Impact of macronutrients intake on glycemic homeostasis of preterm infants: evidence from continuous glucose monitoring.

Nutritional intake could influence the blood glucose profile during early life of preterm infants. We investigated the impact of macronutrient intake on glycemic homeostasis using continuous glucose monitoring (CGM). We analyzed macronutrient intake in infants born ≤ 32 weeks gestational age (GA) and/or with birth weight ≤ 1500 g. CGM was started within 48 h of birth and maintained for 5 days. Mild and severe hypoglycemia were defined as sensor glucose (SG) < 72 mg/dL and <47 mg/dL, respectively, while mild and severe hyperglycemia were SG > 144 mg/dL and >180 mg/dL. Data from 30 participants were included (age 29.9 weeks (29.1; 31.2), birthweight 1230.5 g (1040.0; 1458.6)). A reduced time in mild hypoglycemia was associated to higher amino acids intake (p = 0.011) while increased exposure to hyperglycemia was observed in the presence of higher lipids intake (p = 0.031). The birthweight was the strongest predictor of neonatal glucose profile with an inverse relationship between the time spent in hyperglycemia and birthweight (p = 0.007).  Conclusions: Macronutrient intakes influence neonatal glucose profile as described by continuous glucose monitoring. CGM might contribute to adjust nutritional intakes in preterm infants. What is Known: • Parenteral nutrition may affect glucose profile during the first days of life of preterm infants. What is New: • Continuous glucose monitoring describes the relationship between daily parenteral nutrient intakes and time spent in hypo and hyperglycemic ranges.

On the functional independence of numerical acuity and visual working memory.

Deciding where to direct our vehicle in a crowded parking area or where to line up at an airport gateway relies on our ability to appraise the numerosity of multitudes at a glimpse and react accordingly. Approximating numerosities without actually counting is an ontogenetically and phylogenetically primordial ability, given its presence in human infants shortly after birth, and in primate and non-primate animal species. Prior research in the field suggested that numerosity approximation is a ballistic automatism that has little to do with human cognition as commonly intended. Here, we measured visual working memory capacity using a state-of-the-art change detection task and numerosity approximation using a dot-comparison task, and found a null correlation between these two parametrical domains. By checking the evidential strength of the tested correlation using both classic and Bayesian analytical approaches, as well as the construct validity for working memory capacity and numerosity approximation estimates, we concluded that the present psychophysical evidence was sufficiently strong to support the view that visual working memory and numerosity approximation are likely to rely on functionally independent stages of processing of the human cognitive architecture.

Using multi-modal neuroimaging to characterise social brain specialisation in infants.

The specialised regional functionality of the mature human cortex partly emerges through experience-dependent specialisation during early development. Our existing understanding of functional specialisation in the infant brain is based on evidence from unitary imaging modalities and has thus focused on isolated estimates of spatial or temporal selectivity of neural or haemodynamic activation, giving an incomplete picture. We speculate that functional specialisation will be underpinned by better coordinated haemodynamic and metabolic changes in a broadly orchestrated physiological response. To enable researchers to track this process through development, we develop new tools that allow the simultaneous measurement of coordinated neural activity (EEG), metabolic rate, and oxygenated blood supply (broadband near-infrared spectroscopy) in the awake infant. In 4- to 7-month-old infants, we use these new tools to show that social processing is accompanied by spatially and temporally specific increases in coupled activation in the temporal-parietal junction, a core hub region of the adult social brain. During non-social processing, coupled activation decreased in the same region, indicating specificity to social processing. Coupling was strongest with high-frequency brain activity (beta and gamma), consistent with the greater energetic requirements and more localised action of high-frequency brain activity. The development of simultaneous multimodal neural measures will enable future researchers to open new vistas in understanding functional specialisation of the brain.

Don't plan, just do it: Cognitive and sensorimotor contributions to manual dexterity.

