings is that some of the peptides found so far may have arisen from a smaller number of ancestral molecules, possibly at the prokaryote stage (Joosse 1987).

A large part of the present volume concerns the molecular diversity and functions of neuropeptides in invertebrates. In view of the great diversity in structure and function of neuropeptides and their presence throughout the animal kingdom, the question arises as to the adaptive value of peptide variety.

Introduction

Coelenterates have the simplest nervous system in the animal kingdom, and it was probably within this group of animals that nervous systems first evolved. Extant coelenterates are diverse and comprise two phyla. The classes Hydrozoa (for example hydroids and their medusae), Cubozoa (box jellyfishes), Scyphozoa (true jellyfishes), and Anthozoa (for example sea anemones and corals) constitute the phylum Cnidaria. A companion phylum is that of the Ctenophora (comb jellies), or Acnidaria. The general plan of the coelenterate nervous system has often been described as a nerve net. This is an oversimplification because many species show condensation of neurones to form linear or circular tracts. Linear tracts occur in the stem and tentacles of physonectid siphonophores (Mackie 1973; Grimmelikhuijzen et al. 1986), between the ocelli and marginal nerve rings of anthomedusae (Singla & Weber 1982; Grimmelikhuijzen & Spencer 1984), and at the bases of mesenteries in sea anemonies (Batham et al. 1960). Circular tracts, or nerve rings, have been found in the bell margin of hydrozoan medusae (Hertwig & Hertwig 1878; Jha & Mackie 1967; Spencer 1979; Grimmelikhuijzen et al. 1986) and at the base of the hypostome in some hydrozoan and cubozoan polyps (Werner et al. 1976; Grimmelikhuijzen 1985). Presumably, these tracts have evolved to form pathways for rapid conduction of information. The marginal nerve rings of hydromedusae, in addition, form a circular CNS, which is capable of both integrating a variety of sensory inputs, and of transmitting the input rapidly throughout the margin (Spencer & Arkett 1984).

The crustacean neuro-endocrine system has an extensive and diverse organisation (GABE 1966). It includes the Y-organs, mandibular organs and gonads as well as all parts of the nervous sytem (NS) (Echalier 1954; Le Roux 1968; Charniaux-Cotton 1954; Juchault 1966).

This chapter will concentrate on the peptidergic and aminergic areas of the NS, utilizing the isopod model as a framework upon which to base comparative data obtained from decapods.

The neurosecretory cells

The Isopod brain comprises 3 major areas: protocerebrum, innervating the compound eyes; deutocerebrum, innervating the antennule; and tritocerebrum, innervating the antennary.

Neurosecretory products are often revealed by standard histological techniques such as paraldehyde fuchsin (PF) and chrome hematoxylin phloxine (CHP). We have used these techniques to locate 4 types and subtypes of neurosecretory cells (NSC) in the NS (Martin 1981), and the ones described here will be restricted to those terminating in the sinus gland (SG), following the pattern established by the cobalt back-filling experiments of Chiang and Steel (1985a). NSC are classified according to the terminology introduced by Matsumoto (1959).

β-cells: These comprise a group of heterogeneous cells, located in the anterior part of the protocerebrum, on each side of the midline (Fig. 1a; 1c).

Subgroup β1 contains 6 cells, which are polygonal, 14–28 μm in diameter which stain intensely with both PF and CHP. Ultrastructure shows an ovoid nucleus, stacks of RER, Golgi-derived electron dense granules (160-180 nm) and glycogen particles associated with electron lucent vacuoles (Fig. 1d).

In vertebrate endocrinology, significant progress has been made over the past 30 years due to the availability of immunochemical techniques. Marshall (1951) obtained the first immunohistological result in the adenohypophysis of several mammalian species using an anti-ACTH antiserum. These immunohistological investigations were made possible because of the early isolation of vertebrate hormones and neurohormones.

Invertebrate neuropeptides, however, were not purified and sequenced until more recently because of the small size of central nervous systems (CNS) or neurohaemal organs. The first invertebrate neuropeptide to be isolated was proctolin from the cockroach, Periplaneta americana (Brown & Starratt 1975). Invertebrate neurosecretory cells have however been visualized by histochemical staining methods for about forty years.

