THE DESIGN AND ANALYSIS OF EXPERIMENTS. By Oscar Kempthorne. New York, John Wiley and Sons, Inc., 1952. 631 pp. $8.50. This book by a teacher of statistics (as well as a consultant for \"experimenters\") is a comprehensive study of the philosophical background for the statistical design of experiment. It is necessary to have some facility with algebraic notation and manipulation to be able to use the volume intelligently. The problems are presented from the theoretical point of view, without such practical examples as would be helpful for those not acquainted with mathematics. The mathematical justification for the techniques is given. As a somewhat advanced treatment of the design and analysis of experiments, this volume will be interesting and helpful for many who approach statistics theoretically as well as practically. With emphasis on the \"why,\" and with description given broadly, the author relates the subject matter to the general theory of statistics and to the general problem of experimental inference. MARGARET J. ROBERTSON

The Design and Analysis of Experiments

J. A. Gray (1981, 1982) holds that 2 general motivational systems underlie behavior and affect: a behavioral inhibition system (BIS) and a behavioral activation system (BAS). Self-report scales to assess dispositional BIS and BAS sensitivities were created. Scale development (Study 1) and convergent and discriminant validity in the form of correlations with alternative measures are reported (Study 2). In Study 3, a situation in which Ss anticipated a punishment was created. Controlling for initial nervousness, Ss high in BIS sensitivity (assessed earlier) were more nervous than those low in BIS sensitivity. In Study 4, a situation in which Ss anticipated a reward was created. Controlling for initial happiness, Ss high in BAS sensitivity (Reward Responsiveness and Drive scales) were happier than those low in BAS sensitivity. In each case the new scales predicted better than an alternative measure. Discussion is focused on conceptual implications.

Behavioral inhibition, behavioral activation, and affective responses to impending reward and punishment: The BIS/BAS Scales

The adolescent brain and age-related behavioral manifestations

A model of the neuropsychology of anxiety is proposed. The model is based in the first instance upon an analysis of the behavioural effects of the antianxiety drugs (benzodiazepines, barbiturates, and alcohol) in animals. From such psychopharmacologi-cal experiments the concept of a “behavioural inhibition system” (BIS) has been developed. This system responds to novel stimuli or to those associated with punishment or nonreward by inhibiting ongoing behaviour and increasing arousal and attention to the environment. It is activity in the BIS that constitutes anxiety and that is reduced by antianxiety drugs. The effects of the antianxiety drugs in the brain also suggest hypotheses concerning the neural substrate of anxiety. Although the benzodiazepines and barbiturates facilitate the effects of γ-aminobutyrate, this is insufficient to explain their highly specific behavioural effects. Because of similarities between the behavioural effects of certain lesions and those of the antianxiety drugs, it is proposed that these drugs reduce anxiety by impairing the functioning of a widespread neural system including the septo-hippocampal system (SHS), the Papez circuit, the prefrontal cortex, and ascending monoaminergic and cholinergic pathways which innervate these forebrain structures. Analysis of the functions of this system (based on anatomical, physiological, and behavioural data) suggests that it acts as a comparator: it compares predicted to actual sensory events and activates the outputs of the BIS when there is a mismatch or when the predicted event is aversive. Suggestions are made as to the functions of particular pathways within this overall brain system. The resulting theory is applied to the symptoms and treatment of anxiety in man, its relations to depression, and the personality of individuals who are susceptible to anxiety or depression.

https://www.cambridge.org/core/services/aop-cambridge-core/content/view/S0140525X00013066

Précis of The Neuropsychology of Anxiety: An Enquiry into the Functions of the Septo-Hippocampal System..

People are capable of thinking about the future, the past, remote locations, another person's perspective, and counterfactual alternatives. Without denying the uniqueness of each process, it is proposed that they constitute different forms of traversing psychological distance. Psychological distance is egocentric: Its reference point is the self in the here and now, and the different ways in which an object might be removed from that point-in time, in space, in social distance, and in hypotheticality-constitute different distance dimensions. Transcending the self in the here and now entails mental construal, and the farther removed an object is from direct experience, the higher (more abstract) the level of construal of that object. Supporting this analysis, research shows (a) that the various distances are cognitively related to each other, (b) that they similarly influence and are influenced by level of mental construal, and (c) that they similarly affect prediction, preference, and action.

