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In this paper it will be necessary to enter on minute details of the anatomy; but they regard a subject hitherto untouched, although essential to the comprehension of the nervous system, without which, indeed, it could not be said that we had a know­ ledge of the nerves as a system. The author has advanced, by slow and laborious researches, from observing the general arrangement of the nerves as they lie in the body, to the investigation of par­ticular nerves and their endowments; and, finally, to the examination of these parts in the centre of the system, the brain and spinal marrow, which enables him to assign the reason of that perfect symmetry which reigns through the whole.

Since the communication above referred to was presented to the Royal Society, I have made a very minute dissection in alcohol of the whole nervous system of the young heifer’s heart. The distribution of the ganglia and nerves over the entire surface of the heart, and the relations of these structures to the blood-vessels and muscular substance, are far more fully displayed in these preparations than in any of my former dissections. On the anterior surface, there are distinctly visible to the naked eye ninety ganglia or ganglionic enlargements on the nerves, which pass obliquely across the arteries and the muscular fibres of the ventricles from their base to the apex. These ganglionic enlargements are observed on the nerves, not only where they are crossing the arteries, but where they are ramifying on the muscular substance without the blood-vessels. On the posterior surface, the principal branches of the coronary arteries plunge into the muscular substance of the heart near the base, and many nerves with ganglia accompany them throughout the walls to the lining membrane and columnse carneæ. From the sudden disappearance of the chief branches of the coronary arteries on the posterior surface, the nervous structure distributed over a consider­ able portion of the left ventricle is completely isolated from the blood-vessels, and on these, numerous ganglionic enlargements are likewise observed, but smaller in size than the chains of ganglia formed over the blood-vessels on the anterior surface of the heart. In the accompanying beautiful drawings, Mr. West has depicted with the greatest accuracy and minuteness the whole nervous structures demon­strable in these preparations on the surface of the heart. But the ganglia and nerves represented in these drawings constitute only a small portion of the nervous system of the heart, numerous ganglia being formed in the walls of the heart which no artist can represent. It can be clearly demonstrated that every artery distributed throughout the walls of the Uterus and Heart, and every muscular fasciculus of these organs, is supplied with nerves upon which ganglia are formed.

Uncertainty is an inherent feature of strategies to contain animal disease. In this paper, an interdisciplinary framework for representing strategies of containment, and analysing how uncertainties are embedded and propagated through them, is developed and illustrated. Analysis centres on persistent, periodic and emerging disease threats, with a particular focus on cryptosporidiosis, foot and mouth disease and avian influenza. Uncertainty is shown to be produced at strategic, tactical and operational levels of containment, and across the different arenas of disease prevention, anticipation and alleviation. The paper argues for more critically reflexive assessments of uncertainty in containment policy and practice. An interdisciplinary approach has an important contribution to make, but is absent from current real-world containment policy.

This paper contributes to a debate in the palaeoarchaeological community about the major time-lag between the origin of anatomically modern humans and the appearance of typically human cultural behaviour. Why did humans take so long—at least 100 000 years—to become ‘behaviourally modern’? The transition is often explained as a change in the intrinsic cognitive competence of modern humans: often in terms of a new capacity for symbolic thought, or the final perfection of language. These cognitive breakthrough models are not satisfactory, for they fail to explain the uneven palaeoanthropological record of human competence. Many supposed signature capacities appear (and then disappear) before the supposed cognitive breakthrough; many of the signature capacities disappear again after the breakthrough. So, instead of seeing behavioural modernity as a simple reflection of a new kind of mind, this paper presents a niche construction conceptual model of behavioural modernity. Humans became behaviourally modern when they could reliably transmit accumulated informational capital to the next generation, and transmit it with sufficient precision for innovations to be preserved and accumulated. In turn, the reliable accumulation of culture depends on the construction of learning environments, not just intrinsic cognitive machinery. I argue that the model is (i) evolutionarily plausible: the elements of the model can be assembled incrementally, without implausible selective scenarios; (ii) the model coheres with the broad palaeoarchaeological record; (iii) the model is anthropologically and ethnographically plausible; and (iv) the model is testable, though only in coarse, preliminary ways.

Current drug treatments for post-menopausal osteoporosis cannot eliminate bone fractures, possibly because the mechanisms responsible for bone loss are not fully understood. Although research within various disciplines has significantly advanced the state of knowledge, fundamental findings are not widely understood between different disciplines. For that reason, this paper presents noteworthy experimental findings from discrete disciplines focusing on post-menopausal osteoporosis. These studies have established that, in addition to bone loss, significant changes in bone micro-architecture, tissue composition and micro-damage occur. Cellular processes and molecular signalling pathways governing pathological bone resorption have been identified to a certain extent. Ongoing studies endeavour to determine how such changes are initiated at the onset of oestrogen deficiency. It emerges that, because of the discrete nature of previous research studies, the sequence of events that lead to bone fracture is not fully understood. In this paper, two sequences of multi-scale changes are proposed and the experimental challenges that need to be overcome to fully define this sequence are outlined. Future studies must comprehensively characterize the time sequence of molecular-, cellular- and tissue-level changes to attain a coherent understanding of the events that ultimately lead to bone fracture and inform the future development of treatments for post-menopausal osteoporosis.

In this paper, we propose a mechanism which the neocortex may use to store sequences of patterns. Storing and recalling sequences are necessary for making predictions, recognizing time-based patterns and generating behaviour. Since these tasks are major functions of the neocortex, the ability to store and recall time-based sequences is probably a key attribute of many, if not all, cortical areas. Previously, we have proposed that the neocortex can be modelled as a hierarchy of memory regions, each of which learns and recalls sequences. This paper proposes how each region of neocortex might learn the sequences necessary for this theory. The basis of the proposal is that all the cells in a cortical column share bottom-up receptive field properties, but individual cells in a column learn to represent unique incidences of the bottom-up receptive field property within different sequences. We discuss the proposal, the biological constraints that led to it and some results modelling it.

This paper discusses the relationship between culture and intelligence. The main message of the paper is that intelligence cannot fully or even meaningfully be understood outside its cultural context. Behaviour that is considered intelligent in one culture may be considered unintelligent in another culture, andvice versa. Moreover, people in different cultures have different implicit (folk) theories of intelligence, so may not even mean the same thing by the word. The relationships between different aspects of intelligence can vary across cultures, with correlations that are positive in one setting proving to be negative in another. The paper opens with a general discussion of issues regarding the relationship between the two concepts. It then describes the theory of successful intelligence, which motivates our work on the interface between culture and intelligence. Finally, the article draws some conclusions.

