2D:4D biomarker reliability and validity in a within-subject pregnancy-childhood-adolescence cohort.

BACKGROUND: A lot of studies use the second-to-fourth digit length ratio (2D:4D) as a biomarker for intrauterine androgen load to predict behavioral and mental health problems. Thus, knowledge of 2D:4D's metric properties, namely reliability and validity, is essential. METHOD: 2D:4D handscans were available from 149 adolescents (M = 13.32 years, SD = 0.35) and their mothers. For 88 adolescents, there were also primary-school age handscans (M = 7.87 years, SD = 0.68). Prenatal risks for the 1st to 3rd trimesters were recorded during the 3rd trimester of pregnancy (alcohol exposition: meconium biomarker and maternal self-report; nicotine exposition: maternal self-report; maternal depressive symptoms and subjective stress: questionnaires). RESULTS: The 2D:4D ratio was highly stable from childhood to early adolescence. However, both developmental and sex effects were present: The 2D:4D ratio increased with age and was higher in adolescent girls vs. boys. Significant 2D:4D mother-child associations were found for girls. Significant main effects could be found for the prenatal risk factors alcohol (self-report) and nicotine consumption. CONCLUSION: In line with earlier studies, the 2D:4D biomarker proved to be an inter-individually stable measure with an intra-individual increase from childhood to early adolescence. Sex differences in adolescence and associations with maternal prenatal health behaviour underline the validity of the biomarker. Findings on heritability emphasize the importance of interpreting 2D:4D results in a sex-specific manner.

Markers of Prenatal Androgen Exposure Correlate With Online Sexual Compulsivity and Erectile Function in Young Men.

Pornography addiction and sexual dysfunction are increasingly prevalent in young men. Previous studies suggest that prenatal androgen exposure plays a role in addiction and sexual functionality. Here, we tested whether lower second-to-fourth finger length ratio (2D:4D) and later age at spermarche, both putative indicators of higher androgen levels in utero, correlate with online sexual compulsivity (OSC scale of ISST), erectile function (IIEF-5), and ejaculatory control (PEPA) in 4,370 young men (age IQR: 25-26 years) of the Cohort Study on Substance Use Risk Factors. Statistical analyses revealed that lower 2D:4D correlated with higher scores on the OSC scale. Moreover, higher age at spermarche correlated with higher OSC scores and decreased erectile function. Interestingly, OSC severity, but not the frequency of pornography use, correlated negatively with erectile function and ejaculatory control. This is the first study to associate two independent proxies of prenatal testosterone level with OSC. These findings provide novel insight into intrauterine predisposition of sexual behavior and related sexual function in adulthood.

Lower Digit Ratio (2D:4D) Indicative of Excess Prenatal Androgen Is Associated With Increased Sociability and Greater Social Capital.

Positive social interactions are crucial for human well-being. Elevated prenatal exposure to testosterone as indicated by a low second-to-fourth finger length ratio (2D:4D) relates to more aggressive/hostile behavior in men of low 2D:4D, especially in challenging situations. How much people enjoy interacting with others is determined by the personality trait sociability. Given its role in approach and avoidance behavior, sociability might also be influenced by prenatal sex hormones, but studies are inconclusive so far. Here, we investigated the association between 2D:4D and the personality trait sociability complemented by personal social capital and personal social network size, in a population-based cohort of 4998 men. Lower 2D:4D correlated significantly with higher trait sociability, bigger personal social capital, and larger personal social network size. These effects were consistent across both hands separately and their mean value. Furthermore, both factors of sociability (1) liking party and company of friends and (2) isolation intolerance, correlated significantly with the prenatal testosterone marker. The exploratory analysis revealed no link between 2D:4D and responses to the personality trait aggression items or items of anti-social-personality disorder. Our data suggest that prenatal androgen exposure organizes the brain with lasting effects on social behavior.

Alpha-band oscillations reflect external spatial coding for tactile stimuli in sighted, but not in congenitally blind humans.