Manual dexterity is referred to as the skill to perform fine motor movements and it has been assumed to be associated to the cognitive domain, as well as the sensorimotor one. In this work, we investigated with functional near-infrared spectroscopy the cortical activations elicited by the execution of the 9-HPT, i.e., a standard test evaluating manual dexterity in which nine pegs were taken, placed into and then removed from nine holes on a board as quickly as possible. For comparison, we proposed a new active control task mainly involving the sensorimotor domain, in which the pegs must be placed and removed using the same single hole (1-HPT). Behaviorally, we found two distinct groups based on the difference between the execution time of the 9-HPT and the 1-HPT (ΔHPT). Cortical areas belonging to the network controlling reaching and grasping movements were active in both groups; however, participants showing a large ΔHPT presented significantly higher activation in prefrontal cortical areas (right BA10 and BA11) during 9-HPT and 1-HPT performance with respect to the participants with a small ΔHPT, who showed a deactivation in BA10. Unexpectedly, we observed a significant linear relationship between ΔHPT and right BA10 activity. This suggested that participants performing the 9-HPT more slowly than the 1-HPT recruited prefrontal areas implicitly exploiting the cognitive skills of planning, perhaps in search of a motor strategy to solve the test activating attentional and cognitive control processes, but this resulted not efficient and instead increased the time to accomplish a manual dexterity task.

Time-of-day influences resting-state functional cortical connectivity.

Time-of-day is rarely considered during experimental protocols investigating motor behavior and neural activity. The goal of this work was to investigate differences in functional cortical connectivity at rest linked to the time of the day using functional Near-Infrared Spectroscopy (fNIRS). Since resting-state brain is shown to be a succession of cognitive, emotional, perceptual, and motor processes that can be both conscious and nonconscious, we studied self-generated thought with the goal to help in understanding brain dynamics. We used the New-York Cognition Questionnaire (NYC-Q) for retrospective introspection to explore a possible relationship between the ongoing experience and the brain at resting-state to gather information about the overall ongoing experience of subjects. We found differences in resting-state functional connectivity in the inter-hemispheric parietal cortices, which was significantly greater in the morning than in the afternoon, whilst the intra-hemispheric fronto-parietal functional connectivity was significantly greater in the afternoon than in the morning. When we administered the NYC-Q we found that the score of the question 27 ("during RS acquisition my thoughts were like a television program or film") was significantly greater in the afternoon with respect to the morning. High scores in question 27 point to a form of thought based on imagery. It is conceivable to think that the unique relationship found between NYC-Q question 27 and the fronto-parietal functional connectivity might be related to a mental imagery process during resting-state in the afternoon.

Towards assessing subcortical "deep brain" biomarkers of PTSD with functional near-infrared spectroscopy.

Assessment of brain function with functional near-infrared spectroscopy (fNIRS) is limited to the outer regions of the cortex. Previously, we demonstrated the feasibility of inferring activity in subcortical "deep brain" regions using cortical functional magnetic resonance imaging (fMRI) and fNIRS activity in healthy adults. Access to subcortical regions subserving emotion and arousal using affordable and portable fNIRS is likely to be transformative for clinical diagnostic and treatment planning. Here, we validate the feasibility of inferring activity in subcortical regions that are central to the pathophysiology of posttraumatic stress disorder (PTSD; i.e. amygdala and hippocampus) using cortical fMRI and simulated fNIRS activity in a sample of adolescents diagnosed with PTSD (N = 20, mean age = 15.3 ± 1.9 years) and age-matched healthy controls (N = 20, mean age = 14.5 ± 2.0 years) as they performed a facial expression task. We tested different prediction models, including linear regression, a multilayer perceptron neural network, and a k-nearest neighbors model. Inference of subcortical fMRI activity with cortical fMRI showed high prediction performance for the amygdala (r > 0.91) and hippocampus (r > 0.95) in both groups. Using fNIRS simulated data, relatively high prediction performance for deep brain regions was maintained in healthy controls (r > 0.79), as well as in youths with PTSD (r > 0.75). The linear regression and neural network models provided the best predictions.

Glucose variability increases during minimally invasive procedures in very preterm infants.