/pdf/construal-level-theory-of-psychological-distance-g5kjiydrew.pdf

Construal-Level Theory of Psychological Distance

Fetal raphe cells transplanted into adult rat brain survive and form functional synaptic connections,' but little is known about metabolism and release of serotonin (5-HT) from transplanted neurons. Serotonergic neurons are autoactive and thus, even in the absence of presynaptic input, may release 5-HT. As indices of rieuronal activity, rates of 5-HT synthesis and catabolism were measured before and after neurotoxin lesions of the serotonergic innervation of the hippocampus in adult rats and after transplantation of fetal raphe tissue into the 5-HT-denervated hippocampus. For bilateral lesions of the serotonergic innervation of the hippocampus, male rats (280-350 g ) received desmethylimipramine ( 10 mg/kg, i.p.) and then were injected with 5,7-dihydroxytryptamine (5,7-DHT) into the dorsal and medial raphe nuclei (coordinates relative to the midsagittal line at lambda: 0.0 mm L, 0.2 mm A, and 6.8-7.8 mm V). Two weeks after these lesions, rats were given a unilateral injection of minced tissue from the raphe area of day 15 rat fetuses. Hippocampal coordinates were 1.0-5.0 mm L, 4.5 mm A, and 3.7 mm V. One month after transplantation, rats were used'in studies of 5-HT metabolism. The rate of 5-HT synthesis was estimated by the accumulation of 5-hydroxytryptophan (5-HTP) 1 hr after injecting rats with m-hydroxybenzylhydrazine (100 mg/ kg, i.p.). The metabolites and 5-HT were analyzed by high-performance liquid chromatography.2,' The normal value for 5-HTP accumulation in the hippocampus was 0.23 5 0.02 ng/mg wet wt (mean 5 SEM), as shown in TABLE 1. The 5,7-DHT lesion reduced 5-HTP accumulation to 65% of the normal value. In contrast, 5-HTP accumulation in hippocampus that had received a lesion and raphe transplants was significantly increased, to 65% above normal. TABLE 1 also shows that the 5,7-DHT lesion reduced 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) levels to about 50% of normal, and raphe transplants restored the 5-HT level to 138% and the 5-HIAA level to 118% of normal. Catabolism of 5-HT was estimated by the increase in the

Serotonin Metabolism in Raphe Neurons Transplanted into Rat Hippocampus

Fimbrial and cingulum bundle serotonin afferents to hippocampus

The mechanism of serotonin 1A receptor (5-HT1A-R) mediated activation of NF-κB has been studied in non-neural cells, but this pathway has not been elucidated in neuronal cells. We have used inducible expression of the 5-HT1A-R in the hippocampal neuron-derived HN2 cells to analyze the coupling of this receptor to NF-κB. A construct harboring luciferase cDNA driven by a minimal promoter under the control of an NF-κB-specific enhancer element was transfected into these 5-HT1A-R-expressing HN2 cells. Using luciferase expression in the transfected cells, we have studied 5-HT1A-R agonist evoked activation of NF-κB. Inhibition of either mitogen activated protein kinase (MAPK) pathway with PD98059 or protein kinase C (PKC) with GFX caused elevation of the basal level of NF-κB activity but did not affect 5-HT1A-R mediated activation of NF-κB. Furthermore, neither the basal level of NF-κB nor its activation by a 5-HT1A-R agonist was altered by dibutyrylcAMP. Thus, the MAPK pathway and PKC cause inhibition of the basal NF-κB activity and the 5-HT1A-R-linked NF-κB activation does not require MAPK, PKC, and cAMP. Intriguingly, Western blot analysis showed that 5-HT1A-R mediates activation of both CaMKII and PI-3K. This 5-HT1A-R-evoked the stimulation of CaMKII was reversed in the presence of a PI-3K inhibitor. Therefore, the likely mechanism of 5-HT1A-R mediated induction of NF-κB in neuronal cells involves activation of PI-3K upstream of CaMKII. This reveals a novel pathway that could be crucial in the functional activity of brain neurons.

Serotonin 1A receptor coupling to NF‐κB studied using inducible receptor expression in hippocampal neuron‐derived cells

Astroglial cells play important roles in determining brain structure and function throughout life; the astrocyte must be able to change its function in order to play the appropriate age-dependent role. One such role is the production of neuronal growth factors. During development, the astrocyte may produce and release large amounts of growth factors, while in mature states, the astrocytes may produce and release very low levels, just enough to aid in synaptic turnover. In responding to a lesion of the neuron, the astrocyte may again greatly increase its growth factor output.

The Role of 5-HT1A Receptors in Development and Adult Plasticity of the Serotonergic System

If transplanted fetal cells are to have maximal benefits in the adult brain, the donor and host neurons must fully interact. In this report, we have discussed procedures for the preparation of the fetal cells to insure best survival and methods to identify transplanted neurons whose neurotransmitter content is known. Furthermore, we provide several strategies for reducing the glial scar, enhancing fetal cell survival (co-transplantation), inducing host brain trophic factors (prior lesions or preparation of a soluble extract) and providing adhesive molecules to encourage outgrowth. Many additional strategies need to be developed to produce an optimal integration of fetal and adult cells. Once achieved, brain transplantation can provide a powerful and unparalleled tool to regulate cell function and combat diseases.

Efrain C. Azmitia

Papers

Serotonin Metabolism in Raphe Neurons Transplanted into Rat Hippocampus

Fimbrial and cingulum bundle serotonin afferents to hippocampus

Serotonin 1A receptor coupling to NF‐κB studied using inducible receptor expression in hippocampal neuron‐derived cells

The Role of 5-HT1A Receptors in Development and Adult Plasticity of the Serotonergic System

Strategies For Improving Fetal Neuronal Integration with Adult Brain Following Brain Transplantation