We investigated the function of oscillatory alpha-band activity in the neural coding of spatial information during tactile processing. Sighted humans concurrently encode tactile location in skin-based and, after integration with posture, external spatial reference frames, whereas congenitally blind humans preferably use skin-based coding. Accordingly, lateralization of alpha-band activity in parietal regions during attentional orienting in expectance of tactile stimulation reflected external spatial coding in sighted, but skin-based coding in blind humans. Here, we asked whether alpha-band activity plays a similar role in spatial coding for tactile processing, that is, after the stimulus has been received. Sighted and congenitally blind participants were cued to attend to one hand in order to detect rare tactile deviant stimuli at this hand while ignoring tactile deviants at the other hand and tactile standard stimuli at both hands. The reference frames encoded by oscillatory activity during tactile processing were probed by adopting either an uncrossed or crossed hand posture. In sighted participants, attended relative to unattended standard stimuli suppressed the power in the alpha-band over ipsilateral centro-parietal and occipital cortex. Hand crossing attenuated this attentional modulation predominantly over ipsilateral posterior-parietal cortex. In contrast, although contralateral alpha-activity was enhanced for attended versus unattended stimuli in blind participants, no crossing effects were evident in the oscillatory activity of this group. These findings suggest that oscillatory alpha-band activity plays a pivotal role in the neural coding of external spatial information for touch.

Belief of agency changes dynamics in sensorimotor networks.

Controlling an event through one's own action usually induces a sense of agency, a feeling that arises when an expected outcome matches the intention. The neural correlates of this feeling remain controversial however, as experimental manipulation of the action-outcome chain often introduces mismatch or prediction errors that strongly correlate with the sense of agency. Here, we took a different approach and manipulated the causal belief (self-attribution vs. computer-attribution) by external cues during matched visuo-motor tapping conditions. With magneto-encephalography, we studied the sense of agency from a network perspective, investigating in source space the modulation of local population activity and changes in functional connectivity with motor cortex. Our results show that during the belief of agency primary motor cortex (M1) shows stronger functional connectivity (mediated by the beta band) to inferior parietal lobe and right middle temporal gyrus (MTG). Furthermore, the local feed-forward activity (gamma band power) in extrastriate body area and MTG disappears with that belief. After changes in action context, left M1 shows stronger connectivity in the alpha band with right premotor cortex and left insular-temporal cortex a network that might support active inference in social action context. Finally, a better tapping performance in this rhythmic task was related to alpha power modulations in the bilateral cerebellum and bilateral fusiform body-area, with power suppression during a more precise performance. These findings highlight the role of multiple networks supporting the sense of agency by changing their relative contribution for different causal beliefs.

Mindfulness-based Stress Reduction in Pregnancy: an App-Based Programme to Improve the Health of Mothers and Children (MINDFUL/PMI Study).

Unfavourable intrauterine environmental factors increase the risk of delivery complications as well as postpartum developmental and behavioural problems in children and adolescents with ongoing effects into older age. Biomarker studies show that maternal stress and the use of alcohol and tobacco during pregnancy are associated with a higher intrauterine testosterone exposure of the child. The antenatal testosterone load, in turn, is a risk factor for lasting adverse health effects which extend into adulthood. A 15-week, mindfulness-oriented, app-based programme for the reduction of stress as well as for the reduction of alcohol and tobacco use in pregnant women is established. In the monocentre, prospective, controlled, and investigator-blinded MINDFUL/PMI (Maternal Health and Infant Development in the Follow-up after Pregnancy and a Mindfulness Intervention) study, pregnant women carry out the programme. Its effect on antenatal testosterone exposure of the child is examined by assessing the index/ring finger length ratio and other biomarkers in the 1-year-old children. In addition, the programme's effects on self-regulation, the developmental status and the mental health of the children at the age of one year will be investigated. Additional aspects of the course of the pregnancy and delivery represent exploratory study objectives. This longitudinal study project is intended to improve the understanding of the impact of intrauterine environmental factors on early childhood development and health. Maternal stress as well as alcohol and tobacco use during pregnancy are modifiable factors and represent potential preventive targets.

Oscillatory activity reflects differential use of spatial reference frames by sighted and blind individuals in tactile attention.

