Tactile sensory processing as a precursor of executive attention: Toward early detection of attention impairments and neurodevelopmental disorders.

Recent studies in developmental neuroscience tend to show the existence of neural attention networks from birth. Their construction is based on the first sensory experiences that allow us to learn the patterns of the world surrounding us and preserve our limited attentional resources. Touch is the first sensory modality to develop, although it is still little studied in developmental psychology in contrast to distal modalities such as audition or vision. Atypical tactile sensory processing at an early age could predict later attention dysfunction, both of them being part of the symptomatology of neurodevelopmental disorders (NDD). We review the state of knowledge on tactile sensory processing and its links with attention, executive attention (EA) in particular, and propose that abnormal tactile sensory processing at an early age could provide markers of EA dysfunctions, contributing to the early detection of NDD. This article is categorized under: Psychology > Attention.

Somatosensory prediction in the premature neonate brain.

Sensory prediction (SP) is at the core of early cognitive development. Impaired SP may be a key to understanding the emergence of neurodevelopmental disorders, however there is little data on how and when this skill emerges. We set out to provide evidence of SP in the brain of premature neonates in the fundamental sensory modality: touch. Using Diffuse Correlation Spectroscopy, we measured blood flow changes in the somatosensory cortex of premature neonates presented with a vibrotactile stimulation-omission sequence. When ISI was fixed, participants presented a decrease in blood flow during stimulus omissions, starting when a stimulus should begin: the expectation of a certain stimulus onset induced deactivation of the somatosensory cortex. When ISI was jittered, we observed an increase in blood flow during omissions: the expectation of a likely but not certain stimulus onset induced activation of the somatosensory cortex. Our results reveal SP in the brain as early as four weeks before term, based on the temporal structure of a unimodal somatosensory stimulation, and show that SP produces opposite regulation of activity in the somatosensory cortex depending on how liable is stimulus onset. Future studies will investigate the predictive value of somatosensory prediction on neurodevelopment in this vulnerable population.

The manual orienting response habituation to repeated tactile stimuli in preterm neonates: Discrimination of stimulus locations and interstimulus intervals.

Preterm infants frequently develop atypical sensory profiles, the tactile modality being particularly affected. However, there is a lack of recent investigation of neonatal tactile perception in a passive context, especially in preterms who are particularly exposed to this tactile stimuli. Our aims were to provide evidence of orienting responses (behavioral modifications directing subject's attention towards stimuli) and habituation to passive tactile stimuli in preterm neonates, to explore their ability to perceive spatial and temporal aspects of the stimulus, and to evaluate the effect of clinical factors on these abilities. We included 61 preterm neonates, born between 32 and 34 weeks of gestational age. At 35 weeks of corrected gestational age, we measured orienting responses (forearm, hand, and fingers movements) during vibrotactile stimulation of their hand and forearm; during a habituation and dishabituation paradigm, the dishabituation being either a location change or a pause in the stimulation sequence. Preterm newborns displayed a manual orienting response to vibrotactile stimuli which significantly decreased when the stimulus was repeated, regardless of the stimulated location on the limb. Habituation was delayed in subjects born at a younger gestational age, smaller birth weight, and having experienced more painful care procedures. Preterm neonates perceived changes in stimulus location and interstimulus time interval. Our findings provide insights on several aspects of the perception of repeated tactile stimuli by preterm neonates, and the first evidence of the early development of temporal processing abilities in the tactile modality. Future work will investigate the links between this ability and neurodevelopmental disorders.

Somatosensory evoked changes in cerebral oxygen consumption measured non-invasively in premature neonates.