This paper describes circumstances around the discovery of long-term potentiation (LTP). In 1966, I had just begun independent work for the degree of Dr medicinae (PhD) in Per Andersen's laboratory in Oslo after an eighteen-month apprenticeship with him. Studying the effects of activating the perforant path to dentate granule cells in the hippocampus of anaesthetized rabbits, I observed that brief trains of stimuli resulted in increased efficiency of transmission at the perforant path-granule cell synapses that could last for hours. In 1968, Tim Bliss came to Per Andersen's laboratory to learn about the hippocampus and field potential recording for studies of possible memory mechanisms. The two of us then followed up my preliminary results from 1966 and did the experiments that resulted in a paper that is now properly considered to be the basic reference for the discovery of LTP.

The central argument presented in this paper is that statistical learning (SL) is an ability comprised of multiple components that operate largely implicitly. Components relating to the stimulus encoding, retention and abstraction required for SL may include, but are not limited to, certain types of attention, processing speed and memory. It is likely that individuals vary in terms of the efficiency of these underlying components, and in patterns of connectivity among these components, and that SL tasks differ from one another in how they draw on certain underlying components more than others. This theoretical framework is of value because it can assist in gaining a clearer understanding of how SL is linked with individual differences in complex mental activities such as language processing. Variability in language processing across individuals is of central concern to researchers interested in child development, including those interested in neurodevelopmental disorders where language can be affected such as autism spectrum disorders (ASD). This paper discusses the link between SL and individual differences in language processing in the context of age-related changes in SL during infancy and childhood, and whether SL is affected in ASD. Viewing SL as a multi-component ability may help to explain divergent findings from previous empirical research in these areas and guide the design of future studies. This article is part of the themed issue ‘New frontiers for statistical learning in the cognitive sciences’.

The field of functional neuroimaging (FNI) methodology has developed into a mature but evolving area of knowledge and its applications have been extensive. A general problem in the analysis of FNI data is finding a signal embedded in noise. This is sometimes called signal detection. Signal detection theory focuses in general on issues relating to the optimization of conditions for separating the signal from noise. When methods from probability theory and mathematical statistics are directly applied in this procedure it is also called statistical inference. In this paper we briefly discuss some aspects of signal detection theory relevant to FNI and, in addition, some common approaches to statistical inference used in FNI. Low–pass filtering in relation to functional–anatomical variability and some effects of filtering on signal detection of interest to FNI are discussed. Also, some general aspects of hypothesis testing and statistical inference are discussed. This includes the need for characterizing the signal in data when the null hypothesis is rejected, the problem of multiple comparisons that is central to FNI data analysis, omnibus tests and some issues related to statistical power in the context of FNI. In turn, random field, scale space, non–parametric and Monte Carlo approaches are reviewed, representing the most common approaches to statistical inference used in FNI. Complementary to these issues an overview and discussion of non–inferential descriptive methods, common statistical models and the problem of model selection is given in a companion paper. In general, model selection is an important prelude to subsequent statistical inference. The emphasis in both papers is on the assumptions and inherent limitations of the methods presented. Most of the methods described here generally serve their purposes well when the inherent assumptions and limitations are taken into account. Significant differences in results between different methods are most apparent in extreme parameter ranges, for example at low effective degrees of freedom or at small spatial autocorrelation. In such situations or in situations when assumptions and approximations are seriously violated it is of central importance to choose the most suitable method in order to obtain valid results.

International audience; In this paper, we propose that experimental protocols involving artificial agents, in particular the embodied humanoid robots, provide insightful information regarding social cognitive mechanisms in the human brain. Using artificial agents allows for manipulation and control of various parameters of behaviour, appearance and expressiveness in one of the interaction partners (the artificial agent), and for examining effect of these parameters on the other interaction partner (the human). At the same time, using artificial agents means introducing the presence of artificial, yet human-like, systems into the human social sphere. This allows for testing in a controlled, but ecologically valid, manner human fundamental mechanisms of social cognition both at the behavioural and at the neural level. This paper will review existing literature that reports studies in which artificial embodied agents have been used to study social cognition and will address the question of whether various mechanisms of social cognition (ranging from lower-to higher-order cognitive processes) are evoked by artificial agents to the same extent as by natural agents, humans in particular. Increasing the understanding of how be-havioural and neural mechanisms of social cognition respond to artificial anthropomorphic agents provides empirical answers to the conundrum 'What is a social agent?'

Modern stem cell biology has achieved a transformation that was thought by many to be every bit as unattainable as the ancient alchemists' dream of transforming base metals into gold. Exciting opportunities arise from the process known as ‘cellular reprogramming’ in which cells can be reliably changed from one tissue type to another. This is enabling novel approaches to more deeply investigate the fundamental basis of cell identity. In addition, new opportunities have also been created to study (perhaps even to treat) human genetic and degenerative diseases. Specific cell types that are affected in inherited disease can now be generated from easily accessible cells from the patient and compared with equivalent cells from healthy donors. The differences in cellular phenotype between the two may then be identified, and assays developed to establish therapies that prevent the development or progression of disease symptoms. Cellular reprogramming also has the potential to create new cells to replace those whose death or dysfunction causes disease symptoms. For patients suffering from inherited cases of degenerative diseases like Parkinson's disease or amyotrophic lateral sclerosis (also known as motor neuron disease), the future realization of such cell-based therapies would truly be worth its weight in gold. However, before this enormous potential can become a reality, several significant biological and technical challenges must be overcome. Furthermore, to maintain the credibility of the scientific community with the general public, it is important that hope-inspiring advances are not over-hyped. The papers in this issue of the Philosophical Transactions of the Royal Society B : Biological Sciences cover many areas relevant to this topic. In this Introduction , we provide an overall context in which to consider these individual papers.

The influence of the nervous system over the metabolism of the carbohydrates was demonstrated by Claude Bernard’s famous piqûre experiment (1855) many years before that of hormones, but recently attention has been paid mainly to the latter. As our knowledge of the influence hormones in general has expanded, the possibility that the activities of the glands which produce them are regulated through the nervous system has been considered, and the question arises whether it is indirectly through this control that the nervous system affects carbohydrate metabolism. It was with the object of solving this question that the present research was primarily undertaken. Our original plan was to investigate the nature of the changes in carbohydrate metabolism brought about by piqûre, but we very soon found that this operation, as usually practised, is uncertain in its results and, moreover, that it is impossible to differentiate these results from the disturbances in carbohydrate metabolism which anæsthesia in itself induces. This led us to adopt the method of decerebration rather than piqûre and, by its use, we have succeeded both in localising within fairly narrow limits, the part of the brain which is principally concerned with the nervous control of carbohydrate metabolism and in throwing some light on the nature of the biochemical changes over which this control is exercised. In the present paper, we will first of all give a brief account of the experiments which led us to adopt the decerebration method rather than that of piqûre, and then consider more in detail the results which have enabled us to localise the diabetic centre. In subsequent papers we will deal with the metabolic disturbances resulting from the decerebration and with the modification of these disturbances which occur when the nervous pathways through which the centre exercises its control are interfered with.

