Peter C. M. Molenaar

A manifesto on Psychology as idiographic science: bringing the person back into scientific psychology, this time forever

Psychology is focused on variation between cases (interindividual variation). Results thus obtained are considered to be generalizable to the understanding and explanation of variation within single cases (intraindividual variation). It is indicated, however, that the direct consequences of the classical ergodic theorems for psychology and psychometrics invalidate this conjectured generalizability: only under very strict conditions-which are hardly obtained in real psychological processes-can a generalization be made from a structure of interindividual variation to the analogous structure of intraindividual variation. Illustrations of the lack of this generalizability are given in the contexts of psychometrics, developmental psychology, and personality theory.

The New Person-Specific Paradigm in Psychology

Most research methodology in the behavioral sciences employs interindividual analyses, which provide information about the state of affairs of the population. However, as shown by classical mathematical-statistical theorems (the ergodic theorems), such analyses do not provide information for, and cannot be applied at, the level of the individual, except on rare occasions when the processes of interest meet certain stringent conditions. When psychological processes violate these conditions, the interindividual analyses that are now standardly applied have to be replaced by analysis of intraindividual variation in order to obtain valid results. Two illustrations involving analysis of intraindividual variation of personality and emotional processes are given.

Stagewise Cognitive Development : An Application of Catastrophe Theory

In this article an overview is given of traditional methodological approaches to stagewise cognitive developmental research. These approaches are evaluated and integrated on the basis of catastrophe theory. In particular, catastrophe theory specifies a set of common criteria for testing the discontinuity hypothesis proposed by Piaget. Separate criteria correspond to distinct methods used in cognitive developmental research. Such criteria are, for instance, the detection of spurts in development, bimodality of test scores, and increased variability of responses during transitional periods. When a genuine stage transition is present, these criteria are expected to be satisfied. A revised catastrophe model accommodating these criteria is proposed for the stage transition in cognitive development from the preoperational to the concrete operational stage.

A dynamic factor model for the analysis of multivariate time series

As a method to ascertain the structure of intra-individual variation,P-technique has met difficulties in the handling of a lagged covariance structure. A new statistical technique, coined dynamic factor analysis, is proposed, which accounts for the entire lagged covariance function of an arbitrary second order stationary time series. Moreover, dynamic factor analysis is shown to be applicable to a relatively short stretch of observations and therefore is considered worthwhile for psychological research. At several places the argumentation is clarified through the use of examples.

Abnormal myotonic dystrophy protein kinase levels produce only mild myopathy in mice.

Myotonic dystrophy (DM) is commonly associated with CTG repeat expansions within the gene for DM–protein kinase (DMPK). The effect of altered expression levels of DMPK, which is ubiquitously expressed in all muscle cell lineages during development, was examined by disrupting the endogenous Dmpk gene and overexpressing a normal human DMPK transgene in mice. Nullizygous (−/−) mice showed only inconsistent and minor size changes in head and neck muscle fibres at older age, animals with the highest DMPK transgene expression showed hypertrophic cardiomyopathy and enhanced neonatal mortality. However, both models lack other frequent DM symptoms including the fibre–type dependent atrophy, myotonia, cataract and male–infertility. These results strengthen the contention that simple loss– or gain–of–expression of DMPK is not the only crucial requirement for development of the disease.

Characterization and localization of endothelin receptor subtypes in the human atrioventricular conducting system and myocardium.

The characterization and localization of endothelin A (ETA) and endothelin B (ETB) receptors have been determined in tissue sections of the human atrioventricular conducting system, surrounding regions of atrial and ventricular myocardium, and the left ventricular free wall by use of radioligand binding, polymerase chain reaction, and in situ hybridization. Selective ETA (BQ123) and ETB (BQ3020) compounds in conjunction with [125I]endothelin-1 revealed the presence of ETA and ETB receptors in the left ventricular free wall (BQ123: 57 +/- 5% ETA, 43 +/- 2% ETB, n = 3; BQ3020: 67 +/- 3% ETA, 33 +/- 3% ETB, n = 3). Autoradiography using [125I]endothelin-1 in the absence or presence of BQ3020, BQ123, or endothelin-1 showed ETA and ETB receptors localized to atrial and ventricular myocardium, the atrioventricular conducting system, and endocardial cells. There was a higher proportion of ETB receptors in the atrioventricular node and the penetrating and branching bundles of His than in the surrounding intervent...

Molecular Architecture of the Human Sinus Node Insights Into the Function of the Cardiac Pacemaker

Background— Although we know much about the molecular makeup of the sinus node (SN) in small mammals, little is known about it in humans. The aims of the present study were to investigate the expression of ion channels in the human SN and to use the data to predict electrical activity. Methods and Results— Quantitative polymerase chain reaction, in situ hybridization, and immunofluorescence were used to analyze 6 human tissue samples. Messenger RNA (mRNA) for 120 ion channels (and some related proteins) was measured in the SN, a novel paranodal area, and the right atrium (RA). The results showed, for example, that in the SN compared with the RA, there was a lower expression of Nav1.5, Kv4.3, Kv1.5, ERG, Kir2.1, Kir6.2, RyR2, SERCA2a, Cx40, and Cx43 mRNAs but a higher expression of Cav1.3, Cav3.1, HCN1, and HCN4 mRNAs. The expression pattern of many ion channels in the paranodal area was intermediate between that of the SN and RA; however, compared with the SN and RA, the paranodal area showed greater expression of Kv4.2, Kir6.1, TASK1, SK2, and MiRP2. Expression of ion channel proteins was in agreement with expression of the corresponding mRNAs. The levels of mRNA in the SN, as a percentage of those in the RA, were used to estimate conductances of key ionic currents as a percentage of those in a mathematical model of human atrial action potential. The resulting SN model successfully produced pacemaking. Conclusions— Ion channels show a complex and heterogeneous pattern of expression in the SN, paranodal area, and RA in humans, and the expression pattern is appropriate to explain pacemaking.