Touch can be localized either on the skin in anatomical coordinates, or, after integration with posture, in external space. Sighted individuals are thought to encode touch in both coordinate systems concurrently, whereas congenitally blind individuals exhibit a strong bias for using anatomical coordinates. We investigated the neural correlates of this differential dominance in the use of anatomical and external reference frames by assessing oscillatory brain activity during a tactile spatial attention task. The EEG was recorded while sighted and congenitally blind adults received tactile stimulation to uncrossed and crossed hands while detecting rare tactile targets at one cued hand only. In the sighted group, oscillatory alpha-band activity (8-12Hz) in the cue-target interval was reduced contralaterally and enhanced ipsilaterally with uncrossed hands. Hand crossing attenuated the degree of posterior parietal alpha-band lateralization, indicating that attention deployment was affected by external spatial coordinates. Beamforming suggested that this posture effect originated in the posterior parietal cortex. In contrast, cue-related lateralization of central alpha-band as well as of beta-band activity (16-24Hz) were unaffected by hand crossing, suggesting that these oscillations exclusively encode anatomical coordinates. In the blind group, central alpha-band activity was lateralized, but did not change across postures. The pattern of beta-band activity was indistinguishable between groups. Because the neural mechanisms for posterior alpha-band generation seem to be linked to developmental vision, we speculate that the lack of this neural mechanism in blind individuals is related to their preferred use of anatomical over external spatial codes in sensory processing.

Tactile remapping: from coordinate transformation to integration in sensorimotor processing.

Tactile localization entails the transformation of the initial skin-based location into an external reference frame that accounts for body posture and subsequent flexible integration of these two reference frames. The mechanisms underlying this tactile remapping are not well understood. Notably, there is a gap between the principles uncovered by psychophysical research and the mechanistic explanations offered by neuroscientific studies. We suggest that spatial localization is best viewed as a process of integrating multiple concurrently active spatial representations rather than a sequential transformation process. To achieve integration, large-scale interactions are required that link these different representations. Coordinated oscillatory activity may be a suitable mechanism that allows parallel representation of multiple spatial formats and the formation of an integrated location estimate.

Different roles of alpha and beta band oscillations in anticipatory sensorimotor gating.

Alpha (8-12 Hz) and beta band (18-30 Hz) oscillations have been implicated in sensory anticipation and motor preparation. Here, using magneto-encephalography, we tested whether they have distinct functional roles in a saccade task that induces a remapping between sensory and motor reference frames. With a crossed hands posture, subjects had to saccade as fast and accurate as possible toward a tactile stimulus delivered to one of two non-visible index fingers, located to the left or right of gaze. Previous studies have shown that this task, in which the somatotopic stimulus must be remapped to activate oculomotor system in the opposing hemisphere, is occasionally preceded by intrahemispheric remapping, driving a premature saccade into the wrong direction. To test whether the brain could anticipate the remapping, we provided auditory predictive cues (80% validity), which indicated which finger is most likely to be stimulated. Both frequency bands showed different lateralization profiles at central vs. posterior sensors, indicating anticipation of somatosensory and oculomotor processing. Furthermore, beta band power in somatosensory cortex correlated positively with saccade reaction time (SRT), with correlation values that were significantly higher with contralateral vs. ipsilateral activation. In contrast, alpha band power in parietal cortex correlated negatively with SRT, with correlation values that were significantly more negative with ipsilateral than contralateral activation. These results suggest distinct functional roles of beta and alpha band activity: (1) somatosensory gating by beta oscillations, increasing excitability in contralateral somatosensory cortex (positive correlation); and (2) oculomotor gating by posterior alpha oscillations, inhibiting gaze-centered oculomotor regions involved in generating the saccade to the wrong direction (negative correlation). Our results show that low frequency rhythms gate upcoming sensorimotor transformations.

Parietal oscillations code nonvisual reach targets relative to gaze and body.

Recent blood oxygenation level-dependent (BOLD) imaging work has suggested flexible coding frames for reach targets in human posterior parietal cortex, with a gaze-centered reference frame for visually guided reaches and a body-centered frame for proprioceptive reaches. However, BOLD activity, which reflects overall population activity, is insensitive to heterogeneous responses at the neuronal level and temporal dynamics between neurons. Neurons could synchronize in different frequency bands to form assemblies operating in different reference frames. Here we assessed the reference frames of oscillatory activity in parietal cortex during reach planning to nonvisible tactile stimuli. Under continuous recording of magneto-encephalographic data, subjects fixated either to the left or right of the body midline, while a tactile stimulus was presented to a nonvisible fingertip, located either to the left or right of gaze. After a delay, they had to reach toward the remembered stimulus location with the other hand. Our results show body-centered and gaze-centered reference frames underlying the power modulations in specific frequency bands. Whereas beta-band activity (18-30 Hz) in parietal regions showed body-centered spatial selectivity, the high gamma band (>60 Hz) demonstrated a transient remapping into gaze-centered coordinates in parietal and extrastriate visual areas. This gaze-centered coding was sustained in the low gamma (<60 Hz) and alpha (∼10 Hz) bands. Our results show that oscillating subpopulations encode remembered tactile targets for reaches relative to gaze, even though neither the sensory nor the motor output processes operate in this frame. We discuss these findings in the light of flexible control mechanisms across modalities and effectors.