The objective of this study is to assess the effect of neonatal procedures on glucose variability in very preterm infants. Preterm infants (≤ 32 weeks gestation and/or birthweight ≤ 1500 g) were started on continuous glucose monitoring (CGM) on day 2 of birth and monitored for 5 days. Minimally invasive (heel stick, venipunctures) and non-invasive (nappy change, parental presence) procedures were recorded. CGM data were analyzed 30 min before and after each procedure. The primary outcome was the coefficient of glucose variation (CV = SD/mean) before and after the procedure; SD and median glucose were also evaluated. We analyzed 496 procedures in 22 neonates (GA 30.5 weeks [29-31]; birthweight 1300 g [950-1476]). Median glucose did not change before and after each procedure, while CV and SD increased after heel prick (p = 0.017 and 0.030), venipuncture (p = 0.010 and 0.030), and nappy change (p < 0.001 and < 0.001), in the absence of a difference during parental presence. CONCLUSIONS: Non-invasive and minimally invasive procedures increase glucose variability in the absence of changes of mean glucose. WHAT IS KNOWN: • Minimally invasive procedures - including nappy change - may increase neonatal stress in preterm infants. WHAT IS NEW: • Continuous glucose monitoring provides a quantitative measure of neonatal stress during neonatal care procedures demonstrating an increase of glucose variability.

Optical imaging and spectroscopy for the study of the human brain: status report.

This report is the second part of a comprehensive two-part series aimed at reviewing an extensive and diverse toolkit of novel methods to explore brain health and function. While the first report focused on neurophotonic tools mostly applicable to animal studies, here, we highlight optical spectroscopy and imaging methods relevant to noninvasive human brain studies. We outline current state-of-the-art technologies and software advances, explore the most recent impact of these technologies on neuroscience and clinical applications, identify the areas where innovation is needed, and provide an outlook for the future directions.

On target selection as reflected by posterior ERP components in feature-guided visual search.

The N2pc event-related potential is a widely studied ERP component that reflects the covert deployment of visuo-spatial attention to target stimuli displayed laterally relative to fixation. Recently, an analogous ERP component, named N2pcb, has been proposed as a marker of the deployment of visuo-spatial attention to targets displayed on the vertical midline. Two studies that investigated the N2pcb component found analogous results, using however two different algorithms to compute the amplitude of N2pcb. One study subtracted the ipsilateral activity elicited by a lateral target from the bilateral activity elicited by a target displayed on the vertical midline, whereas the other study subtracted the bilateral activity elicited by target-absent displays from the bilateral activity elicited by a target displayed on the vertical midline. Here we show both algorithms estimate properly the N2pc as well as the N2pcb components. In addition, we explored whether the singleton detection positivity (SDP) component, a posterior bilateral positivity temporally concomitant to N2pc recently reported in studies using singleton search, could be observed in the present study in which a target was defined by a combination of features. Given that such component was indeed found using feature search, we named this component posterior processing positivity (PPP), and showed that bilateral activity elicited by target-absent displays is an adequate baseline for its correct isolation.

Smartphone-based photogrammetry provides improved localization and registration of scalp-mounted neuroimaging sensors.

Functional near infrared spectroscopy and electroencephalography are non-invasive techniques that rely on sensors placed over the scalp. The spatial localization of the measured brain activity requires the precise individuation of sensor positions and, when individual anatomical information is not available, the accurate registration of these sensor positions to a head atlas. Both these issues could be successfully addressed using a photogrammetry-based method. In this study we demonstrate that sensor positions can be accurately detected from a video recorded with a smartphone, with a median localization error of 0.7 mm, comparable if not lower, to that of conventional approaches. Furthermore, we demonstrate that the additional information of the shape of the participant's head can be further exploited to improve the registration of the sensor's positions to a head atlas, reducing the median sensor localization error of 31% compared to the standard registration approach.

A bilateral SPCN is elicited by to-be-memorized visual stimuli displayed along the vertical midline.