Mr. Knight, in the papers formerly communicated by him to the Royal Society, endeavoured to prove that the fluid by which the va­rious parts added to trees, &c. are generated, has previously circu­lated through their leaves, either in the same or in the preceding season, and has subsequently descended through their barks. There is, however, a circumstance stated by Hales and by Du Hamel, which appears to militate against the above hypothesis, namely, that when two circular incisions are made, at a small distance from each other, through the hark, round the stem of a tree, and the bark between these incisions is wholly taken away; that portion of the stem which is below the incisions continues to live, and to increase in size, though much more slowly than the parts above the incisions. The above-mentioned naturalists have also observed, that a small elevated ridge is formed round the lower lip of the wound, which makes some slight advances to meet the hark and wood, projected in larger quantities from the upper lip of the wound. Our author, in a former paper, attempted to explain the above cir­cumstance, by supposing that a small part of the true sap, descending from the leaves, escapes downwards, through the porous substance of the alburnum: in another paper he has shown, from the growth of inverted cuttings, the existence of a power in the alburnum to carry the sap in different directions; and he now describes some ex­periments made in order to show that the conclusions drawn by him are not inconsistent with the facts stated by Hales and Du Hamel; and that although the ascending sap usually rises through the al­burnum and central vessels, yet the alburnous vessels appear to be also capable of an inverted action, when such action becomes neces­sary to preserve the existence of the plant.

The general characteristics of the muscular manifestations, which ensue on faradic stimulation of cerebellar nuclei, were described in a previous paper (28). In the present investigation an analysis of the nuclear responses was affected by recording the changes in tone in individual muscles of the foreand hindlimbs. Prior to our own work faradic stimulation had been applied to the cerebellar nuclei by Horsley and Clarke (17); they did not record the muscular changes graphically, but only observed the movements of the limb; these movements, to judge from their somewhat casual report, resembled those observed by ourselves. The belief that the responses observed by Horsley and Clarke were evoked by actual stimulation of the nuclei was clearly implied in their article; but in a paper by R. H. Clarke (6), published posthumously, the opinion is expressed that the reactions, supposedly of nuclear origin, were of a fallacious character, depending on current diffusion to Deiter's nucleus and various motor centres. Speaking more particulary for our own work we must state positively that our reactions were evoked by stimulation of the intracerebellar nuclei themselves, and were not due in any sense to spread of current beyond the cerebellum. Phenomena caused by spread of current are readily recognisable, and were avoided by using currents of threshold value for the nuclei, the excitability of which was carefully preserved. Our conclusions are thus more nearly in agreement with those of Horsley and Clarke than with those recorded in the posthumous paper of Clarke.

The experiments described in the preceding four papers bear on various problems presented by reflex activity. Their results confirm some of the inferences already drawn elsewhere from other experimental work, and they allow certain further inferences. A brief prefatory statement of all these inferences and of the experimental evidence which allows them will advantageously introduce the description of the processes set up in the ipselateral flexor centres of the spinal cord by a single centripetal volley and by a single antidromic volley. Then, finally, discussion of the theories of reflex excitation can be undertaken in the light of the present experimental observations. the statement treats of the subject in its present phase only; the references to relevant papers are therefore restricted in the main to the more recent ones. II. Inferences from Experimental Observations. 1.The convergence of Different Afferent Paths on the same MotoneuronesThe following evidence shows that this occurs:- (a)Histological.-Each motoneurone receives its “boutons terminaux” from many individual afferent terminals (Cajal, 1903). (b)Physiological.-Centripetal volleys set up indifferentafferent nerves excite the same motoneurones (Camis, 1909; Cooper, Denny-Brown, and Sherrington, 1926; 1927; Sherrington, 1929; Cooper and Denny-Brown, 1929 ; Eccles and Sherrington, 1930 ; 1931,a; 1931,b).

The object of the present paper is to define by histological methods the exact limitations of the visuo-sensory area of the human cortex cerebri. The investigation to be described has occupied upwards of three years. It was commenced during the summer of 1896 in the pathological laboratory of the County Asylum, Rainhill, Lancashire; it was continued during the next three years in the physiological laboratory of Mason University College, Birmingham; and it has been completed in the pathological laboratory of the London County Council at Claybury. Owing to the remarkable facilities for research granted to workers in the last-named laboratory, it has been possible to bring this investigation to a much more rapid conclusion than would otherwise have been possible. A general summary of the paper follows this introduction, and it is succeeded for convenience of reference by a list of the sections into which the paper is divided.

The present paper deals with some features of inhibitory relaxation of muscular contraction as observable in the knee extensor (decerebrate cat) when the crossed extensor reflex is subjected to inhibition by stimulation of an afferent nerve of the ipsilateral limb. The myograms have been obtained with the isometric optical myograph described in a previous paper, and the method of preparation, etc., has been as before. I.Relaxation-speed under Strong Inhibition. The speed of the muscular relaxation produced by the inhibition is often notably high. It then compares in rate with that of the lapse of a peripheral tetanus at cessation of the faradic stimulation of the muscle’s motor nerve (19).

Time research has been a neglected topic in the cognitive neurosciences of the last decades: how do humans perceive time? How and where in the brain is time processed? This introductory paper provides an overview of the empirical and theoretical papers on the psychological and neural basis of time perception collected in this theme issue. Contributors from the fields of cognitive psychology, psychiatry, neurology and neuroanatomy tackle this complex question with a variety of techniques ranging from psychophysical and behavioural experiments to pharmacological interventions and functional neuroimaging. Several (and some new) models of how and where in the brain time is processed are presented in this unique collection of recent research that covers experienced time intervals from milliseconds to minutes. We hope this volume to be conducive in developing a better understanding of the sense of time as part of complex set of brain–body factors that include cognitive, emotional and body states.

