Maternal prenatal depressive symptoms and child brain responses to affective touch at two years of age.

BACKGROUND: Touch is an essential form of mother-child interaction, instigating better social bonding and emotional stability. METHODS: We used diffuse optical tomography to explore the relationship between total haemoglobin (HbT) responses to affective touch in the child's brain at two years of age and maternal self-reported prenatal depressive symptoms (EPDS). Affective touch was implemented via slow brushing of the child's right forearm at 3 cm/s and non-affective touch via fast brushing at 30 cm/s and HbT responses were recorded on the left hemisphere. RESULTS: We discovered a cluster in the postcentral gyrus exhibiting a negative correlation (Pearson's r = -0.84, p = 0.015 corrected for multiple comparisons) between child HbT response to affective touch and EPDS at gestational week 34. Based on region of interest (ROI) analysis, we found negative correlations between child responses to affective touch and maternal prenatal EPDS at gestational week 14 in the precentral gyrus, Rolandic operculum and secondary somatosensory cortex. The responses to non-affective touch did not correlate with EPDS in these regions. LIMITATIONS: The number of mother-child dyads was 16. However, by utilising high-density optode arrangements, individualised anatomical models, and video and accelerometry to monitor movement, we were able to minimize methodological sources of variability in the data. CONCLUSIONS: The results show that maternal depressive symptoms during pregnancy may be associated with reduced child responses to affective touch in the temporoparietal cortex. Responses to affective touch may be considered as potential biomarkers for psychosocial development in children. Early identification of and intervention in maternal depression may be important already during early pregnancy.

Effects of atlas-based anatomy on modelled light transport in the neonatal head.

Objective.Diffuse optical tomography (DOT) provides a relatively convenient method for imaging haemodynamic changes related to neuronal activity on the cerebral cortex. Due to practical challenges in obtaining anatomical images of neonates, an anatomical framework is often created from an age-appropriate atlas model, which is individualized to the subject based on measurements of the head geometry. This work studies the approximation error arising from using an atlas instead of the neonate's own anatomical model.Approach.We consider numerical simulations of frequency-domain (FD) DOT using two approaches, Monte Carlo simulations and diffusion approximation via finite element method, and observe the variation in (1) the logarithm of amplitude and phase shift measurements, and (2) the corresponding inner head sensitivities (Jacobians), due to varying segmented anatomy. Varying segmentations are sampled by registering 165 atlas models from a neonatal database to the head geometry of one individual selected as the reference model. Prior to the registration, we refine the segmentation of the cerebrospinal fluid (CSF) by separating the CSF into two physiologically plausible layers.Main results.In absolute measurements, a considerable change in the grey matter or extracerebral tissue absorption coefficient was found detectable over the anatomical variation. In difference measurements, a small local 10%-increase in brain absorption was clearly detectable in the simulated measurements over the approximation error in the Jacobians, despite the wide range of brain maturation among the registered models.Significance.Individual-level atlas models could potentially be selected within several weeks in gestational age in DOT difference imaging, if an exactly age-appropriate atlas is not available. The approximation error method could potentially be implemented to improve the accuracy of atlas-based imaging. The presented CSF segmentation algorithm could be useful also in other model-based imaging modalities. The computation of FD Jacobians is now available in the widely-used Monte Carlo eXtreme software.

Imaging affective and non-affective touch processing in two-year-old children.

Touch is an important component of early parent-child interaction and plays a critical role in the socio-emotional development of children. However, there are limited studies on touch processing amongst children in the age range from one to three years. The present study used frequency-domain diffuse optical tomography (DOT) to investigate the processing of affective and non-affective touch over left frontotemporal brain areas contralateral to the stimulated forearm in two-year-old children. Affective touch was administered by a single stroke with a soft brush over the child's right dorsal forearm at 3 cm/s, while non-affective touch was provided by multiple brush strokes at 30 cm/s. We found that in the insula, the total haemoglobin (HbT) response to slow brushing was significantly greater than the response to fast brushing (slow > fast). Additionally, a region in the postcentral gyrus, Rolandic operculum and superior temporal gyrus exhibited greater response to fast brushing than slow brushing (fast > slow). These findings confirm that an adult-like pattern of haemodynamic responses to affective and non-affective touch can be recorded in two-year-old subjects using DOT. To improve the accuracy of modelling light transport in the two-year-old subjects, we used a published age-appropriate atlas and deformed it to match the exterior shape of each subject's head. We estimated the combined scalp and skull, and grey matter (GM) optical properties by fitting simulated data to calibrated and coupling error corrected phase and amplitude measurements. By utilizing a two-compartment cerebrospinal fluid (CSF) model, the accuracy of estimation of GM optical properties and the localization of activation in the insula was improved. The techniques presented in this paper can be used to study neural development of children at different ages and illustrate that the technology is well-tolerated by most two-year-old children and not excessively sensitive to subject movement. The study points the way towards exciting possibilities in functional imaging of deeper functional areas near sulci in small children.