The hemodynamic functional response is used as a reliable marker of neuronal activity in countless studies of brain function and cognition. In newborns and infants, however, conflicting results have appeared in the literature concerning the typical response, and there is little information on brain metabolism and functional activation. Measurement of all hemodynamic components and oxygen metabolism is critical for understanding neurovascular coupling in the developing brain. To this end, we combined multiple near infrared spectroscopy techniques to measure oxy- and deoxy-hemoglobin concentrations, cerebral blood volume (CBV), and relative cerebral blood flow (CBF) in the somatosensory cortex of 6 preterm neonates during passive tactile stimulation of the hand. By combining these measures we estimated relative changes in the cerebral metabolic rate of oxygen consumption (rCMRO2). CBF starts increasing immediately after stimulus onset, and returns to baseline before blood volume. This is consistent with the model of pre-capillary arteriole active dilation driving the CBF response, with a subsequent CBV increase influenced by capillaries and veins dilating passively to accommodate the extra blood. rCMRO2 estimated using the steady-state formulation shows a biphasic pattern: an increase immediately after stimulus onset, followed by a post-stimulus undershoot due to blood flow returning faster to baseline than oxygenation. However, assuming a longer mean transit time from the arterial to the venous compartment, due to the immature vascular system of premature infants, reduces the post-stimulus undershoot and increases the flow/consumption ratio to values closer to adult values reported in the literature. We are the first to report changes in local rCBF and rCMRO2 during functional activation in preterm infants. The ability to measure these variables in addition to hemoglobin concentration changes is critical for understanding neurovascular coupling in the developing brain, and for using this coupling as a reliable functional imaging marker in neonates.

Cerebral oxygen metabolism in neonatal hypoxic ischemic encephalopathy during and after therapeutic hypothermia.

Pathophysiologic mechanisms involved in neonatal hypoxic ischemic encephalopathy (HIE) are associated with complex changes of blood flow and metabolism. Therapeutic hypothermia (TH) is effective in reducing the extent of brain injury, but it remains uncertain how TH affects cerebral blood flow (CBF) and metabolism. Ten neonates undergoing TH for HIE and seventeen healthy controls were recruited from the NICU and the well baby nursery, respectively. A combination of frequency domain near infrared spectroscopy (FDNIRS) and diffuse correlation spectroscopy (DCS) systems was used to non-invasively measure cerebral hemodynamic and metabolic variables at the bedside. Results showed that cerebral oxygen metabolism (CMRO2i) and CBF indices (CBFi) in neonates with HIE during TH were significantly lower than post-TH and age-matched control values. Also, cerebral blood volume (CBV) and hemoglobin oxygen saturation (SO2) were significantly higher in neonates with HIE during TH compared with age-matched control neonates. Post-TH CBV was significantly decreased compared with values during TH whereas SO2 remained unchanged after the therapy. Thus, FDNIRS-DCS can provide information complimentary to SO2 and can assess individual cerebral metabolic responses to TH. Combined FDNIRS-DCS parameters improve the understanding of the underlying physiology and have the potential to serve as bedside biomarkers of treatment response and optimization.

Non-invasive optical measurement of cerebral metabolism and hemodynamics in infants.

Perinatal brain injury remains a significant cause of infant mortality and morbidity, but there is not yet an effective bedside tool that can accurately screen for brain injury, monitor injury evolution, or assess response to therapy. The energy used by neurons is derived largely from tissue oxidative metabolism, and neural hyperactivity and cell death are reflected by corresponding changes in cerebral oxygen metabolism (CMRO2). Thus, measures of CMRO2 are reflective of neuronal viability and provide critical diagnostic information, making CMRO2 an ideal target for bedside measurement of brain health. Brain-imaging techniques such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) yield measures of cerebral glucose and oxygen metabolism, but these techniques require the administration of radionucleotides, so they are used in only the most acute cases. Continuous-wave near-infrared spectroscopy (CWNIRS) provides non-invasive and non-ionizing radiation measures of hemoglobin oxygen saturation (SO2) as a surrogate for cerebral oxygen consumption. However, SO2 is less than ideal as a surrogate for cerebral oxygen metabolism as it is influenced by both oxygen delivery and consumption. Furthermore, measurements of SO2 are not sensitive enough to detect brain injury hours after the insult, because oxygen consumption and delivery reach equilibrium after acute transients. We investigated the possibility of using more sophisticated NIRS optical methods to quantify cerebral oxygen metabolism at the bedside in healthy and brain-injured newborns. More specifically, we combined the frequency-domain NIRS (FDNIRS) measure of SO2 with the diffuse correlation spectroscopy (DCS) measure of blood flow index (CBFi) to yield an index of CMRO2 (CMRO2i). With the combined FDNIRS/DCS system we are able to quantify cerebral metabolism and hemodynamics. This represents an improvement over CWNIRS for detecting brain health, brain development, and response to therapy in neonates. Moreover, this method adheres to all neonatal intensive care unit (NICU) policies on infection control and institutional policies on laser safety. Future work will seek to integrate the two instruments to reduce acquisition time at the bedside and to implement real-time feedback on data quality to reduce the rate of data rejection.