The intention of the author in the present paper, is, not to bring forwards any new facts, but to take a general review of the inferences deducible from the series of facts detailed by him in previous papers communicated to this Society. He divides the nerves into two classes, essentially differing in their functions. The first comprehends those nerves, which, proceeding directly from the brain and spinal cord to other parts, convey in the one case to those parts the influence of those organs only from which they originate, and thus excite to con­traction the muscles of voluntary motion ; and in the other case transmit to the sensorium impressions made on the parts to which they are distributed. The second class comprises what may betermed the Ganglionic nerves, or those which enter ganglions, pro­perly so called; that term being limited to such protuberances only as receive branches of nerves proceeding from the brain and spiral cord. These nerves are distributed more especially to the vital or­ gans, as the thoracic and abdominal viscera, and to the muscles sub­servient to their functions. The nerves belonging to this class also convey impressions to the sensorium, and occasionally excite the muscles of involuntary motion, which, in common with all muscles, possess an inherent power of contractility dependent solely on their own mechanism, and which in ordinary cases are excited by stimuli peculiar to themselves. But the most important function of the gan­glionic nerves, is that of supporting the processes of secretion and assimilation, which require for their performance the combined influ­ence of the whole brain and spinal cord. Viewed as a whole, the system of ganglionic nerves, therefore, constitutes, in the strictest sense, a vital organ. Thus the sensorium, though connected by means of the cerebral and spinal nerves only partially with the organs of sense and voluntary motion, is, by means of the ganglionic nerves, connected generally with all the functions of the animal body. Hence affections of the stomach and other vital organs extend their influence over every part of the frame; while those of a muscle of voluntary motion, or even of an organ of sense, although possessing greater sensibility, are confined to the injured part. From a due consideration of the phenomena of the nervous system, it would appear that they imply the operation of more than one prin­ciple of action. The sensorial power is wholly distinct from the ner­vous power; the former residing chiefly in the brain, while the latter belongs equally to the spinal cord and brain, and may be exercised independently of the sensorial power. In like manner, the muscular power resides in the muscles, and may be called into action by various irritations independently of the nervous power, though fre­quently excited by the action of that power. The muscles of volun­tary motion are subjected to the sensorial power through the inter­vention of the nervous system; and those of involuntary motion are also, under certain circumstances, capable of being excited through the nerves by the sensorial power, particularly when under the influ­ence of the passions. The same observation applies also to other actions which properly belong to the nervous power, such as the evolution of caloric from the blood, and the various processes of se­cretion and of assimilation. That the nervous power is in these instances merely the agent of other powers, and is independent of the peculiar organization of the nerves, is proved by the same effects being produced by galvanism, transmitted through conductors diffe­rent from the nerves. The successive subordination of these several powers is shown during death, when the sensorial functions are the first to cease, and the animal no longer feels or wills, but yet the nervous power still continues to exist, as is proved by the nerves be­ing capable, when stimulated, of exciting contractions in the muscles, both of voluntary and of involuntary motion,of producing the evolution of caloric and of renewing the processes of secretion. In like manner the power of contraction, inherent in the muscular fibre, survives the destniction of both the sensorial and nervous powers, having an existence independent of either, although in the entire state of the functions they are subjected to the entire influence of both.

We present a differential equations model in which contagious disease transmission is affected by contagious fear of the disease and contagious fear of the control, in this case vaccine. The three contagions are coupled. The two fears evolve and interact in ways that shape distancing behaviour, vaccine uptake, and their relaxation. These behavioural dynamics in turn can amplify or suppress disease transmission, which feeds back to affect behaviour. The model reveals several coupled contagion mechanisms for multiple epidemic waves. Methodologically, the paper advances infectious disease modelling by including human behavioural adaptation, drawing on the neuroscience of fear learning, extinction and transmission.

This paper introduces a Theme Issue presenting the latest developments in research on the interplay between flexibility and constraint in social behaviour, using comparative datasets, long-term field studies and experimental data from both field and laboratory studies of mammals. We first explain our focus on mammals and outline the main components of their social systems, focusing on variation within- and among-species in numerous aspects of social organization, mating system and social structure. We then review the current state of primarily ultimate explanations of this diversity in social behaviour. We approach the question of how and why the balance between behavioural flexibility and continuity is achieved by discussing the genetic, developmental, ecological and social constraints on hypothetically unlimited behavioural flexibility. We introduce the other contributions to this Theme Issue against this background and conclude that constraints are often crucial to the evolution and expression of behavioural flexibility. In exploring these issues, the enduring relevance of Tinbergen's seminal paper ‘On aims and methods in ethology’, with its advocacy of an integrative, four-pronged approach to studying behaviour becomes apparent: an exceptionally fitting tribute on the 50th anniversary of its publication.

Interactions along the neuro-cardiac axis are being explored with regard to their involvement in cardiac diseases, including catecholaminergic polymorphic ventricular tachycardia, hypertension, atrial fibrillation, long QT syndrome and sudden death in epilepsy. Interrogation of the pathophysiology and pathogenesis of neuro-cardiac diseases in animal models present challenges resulting from species differences, phenotypic variation, developmental effects and limited availability of data relevant at both the tissue and cellular level. By contrast, tissue-engineered models containing cardiomyocytes and peripheral sympathetic and parasympathetic neurons afford characterization of cellular- and tissue-level behaviours while maintaining precise control over developmental conditions, cellular genotype and phenotype. Such approaches are uniquely suited to long-term, high-throughput characterization using optical recording techniques with the potential for increased translational benefit compared to more established techniques. Furthermore, tissue-engineered constructs provide an intermediary between whole animal/tissue experiments and in silico models. This paper reviews the advantages of tissue engineering methods of multiple cell types and optical imaging techniques for the characterization of neuro-cardiac diseases.

Aggregation of amyloid- β (A β ) peptides is a significant event that underpins Alzheimer's disease (AD). A β aggregates, especially the low-molecular weight oligomers, are the primary toxic agents in AD pathogenesis. Therefore, there is increasing interest in understanding their formation and behaviour. In this paper, we use our previously established results on heterotypic interactions between A β and fatty acids (FAs) to investigate off-pathway aggregation under the control of FA concentrations to develop a mathematical framework that captures the mechanism. Our framework to define and simulate the competing on- and off-pathways of A β aggregation is based on the principles of game theory. Together with detailed simulations and biophysical experiments, our models describe the dynamics involved in the mechanisms of A β aggregation in the presence of FAs to adopt multiple pathways. Specifically, our reduced-order computations indicate that the emergence of off- or on-pathway aggregates are tightly controlled by a narrow set of rate constants, and one could alter such parameters to populate a particular oligomeric species. These models agree with the detailed simulations and experimental data on using FA as a heterotypic partner to modulate the temporal parameters. Predicting spatio-temporal landscape along competing pathways for a given heterotypic partner such as lipids is a first step towards simulating scenarios in which the generation of specific ‘conformer strains’ of A β could be predicted. This approach could be significant in deciphering the mechanisms of amyloid aggregation and strain generation, which are ubiquitously observed in many neurodegenerative diseases.

