Jukka M. Leppänen

Serotonin and early cognitive development: variation in the tryptophan hydroxylase 2 gene is associated with visual attention in 7-month-old infants

BACKGROUND Allelic variation in the promoter region of a gene that encodes tryptophan hydroxylase isoform 2 (TPH2), a rate-limiting enzyme of serotonin synthesis in the central nervous system, has been associated with variations in cognitive function and vulnerability to affective spectrum disorders. Little is known about the effects of this gene variant on cognition during development and about possible intermediate developmental steps that lead to the adult phenotype. Here, we examined the hypothesis that the TPH2 -703 may act during early stages of development and bias the acquisition of elementary cognitive processes involved in attention and emotion regulation. METHODS Seven-month-old infants (n = 66) were genotyped for the TPH2 -703 G/T polymorphism (rs4570625) and tested for the efficiency of attention shifts from a stimulus at fixation to a new stimulus in the visual periphery. RESULTS Compared to TPH2 G/G homozygotes, infants with the T-carrier genotype exhibited a significantly higher number of missing attention shifts. This genotype effect tended to be particularly pronounced when infants had to disengage from an affectively salient stimulus before shifting attention to the peripheral stimulus. The results also showed that TPH2 genotype was indirectly associated, via its effect on attention disengagement, with temperamental emotion regulation (soothability). CONCLUSIONS Together, these results implicate serotonin system genes in early cognitive development and suggest variations in the early-emerging cognitive capacities as a potential developmental precursor of individual differences in emotion regulation and vulnerability to affective disorders.

Cardiac and behavioral evidence for emotional influences on attention in 7-month-old infants

To examine the ontogeny of emotion—attention interactions, we investigated whether infants exhibit adult-like biases in automatic and voluntary attentional processes towards fearful facial expressions. Heart rate and saccadic eye movements were measured from 7-month-old infants (n = 42) while viewing non-face control stimuli, and neutral, happy, and fearful facial expressions flanked after 1000 ms by a peripheral distractor. Relative to neutral and happy expressions, fearful expressions resulted in a greater cardiac deceleration response during the first 1000 ms of face-viewing and in a relatively long-lasting suppression of face-to-distractor saccades. The results suggest that the neural architecture for the integration of emotional significance with automatic attentional orienting as well as more voluntary attentional prioritization processes is present early in life.

Dynamic Eye Tracking Based Metrics for Infant Gaze Patterns in the Face-Distractor Competition Paradigm

Objective To develop new standardized eye tracking based measures and metrics for infants’ gaze dynamics in the face-distractor competition paradigm. Method Eye tracking data were collected from two samples of healthy 7-month-old (total n = 45), as well as one sample of 5-month-old infants (n = 22) in a paradigm with a picture of a face or a non-face pattern as a central stimulus, and a geometric shape as a lateral stimulus. The data were analyzed by using conventional measures of infants’ initial disengagement from the central to the lateral stimulus (i.e., saccadic reaction time and probability) and, additionally, novel measures reflecting infants gaze dynamics after the initial disengagement (i.e., cumulative allocation of attention to the central vs. peripheral stimulus). Results The results showed that the initial saccade away from the centrally presented stimulus is followed by a rapid re-engagement of attention with the central stimulus, leading to cumulative preference for the central stimulus over the lateral stimulus over time. This pattern tended to be stronger for salient facial expressions as compared to non-face patterns, was replicable across two independent samples of 7-month-old infants, and differentiated between 7 and 5 month-old infants. Conclusion The results suggest that eye tracking based assessments of infants’ cumulative preference for faces over time can be readily parameterized and standardized, and may provide valuable techniques for future studies examining normative developmental changes in preference for social signals. Significance Standardized measures of early developing face preferences may have potential to become surrogate biomarkers of neurocognitive and social development.

A graphical user interface for infant ERP analysis

Recording of event-related potentials (ERPs) is one of the best-suited technologies for examining brain function in human infants. Yet the existing software packages are not optimized for the unique requirements of analyzing artifact-prone ERP data from infants. We developed a new graphical user interface that enables an efficient implementation of a two-stage approach to the analysis of infant ERPs. In the first stage, video records of infant behavior are synchronized with ERPs at the level of individual trials to reject epochs with noncompliant behavior and other artifacts. In the second stage, the interface calls MATLAB and EEGLAB (Delorme & Makeig, Journal of Neuroscience Methods 134(1):9–21, 2004) functions for further preprocessing of the ERP signal itself (i.e., filtering, artifact removal, interpolation, and rereferencing). Finally, methods are included for data visualization and analysis by using bootstrapped group averages. Analyses of simulated and real EEG data demonstrated that the proposed approach can be effectively used to establish task compliance, remove various types of artifacts, and perform representative visualizations and statistical comparisons of ERPs. The interface is available for download from http://www.uta.fi/med/icl/methods/eeg.html in a format that is widely applicable to ERP studies with special populations and open for further editing by users.