Regional and hemispheric asymmetries of cerebral hemodynamic and oxygen metabolism in newborns.

Understanding the evolution of regional and hemispheric asymmetries in the early stages of life is essential to the advancement of developmental neuroscience. By using 2 noninvasive optical methods, frequency-domain near-infrared spectroscopy and diffuse correlation spectroscopy, we measured cerebral hemoglobin oxygenation (SO(2)), blood volume (CBV), an index of cerebral blood flow (CBF(i)), and the metabolic rate of oxygen (CMRO(2i)) in the frontal, temporal, and parietal regions of 70 premature and term newborns. In concordance with results obtained using more invasive imaging modalities, we verified both hemodynamic (CBV, CBF(i), and SO(2)) and metabolic (CMRO(2i)) parameters were greater in the temporal and parietal regions than in the frontal region and that these differences increased with age. In addition, we found that most parameters were significantly greater in the right hemisphere than in the left. Finally, in comparing age-matched males and females, we found that males had higher CBF(i) in most cortical regions, higher CMRO(2i) in the frontal region, and more prominent right-left CBF(i) asymmetry. These results reveal, for the first time, that we can detect regional and hemispheric asymmetries in newborns using noninvasive optical techniques. Such a bedside screening tool may facilitate early detection of abnormalities and delays in maturation of specific cortical areas.

Near-infrared spectroscopy assessment of cerebral oxygen metabolism in the developing premature brain.

Little is known about cerebral blood flow, cerebral blood volume (CBV), oxygenation, and oxygen consumption in the premature newborn brain. We combined quantitative frequency-domain near-infrared spectroscopy measures of cerebral hemoglobin oxygenation (SO(2)) and CBV with diffusion correlation spectroscopy measures of cerebral blood flow index (BF(ix)) to determine the relationship between these measures, gestational age at birth (GA), and chronological age. We followed 56 neonates of various GA once a week during their hospital stay. We provide absolute values of SO(2) and CBV, relative values of BF(ix), and relative cerebral metabolic rate of oxygen (rCMRO(2)) as a function of postmenstrual age (PMA) and chronological age for four GA groups. SO(2) correlates with chronological age (r=-0.54, P value ≤0.001) but not with PMA (r=-0.07), whereas BF(ix) and rCMRO(2) correlate better with PMA (r=0.37 and 0.43, respectively, P value ≤0.001). Relative CMRO2 during the first month of life is lower when GA is lower. Blood flow index and rCMRO(2) are more accurate biomarkers of the brain development than SO(2) in the premature newborns.

Assessment of the frequency-domain multi-distance method to evaluate the brain optical properties: Monte Carlo simulations from neonate to adult.

The near infrared spectroscopy (NIRS) frequency-domain multi-distance (FD-MD) method allows for the estimation of optical properties in biological tissue using the phase and intensity of radiofrequency modulated light at different source-detector separations. In this study, we evaluated the accuracy of this method to retrieve the absorption coefficient of the brain at different ages. Synthetic measurements were generated with Monte Carlo simulations in magnetic resonance imaging (MRI)-based heterogeneous head models for four ages: newborn, 6 and 12 month old infants, and adult. For each age, we determined the optimal set of source-detector separations and estimated the corresponding errors. Errors arise from different origins: methodological (FD-MD) and anatomical (curvature, head size and contamination by extra-cerebral tissues). We found that the brain optical absorption could be retrieved with an error between 8-24% in neonates and infants, while the error increased to 19-44% in adults over all source-detector distances. The dominant contribution to the error was found to be the head curvature in neonates and infants, and the extra-cerebral tissues in adults.

