Individual Differences in Autistic Traits are Associated with Serotonin Transporter Gene Polymorphism Through Medial Prefrontal Function: A Study Using NIRS.

Autism spectrum disorder (ASD) is a heritable neurodevelopmental disorder that can vary considerably in severity. Autistic traits are distributed continuously across populations, even in sub-clinical individuals. Serotonin transporter-gene polymorphic region (5-HTTLPR) has been studied as a candidate genetic factor related to ASD, however results have been inconsistent. 5-HTTLPR is implicated in the function of medial prefrontal cortex (mPFC), a region associated with the social abnormalities found in ASD. Here we hypothesize that autistic traits are affected by the 5-HTTLPR genotype indirectly through mPFC mediation. Using near-infrared spectroscopy (NIRS), we first examined mPFC activation in people with ASD when they performed a facial affect-labeling task. Compared with a typical development group, the ASD group showed significantly lower mPFC activation during the task. Using the same task paradigm, we next investigated the relationship between autistic traits and 5-HTTLPR in sub-clinical participants, and whether associations were mediated by mPFC function. Correlation analyses indicated that participants with a large number of 5-HTTLPR L-alleles had high-level autistic traits related to social skills and low right mPFC activation. We also observed a significant negative correlation between autistic traits related to social skills and right mPFC activation. Structural equation analysis suggested a significant indirect effect of 5-HTTLPR on Autism-Spectrum Quotients, with right mPFC activation acting as a mediator. These results suggest that the diverse autistic traits related to social skills seen in the general population are associated with the 5-HTTLPR genotype, and that this association is mediated by right mPFC function.

Perceived Parenting Mediates Serotonin Transporter Gene (5-HTTLPR) and Neural System Function during Facial Recognition: A Pilot Study.

This study examined changes in prefrontal oxy-Hb levels measured by NIRS (Near-Infrared Spectroscopy) during a facial-emotion recognition task in healthy adults, testing a mediational/moderational model of these variables. Fifty-three healthy adults (male = 35, female = 18) aged between 22 to 37 years old (mean age = 24.05 years old) provided saliva samples, completed a EMBU questionnaire (Swedish acronym for Egna Minnen Beträffande Uppfostran [My memories of upbringing]), and participated in a facial-emotion recognition task during NIRS recording. There was a main effect of maternal rejection on RoxH (right frontal activation during an ambiguous task), and a gene × environment (G × E) interaction on RoxH, suggesting that individuals who carry the SL or LL genotype and who endorse greater perceived maternal rejection show less right frontal activation than SL/LL carriers with lower perceived maternal rejection. Finally, perceived parenting style played a mediating role in right frontal activation via the 5-HTTLPR genotype. Early-perceived parenting might influence neural activity in an uncertain situation i.e. rating ambiguous faces among individuals with certain genotypes. This preliminary study makes a small contribution to the mapping of an influence of gene and behaviour on the neural system. More such attempts should be made in order to clarify the links.

Maternal breast milk odour induces frontal lobe activation in neonates: a NIRS study.

We used near-infrared spectroscopy (NIRS) to examine differences in neonates' orbito-frontal cortical activation in response to the odours of maternal breast milk and formula milk in terms of changes in the oxygenation of cerebral blood flow. Twenty-six healthy neonates were tested in their cribs while they slept in a silent room. The neonates were exposed to each olfactory stimulus by an experimenter. NIRS monitoring was performed using optodes placed above the bilateral anterior orbito-frontal gyri. The differences in oxygenated haemoglobin (oxy-Hb) values between baseline and stimulation were defined as the change in oxy-Hb. The degrees of change were calculated by an analysis of variance (ANOVA). A 2 (stimulus: breast milk and formula milk) × 2 (probe location: right and left) ANOVA showed that the odour of maternal breast milk (right/left: M=0.28/0.48) induced a significantly (F=6.36, p<0.05) greater increase in the oxygenated blood of the orbito-frontal region than did the odour of formula milk (right/left: M=-0.03/-0.07). Differences in the intensity of odour had no significant influence on the blood oxygenation of the orbito-frontal region. Maternal breast milk odour increased oxygenated blood flow in the orbito-frontal region to a greater extent than did formula milk odour. These results suggest that neonates can distinguish between the odours of maternal breast milk versus formula.

Frontal brain activation in premature infants' response to auditory stimuli in neonatal intensive care unit.

The present study was focusing on the very few contacts with the mother's voice that NICU infants have in the womb as well as after birth, we examined whether they can discriminate between their mothers' utterances and those of female nurses in terms of the emotional bonding that is facilitated by prosodic utterances. Twenty-six premature infants were included in this study, and their cerebral blood flows were measured by near-infrared spectroscopy. They were exposed to auditory stimuli in the form of utterances made by their mothers and female nurses. A two (stimulus: mother and nurse) x two (recording site: right frontal area and left frontal area) analysis of variance (ANOVA) for these relative oxy-Hb values was conducted. The ANOVA showed a significant interaction between stimulus and recording site. The mother's and the nurse's voices were activated in the same way in the left frontal area, but showed different reactions in the right frontal area. We presume that the nurse's voice might become associated with pain and stress for premature infants. Our results showed that the premature infants reacted differently to the different voice stimuli. Therefore, we presume that both mothers' and nurses' voices represent positive stimuli for premature infants because both activate the frontal brain. Accordingly, we cannot explain our results only in terms of the state-dependent marker for infantile individual differences, but must also address the stressful trigger of nurses' voices for NICU infants.