A Model-Based Iterative Learning Approach for Diffuse Optical Tomography.

Diffuse optical tomography (DOT) utilises near-infrared light for imaging spatially distributed optical parameters, typically the absorption and scattering coefficients. The image reconstruction problem of DOT is an ill-posed inverse problem, due to the non-linear light propagation in tissues and limited boundary measurements. The ill-posedness means that the image reconstruction is sensitive to measurement and modelling errors. The Bayesian approach for the inverse problem of DOT offers the possibility of incorporating prior information about the unknowns, rendering the problem less ill-posed. It also allows marginalisation of modelling errors utilising the so-called Bayesian approximation error method. A more recent trend in image reconstruction techniques is the use of deep learning, which has shown promising results in various applications from image processing to tomographic reconstructions. In this work, we study the non-linear DOT inverse problem of estimating the (absolute) absorption and scattering coefficients utilising a 'model-based' learning approach, essentially intertwining learned components with the model equations of DOT. The proposed approach was validated with 2D simulations and 3D experimental data. We demonstrated improved absorption and scattering estimates for targets with a mix of smooth and sharp image features, implying that the proposed approach could learn image features that are difficult to model using standard Gaussian priors. Furthermore, it was shown that the approach can be utilised in compensating for modelling errors due to coarse discretisation enabling computationally efficient solutions. Overall, the approach provided improved computation times compared to a standard Gauss-Newton iteration.

Relationship between maternal pregnancy-related anxiety and infant brain responses to emotional speech - a pilot study.

BACKGROUND: Maternal pregnancy-related anxiety (PRA) is reportedly related to neurodevelopmental outcomes of infants. However, the relationship between maternal PRA and the processing of emotions in the infant brain has not been extensively studied with neuroimaging. The objective of the present pilot study is to investigate the relationship between maternal PRA and infant hemodynamic responses to emotional speech at two months of age. METHODS: The study sample included 19 mother-infant dyads from a general sample of a population of Caucasian mothers. Self-reported Pregnancy-Related Anxiety Questionnaire (PRAQ-R2) data was collected from mothers during pregnancy at gestational weeks (gwks) 24 (N = 19) and 34 (N = 18). When their infants were two months old, the infants' brains functional responses to emotional speech in the left fronto-temporoparietal cortex were recorded using diffuse optical tomography (DOT). RESULTS: Maternal PRAQ-R2 scores at gwk 24 correlated negatively with the total hemoglobin (HbT) responses to sad speech on both sides of the temporoparietal junction (Spearman's rank correlation coefficient ρ = -0.87). The correlation was significantly greater at gwk 24 than gwk 34 (ρ = -0.42). LIMITATIONS: The field of view of the measurement did not include the right hemisphere or parts of the frontal cortex. The sample size is moderate and the mothers were relatively highly educated, thus there may be some differences between the study sample and the general population. CONCLUSIONS: Maternal pregnancy-related anxiety may affect child brain emotion processing development. Further research is needed to understand the functional and developmental significance of the findings.

Hemodynamic responses to emotional speech in two-month-old infants imaged using diffuse optical tomography.