Most antibodies used in vertebrate immunocytochemistry are raised against mammalian hormones or neurohormones. They nevertheless give positive immunoreactions at the level of lower vertebrate hypophyseal and hypothalamic cells. It was tempting therefore to discover if such antisera could also generate positive results in invertebrates. The first evidence of the existence of an immunochemical relationship between vertebrate and invertebrate neuropeptides was produced in 1975 by Grimm-Jorgensen & MacKelvy. Using radioimmunoassays, they found an immunoreactive thyrotropin releasing hormone (TRH)-like substance in gastropod ganglia.

In 1977, some invertebrate neurosecretory cells synthesizing neurosecretory products related to vertebrate neuropeptides or vertebrate gastro-entero-pancreatic peptides, were visualized by immunocytochemical techniques, in earthworm ganglia (Sundler et al. 1977) and insect suboesophageal ganglia (Rémy et al. 1977). These early findings caused surprise and even scepticism among several scientists. There are now over two hundred different immunocytochemical results in this area, about seventy five of which concern insects.

Introduction

In molluscs, bioactive peptides are produced by peptidergic neurons, endocrine glands and other tissues, such as cells of the intestinal tract. These peptides function as neurotransmitters/neuromodulators and (neuro)hormones, and control a wide range of events concerned with behaviour, reproduction, and metabolism. Particular attention has been paid to the peptidergic model systems in Lymnaea and Aplysia, to FMRFamide and related peptides which also exhibit an extra-molluscan distribution, and to the presence and function of vertebrate peptides in molluscs.

Our knowledge of biologically active peptides in molluscs is expanding rapidly due to the introduction, among other things, of sophisticated chromatographic and sequence techniques, and the methods of molecular biology. A review of this length must, of necessity, be selective. We have attempted to give a critical account of the data concerning the physiological role and the nature of (presumed) bioactive peptides, and avoided discussions of non-relevant details. Recent reviews present a wealth of complementary data (e.g. Joosse & Geraerts 1983; Geraerts & Joosse 1984; Roubos 1984; Rothman et al 1985; Geraerts et al. 1987. See also Chapters 2 and 14 this volume).

The FMRFamide family, and opioid peptides

The FMRFamide family

The neuropeptide FMRFamide was isolated originally from the clam Macrocallista nimbosa (Price & Greenberg 1977). In addition to FMRFamide, various related peptides have subsequently been isolated from the brain of a number of species belonging to different classes of the molluscs (Table 1).

Introduction

A seemingly bewildering array of factors with putative neurohormonal function have been described in (mainly decapod) Crustacea (see Kleinholz & Keller 1979; Cooke & Sullivan 1982; Keller 1983; Kleinholz 1985). They are implicated in almost every aspect of crustacean physiology, including pigment dispersion and concentration, inhibition of moulting, limb regeneration and gonad development, cardiac control, blood glucose, metabolism and respiratory control, ion and water balance, endogenous rhythmicity and locomotion. Several of these factors are produced by neurosecretory structures in the eyestalk, which can be easily ablated. This accessibility has unfortunately led to a tendency to assign hormonal regulation of physiological mechanisms based solely upon the results of eyestalk removal, often without the rigorous application of deficiency and replacement protocols using physiologically relevant doses of extracts or further purification of the active principle. Thus, apart from the well known neuropeptides, it is not known how many of these described ‘factors’ genuinely control individual processes and little is known of their precise chemical identity.

Evidence from immunocytochemical studies suggests that many neuropeptides classically known as ‘vertebrate’ peptides and also neuropeptides that have originally been found in invertebrates (e.g. FMRF amide, proctolin) are ubiquitous in crustaceans (Mancillas et al. 1981; Jacobs & Van Herp 1984; Jaros et al. 1985; Van Deijnen et al. 1985; Stangier et al. 1986). However, there is at present little information concerning the role of ‘vertebrate-type’ peptides in physiological integration.