We recently showed that deploying attention to target stimuli displayed along the vertical meridian elicits a bilateral N2pc, that we labeled N2pcb (Psychophysiology). Here we investigated whether a different component, the sustained posterior contralateral negativity (SPCN), shows the same property when a varying number of visual stimuli are displayed either laterally or on the vertical meridian. We displayed one or two cues that designated candidate targets to be detected in a search array that was displayed after a retention interval. The cues were either on the horizontal meridian or on the vertical meridian. When the cues were on the horizontal meridian, we observed an N2pc followed by an SPCN in their classic form, as negativity increments contralateral to the cues. As expected, SPCN amplitude was greater when two cues had to be memorized than when only one cue had to be memorized. When the cues were on the vertical meridian, we observed an N2pcb followed by a bilateral SPCN (or SPCNb). Critically, like SPCN, SPCNb amplitude was greater when two cues had to be memorized than when only one cue had to be memorized. A series of additional parametrical and topographical comparisons between N2pcb and SPCNb revealed similarities but also some important differences between these two components that we interpreted as evidence for their distinct neural sources.

A neural network predicting the amplitude of the N2pc in individual EEG datasets.

Objective.The N2pc is a small amplitude transient interhemispheric voltage asymmetry used in cognitive neuroscience to investigate subject's allocation of selective visuo-spatial attention. N2pc is typically estimated by averaging the sweeps of the electroencephalographic (EEG) signal but, in absence of explicit normative indications, the number of sweeps is often based on arbitrariness or personal experience. With the final aim of reducing duration and cost of experimental protocols, here we developed a new approach to reliably predict N2pc amplitude from a minimal EEG dataset.Approach.First, features predictive of N2pc amplitude were identified in the time-frequency domain. Then, an artificial neural network (NN) was trained to predict N2pc mean amplitude at the individual level. By resorting to simulated data, accuracy of the NN was assessed by computing the mean squared error (MSE) and the amplitude discretization error (ADE) and compared to the standard time averaging (TA) technique. The NN was then tested against two real datasets consisting of 14 and 12 subjects, respectively.Main result.In simulated scenarios entailing different number of sweeps (between 10 and 100), the MSE obtained with the proposed method resulted, on average, 1/5 of that obtained with the TA technique. Implementation on real EEG datasets showed that N2pc amplitude could be reliably predicted with as few as 40 EEG sweeps per cell of the experimental design.Significance.The developed approach allows to reduce duration and cost of experiments involving the N2pc, for instance in studies investigating attention deficits in pathological subjects.

fNIRS & e-drum: An ecological approach to monitor hemodynamic and behavioural effects of rhythmic auditory cueing training.

Converging evidence suggests a beneficial effect of rhythmic music-therapy in easing motor dysfunctions. Nevertheless, the neural systems underpinning both the direct effect and the influence of rhythm on movement control and execution during training in ecological settings are still largely unknown. In this study, we propose an ecological approach to monitor brain activity and behavioural performance during rhythmic auditory cueing short-term training. Our approach envisages the combination of functional near-infrared spectroscopy (fNIRS), which is a non-invasive neuroimaging technique that allows unconstrained movements of participants, with electronic drum (e-drum), which is an instrument able to collect behavioural tapping data in real time. The behavioural and brain effects of this short-term training were investigated on a group of healthy participants, who well tolerated the experimental settings, since none of them withdrew from the study. The rhythmic auditory cueing short-term training improved beat regularity and decreased group variability. At the group level, the training resulted in a reduction of brain activity primarily in premotor areas. Furthermore, participants with the highest behavioural improvement during training showed the smallest reduction in brain activity. Overall, we conclude that our study could pave the way towards translating the proposed approach to clinical settings.

Multivariate analysis of the systemic response to auditory stimulation: An integrative approach.