Emotional speech is one of the principal forms of social communication in humans. In this study, we investigated neural processing of emotional speech (happy, angry, sad and neutral) in the left hemisphere of 21 two-month-old infants using diffuse optical tomography. Reconstructed total hemoglobin (HbT) images were analysed using adaptive voxel-based clustering and region-of-interest (ROI) analysis. We found a distributed happy > neutral response within the temporo-parietal cortex, peaking in the anterior temporal cortex; a negative HbT response to emotional speech (the average of the emotional speech conditions < baseline) in the temporo-parietal cortex, neutral > angry in the anterior superior temporal sulcus (STS), happy > angry in the superior temporal gyrus and posterior superior temporal sulcus, angry < baseline in the insula, superior temporal sulcus and superior temporal gyrus and happy < baseline in the anterior insula. These results suggest that left STS is more sensitive to happy speech as compared to angry speech, indicating that it might play an important role in processing positive emotions in two-month-old infants. Furthermore, happy speech (relative to neutral) seems to elicit more activation in the temporo-parietal cortex, thereby suggesting enhanced sensitivity of temporo-parietal cortex to positive emotional stimuli at this stage of infant development.

Emotional Processing in the First 2 Years of Life: A Review of Near-Infrared Spectroscopy Studies.

Emotional stimuli processing during childhood helps us to detect salient cues in our environment and prepares us for our social life. In early childhood, the emotional valences of auditory and visual input are salient and relevant cues of social aspects of the environment, and it is of special interest to understand how exactly the processing of emotional stimuli develops. Near-infrared spectroscopy (NIRS) is a noninvasive neuroimaging tool that has proven valuable in studying emotional processing in children. After conducting a systematic search of PubMed, Web of Science, and Embase databases, we examined 50 NIRS studies performed to study emotional stimuli processing in children in the first 2 years of age. We found that the majority of these studies are done in infants and the most commonly used stimuli are visual and auditory. Many of the reviewed studies suggest the involvement of bilateral temporal areas in emotional processing of visual and auditory stimuli. It is unclear which neural activation patterns reflect maturation and at what age the emotional encoding reaches those typically seen in adults. Our review provides an overview of the database on emotional processing in children up to 2 years of age. Furthermore, it demonstrates the need to include the less-studied age range of 1 to 2 years, and suggests the use of combined audio-visual stimuli and longitudinal studies for future research on emotional processing in children. Thus, NIRS might be a vital tool to study the associations between the early pattern of neural responses and socioemotional development later in life.

Affective and non-affective touch evoke differential brain responses in 2-month-old infants.

Caressing touch is an effective way to communicate emotions and to create social bonds. It is also one of the key mediators of early parental bonding. The caresses are generally thought to represent a social form of touching and indeed, slow, gentle brushing is encoded in specialized peripheral nerve fibers, the C-tactile (CT) afferents. In adults, areas such as the posterior insula and superior temporal sulcus are activated by affective, slow stroking touch but not by fast stroking stimulation. However, whether these areas are activated in infants, after social tactile stimulation, is unknown. In this study, we compared the total hemoglobin responses measured with diffuse optical tomography (DOT) in the left hemisphere following slow and fast stroking touch stimulation in 16 2-month-old infants. We compared slow stroking (optimal CT afferent stimulation) to fast stroking (non-optimal CT stimulation). Activated regions were delineated using two methods: one based on contrast between the two conditions, and the other based on voxel-based statistical significance of the difference between the two conditions. The first method showed a single activation cluster in the temporal cortex with center of gravity in the middle temporal gyrus where the total hemoglobin increased after the slow stroking relative to the fast stroking (p = 0.04 uncorrected). The second method revealed a cluster in the insula with an increase in total hemoglobin in the insular cortex in response to slow stroking relative to fast stroking (p = 0.0005 uncorrected; p = 0.04 corrected for multiple comparisons). These activation clusters encompass areas that are involved in processing of affective, slow stroking touch in the adult brain. We conclude that the infant brain shows a pronounced and adult-like response to slow stroking touch compared to fast stroking touch in the insular cortex but the expected response in the primary somatosensory cortex was not found at this age. The results imply that emotionally valent touch is encoded in the brain in adult-like manner already soon after birth and this suggests a potential for involvement of touch in bonding with the caretaker.

Nonlinear approach to difference imaging in diffuse optical tomography.