NIRS-measured oxy- and deoxyhemoglobin changes associated with EEG spike-and-wave discharges in a genetic model of absence epilepsy: the GAERS.

PURPOSE: Absence epilepsy may be severe and is frequently accompanied by cognitive delay, yet its metabolic/hemodynamic aspects have not been established. The Genetic Absence Epilepsy Rats from Strasbourg (GAERS) are an isomorphic, predictive, and homologous model of human absence epilepsy. We studied hemodynamic changes related to generalized spike-and-wave discharges (GSWDs) in GAERS by using a technique with high temporal resolution: near-infrared spectroscopy (NIRS). We hypothesized that conflicting results from other techniques might be due to the averaging of a biphasic response such as the one we described in children. METHODS: NIRS is particularly suitable for monitoring changes in the concentrations of oxy-, deoxy-, and total hemoglobin (HbO2, HHb, and HbT), using the specific absorption properties of living tissues in the near infrared range. We obtained concomitant high quality electroencephalography (EEG)-NIRS recordings in six GAERS (total of 444 seizures), and tested whether the discharges were related to changes in cardiac or respiration rates. RESULTS: The onset of GSWDs was preceded by a deactivation, followed by an activation that was possibly due to seizure-suppression mechanisms. The end was marked by a deactivation. The onset of GSWDs was associated with a decrease and the end with a brief increase in respiratory rate. DISCUSSION: Our results differ partially from those of previous studies on hemodynamic aspects of GSWDs (many of which describe a simple deactivation), probably due to differences in temporal resolution and data processing; however, they are consistent with metabolic studies, functional magnetic resonance imaging (fMRI) studies on WAG/Rij rats, and some results in children with absence epilepsy.

Noninvasive optical measures of CBV, StO(2), CBF index, and rCMRO(2) in human premature neonates' brains in the first six weeks of life.

With the causes of perinatal brain injuries still unclear and the probable role of hemodynamic instability in their etiology, bedside monitoring of neonatal cerebral hemodynamics with standard values as a function of age are needed. In this study, we combined quantitative frequency domain near infrared spectroscopy (FD-NIRS) measures of cerebral tissue oxygenation (StO(2)) and cerebral blood volume (CBV) with diffusion correlation spectroscopy (DCS) measures of a cerebral blood flow index (CBF(ix)) to test the validity of the CBV-CBF relationship in premature neonates and to estimate cerebral metabolic rate of oxygen (rCMRO(2)) with or without the CBF(ix) measurement. We measured 11 premature neonates (28-34 weeks gestational age) without known neurological issues, once a week from one to six weeks of age. In nine patients, cerebral blood velocities from the middle cerebral artery were collected by transcranial Doppler (TCD) and compared with DCS values. Results show a steady decrease in StO(2) during the first six weeks of life while CBV remains stable, and a steady increase in CBF(ix). rCMRO(2) estimated from FD-NIRS remains constant but shows wide interindividual variability. rCMRO(2) calculated from FD-NIRS and DCS combined increased by 40% during the first six weeks of life with reduced interindividual variability. TCD and DCS values are positively correlated. In conclusion, FD-NIRS combined with DCS offers a safe and quantitative bedside method to assess CBV, StO(2), CBF, and rCMRO(2) in the premature brain, facilitating individual follow-up and comparison among patients. A stable CBV-CBF relationship may not be valid for premature neonates.

Increased cerebral blood volume and oxygen consumption in neonatal brain injury.

