Spatial navigation in complex and radial mazes in APP23 animals and neurotrophin signaling as a biological marker of early impairment

Impairment of hippocampal function precedes frontal and parietal cortex impairment in human Alzheimer's disease (AD). Neurotrophins are critical for behavioral performance and neuronal survival in AD. We used complex and radial mazes to assess spatial orientation and learning in wild-type and B6-Tg(ThylAPP)23Sdz (APP23) animals, a transgenic mouse model of AD. We also assessed brain content of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3). Performance was alike in wild-type and APP23 animals in the radial maze. In contrast, performance in the complex maze was better in wild-type than APP23 animals. Contrary to the wild-type, hippocampal BDNF levels decreased on training in APP23 animals. Hippocampal and frontal cortex NGF levels in APP23 animals correlated with the time to solve the complex maze, but correlated inversely with escape time in wild-type animals. NT-3 levels were alike in wild-type and APP23 animals and were unchanged even after training. Both types of mazes depend on hippocampal integrity to some extent. However, according to the cognitive mapping theory of spatial learning, the complex maze because of the increased complexity of the environment most likely depends more strongly on preserved hippocampal function than the radial maze in the working memory configuration applied here. Greater impairment in complex maze performance than in radial maze performance thus resembles the predominant affliction of the loss of hippocampal function in human AD. NGF and BDNF levels on maze learning are different in wild-type and transgenic animals, indicating that biological markers of AD may be altered on challenge even though equilibrium levels are alike.     

Selective attention, inhibition for repeated events and hemispheric specialization

When two visual events appear consecutively in the same spatial location, our response to the second event is slower than to the first. This inhibition for repeated events may reflect a bias toward sampling novel locations, a bias useful for exploring visual space. It has been shown that the left hemisphere is more specialized in selective attentional processes than the right one. The aim of the present experiment was to test if this hemispheric specialization for selective attention may also affect the inhibition for repeated events. For this purpose, we asked 11 normal subjects to perform an identity-based discrimination task in which the target to be detected could appear alone or surrounded by flanking letters, in the left or in the right visual field. Results show that inhibition for repeated events is present only when selective attention is required and when the task is performed in the right specialized visual field.     

Assumptions and consequences of treating providers in therapy studies as fixed versus random effects: reply to Crits-Christoph, Tu, and Gallop (2003) and Serlin, Wampold, and Levin (2003)

In their comments on the authors' article, R. C. Serlin, B. E. Wampold, and J. R. Levin and P. Crits-Christoph, X. Tu, and R. Gallop took issue with the authors' suggestion to evaluate therapy studies with nested providers with a fixed model approach. In this rejoinder, the authors' comment on Serlin et al's critique by showing that their arguments do not apply, are based on misconceptions about the purpose and nature of statistical inference, or are based on flawed reasoning. The authors also comment on Crits-Christoph et al's critique by showing that the proposed approach is very similar to, but less inclusive than, their own suggestion.     

Power and measures of effect size in analysis of variance with fixed versus random nested factors

Ignoring a nested factor can influence the validity of statistical decisions about treatment effectiveness. Previous discussions have centered on consequences of ignoring nested factors versus treating them as random factors on Type I errors and measures of effect size (B. E. Wampold & R. C. Serlin). The authors (a) discuss circumstances under which the treatment of nested provider effects as fixed as opposed to random is appropriate; (b) present 2 formulas for the correct estimation of effect sizes when nested factors are fixed; (c) present the results of Monte Carlo simulations of the consequences of treating providers as fixed versus random on effect size estimates, Type I error rates, and power; and (d) discuss implications of mistaken considerations of provider effects for the study of differential treatment effects in psychotherapy research.     

Illness, disease and sin: the connection between genetics and spirituality.

The New Testament, while rejecting any superficial connection between illness and sin, does not reject a possible connection between illness and a person's relationship with God. An example can be seen in the story of the young blind man who was healed (St. John 9:3). His blindness does not result from any fault he or his parents had committed but apparently from God's wish to reveal his own healing power. The inner blindness of the Pharisees is a different type of blindness far more difficult to heal. The blind young man was actually healed, not only in body but also in soul. Such miraculous healings are rare nowadays. However, if one takes a closer look at modern genetics and psycho-neuro-immunological findings, one may come to a better understanding of how miracle healings are linked to man's inner life and therefore also to his religiousness. Many diseases have genetic backgrounds. Defective genes, however, do not necessarily lead to subsequent illness. Genes have to be switched on or off. Only activated genes trigger pathological change. The human brain and all of man's thinking and feeling are intimately connected with such activations. We may thus conclude that both inner life and religious outlook on life are relevant to the origin and development of diseases.