Difference imaging aims at recovery of the change in the optical properties of a body based on measurements before and after the change. Conventionally, the image reconstruction is based on using difference of the measurements and a linear approximation of the observation model. One of the main benefits of the linearized difference reconstruction is that the approach has a good tolerance to modeling errors, which cancel out partially in the subtraction of the measurements. However, a drawback of the approach is that the difference images are usually only qualitative in nature and their spatial resolution can be weak because they rely on the global linearization of the nonlinear observation model. To overcome the limitations of the linear approach, we investigate a nonlinear approach for difference imaging where the images of the optical parameters before and after the change are reconstructed simultaneously based on the two datasets. We tested the feasibility of the method with simulations and experimental data from a phantom and studied how the approach tolerates modeling errors like domain truncation, optode coupling errors, and domain shape errors.

Effect of task-related extracerebral circulation on diffuse optical tomography: experimental data and simulations on the forehead.

The effect of task-related extracerebral circulatory changes on diffuse optical tomography (DOT) of brain activation was evaluated using experimental data from 14 healthy human subjects and computer simulations. Total hemoglobin responses to weekday-recitation, verbal-fluency, and hand-motor tasks were measured with a high-density optode grid placed on the forehead. The tasks caused varying levels of mental and physical stress, eliciting extracerebral circulatory changes that the reconstruction algorithm was unable to fully distinguish from cerebral hemodynamic changes, resulting in artifacts in the brain activation images. Crosstalk between intra- and extracranial layers was confirmed by the simulations. The extracerebral effects were attenuated by superficial signal regression and depended to some extent on the heart rate, thus allowing identification of hemodynamic changes related to brain activation during the verbal-fluency task. During the hand-motor task, the extracerebral component was stronger, making the separation less clear. DOT provides a tool for distinguishing extracerebral components from signals of cerebral origin. Especially in the case of strong task-related extracerebral circulatory changes, however, sophisticated reconstruction methods are needed to eliminate crosstalk artifacts.

Magnetic-stimulation-related physiological artifacts in hemodynamic near-infrared spectroscopy signals.

Hemodynamic responses evoked by transcranial magnetic stimulation (TMS) can be measured with near-infrared spectroscopy (NIRS). This study demonstrates that cerebral neuronal activity is not their sole contributor. We compared bilateral NIRS responses following brain stimulation to those from the shoulders evoked by shoulder stimulation and contrasted them with changes in circulatory parameters. The left primary motor cortex of ten subjects was stimulated with 8-s repetitive TMS trains at 0.5, 1, and 2 Hz at an intensity of 75% of the resting motor threshold. Hemoglobin concentration changes were measured with NIRS on the stimulated and contralateral hemispheres. The photoplethysmograph (PPG) amplitude and heart rate were recorded as well. The left shoulder of ten other subjects was stimulated with the same protocol while the hemoglobin concentration changes in both shoulders were measured. In addition to PPG amplitude and heart rate, the pulse transit time was recorded. The brain stimulation reduced the total hemoglobin concentration (HbT) on the stimulated and contralateral hemispheres. The shoulder stimulation reduced HbT on the stimulated shoulder but increased it contralaterally. The waveforms of the HbT responses on the stimulated hemisphere and shoulder correlated strongly with each other (r = 0.65-0.87). All circulatory parameters were also affected. The results suggest that the TMS-evoked NIRS signal includes components that do not result directly from cerebral neuronal activity. These components arise from local effects of TMS on the vasculature. Also global circulatory effects due to arousal may affect the responses. Thus, studies involving TMS-evoked NIRS responses should be carefully controlled for physiological artifacts and effective artifact removal methods are needed to draw inferences about TMS-evoked brain activity.

Correlation of visual-evoked hemodynamic responses and potentials in human brain.