Greater benefits of multisensory integration during complex sensorimotor transformations.

Multisensory integration enables rapid and accurate behavior. To orient in space, sensory information registered initially in different reference frames has to be integrated with the current postural information to produce an appropriate motor response. In some postures, multisensory integration requires convergence of sensory evidence across hemispheres, which would presumably lessen or hinder integration. Here, we examined orienting gaze shifts in humans to visual, tactile, or visuotactile stimuli when the hands were either in a default uncrossed posture or a crossed posture requiring convergence across hemispheres. Surprisingly, we observed the greatest benefits of multisensory integration in the crossed posture, as indexed by reaction time (RT) decreases. Moreover, such shortening of RTs to multisensory stimuli did not come at the cost of increased error propensity. To explain these results, we propose that two accepted principles of multisensory integration, the spatial principle and inverse effectiveness, dynamically interact to aid the rapid and accurate resolution of complex sensorimotor transformations. First, early mutual inhibition of initial visual and tactile responses registered in different hemispheres reduces error propensity. Second, inverse effectiveness in the integration of the weakened visual response with the remapped tactile representation expedites the generation of the correct motor response. Our results imply that the concept of inverse effectiveness, which is usually associated with external stimulus properties, might extend to internal spatial representations that are more complex given certain body postures.

Multiple reference frames in cortical oscillatory activity during tactile remapping for saccades.

Single-unit recordings have shown that the brain uses multiple reference frames in spatial processing. The brain could use this neural architecture to implicitly create multiple modes of representation at the population level, with each reference frame weighted as a function of task demands. Using magnetoencephalography, we tested this hypothesis by studying the reference frames in rhythmic neuronal synchronization--a population measure--during tactile remapping for saccades. Human subjects fixated either to the left or right of the body midline, while a tactile stimulus was applied to an invisible fingertip, located either left or right of fixation. After a variable delay, they looked at the remembered stimulus location. Results show a transient body-centered, stimulus-induced gamma-band response (70-90 Hz) in somatosensory areas, contralateral to the stimulated hand. Concurrently, a gamma-band response occurred in posterior parietal cortex (PPC), contralateral to the gaze-centered location of the stimulus, even though the stimulus was not seen. The temporal overlap of these early representations suggests that there is a fast bottom-up sensory-induced remapping in PPC, taking into account the relative positions of eyes and hand. The gaze-centered representation in PPC was sustained in a high gamma range (85-115 Hz) and increased in power closer to the initiation of the saccade. Lower-frequency rhythms (alpha, beta) showed body-centered power modulations in somatosensory areas in anticipation of the stimulus and a mixture of reference frames in PPC after stimulus presentation. We conclude that oscillatory activity reflects the time-varying coding of information in body- and gaze-centered reference frames during tactile remapping for saccades.

Parietofrontal circuits in goal-oriented behaviour.

Parietal and frontal cortical areas play important roles in the control of goal-oriented behaviour. This review examines how signal processing in the parietal and frontal eye fields is involved in coding and storing space, directing attention and processing the sensorimotor transformation for saccades. After a survey of the functional specialization of these areas in monkeys, we discuss homologous regions in the human brain in terms of topographic organization, storage capacity, target selection, spatial remapping, reference frame transformations and effector specificity. The overall picture suggests that bottom-up sensory, top-down cognitive signals and efferent motor signals are integrated in dynamic sensorimotor maps as part of a functionally flexible parietofrontal network. Neuronal synchronization in these maps may be instrumental in amplifying behaviourally relevant representations and setting up a functional pathway to route information in this parietofrontal circuit.