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Blanco, B.

Publications and source records attributed to Blanco, B..

10 recordsLinked to original sources

Caregiver-infant interactions selectively shape emerging functional connectivity in the neonatal brain

From birth, human infants engage in multi-modal social exchanges with caregivers that involve the coordination of gaze and touch to guide attention and support neurodevelopment. However, little is known about the association between these first interactive experiences and the functional organization of the developing brain during the first postnatal month, a window of remarkable brain growth in humans. We address this gap by combining microanalytic coding of caregiver- infant interactions with task-free functional connectivity (FC), measured using high-density diffuse optical tomography (HD-DOT) in infants homes during the first postnatal month. Task-free FC measures the intrinsic functional organization of the developing brain, shedding light on the early development of neural systems supporting perception, regulation, and social interactions. Infants were assessed up to three times (1 week, 2 weeks, 1 month), enabling characterization of both early FC and its rapid developmental change. Caregiver-infant interactions were associated with both concurrent organization and rapid longitudinal change in FC. Dyadic engagement in the context of face-to-face interaction was associated with the refinement of short-range connectivity and the integration of long-range connectivity particularly between social brain regions, while affectionate touch was associated with general increases in long-distance connectivity. These results demonstrate that caregiving experiences influence the development of the brains functional architecture in the first postnatal month, highlighting a critical window for shaping infant brain function. Significance StatementThe first postnatal weeks are a period of rapid brain development, when the brain may be especially sensitive to experience. A key early experience is social interaction between infants and their caregivers, yet it remains unknown if these interactions influence neonate brain function. By combining observations of caregiver-infant interactions at one month with repeated home-based brain imaging, we show that variations in dyadic engagement and affectionate touch influence how infant brain functional connectivity is organized and develops. These findings highlight the importance of supporting perinatal life and early interactions for infant brain development.

neuroscience↗

Young children rely on visual information to process degraded speech: Evidence from behavioural and neuroimaging measures

Young children acquire language in environments where speech is often acoustically degraded, yet little is known about how developing brains adapt to reduced speech intelligibility. Using a combination of eye-tracking and functional near-infrared spectroscopy (fNIRS), we investigated young childrens attentional allocation to a speaking face at varying levels of speech intelligibility and the brain activity supporting this behaviour during development. Infants (8-10 months) and toddlers (27-30 months) viewed videos of a speaker in three conditions: producing clear speech, spectrally degraded (vocoded) speech, and silent (audio muted) speech. Visual attention to the speakers mouth increased when speech was degraded relative to clear speech in both age groups, indicating an early-emerging compensatory strategy. However, this shared behavioural response was supported by brain activity that differed by age. Degraded speech elicited greater recruitment of prefrontal regions associated with effortful listening, particularly in infants, whereas toddlers showed stronger engagement of posterior temporal regions implicated in audiovisual integration. In response to silent speech, there was no evidence for increased visual attention to the mouth compared to the clear speech condition, but there was reduced temporal activation and increased prefrontal brain responses, especially in infants. Together, these findings suggest that experience with audiovisual correspondences and linguistic maturity contribute to a more efficient processing of speech, particularly relevant when speech is degraded. By combining behavioural and neuroimaging measures, this study advances mechanistic accounts of audiovisual speech processing and provides insights relevant to populations experiencing spectrally degraded input, such as children using cochlear implants.

neuroscience↗

Investigating the effect of channel pruning on functional near-infrared spectroscopy data collected from children aged 5-24 months