The interaction of brain hemodynamics and neuronal activity has been intensively studied in recent years to yield better understanding of brain function. We investigated the relationship between visual-evoked hemodynamic responses (HDRs), measured with near-infrared spectroscopy (NIRS), and neuronal activity in humans, approximated with the stimulus train duration or with visual-evoked potentials (VEPs). Concentration changes of oxyhemoglobin (HbO(2)) and deoxyhemoglobin (HbR) in tissue and VEPs were recorded simultaneously over the occipital lobe of ten healthy subjects to 3, 6, and 12 s pattern-reversing checkerboard stimulus trains having a reversal frequency of 2 Hz. We found that the area-under-the-curves (Sigma) of HbO(2) and HbR were linearly correlated with the stimulus train duration and with the SigmaVEP summed over the 3, 6, and 12 s stimulus train durations. The correlation was stronger between the SigmaHbO(2) or the SigmaHbR and the SigmaVEP than between the SigmaHbO(2) or the SigmaHbR and the stimulus train duration. The SigmaVEPs explained 55% of the SigmaHbO(2) and 74% of the SigmaHbR variance, whereas the stimulus train duration explained only 45% of the SigmaHbO(2) and 51% of the SigmaHbR variance. We used Sigma of the NIRS responses and VEPs because we wanted to incorporate all possible processes (e.g., attention, habituation, etc.) affecting the responses. The results indicate that the relationship between brain HDRs and VEPs is approximately linear for 3-12 s long stimulus trains consisting of checkerboard patterns reversing at 2 Hz. To interpret hemodynamic responses, the measurement of evoked potentials is beneficial compared to the use of indirect parameters such as the stimulus duration. In addition, interindividual differences in the HbO(2) and HbR responses may be partly explained with differences in the VEPs.

Hemodynamic responses to speech and music in newborn infants.

We used near-infrared spectroscopy (NIRS) to study responses to speech and music on the auditory cortices of 13 healthy full-term newborn infants during natural sleep. The purpose of the study was to investigate the lateralization of speech and music responses at this stage of development. NIRS data was recorded from eight positions on both hemispheres simultaneously with electroencephalography, electrooculography, electrocardiography, pulse oximetry, and inclinometry. In 11 subjects, statistically significant (P < 0.02) oxygenated (HbO2) and total hemoglobin (HbT) responses were recorded. Both stimulus types elicited significant HbO2 and HbT responses on both hemispheres in five subjects. Six of the 11 subjects had positive HbO2 and HbT responses to both stimulus types, whereas one subject had negative responses. Mixed positive and negative responses were observed in four neonates. On both hemispheres, speech and music responses were significantly correlated (r = 0.64; P = 0.018 on the left hemisphere (LH) and r = 0.60; P = 0.029 on the right hemisphere (RH)). On the group level, the average response to the speech stimuli was statistically significantly greater than zero in the LH, whereas responses on the RH or to the music stimuli did not differ significantly from zero. This suggests a more coherent response to speech on the LH. However, significant differences in lateralization of the responses or mean response amplitudes of the two stimulus types were not observed on the group level.

Approximation errors and model reduction in three-dimensional diffuse optical tomography.

Model reduction is often required in diffuse optical tomography (DOT), typically because of limited available computation time or computer memory. In practice, this means that one is bound to use coarse mesh and truncated computation domain in the model for the forward problem. We apply the (Bayesian) approximation error model for the compensation of modeling errors caused by domain truncation and a coarse computation mesh in DOT. The approach is tested with a three-dimensional example using experimental data. The results show that when the approximation error model is employed, it is possible to use mesh densities and computation domains that would be unacceptable with a conventional measurement error model.

Probabilistic atlas can improve reconstruction from optical imaging of the neonatal brain.

Diffuse optical imaging is an emerging medical imaging modality based on near-infrared and visible red light. The method can be used for imaging activations in the human brain. In this study, a deformable probabilistic atlas of the distribution of tissue types within the term neonatal head was created based on MR images. The use of anatomical prior information provided by such atlas in reconstructing brain activations from optical imaging measurements was studied using Monte Carlo simulations. The results suggest that use of generic anatomical information can greatly improve the spatial accuracy and robustness of the reconstruction when noise is present in the data.

Study of neurovascular coupling in humans via simultaneous magnetoencephalography and diffuse optical imaging acquisition.

By combining diffuse optical imaging (DOI) and magnetoencephalography (MEG) we investigate neurovascular coupling non-invasively in human subjects using median-nerve stimulation. Previous fMRI studies have shown a habituation effect in the hemodynamic blood oxygen level-dependent (BOLD) response for stimulation periods longer than 2 s. With DOI and MEG we can test whether this effect in hemodynamic response can be accounted for by a habituation effect in the neural response. Our experimental results show that the habituation effect in the hemodynamic response is stronger than that in the earliest cortical neural response (N20). Using a linear convolution model to predict hemodynamic responses we found that including late neural components (> or = 30 ms) improves the prediction of the hemoglobin response. This finding suggests that in addition to the initial evoked-response deflections related to the talamic afferent input, later cortical activity is needed to predict the hemodynamic response.