As one of the first model systems in biology, the basal metazoanHydrahas been revealing fundamental features of living systems since it was first discovered by Antonie van Leeuwenhoek in the early eighteenth century. While it has become well-established within cell and developmental biology, this tiny freshwater polyp is only now being re-introduced to modern neuroscience where it has already produced a curious finding: the presence of low-frequency spontaneous neural oscillations at the same frequency as those found in the default mode network in the human brain. Surprisingly, increasing evidence suggests such spontaneous electrical low-frequency oscillations (SELFOs) are found across the wide diversity of life on Earth, from bacteria to humans. This paper reviews the evidence for SELFOs in diverse phyla, beginning with the importance of their discovery inHydra, and hypothesizes a potential role as electrical organism organizers, which supports a growing literature on the role of bioelectricity as a ‘template’ for developmental memory in organism regeneration.This article is part of the theme issue ‘Basal cognition: conceptual tools and the view from the single cell’.

Multisite phosphorylation is a basic way of chemically encoding substrate function and a recurring feature of cell signalling pathways. A number of studies have explored information processing characteristics of multisite phosphorylation, through studies of the intrinsic kinetics. Many of these studies focus on the module in isolation. In this paper, we build a bridge to connect the behaviour of multisite modification in isolation to that as part of pathways. We study the effect of activation of the enzymes (which are basic ways in which the module may be regulated), as well the effects of the modified substrates being involved in further modifications or exiting reaction compartments. We find that these effects can induce multiple kinds of transitions, including to behaviour not seen intrinsically in the multisite modification module. We then build on these insights to investigate how these multisite modification systems can be tuned by enzyme activation to realize a range of information processing outcomes for the design of synthetic phosphorylation circuits. Connecting the complexity of multisite modification kinetics, with the pathways in which they are embedded, serves as a basis for teasing out many aspects of their interaction, providing insights of relevance in systems biology, synthetic biology/chemistry and chemical information processing.

cooled to 2°K or lower. Rollin (1936) found that the thermal insulation of vessels containing liquid helium was much worse below than above the A point. He explained his observation by assuming the existence of a thin layer of liquid helium on the inside wall of the connecting tube, and thought it probable that the change in thermal conductivity of this film at the A point gave rise to the anomalous effects observed. As the result of more recent (unpublished) experiments Rollin and Simon* have put forward the other explanation that the film creeps up the tube and evaporates eventually. It is obvious that all these phenomena may have a common explanation and it was the object of the experiments described in this paper and the following paper to investigate the behaviour of He 11 in contact with solid surfaces systematically. The phenomena had to be investigated from various aspects and this made experiments necessary which varied in purpose and character to some extent. For simplicity’s sake we will therefore give, together with the description of each experiment, a short discussion and summarize at the end of the second paper all results in a general discussion on the whole phenomenon. All experiments were carried out in the same cryostat; and for different experiments only the experimental chamber and the experimental arrangement in it were altered.

The observations with which the present communication deals were met with in experiments continuing those on reciprocal innervation of symmetrical muscles. In my previous paper on that subject it had been reported that in regard to symmetrical extensors of the knee the ratio borne by intensity of the ipsilateral inhibition to the contralateral excitation is such that with equal stimuli to right and left symmetrical afferent nerves there is inhibitory suppression of contraction in both the muscles. In other words, under double reciprocal innervation the ipsilateral inhibition by each nerve completely overcomes the contralateral excitation of the other. It was shown that this mutual suppression holds over a wide range of the scale of intensities of stimulation. It was also shown that with quite weak stimuli a simultaneous stimulation of both nerves, stimuli being equal in intensity, often results in concurrent contraction of both muscles. Indeed, with quite weak stimuli, the effect of stimulation of each afferent nerve by itself is, in the decerebrate preparation, usually contraction of the ipsilateral as well as of the contralateral muscle. This being so, it is evident that at some point in the scale of intensities of stimulation there should be a place below which contralateral excitation is stronger than ipsilateral inhibition, whereas above it ipsilateral inhibition is stronger than contralateral excitation.

During the past few years, one of us (F. W. M.) has had exceptional opportunities of seeing patients suffering from various mental complaints, and of comparing the results of post-mortem examinations with the symptoms exhibited during life. One of the commonest complaints seen in the London County Asylums is General Paralysis of the Insane, and it was with a view of elucidating some of the pathological problems connected with this disease that the present enquiry was originally undertaken. How far this object has been attained will be discussed at the conclusion of the paper. The disease is one which is characterised by an extensive degenerative and wasting process occurring in the cerebral cortex, especially in the frontal and central convolutions ; during the course of the disease there are frequent seizures of a congestive, epileptiform or apoplectiform kind, and after the recovery of the patient from each of these fits, he is, as a rule, worse mentally. Each fit probably indicates the breakdown of a new focus of cerebral matter. The disease is a premature, primary, progressive decay of the neuron affecting especially those structures which have been developed latest. It is a para-syphilitic affection like tabes, with which it is, pathologically speaking, identical.

The constitution of the enteric plexuses (the plexus myentericus or plexus of Auerbach and the plexus submucosus or plexus of Meissner) and their rôle in the initiation and regulation of the gut-movements are problems which have been discussed by numerous investigators, and the literature relating to them is voluminous. Nevertheless, it can hardly be said that there is even to-day any general consensus of opinion in regard to them. The work detailed in the present paper arose out of an endeavour to provide demonstration reparations of the gut-plexuses for teaching purposes. Eventually, with the generous and unstinted help of the late Prof. N. Kulchitsky, a method of partially isolating the plexuses and of staining them with a modified Bielchowsky silver technique was evolved, which yielded preparations of such excellence that I was induced to make the attempt to work out their histological constitution. I propose to give first of all a very brief summary of the purely histological results obtained by previous workers in this field, and later, when setting forth my own observations, to deal more in detail with the related literature.

The following research was carried out in consequence of suggestions made to me by Professor Victor Horsley, to whom I wish to express my thanks for placing the facilities of his laboratory at my disposal, and for his advice and criticisms during the prosecution of the work and in the preparation of the paper. I also wish to return my best thanks to Professor Johannes Gad, in whose laboratory tire first part of the work was carried out, for his ever-ready and constant help and advice. I have further to thank my friend Dr. Risien Russell for his kindness in assisting me in some of my earlier experiments on the monkey. The researches were undertaken with the view of throwing light upon the degree to which certain movements or, speaking more precisely, sensori-motor (kinæsthetic) phenomena are represented in any given segment of the lumbo-sacral region of the mammalian spinal cord, and further what relationship exists between the representation of one movement and that of another. It is clear that at least three methods suggest themselves as means whereby this problem may be attacked, e. g. , (1) the excitation method, (2) the method of exclusion by ablation, and (3) the so-called degeneration method. Of these Nos. (2) and (3) have been already in part employed (No. (2) Sherrington, Risien Russell, No. (3) Grünbaum), but believing that with suitable precautions more exact localisation could be obtained by the excitation method, I have so far adopted that alone.