SignificanceInfant functional near-infrared spectroscopy (fNIRS) data are particularly vulnerable to noise; participant behaviour can result in motion artefacts and reduced set-up times can cause poor optode coupling. Accurate channel pruning is therefore essential but approaches vary and often use adult-derived thresholds, risking unnecessary data loss. AimThis work systematically compared pruning approaches and parameter choices to evaluate their effects on data quality and retention in infant fNIRS. ApproachData from 5-24 month-old infants were collected across two cohorts, using two paradigms. Channel pruning was performed using the coefficient of variation (CV) and the Quality Testing of Near Infrared Scans (QT-NIRS) tool, varying key thresholds. Multilevel models assessed effects of pruning method, parameter choice, age, motion, and testing site on signal-to-noise ratio (SNR) and channels retained. ResultsQT-NIRS produced significantly higher SNR than CV pruning across nearly all age, task, and cohort combinations, when matched for data retention. Higher QT-NIRS thresholds improved quality but reduced retention. Motion prevalence strongly reduced both SNR and retention; testing site and age had smaller but notable effects. ConclusionsQT-NIRS offers a better balance of data quality and retention than CV pruning. Lower QT-NIRS thresholds than adult defaults are recommended for infant data. These findings provide practical guidance for preprocessing pipelines in developmental fNIRS research.

neuroscience↗

Examining Cross-Paradigm fNIRS Brain Activity in Neonates across The Gambia and UK

SignificanceNeonates undergo rapid development, yet the examination of emerging brain markers across paradigms, cognitive domains and diverse global populations remains limited. AimThis study investigated whether brain responses at one-month-of-age could be interrogated across paradigms to offer deeper context-specific insights into neurodevelopment. ApproachFunctional near-infrared spectroscopy (fNIRS) was used to assess frontal and temporal brain responses during natural sleep in 181 Gambian (GM) and 58 UK infants during three auditory paradigms: Social Selectivity, Habituation and Novelty Detection (HaND) and Functional Connectivity (FC). Paradigm-level brain responses were analysed using threshold-free cluster enhancement and cross-paradigm comparisons of individual responses. ResultsAt the group level, both GM and UK infants showed habituation but not novelty responses, higher inter-versus intra-hemispheric connectivity, stronger inter-hemispheric connectivity in temporal regions relative to frontal regions, stronger inter-regional connectivity between right temporal and left frontal regions, and UK infants also showed non-vocal > vocal selectivity. ConclusionsCross-cohort differences in the cross-paradigm analyses suggest context-specific developmental markers are evident within the first month of life and show high individual variability. Cross-paradigm analyses revealed that greater vocal selectivity (UK) was associated with higher inter-hemispheric connectivity, potentially allowing us to identify biomarkers of more mature neurodevelopment within the first weeks of postnatal life.

neuroscience↗

Effect of sleep stages on patterns of fNIRS hemodynamic response to auditory paradigms in one-month-old Gambian and UK infants

SignificanceFunctional near-infrared spectroscopy (fNIRS) has advanced our understanding of early brain development, especially infant responses to social and auditory stimuli. Unlike older children and adults, very young infants are often assessed during natural sleep to reduce movement and ensure sufficient data quality. Yet the impact of sleep stage on fNIRS signals and how it might affect interpretations of early brain activation patterns remains unclear. AimThis study investigates the effect of sleep stages on fNIRS-measured hemodynamic responses to two auditory paradigms across different global populations of one-month-old infants. ApproachIn total, 46 Gambian and 40 UK infants in quiet or active sleep were tested using (1) social selectivity and (2) a habituation and novelty detection paradigms. ResultsIn the UK cohort, active sleep was associated with a stronger initial response and greater habituation compared to quiet sleep. In contrast, Gambian infants in quiet sleep showed more widespread activation and evidence of habituation, while infants in active sleep showed no habituation. No sleep stage effects were observed for response in the social selectivity paradigm in either group. ConclusionsDifferent effects of sleep stages were observed across the two cohorts and paradigms and should be carefully considered in neuroimaging studies.

neuroscience↗

Functional specialisation across the first five years of life: a longitudinal characterisation of social perception with fNIRS