Independent age cues for infancy and older age in one face: evidence for rivalry in age perception.

Participants estimated the ages of infants, teens, and adults in their 20s and 60s, using averaged facial images, as well as digitally transformed images of two different age groups. Since a blended face has intermediate features of the component faces, age of the combined faces was hypothesized to be perceived as the mean age of the component faces. However, the perceived age was underestimated when the transformed face included an infant, but overestimated when the face included a person in their 60s. From this one may infer the faces of infants and adults in their 60s have strong age cues. The estimated ages for blended images of infants and adults in their 60s showed a clear bipolar distribution, with one peak at 5-9 years and the other at 50-54 years. Analysis of individual variation showed that the different response to infants-60s faces was related to variations in sensitivity to 60s faces, not to a general perceptual tendency or confused responses to ambiguous appearing faces. Thus, cues for infancy and older age are qualitatively independent and can co-exist in one face, yielding a rivalry in age perception.

[Spatial frequency characteristics in recognizing the age and sex of faces].

The present study investigated the role of spatial frequency components in recognizing age and sex in facial images. In Experiment 1, low (LSF) and high spatial frequencies (HSF) of facial images were morphed between different age groups (one-year-olds, teens, twenties, and sixties), and the participants were required to estimate the age. The results showed that the manipulation of spatial frequency affected age recognition more for the faces including aged than for the faces including infant, suggesting that people use different cues for them. In addition, the recognized age was affected more by HSF components throughout. Recognition of sex was investigated in Experiments 2a and 2b, using the same faces but morphing male and female. In the judgment of sex, unlike for age estimation, the recognition system clearly depended on the LSF. These results were discussed in terms of the different roles of age and sex information and the development of the visual system in early infancy.

The function of the frontal lobe in neonates for response to a prosodic voice.

We examined how neonates responded at the brain level to an element of acoustic stimulation using near-infrared spectroscopy (NIRS). Twenty full-term, healthy neonates were included in the study. The neonates were tested in their cribs while they slept in a silent room. First, two probe holders were placed on the left and right sides of the forehead over the eyebrows using double-sided adhesive tape. Then the neonates were exposed to the auditory stimuli from an external auditory speaker. The stimuli, readings of the first scene of "Little Red Riding Hood," were made with a digital voice. The stimuli consisted of two conditions: variably pitched speech (variable speech: VS) and monotonous flat-pitched speech (monotonous speech: MS). The analyses focused on changes in O(2)Hb because O(2)Hb is the most sensitive indicator of changes in cerebral blood flow in NIRS measurement. The O(2)Hb level promptly increased at the beginning of the VS condition, and then returned to baseline again, while O(2)Hb did not show any changes during the MS condition. Differences between baseline-stimulation relative values were used to perform a 2 (condition)x2 (recording site)x2 (gender) analysis of variance. The results show that VS (M=0.45, S.D.=1.33) produced a greater increase of oxygenated blood to the frontal area of the brain area than MS (M=-0.19, S.D.=1.28). Neonates' brain activation patterns suggest that they can discriminate differences in the prosodic patterns of utterances.

Learning performance on the discrimination-shift task in patients with cortical and subcortical lesions.

Patients with brain damage completed reversal and nonreversal shift-learning tasks and we compared their performance with that of normal adults. The overall group differences revealed that many patients could not reach the task criterion regardless of the location of damage and the shift condition of the task. When we compared patients with subcortical and cortical damage, we also found no group differences with regard to the total number of trials required to reach the learning criterion and in terms of their learning processes during shift learning. However, when we compared patients with subcortical and unilateral cortical damage, the results revealed that the learning processes of patients with subcortical damage were normal, whereas the patients with unilateral cortical damage showed lesion-specific effects on shift learning. These findings are discussed in light of previous developmental findings and the proposed role of subcortical structures in learning.

Familiarity effect on retrieval: a neuropsychological case study.

NM, who suffered traumatic brain injury (TBI) to the prefrontal cortex (PFC), was compared with a diffuse axonal injury (DAI) patient on tasks of free recall, cued recall and recognition memory. We manipulated the familiarity of items to explore the effects of item strength on retrieval. On free recall, NM performed best during the high-familiarity picture condition. On cued recall, he performed best during the high-familiarity word condition. Although high familiarity improved his accuracy on picture items in free recall, low familiarity improved his recognition of words. The patient with DAI did not show these patterns. The role of the PFC in memory is discussed in terms of plausible recognition processes.