NEW FINDINGS: What is the central question of this study? Auditory stimulation produces a response in different physiological systems: cardiac, peripheral blood flow, electrodermal, cortical and peripheral haemodynamic responses and auditory event-related potentials. Do all these subsystems covary when responding to auditory stimulation, suggesting a unified locus of control, or do they not covary, suggesting independent loci of control for these physiological responses? What is the main finding and its importance? Auditory sensory gating reached a fixed level of neural activity independently of the intensity of auditory stimulation. The use of multivariate techniques revealed the presence of different regulatory mechanisms for the different physiologically recorded signals. ABSTRACT: We studied the effects of an increasing amplitude of auditory stimulation on a variety of autonomic and CNS responses and their possible interdependence. The subjects were stimulated with an increasing amplitude of auditory tones while the auditory event-related potentials (ERPs), the cortical and extracerebral functional near-infrared spectroscopy (fNIRS) signal of standard and short separation channel recordings, the peripheral pulse measured by photoplethysmography, heart rate and electrodermal responses were recorded. Trials with eight tones of equal amplitude were presented. The results showed a parallel increase of activity in ERPs, fNIRS and peripheral responses with the increase in intensity of auditory stimulation. The ERPs, measured as peak-to-peak N1-P2, showed an increase in amplitude with auditory stimulation and a high attenuation from the first presentation with respect to the second to eighth presentations. Peripheral signals and standard and short channel fNIRS responses showed a decrease in amplitude in the high-intensity auditory stimulation conditions. Principal components analysis showed independent sources of variance for the recorded signals, suggesting independent control of the recorded physiological responses. The present results suggest a complex response associated to the increase of auditory stimulation with a fixed amplitude for ERPs, and a decrease in the peripheral and cortical haemodynamic response, possibly mediated by activation of the sympathetic nervous system, constituting a defensive reflex to excessive auditory stimulation.

Altering sensorimotor simulation impacts early stages of facial expression processing depending on individual differences in alexithymic traits.

Simulation models of facial expressions suggest that posterior visual areas and brain areas underpinning sensorimotor simulations might interact to improve facial expression processing. According to these models, facial mimicry, a manifestation of sensorimotor simulation, may contribute to the visual processing of facial expressions by influencing early stages. The aim of this study was to assess whether and how sensorimotor simulation influences early stages of face processing, also investigating its relationship with alexithymic traits given that previous studies have suggested that individuals with high levels of alexithymic traits (vs. individuals with low levels of alexithymic traits) tend to use sensorimotor simulation to a lesser extent. We monitored P1 and N170 ERP components of the event-related potentials (ERP) in participants performing a fine discrimination task of facial expressions and animals, as a control condition. In half of the experiment, participants could freely use their facial mimicry whereas in the other half they had their facial mimicry blocked by a gel. Our results revealed that only individuals with lower compared to high alexithymic traits showed a larger modulation of the P1 amplitude as a function of the mimicry manipulation selectively for facial expressions (but not for animals), while we did not observe any modulation of the N170. Given the null results at the behavioural level, we interpreted the P1 modulation as compensative visual processing in individuals with low levels of alexithymia under conditions of interference on the sensorimotor processing, providing a preliminary evidence in favor of sensorimotor simulation models.

Accurate hemodynamic response estimation by removal of stimulus-evoked superficial response in fNIRS signals.

Objective.We address the problem of hemodynamic response (HR) estimation when task-evoked extra-cerebral components are present in functional near-infrared spectroscopy (fNIRS) signals. These components might bias the HR estimation; therefore, careful and accurate denoising of data is needed.Approach.We propose a dictionary-based algorithm to process each single event-related segment of the acquired signal for both long separation (LS) and short separation (SS) channels. Stimulus-evoked components and physiological noise are modeled by means of two distinct waveform dictionaries. For each segment, after removal of the physiological noise component in each channel, a template is employed to estimate stimulus-evoked responses in both channels. Then, the estimate from the SS channel is employed to correct the evoked superficial response and refine the HR estimate from the LS channel.Main results.Analysis of simulated, semi-simulated and real data shows that, by averaging single-segment estimates over multiple trials in an experiment, reliable results and improved accuracy compared to other methods can be obtained. The average estimation error of the proposed method for the semi-simulated data set is 34% for oxy-hemoglobin (HbO) and 78% for deoxy-hemoglobin (HbR), considering 40 trials. The proposed method outperforms the results of the methods proposed in the literature. While still far from the possibility of single-trial HR estimation, a significant reduction in the number of averaged trials can also be obtained.Significance.This work proves that dedicated dictionaries can be successfully employed to model all different components of fNIRS signals. We demonstrate the effectiveness of a specifically designed algorithm structure in dealing with a complex denoising problem, enhancing the possibilities of fNIRS-based HR analysis.