Monoclonal antibodies raised against Guillain-Barré syndrome–associated Campylobacter jejuni lipopolysaccharides react with neuronal gangliosides and paralyze muscle-nerve preparations

Guillain-Barré syndrome and its variant, Miller-Fisher syndrome, are acute, postinfectious, autoimmune neuropathies that frequently follow Campylobacter jejuni enteritis. The pathogenesis is believed to involve molecular mimicry between sialylated epitopes on C. jejuni LPSs and neural gangliosides. More than 90% of Miller-Fisher syndrome cases have serum anti-GQ1b and anti-GT1a ganglioside antibodies that may also react with other disialylated gangliosides including GD3 and GD1b. Structural studies on LPS from neuropathy-associated C. jejuni strains have revealed GT1a-like and GD3-like core oligosaccharides. To determine whether this structural mimicry results in pathogenic autoantibodies, we immunized mice with GT1a/GD3-like C. jejuni LPS and then cloned mAbs that reacted with both the immunizing LPS and GQ1b/GT1a/GD3 gangliosides. Immunohistology demonstrated antibody binding to ganglioside-rich sites including motor nerve terminals. In ex vivo electrophysiological studies of nerve terminal function, application of antibodies either ex vivo or in vivo via passive immunization induced massive quantal release of acetylcholine, followed by neurotransmission block. This effect was complement-dependent and associated with extensive deposits of IgM and C3c at nerve terminals. These data provide strong support for the molecular mimicry hypothesis as a mechanism for the induction of cross-reactive pathogenic anti-ganglioside/LPS antibodies in postinfectious neuropathies.

Miller Fisher anti-GQ1b antibodies : α-latrotoxin-like effects on motor end plates

In the Miller Fisher syndrome (MFS) variant of the Guillain‐Barré syndrome, weakness is restricted to extraocular muscles and occasionally other craniobulbar muscles. Most MFS patients have serum antibodies against ganglioside type GQ1b of which the pathophysiological relevance is unclear. We examined the in vitro effects of MFS sera, MFS IgG, and a human monoclonal anti‐GQ1b IgM antibody on mouse neuromuscular junctions (NMJs). It was found that anti‐GQ1b antibodies bind at NMJs where they induce massive quantal release of acetylcholine from nerve terminals and eventually block neuromuscular transmission. This effect closely resembled the effect of the paralytic neurotoxin α‐latrotoxin at the mouse NMJs, implying possible involvement of α‐latrotoxin receptors or associated downstream pathways. By using complement‐deficient sera, the effect of anti‐GQ1b antibodies on NMJs was shown to be entirely dependent on activation of complement components. However, neither classical pathway activation nor the formation of membrane attack complex was required, indicating the effects could be due to involvement of the alternative pathway and intermediate complement cascade products. Our findings strongly suggest that anti‐GQ1b antibodies in conjunction with activated complement components are the principal pathophysiological mediators of motor symptoms in MFS and that the NMJ is an important site of their action. Ann Neurol 1999;45:189–199

Stochastic processes in postural center-of-pressure profiles

The stochastic processes of postural center-of-pressure profiles were examined in 3- and 5-year-old children, young adult students (mean 20 years), and an elderly age group (mean 67 years). Subjects stood still in an upright bipedal stance on a force platform under vision and nonvision conditions. The time evolutionary properties of the center-of-pressure dynamic were examined using basic stochastic process models. The amount of motion of the center of pressure decreased with increments of age from 3 to 5 years to young adult but increased again in the elderly age group. The availability of vision decreased the amount of motion of the center of pressure in all groups except the 3-year-old group, where there was less motion of the center of pressure with no vision. The stochastic properties of the center-of-pressure dynamic were assessed using both a two-process, random-walk model of Collins and De Luca and an Ornstein-Uhlenbeck model that is linear and has displacement governed only by a single stiffness term in the random walk. The two-process open- and closed-loop model accounted for about 96% and the Ornstein-Uhlenbeck model 92% of the variance of the diffusion term. Diffusion parameters in both models showed that the data were correlated and that they varied with age in a fashion consistent with developmental accounts of the changing regulation of the degrees of freedom in action. The findings suggest that it is premature to consider the trajectory of the center-of-pressure as a two-process, open- and closed-loop random-walk model given that: (a) the linear Ornstein-Uhlenbeck dynamic equation with only two parameters accommodates almost as much of the variance of the random walk; and (b) the linkage of a discontinuity in the diffusion process with the transition of open- to closed-loop processes is poorly founded. It appears that the nature of the stochastic properties of the random walk of the center-of-pressure trajectory in quiet, upright standing remains to be elucidated.