Evidence for spared attention to faces in 7-month-old infants after prenatal exposure to antiepileptic drugs

INTRODUCTION Prenatal antiepileptic drug (AED) exposure is associated with an increased risk of cognitive impairment and autism spectrum disorders detected mainly at the age of two to six years. We examined whether the developmental aberrations associated with prenatal AED exposure could be detected already in infancy and whether effects on visual attention can be observed at this early age. MATERIAL AND METHODS We compared a prospective cohort of infants with in utero exposure to AED (n=56) with infants without drug exposures (n=62). The assessments performed at the age of seven months included standardized neurodevelopmental scores (Griffiths Mental Developmental Scale and Hammersmith Infant Neurological Examination) as well as a novel eye-tracking-based test for visual attention and orienting to faces. Background information included prospective collection of AED exposure data, pregnancy outcome, neuropsychological evaluation of the mothers, and information on maternal epilepsy type. RESULTS Carbamazepine, oxcarbazepine, and valproate, but not lamotrigine or levetiracetam, were associated with impaired early language abilities at the age of seven months. The general speed of visuospatial orienting or attentional bias for faces measured by eye-tracker-based tests did not differ between AED-exposed and control infants. DISCUSSION Our findings support the idea that prenatal AED exposure may impair verbal abilities, and this effect may be detected already in infancy. In contrast, the early development of attention to faces was spared after in utero AED exposure.

Early development of attention to threat-related facial expressions

Infants from an early age have a bias to attend more to faces than non-faces and after 5 months are particularly attentive to fearful faces. We examined the specificity of this “fear bias” in 5-, 7-, and 12-month-old infants (N = 269) and 36-month-old children (N = 191) and whether its development is associated with features of the early rearing environment, specifically maternal anxiety and depression symptoms. Attention dwell times were assessed by measuring the latencies of gaze shifts from a stimulus at fixation to a new stimulus in the visual periphery. In infancy, dwell times were shorter for non-face control stimuli vs. happy faces at all ages, and happy vs. fearful, but not angry, faces at 7 and 12 months. At 36 months, dwell times were shorter for non-faces and happy faces compared to fearful and angry faces. Individual variations in attention dwell times were not associated with mothers’ self-reported depression or anxiety symptoms at either age. The results suggest that sensitivity to fearful faces precedes a more general bias for threat-alerting stimuli in early development. We did not find evidence that the initial manifestation of these biases is related to moderate variations in maternal depression or anxiety symptoms.

Risk factors for unplanned pregnancy in women with mental illness living in a developing country

Pregnant women in general are at an increased risk of experiencing symptoms of mental illness, and those living in a developing country are even more vulnerable. Research points towards a causal relationship between unplanned pregnancy and perinatal mental illness and suggests that pregnancy planning can aid in reducing the negative impact of mental illness on a woman, her unborn baby, and the rest of the family. In this quantitative, descriptive study, we investigated both socio-demographic factors and variables relating to mental illness itself that may place women at an increased risk of experiencing unplanned pregnancy. Data was gathered at two maternal mental health clinics in Cape Town by means of semi-structured interviews. Univariate analyses of the data revealed five independent key risk factors for unplanned pregnancy: lower levels of education, unmarried status, belonging to the Colored ethnic population, substance use, and having a history of two or more suicide attempts. Some of these factors overlap with findings of similar studies, but others are unique to the specific population (women with mental illness within a developing country). Screening of women based on these risk predictors may pave the way for early interventions and reduce the incidence of unplanned pregnancy and the negative consequences thereof in the South African population.

Mothers’ pupillary responses to infant facial expressions

BackgroundHuman parental care relies heavily on the ability to monitor and respond to a child’s affective states. The current study examined pupil diameter as a potential physiological index of mothers’ affective response to infant facial expressions.MethodsPupillary time-series were measured from 86 mothers of young infants in response to an array of photographic infant faces falling into four emotive categories based on valence (positive vs. negative) and arousal (mild vs. strong).ResultsPupil dilation was highly sensitive to the valence of facial expressions, being larger for negative vs. positive facial expressions. A separate control experiment with luminance-matched non-face stimuli indicated that the valence effect was specific to facial expressions and cannot be explained by luminance confounds. Pupil response was not sensitive to the arousal level of facial expressions.ConclusionsThe results show the feasibility of using pupil diameter as a marker of mothers’ affective responses to ecologically valid infant stimuli and point to a particularly prompt maternal response to infant distress cues.