Research in typically developing infants has shown robust and consistent brain activation to social versus non-social visual and auditory stimuli in a network of brain regions, including the inferior frontal, anterior temporal and posterior superior temporal cortex. However, large-scale, longitudinal neuroimaging studies across early childhood, particularly in low- and middle-income countries are rare, yet important, given that they offer a powerful means of capturing within-person changes in neurodevelopment and identifying targets for intervention and support. Here we investigated brain responses to social perception longitudinally across the first five years of life of participants in The Gambia with functional near-infrared spectroscopy (fNIRS) within the Brain Imaging for Global Health (BRIGHT) Project. We found that social visual stimuli elicited a selective right posterior temporal response across all six age points studied here (5, 8, 12, 18, 24 months and 3-5 years of age), with concurrent selective left responses at four of the six time points (5, 8, 18 months and 3-5 years of age). Inferior frontal regions showed brain activation at multiple ages, with the youngest (5 months) and oldest (24 months to 3-5 years) time points evidencing more widespread frontal social visual responses. Conversely, auditory social stimuli elicited a significantly stronger and more prolonged response than auditory non-social stimuli across all six age points from 5 months to 3-5 years across a range of frontal and temporal areas. Finally, from individual infant trajectories of brain activation, we identified different profiles of age-dependent specialisation to auditory social stimuli, with some specialising earlier than others. Future work could take advantage of such profiles to investigate the effects of adversity and resilience factors on neurodevelopment.

neuroscience↗

Co-Activation Patterns in Neonates using High-Density Diffuse Optical Tomography: Insights into Early Dynamic Functional Connectivity

SignificanceDynamic functional connectivity (FC) in neonates is a growing area of interest due to the developmental significance of early functional networks. There are several emerging techniques to measure dynamic FC, adding new perspectives to well-studied static FC networks. Recent dynamic FC studies suggest that adult resting-state networks are driven by key moments of dynamic activity rather than sustained correlations. Co-activation pattern (CAP) analysis leverages this theory, clustering high-activity frames to identify recurring configurations of significant activity. High-density diffuse optical tomography (HD-DOT) is an infant-friendly modality that measures hemodynamic changes in the cortex and has been used to investigate static FC in term-aged infants. CAP analysis has not yet been applied to neonatal HD-DOT and may reveal temporal features of early functional networks that are not apparent from static methods. AimThis study applies CAP analysis to neonatal HD-DOT to characterize transient co-activation states and provide new insight into early functional brain networks beyond what is known from static FC methods alone. ApproachTask-free HD-DOT data were acquired from a cohort of sleeping term newborns at the Rosie Hospital, Cambridge UK (n = 44, postmenstrual age = 40+3 (range: 38+2-42+6) weeks). In each recording, the top 15% of seed-selected frames were clustered using the K-means algorithm for three regions of interest (ROIs: frontal, central, and parietal) to identify significant seed-associated patterns of co-activation or co-deactivation. These co-activation patterns (CAPs) were characterized for each infant using four metrics: consistency, fractional occupancy, dwell time, and transition likelihood. ResultsDistinct CAPs, reflecting the dynamic organization of neonatal cortical networks, were identified for frontal, central, and parietal regions. These CAPs showed high consistency scores, reflecting high intra-cluster spatial correlation and validating the efficacy of CAP analysis for newborn HD-DOT data. The CAP decomposition revealed significant patterns not observed in conventional static functional connectivity analyses. Several neonatal CAPs exhibited frontoparietal co-activation, potentially reflecting early default mode network activity, which is immature and modular for the first year after birth. ConclusionsThis work demonstrates the utility of CAP analysis with newborn HD-DOT and provides new insight into the dynamics of neonatal functional connectivity.

neuroscience↗

CD4+ tumor-infiltrating lymphocytes secreting T cell-engagers induce regression of autologous patient-derived non-small cell lung cancer xenografts

