Genetic psychophysiology: advances, problems, and future directions

Abstract

This paper presents an overview of historical advances and the current state of genetic psychophysiology, a rapidly developing interdisciplinary research linking genetics, brain, and human behavior, discusses methodological problems, and outlines future directions of research. The main goals of genetic psychophysiology are to elucidate the neural pathways and mechanisms mediating genetic influences on cognition and emotion, identify intermediate brain-based phenotypes for psychopathology, and provide a functional characterization of genes being discovered by large association studies of behavioral phenotypes. Since the initiation of this neurogenetic approach to human individual differences in the 1970s, numerous twin and family studies have provided strong evidence for heritability of diverse aspects of brain function including resting-state brain oscillations, functional connectivity, and event-related neural activity in a variety of cognitive and emotion processing tasks, as well as peripheral psychophysiological responses. These data indicate large differences in the presence and strength of genetic influences across measures and domains, permitting the selection of heritable characteristics for gene finding studies. More recently, candidate gene association studies began to implicate specific genetic variants in different aspects of neurocognition. However, great caution is needed in pursuing this line of research due to its demonstrated proneness to generate false-positive findings. Recent developments in methods for physiological signal analysis, hemodynamic imaging, and genomic technologies offer new exciting opportunities for the investigation of the interplay between genetic and environmental factors in the development of individual differences in behavior, both normal and abnormal.

Keywords: Brain; EEG; ERP; Endophenotype; Genetics; Heritability.

Fig. 1

Major causal paths linking genes, brain, and behavior. The “ascending” paths on the left show that genomic variation influences brain function which, in turn, leads to individual differences in behavior. The “descending” paths on the right show that behavior itself may lead to changes in the brain due to adaptation and learning or brain damage due to exposure to hazardous factors such as alcohol and drugs. These influences on the brain may also lead to epigenetic modifications affecting gene expression in brain cells and thus brain function. Each of these relationships is moderated by environmental factors (not shown for simplicity).

Fig. 2

Twin resemblance for resting-state EEG alpha-band power. A. Scatterplot of intrapair correlation in monozygotic twin. One co-twin is plotted against the other co-twin. B. Scatterplot of test-retest correlations in unrelated individuals. Data from the first EEG recording session is plotted against the second EEG recording from the same individual, with the average interval between two sessions of about 2 weeks.

Fig. 3

EEG phenotypes in twins. Upper panel: regular alpha variant; lower panel: Low-voltage EEG.