Coupling between somatosensory evoked potentials and hemodynamic response in the rat.

We studied the relationship between somatosensory evoked potentials (SEP) recorded with scalp electroencephalography (EEG) and hemoglobin responses recorded non-invasively with diffuse optical imaging (DOI) during parametrically varied electrical forepaw stimulation in rats. Using these macroscopic techniques we verified that the hemodynamic response is not linearly coupled to the somatosensory evoked potentials, and that a power or threshold law best describes the coupling between SEP and the hemoglobin response, in agreement with the results of most invasive studies. We decompose the SEP response in three components (P1, N1, and P2) to determine which best predicts the hemoglobin response. We found that N1 and P2 predict the hemoglobin response significantly better than P1 and the input stimuli (S). Previous electrophysiology studies reported in the literature show that P1 originates in layer IV directly from thalamocortical afferents, while N1 and P2 originate in layers I and II and reflect the majority of local cortico-cortical interactions. Our results suggest that the evoked hemoglobin response is driven by the cortical synaptic activity and not by direct thalamic input. The N1 and P2 components, and not P1, need to be considered to correctly interpret neurovascular coupling.

Image reconstruction in optical tomography in the presence of coupling errors.

Image reconstruction in optical tomography is a nonlinear and generally ill- posed inverse problem. Noise in the measured surface data can give rise to substantial artifacts in the recovered volume images of optical coefficients. Apart from random shot noise caused by the limited number of photons detected at the measurement site, another class of systematic noise is associated with losses specific to individual source and detector locations. A common cause for such losses in data acquisition systems based on fiber-optic light delivery is the imperfect coupling between the fiber tips and the skin of the patient because of air gaps or surface moisture. Thus the term coupling errors was coined for this type of data noise. However, source and detector specific errors can also occur in noncontact measurement systems not using fiber-optic delivery, for example, owing to local skin pigmentation, hair and hair follicles, or instrumentation calibration errors. Often it is not possible to quantify coupling effects in a way that allows us to remove them from the data or incorporate them into the light transport model. We present an alternative method of eliminating coupling errors by regarding the complex-valued coupling factors for each source and detector as unknowns in the reconstruction process and recovering them simultaneously with the images of absorption and scattering. Our method takes into account the possibility that coupling effects have an influence on both the amplitude and the phase shift of the measurements. Reconstructions from simulated and experimental phantom data are presented, which show that including the coupling coefficients in the reconstruction greatly improves the recovery of absorption and scattering images.

Significance of tissue anisotropy in optical tomography of the infant brain.

We study the effect of tissue anisotropy in optical tomography of neonates. A Monte Carlo method capable of modeling photon migration in an arbitrary 3D tissue model with spatially varying optical properties and tissue anisotropy is used for simulating measurements of neonates. Anatomical and diffusion tensor magnetic resonance imaging of neonates are used for creating the anatomical models. We find that tissue anisotropy affects the measured signal and the pattern of sensitivity in optical measurements.

Comparison between a time-domain and a frequency-domain system for optical tomography.

The quality of phase and amplitude data from two medical optical tomography systems were compared. The two systems are a 32-channel time-domain system developed at University College London (UCL) and a 16-channel frequency-domain system developed at Helsinki University of Technology (HUT). Difference data measured from an inhomogeneous and a homogeneous phantom were compared with a finite-element method (diffusion equation) and images of scattering and absorption were reconstructed based on it. The measurements were performed at measurement times between 1 and 30 s per source. The mean rms errors in the data measured by the HUT system were 3.4% for amplitude and 0.51 deg for phase, while the corresponding values for the UCL data were 6.0% and 0.46 deg, respectively. The reproducibility of the data measured with the two systems was tested with a measurement time of 5 s per source. It was 0.4% in amplitude for the HUT system and 4% for the UCL system, and 0.08 deg in phase for both systems. The image quality of the reconstructions from the data measured with the two systems were compared with several quantitative criteria. In general a higher contrast was observed in the images calculated from the HUT data.