Adoptive transfer of tumor-infiltrating lymphocytes (TIL) has shown remarkable results in melanoma, but only modest clinical benefit in other cancers, even after TIL have been genetically modified to improve their tumor homing, cytotoxic potential or overcoming cell exhaustion. The required ex vivo TIL expansion process may induce changes in the T cell clonal composition, which could likely compromise the tumor reactivity of TIL preparations and ultimately the success of TIL therapy. A promising approach based on the production of bispecific T cell engagers (TCE) by engineered T cells (STAb-T therapy) improves the efficacy of current T cell redirection strategies against tumor-associated antigens in hematological tumors. We studied the TCR{beta} repertoire in non-small cell lung cancer (NSCLC) tumors and in ex vivo expanded TIL from two unrelated patients. We generated TIL secreting anti-epidermal growth factor receptor (EGFR) x anti-CD3 TCE (TILSTAb) and tested their antitumor efficacy in vitro and in vivo using a NSCLC patient-derived xenograft (PDX) model in which tumor fragments and TIL from the same patient were transplanted into hIL-2 NOG mice. We confirmed that the standard TIL expansion protocol promotes the loss of tumor-dominant T cell clones and the overgrowth of virus-reactive TCR clonotypes that were marginally detectable in primary tumors. We demonstrated the antitumor activity of TILSTAb both in vitro and in vivo when administered intratumorally and systemically in an autologous immune-humanized PDX EGFR+ NSCLC mouse model, where tumor regression was mediated by TCE-redirected CD4+ TIL bearing non-tumor dominant clonotypes. SIGNIFICANCEEpithelial tumor-derived TIL can be engineered to secrete TCE capable of redirecting T cells bearing non-tumor-dominant clonotypes regardless of their phenotype, which could have broad applications in immunotherapy for solid tumors.

cancer biology↗

Functional brain adaptations during speech processing in 4-month-old bilingual infants

Language learning is influenced by both neural development and environmental experiences. This work investigates the influence of early bilingual experience on the neural mechanisms underlying speech processing in 4-month-old infants. We study how an early environmental factor such as bilingualism interacts with neural development by comparing monolingual and bilingual infants brain responses to speech. We used functional near-infrared spectroscopy (fNIRS) to measure 4-month-old Spanish-Basque bilingual and Spanish monolingual infants brain responses while they listened to forward (FW) and backward (BW) speech stimuli in Spanish. We reveal distinct neural signatures associated with bilingual adaptations, including increased engagement of bilateral inferior frontal and temporal regions during speech processing in bilingual infants, as opposed to left hemispheric specialization observed in monolingual infants. This study provides compelling evidence of bilingualism-induced brain adaptations during speech processing in infants as young as four months. These findings emphasize the role of early language experience in shaping neural plasticity during infancy suggesting that bilingual exposure at this young age profoundly influences the neural mechanisms underlying speech processing. Research HighlightsO_LIThis research sheds light on the intricate relationship between language learning, neural maturation, and environmental factors in early infancy. C_LIO_LIBilingual infants exhibit unique functional brain adaptations during speech processing as early as 4 months of age. C_LIO_LIThis study underscores the critical role of language experience in shaping the developing brain. C_LIO_LIThese findings have implications for our understanding of language acquisition and neuroplasticity in infants growing up in bilingual environments. C_LI

neuroscience↗

Monolingual and bilingual infants rely on the same brain networks: Evidence from resting-state functional connectivity

This study examines whether bilingual exposure has a profound effect on the functional organization of the developing human brain during infancy. Recent behavioural research attests that monolingual vs. bilingual experience affects cognitive and linguistic processes already during the first months of life. However, to what extent the intrinsic organization of the infant human brain adapts to monolingual vs. bilingual environments is unclear. We measured spontaneous hemodynamic brain activity using functional near-infrared spectroscopy (fNIRS) in a large cohort (N=99) of 4-month-old monolingual and bilingual infants. We implemented well-established analysis approaches of functional brain imaging that enabled us to reveal the functional organization of the infant brain in large-scale cortical networks, and to perform group-level comparisons (i.e., monolingual vs. bilingual groups) in a reliable manner. Our results revealed no differences between the intrinsic functional organization of the developing monolingual and bilingual infant brain at 4 months of age.

neuroscience↗