With the increasing interest in treatments for neonatal brain injury, bedside methods for detecting and assessing injury status and evolution are needed. We aimed to determine whether cerebral tissue oxygenation (StO(2)), cerebral blood volume (CBV), and estimates of relative cerebral oxygen consumption (rCMRO(2)) determined by bedside frequency-domain near-infrared spectroscopy (FD-NIRS) have the potential to distinguish neonates with brain injury from those with non-brain issues and healthy controls. We recruited 43 neonates < or =15 days old and >33 weeks gestational age (GA): 14 with imaging evidence of brain injury, 29 without suspicion of brain injury (4 unstable, 6 stable, and 19 healthy). A multivariate analysis of variance with Newman-Keuls post hoc comparisons confirmed group similarity for GA and age at measurement. StO(2) was significantly higher in brain injured compared with unstable neonates, but not statistically different from stable or healthy neonates. Brain-injured neonates were distinguished from all others by significant increases in CBV and rCMRO(2). In conclusion, although NIRS measures of StO(2) alone may be insensitive to evolving brain injury, increased CBV and rCMRO(2) seem to be useful for detecting neonatal brain injury and suggest increased neuronal activity and metabolism occurs acutely in evolving brain injury.

NIRS-measured oxy- and deoxyhemoglobin changes associated with EEG spike-and-wave discharges in children.

PURPOSE: Absence epilepsy is characterized by 3-Hz generalized spike-and-wave discharges (GSWD) on the electroencephalogram, associated with behavioral arrest. It may be severe, and even in childhood benign absence epilepsy cognitive delay is frequent, yet the metabolic/hemodynamic aspects of this kind of epilepsy have not been established. We aimed to determine if the GSWD were related to hemodynamic changes by using a new technique with high temporal resolution: near infrared spectroscopy (NIRS). METHODS: NIRS is gaining acceptance as a technique particularly suitable for routine follow-up in children, using the specific absorption properties of living tissues in the near infrared range to measure changes in the concentrations of oxy-, deoxy- and total hemoglobin (HbO(2), HHb, and HbT, respectively). We performed simultaneous electroencephalography (EEG) and left frontal NIRS recordings in six children with GSWD. We also tested if the discharges were related to changes in cardiac or respiratory rates. RESULTS: GSWD were associated in the frontal area with an oxygenation (beginning 10 s before the GSWD) followed by strong deoxygenation, then oxygenation again with [HbT] increase, and a return to baseline. We did not identify any relationship between the onset of the GSWD and heart or respiratory rates. DISCUSSION: Our results partially differ from previous studies on GSWD hemodynamic aspects (many of which described a simple deactivation), probably due to differences in temporal resolution and data processing. Simultaneous acquisition of EEG and NIRS can optimize the use of both techniques and help shed light on the mechanisms underlying spike-and-wave discharges.

High-resolution electroencephalography and source localization in neonates.

Although Electroencephalography (EEG) source localization is being widely used in adults, this promising technique has not yet been applied to newborns because of technical difficulties, such as lack of data concerning the newborn skull conductivity, thickness, and homogeneity. Using a new type of EEG headcap molded on each baby's head, we aimed to determine whether this technique could be adapted to neonates, and to evaluate the importance of these technical difficulties. We carried out EEG source reconstruction of the recordings of five neonates using dipole fit algorithm. We used four different head models for each neonate, obtained from individual MRI scans: normal skull thickness and conductivity of 0.0042 S/m; normal thickness and conductivity of 0.33 S/m; increased thickness and conductivity of 0.0042 S/m; and normal thickness and conductivity with a modeled bregma fontanel. Dipole locations were consistent with MRI and clinical data. The mean difference between the dipole locations in the 0.0042 and the 0.33 S/m skull layer models was 11.6 +/- 2.5 mm, with an average 29.7% decrease in magnitude for the 0.33 S/m model but no significant changes for the dipoles orientation. Skull layer thickness had a large influence on magnitude, but no significant effect on position and orientation. The mean difference between the dipole locations induced by the modeled fontanel was 2.0 +/- 2.1 mm, with an average 2.1% increase in magnitude. Our results show that EEG source localization is feasible in neonates. With further development, the technique may prove useful for neurological evaluation of neonates.