In my previous paper I dealt with the action of the poison of the Sea snakes as far as it was possible to examine it under the conditions of work in Calcutta, and reserved the consideration of certain questions until I was able to test them with the aid of a well-equipped laboratory. This I have now been able to do in the Physiological Laboratory of the London University, by the courtesy of Dr. A. D. Waller, with results which appear to be worthy of being placed on record in a further paper.

In a former paper ( “ Proc. Roy. Soc.,” vol. 33, p. 462) we laid before the Society the results of a series of experiments by which we had endeavoured to ascertain accurately the differences in the duration of the latent period of contraction of skeletal muscle (frog’s gastrocnemius) which could be brought about by varying the following influences :— 1. The weight of load. 2. The mode of applying weight (supported or unsupported), 3. The strength of stimulation. 4. Temperature. 5. Fatigue. We have since been engaged in determining the relative duration of the latent periods of different skeletal muscles of vertebrate animals. Besides several muscles of the Lana temp., we have examined some from the toad, tortoise, small mammals, and birds. In this paper, which is intended to be a continuation of the one above referred to, we beg leave to lay before the Society the results of these experiments and our general conclusions.

Recent investigations by A. V. Hill (1), Meyerhof (2), Doi (3), and others have made it evident that the heat liberated and tension developed by skeletal muscle during contraction varies for single maximal stimuli as well as for short tetani with the initial passive tension of the muscle, increasing to a point as the initial tension is raised, and then decreasing as the initial tension is raised still further. The mechanism by which this adaptation to differing mechanical conditions is brought about remains as yet obscure. As it seemed possible that a study of the electric responses of muscle subjected to differing mechanical conditions might throw some light upon the question, the following experiments were undertaken. A review of the previous investigations upon this subject has recently been given by Forbes, Ray and Hopkins (4, 1923) in their paper on the effect of tension on the action current of the twitch.

Denny-Brown (1929) and Adrian and Bronk (1929) have described rhythmic discharges from the single motoneurones of extensor muscles during repetitive stimulation of a contralateral afferent nerve. When the stimulation is not too infrequent, e. g. , when more than 10 a second, the rhythm of this reflex discharge bears no direct relation to the rhythm of the stimulation, but within limits it varies with the intensity of the reflex stimulus, which in turn is dependent on both the rate and the strength of the stimulation. Somewhere in the reflex centre the reflex stimulus gives rise to the rhythmic discharge characteristic of the reflex response. This paper describes an investigation into conditions underlying the production of such a rhythmic discharge from a motoneurone. A preliminary account of some of the experimental work has already been published (Eccles and Hoff, 1931).

As a step preliminary to some observations on the reflex functions of the spinal cord of the Monkey, I have attempted to make a rather detailed examination of the distribution of the efferent and afferent roots of each spinal nerve, especially in the lower half of the body of that animal. I have recently published some experimental notes on the arrangement of some motor fibres in the lumbo-sacral plexus, and the present paper deals chiefly with the distribution of the afferent fibres of the roots. Previous Observations. In the researches which have had for their subject the peripheral distribution of the posterior roots of the spinal nerves, the plexuses of the Mammalian fore limb have been more studied than have those pertaining to the hind limb. With the exception of the five experiments extant by L. Turck (1856), there seem no experiments on the cutaneous fields of the afferent spinal roots of the Mammalian bind limb previous to my own. This fact may lend interest to observations, especially on so high a type as the Monkey, and I take this opportunity of expressing my thanks to the Royal Society for pecuniary aid, placing that somewhat expensive laboratory animal within my reach.

The ability of certain organisms, including notably the Mollusca and lower Vertebrata, to respond to their surroundings by appropriate pigmentary changes has long been familiar to biologists; it has been recognised for more than half a century that a special type of effector organs (chromatophores, melanophores, etc.) are actively instrumental in producing such changes, and that, in Vertebrates at least, pigmentary response is partially controlled through the nerves by stimuli received from the organs of vision. During the past two decades it has been shown that the reactions of the pigment cells to stimuli simulate those of other effector organs, especially as regards their responses to certain internal secretions. That a fuller understanding of their properties might prove of service to practical aspects of physiology, as well as the key to a knowledge of “colour adaptation,” was realised by Lister, who concludes his paper on the cutaneous pigmentary system of the Frog (1858) with the following comment: “The pigmentary system also promises to render good service in toxicological enquiry. Hitherto in experiments performed on animals with that object attention has been directed chiefly, if not exclusively, to the effects produced upon the actions of the nervous centres, the nerves, and muscles. In the pigment cells we have a form of tissue with entirely new functions, which, though apparently allied to the most recondite processes, yet produce very obvious effects… Such experiments are so readily performed, and the effects produced are so obviously indicated by the changes in colour of the integument, that I venture to recommend this method of investigation to those who are occupied in studying the action of poisons. …” A considerable literature, which has been reviewed too thoroughly and recently to merit an extensive epitome here, bears witness to the intricacy of the mechanism which underlies pigmental response in Fishes, Amphibia, and Reptiles; and very little work has been done on Molluscs in this connection. It can be safely asserted that as many distinct types of chromatophores are already known as there are different sorts of other effector organs whose properties have been studied. Hence it is obvious that, apart from the intrinsic interest presented by the phenomenon of colour change, a study of the properties of this series of effectors invites consideration in relation to a fuller understanding of the rôle played respectively by the character of tissue and the nature of its nerve supply in the local action of drugs. The research, of which this preliminary communication contains an initial account, of the response of Amphibian melanophores to pituitary extracts, has been approached with both these objectives in view. For present purposes it will suffice to recapitulate briefly what has already been achieved in relation to the endocrine factors in pigmental response.

The experiments, of which this paper is a report, were undertaken with the object of establishing more fully the point of origin of the contraction wave in the mammalian heart, and of unravelling the course which this contraction wave follows in the auricles. As the history of this subject has been summed up but recently by one of us (10), we do not propose to consider it in detail at present. In studying the heart from these points of view, we have adopted the electrical method as being the most accurate at our command, and have investigated the wave of excitation which, though it actually precedes the wave of contraction, is closely associated with the latter. We deal, therefore, with the origin and propagation of the excitatory process in the heart, accepting the information which we so gather as an index of the origin and course of the contraction wave.