Construction and validation of a database of head models for functional imaging of the neonatal brain.

The neonatal brain undergoes dramatic structural and functional changes over the last trimester of gestation. The accuracy of source localisation of brain activity recorded from the scalp therefore relies on accurate age-specific head models. Although an age-appropriate population-level atlas could be used, detail is lost in the construction of such atlases, in particular with regard to the smoothing of the cortical surface, and so such a model is not representative of anatomy at an individual level. In this work, we describe the construction of a database of individual structural priors of the neonatal head using 215 individual-level datasets at ages 29-44 weeks postmenstrual age from the Developing Human Connectome Project. We have validated a method to segment the extra-cerebral tissue against manual segmentation. We have also conducted a leave-one-out analysis to quantify the expected spatial error incurred with regard to localising functional activation when using a best-matching individual from the database in place of a subject-specific model; the median error was calculated to be 8.3 mm (median absolute deviation 3.8 mm). The database can be applied for any functional neuroimaging modality which requires structural data whereby the physical parameters associated with that modality vary with tissue type and is freely available at www.ucl.ac.uk/dot-hub.

Regional Haemodynamic and Metabolic Coupling in Infants.

Metabolic pathways underlying brain function remain largely unexplored during neurodevelopment, predominantly due to the lack of feasible techniques for use with awake infants. Broadband near-infrared spectroscopy (bNIRS) provides the opportunity to explore the relationship between cerebral energy metabolism and blood oxygenation/haemodynamics through the measurement of changes in the oxidation state of mitochondrial respiratory chain enzyme cytochrome-c-oxidase (ΔoxCCO) alongside haemodynamic changes. We used a bNIRS system to measure ΔoxCCO and haemodynamics during functional activation in a group of 42 typically developing infants aged between 4 and 7 months. bNIRS measurements were made over the right hemisphere over temporal, parietal and central cortical regions, in response to social and non-social visual and auditory stimuli. Both ΔoxCCO and Δ[HbO2] displayed larger activation for the social condition in comparison to the non-social condition. Integration of haemodynamic and metabolic signals revealed networks of stimulus-selective cortical regions that were not apparent from analysis of the individual bNIRS signals. These results provide the first spatially resolved measures of cerebral metabolic activity alongside haemodynamics during functional activation in infants. Measuring synchronised changes in metabolism and haemodynamics have the potential for uncovering the development of cortical specialisation in early infancy.

A Time-Frequency Analysis for the Online Detection of the N2pc Event-Related Potential (ERP) Component in Individual EEG Datasets.

The N2pc event-related potential component measures direction and time course of selective visual attention and represents an important biomarker in cognitive neuroscience. While its subtractive origin strongly influences the amplitude, thus hindering its detection, other external factors, such as subject's inefficiency to allocate attention to the cued target, or the heterogeneity of the visual context, may strongly affect the elicitation of the component itself. It would therefore be extremely important to create a tool that, using as few sweeps as possible, could reliably establish whether an N2pc is present in an individual subject. In the present work, we propose an approach by resorting to a time-frequency analysis of N2pc individual signals; in particular, power at each frequency band (α/ß/δ/θ) was computed in the N2 time range and correlated to the estimated amplitude of the N2pc. Preliminary results on fourteen human volunteers of a visual search design showed a very high correlation coefficient (over 0.9) between the low frequency bands power and the mean absolute amplitude of the component, using only 40 sweeps. Results also seemed to suggest that N2pc amplitude values higher than 0.5 µV could be accurately classified according to time-frequency indices.Clinical Relevance - The online detection of the N2pc presence in individual EEG datasets would allow not only to study the factors responsible of N2pc variability across subjects and conditions, but also to investigate novel search variants on participants with a predisposition to show an N2pc, reducing time and costs and the possibility to obtain biased results.