In this paper I shall present evidence from my clinical psychiatric experience to support the view that some abnormalities of behaviour can appropriately be seen as, so to say, para-rituals or meta-rituals; the deritualization of normal human rituals. Ritualization and abnormal are both terms that present some difficulty in a multidisciplinary symposium. If ordinary human speech is an instance of ritualization of behaviour in the ethological sense, then ‘schizophrenese’ is a de-structuring, a deritualizing of the socially shared ritual structuration of those patterns of sound that have acquired symbolic functions and come to be a language. I shall, however, be using ‘ritualization’ here subsequently more in the manner employed by the anthropologists. Within the social sciences, in particular sociology, anthropology and psychiatry, the concept o f‘abnormal’ is itself problematic. Without rehearsing here the different sides of the debate, I shall, for the purpose of this paper, regard abnormal behaviour as behaviour that is socially deviant within a given society. Socially deviant behaviour is simply behaviour that the majority of people regard as such. Some abnormal—that is socially deviant—behaviour is regarded as an expression of ‘mental illness’. Again, the concept of ‘mental illness’ is extremely problematic and has recently been subject to searching criticism from within psychiatry itself (Szasz 1961), as well as by anthropologists and sociologists (Goffman 1961; Scheff 1963, 1964 a, b ). My examples are drawn from that subclass of socially deviant behaviour regarded as coming within the special domain of relevance and field of competence of psychiatry. I put in parentheses in this paper any question of ‘ aetiology ’ of such behaviour (see Laing & Esterson 1964, pp. 2- 9).

In 1864 John Marshall, of University College Hospital, London, published in the ‘ Philosophical Transactions ’ an account of a brain of exceptional interest, that of a Bushwoman. The original documents and photographs relating to this brain were recently handed to Professor Elliot Smith by his daughter, Miss Marshall, On his advice these documents have been studied anew.* In making his drawings from these photographs the lithographer made some slight changes which convey an erroneous impression of the primitive features that confer exceptional importance on this Bushwoman’s brain. The progress of knowledge of this subject since 1864 enables us to interpret the photographs in another way and so make this interesting evidence available for the interpretation of such archaic forms of brain as are revealed in the endocranial casts ofPithecanthropus,Sinanthropus, andEoanthropus. The original photographs represent the dorsal, ventral, lateral, anterior and posterior aspects of both hemispheres and the medial aspect of the left hemisphere. There is no photograph of the medial aspect of the right hemisphere. In addition to the photographs of the brain there are photographs of the head before the removal of the brain, and fortunately a photograph of the left hemispherein situwithin the cranium. Marshall’s photographs are exactly the same size as the lithographic figures ; and he states that the figures agree in size with the preserved brain. He also gives measurements of the cerebrum taken from intracranial casts. There is a small discrepancy between the length of the cerebrum as measured on the photograph showing the brain in the cranium and the figures in his table. The amount of shrinkage is shown in fig. 25, Plate 3. In estimating the form and size of the outline of the endocranial cast of the Bushwoman figured in this paper, Marshall’s maximum figures are taken; allowing for this possible error, his illustrations enable us to reproduce the form fairly accurately. In Marshall' s table of measurements, in which he contrasts the European brain with the Bushwoman’s, the European brain is smaller in certain dimensions. This indicates that he specially selected an abnormally small European brain for comparison.

In a previous paper on concurrent mechanical and electrical responses to stimulation of the motor cortex in the monkey (3), we reported the transmission of stimulus rates of 18 to 68 a second. We were unable at that time to carry the enquiry farther owing to lack of means of obtaining higher variable rates of stimulus. Since then we have improvised apparatus giving higher rates and have been able to continue this part of our investigation, using rates up to 290 a second. The object was to determine the upper limit of rate of stimulus which would be transmitted directly to the muscle. We have also been able to collect much information as to the effects of low rates of stimulus, latent periods and the nature of cortical motor innervation as a whole. In the course of the work six further monkeys were used, all small Macacus Rhesus . Of these two had also been used for experiments having no bearing on the present subject and not of a nature to affect our results. The animals were prepared as previously described and the muscles from which records were obtained were M. brachialis anticus , M. flexor profundus digitorum , M. extensor carpi radialis and M. triceps brachii .

I have much pleasure in thanking Professor Victor Horsley for allowing me to conduct the experiments which form the subject of this paper at the Pathological Laboratory of University College. It has always appeared to me contrary to the best established facts with regard to the cerebral localisation of motor processes that some abduction of the vocal cords should not be represented in the cerebral cortex. That abduction should be less powerfully represented in the cortex than adduction seemed clear, but that there should be no centre at all to subserve this function in the cerebral cortex seemed strange. I therefore decided to test the matter on the lines suggested to me by Dr. Hughlings Jackson in connection with a recent investigation of eye movements, when, after excluding the possibility of the lateral movements of the eyes to the opposite side from the hemisphere stimulated taking place, by dividing the muscles which bring about these movements, I found that it was possible to evoke many other movements of the eyes which hitherto could not be obtained. The conclusion which appeared warranted by these results was that the lateral movements of the eyes are so powerfully represented in the cerebral cortex that they overpower all other movements under normal circumstances.

François-Franck and Pitres (1) in 1878-79 showed, by graphic analysis of movement produced by stimulation of the cortex cerebri, that complete fusion of responses did not occur until the frequency of the stimulation was increased above 45 per second. With the same apparatus they found that a muscle tetanus showed the stimulus rhythm up to the same frequency, and no further. Horsley and Schafer (2) in 1886, after a number of experiments on both voluntary contraction and movement by cortical stimulation, concluded that: “The rate of the rhythm is not the same as that of the excitation except when the frequency of excitation is 10 per second or less. With all higher rates of excitation the rhythm of muscular response is maintained at a fairly uniform rate of about 10 per second” (p. 105). Horsley and Schafer discuss the results of Françis-Franck and Pitres, quoting a statement from which they conclude that these authors modify their former conclusions; Luciani (3) also refers to this so-called modification. We find, however, on referring to François-Franck and Pitres’ paper (4), that their statement is to the effect that the regularity of cortical myograms is not as complete as in muscle nerve tetanus. They do not modify their original assertion that a stimulus rhythm of up to 45 per second to the cortex can appear in the muscle response. It seemed advisable to repeat these experiments, using an accurate torsion-wire myograph. The electromyogram has been recorded simultaneously; as far as we can ascertain this is the first attempt at the analysis of the action-currents due to cortical stimulation. The results obtained from the first three experiments are of some interest, therefore this preliminary communication is being made; further experiments are being carried out.

The chief contents of this paper are the results of an experimental investigation tending to prove that there is a localization of function in special regions of the cerebral hemispheres. In a former paper published by the author in the ‘West Riding Lunatic Asylum Medical Reports,’ vol. iii. 1873, the results were given of experiments on rabbits, cats, and dogs, made specially for the purpose of testing the theory of Hughlings Jackson, that localized and unilateral epilepsies are caused by irritation or “discharging lesions” of the grey matter of the hemispheres in the region of the corpus striatum. Besides confirming Hughlings Jackson’s views, the author’s researches indicated an exact localization in the hemispheres of centres, or regions, for the carrying out of simple and complex muscular movements of a definite character, and described by him as of a purposive, or expressional, nature.

In 1822 Magendie demonstrated that no reflex activities were evoked by impulses passing into the spinal cord by a ventral root. This result has been confirmed and extended by other investigators who showed that no action currents can be detected in other nerves when the central end of a cut ventral root is stimulated (Mislawski, 1895; Bernstein, 1898). Attempts have been made to account for the irreversibility of conduction in the reflex arc by postulating a “dynamical polarisation” of the nerve cell so that the conduction would be solely from dendrite to axon, never the reverse (cajal, 1891; van Gehuchten, 1900). The antidromic impulses “back-fired” into a motoneurone might, however, be blocked at the synapse (sherrington, 1900, p. 798). It seems unlikely that the conduction of nerve impulses in the cell body and dendrites of a motoneurone would differ fundamentally from the conduction in peripheral nerve fibres, e. g ., that impulses passing along the dendrites would suffer an irreciprocal decrement. In the present paper it has been assumed that antidromic impulses in motor nerve fibres are blocked at the synapses of the motoneurones.

The experiments relating to the function of digestion detailed or referred to in a paper which I lately had the honour to present to the Society, appear to throw light on the function of the ganglionic nerves, which hold a higher place in the animal economy than those either of sensation merely or voluntary power, being as essentially a vital organ as the heart or lungs, as will more fully appear, I think, from the review of facts which I now beg leave to submit to the Society. For the last fifteen years I have been engaged in an experimental inquiry relating to the laws of the vital functions; and have from time to time laid the results before the Royal Society in six papers, which the Society has done me the honour to publish. All the experiments on which the statements are founded, having been made in the presence of competent witnesses, the rule from which I never deviated, has been to repeat each experiment till no doubt respecting the result remained in the mind of any one present; and it is satis­factory to me to be enabled to state, that, although many of these experiments have been repeated by the physiologists both of this country and the continent, they have in no instance been found inaccurate. I have always abstained from troubling the Society till I had some new facts to state, which appeared to me to deserve its attention; and I have confined myself to the simple statement of the facts and the means by which they were ascertained.

We have made this attempt to describe and interpret the endocranial cast of Sinanthropus in deference to the wishes of Professor Davidson Black.* When he submitted to the Royal Society his preliminary report (Black, 1933, a ), he explained to us that he did not regard it as a disadvantage that his paper was incomplete, because it opened the way for those who had opportunities for comparing the cast with those of other human fossils and actual brains of primitive men and apes, to undertake the necessary work of comparison and interpretation, and we willingly undertake this duty. Each of us has independently studied the actual fossil skull in the Union Medical College at Peiping and examined the beautiful cast made by Professor Davidson Black from the actual fossils, and we should like to express our gratitude to him for these opportunities and many other kindnesses which he showed us. In studying the endocranial cast obtained from the Piltdown skull one of us (G.E.S.), years ago, was impressed by the extraordinary resemblance presented by the form of the brain in this extinct member of the human family to that of the primitive brain of a modern human being, a Sudanese negress (Elliot Smith, 1927, figs. 40 and 41). The other (J.L.S.) was impressed by the remarkable likeness to the endocranial cast of Sinanthropus of the brain of the Bushwoman, described in 1865 by Professor John Marshall. The recognition of these facts adds particular importance to the consideration that both the authors of this communication have served an apprenticeship to the task by examining large series of primitive brains, aboriginal Australians (J.L.S.) and Sudanese negroes (G.E.S.), and have devoted some attention to the comparison of the brains of the anthropoid apes and primitive men. In attempting to interpret the significance of the endocranial cast of Sinanthropus special attention must obviously be paid to comparison with the casts of Pithecanthropus and Eoanthropus . The comparison with the brains of the larger apes is also important, throwing light as it does upon the characters one ought to expect to find in extremely primitive human brains. In attempting to convey some real conception of the nature of the form of the brain we have resorted to the use of series of contours, figs. 10-14, so that the reader at a glance can obtain a graphic expression of the distinctive peculiarities of form. * The misfortune of his premature death deprives us of the pleasure of presenting this memoir to him.

In a paper published in the year 1893, after describing various experimental results on vascular reflexes, I made use of the following words: “the simplest explanation of the above results is the depressor nerve acting in an inhibitory manner on the former, and in an exciting manner on the latter, while pressor nerves act in an opposite way on both.” The evidence brought forward at that time in support of this view was mainly indirect, and in no way comparable with the brilliant experimental proofs afforded by Sherrington’s masterly researches on the similar phenomena in the case of the reflexes to voluntary muscles. These latter results have, however, given renewed interest to the question, and the following pages contain an investigation whose object was to obtain direct experimental evidence whether or not the phenomena of vascular reflexes can be brought into line with those affecting skeletal muscle.

Twenty years have passed since the Society honoured me by printing my first paper on the functions of the nervous system. It is thirty years since I circulated a short essay, in which the idea of the new principle which has guided me in my inqui­ries into this subject was pointed out. The Society will acknowledge that since that time, investigations into the nervous system have been prosecuted with a success strongly in contrast with that attending the inquiries during the long period of some hundred years, in which a false hypothesis had satisfied the minds of the medical profession, and chained down physiologists in inactivity. In 1821 I had made so much progress in these investigations, that I was encouraged to present my first paper to the Society, as no longer the expression of mere opinions founded on experiments too delicate to be generally appreciated, but demonstrations of substantial facts, easily proved to be correct, and such as the Society has always sought to encourage. After the principle had been once established by anatomy and experiment, that the nerves possess distinct functions in correspondence with their origins from the brain and spinal marrow, time and opportunity were alone wanting for collecting the pathological facts which were to give importance to the observations in these early papers. Those facts I am now desirous of placing before the Society, to complete the subject as far as regards my own labours.