Imaging Cerebral Energy Metabolism in Healthy Infants.

Broadband near-infrared spectroscopy (bNIRS) has the potential to provide non-invasive measures of cerebral haemodynamic changes alongside changes in cellular oxygen utilisation through the measurement of mitochondrial enzyme cytochrome-c-oxidase (oxCCO). It therefore provides the opportunity to explore brain function and specialisation, which remains largely unexplored in infancy. We used bNIRS to measure changes in haemodynamics and changes in oxCCO in 4-to-7-month-old infants over the occipital and right temporal and parietal cortices in response to social and non-social visual and auditory stimuli. Changes in concentration of oxygenated-haemoglobin (Δ[HbO2]), deoxygenated haemoglobin (Δ[HHb]) and change in the oxidation state of oxCCO (Δ[oxCCO]) were calculated using changes in attenuation of light at 120 wavelengths between 780 and900 nm, using the UCLn algorithm. For 4 infants, the attenuation changes in a subset of wavelengths were used to perform image reconstruction, in an age-matched infant model, for channels over the right parietal and temporal cortices, using a multispectral approach which allows direct reconstruction of concentration change data. The volumetric reconstructed images were mapped onto the cortical surface to visualise the reconstructed changes in concentration of HbO2 and HHb and changes in metabolism for both social and non-social stimuli. Spatially localised activation was observed for Δ[oxCCO] and Δ[HbO2] over the temporo-parietal region, in response to the social stimulus. This study provides the first reconstructed images of changes in metabolism in healthy, awake infants.

Estrogen-related receptor gamma regulates mitochondrial and synaptic genes and modulates vulnerability to synucleinopathy.

Many studies implicate mitochondrial dysfunction as a key contributor to cell loss in Parkinson disease (PD). Previous analyses of dopaminergic (DAergic) neurons from patients with Lewy-body pathology revealed a deficiency in nuclear-encoded genes for mitochondrial respiration, many of which are targets for the transcription factor estrogen-related receptor gamma (Esrrg/ERRγ). We demonstrate that deletion of ERRγ from DAergic neurons in adult mice was sufficient to cause a levodopa-responsive PD-like phenotype with reductions in mitochondrial gene expression and number, that partial deficiency of ERRγ hastens synuclein-mediated toxicity, and that ERRγ overexpression reduces inclusion load and delays synuclein-mediated cell loss. While ERRγ deletion did not fully recapitulate the transcriptional alterations observed in postmortem tissue, it caused reductions in genes involved in synaptic and mitochondrial function and autophagy. Altogether, these experiments suggest that ERRγ-deficient mice could provide a model for understanding the regulation of transcription in DAergic neurons and that amplifying ERRγ-mediated transcriptional programs should be considered as a strategy to promote DAergic maintenance in PD.

Special Issue on new therapeutic approaches to Parkinson disease.

Parkinson's disease (PD) is a common neurodegenerative disorder. Age is the biggest risk factor, with the prevalence rising from 1% in 45-54 year age group to 2-4% in 85 year or older. Population increases have led some to predict that we are facing a 'PD Pandemic' with the prevalence doubling in the next two decades. There is thus an urgent need for effective therapies to reduce disease burden. In this Special Issue of Neuropharmacology invited authors have reviewed current and emerging targets for pharmacological therapy for PD covering the areas of disease modification, i.e. addressing the underlying disease processes, through to symptomatic therapies, whether for motor or non-motor symptoms of the disease. The articles are from leaders in the field and represent preclinical and clinical stages of therapeutic development. The Special Issue highlights that there is ongoing significant activity across all these potential indications and a vast array of targets have been identified and validated to different extents. PD is, and will remain for the foreseeable future, for the neuropharmacologist a significant area of research, in both the preclinical and clinical space.

Estrogen-related Receptor Alpha (ERRα) is Required for PGC-1α-dependent Gene Expression in the Mouse Brain.

Deficiency in peroxisome proliferator-activated receptor gamma coactivator 1-alpha. (PGC-1α) expression or function is implicated in numerous neurological and psychiatric disorders. PGC-1α is required for the expression of genes involved in synchronous neurotransmitter release, axonal integrity, and metabolism, especially in parvalbumin-positive interneurons. As a transcriptional coactivator, PGC-1α requires transcription factors to specify cell-type-specific gene programs; while much is known about these factors in peripheral tissues, it is unclear if PGC-1α utilizes these same factors in neurons. Here, we identified putative transcription factors controlling PGC-1α-dependent gene expression in the brain using bioinformatics and then validated the role of the top candidate in a knockout mouse model. We transcriptionally profiled cells overexpressing PGC-1α and searched for over-represented binding motifs in the promoters of upregulated genes. Binding sites of the estrogen-related receptor (ERR) family of transcription factors were enriched, and blockade of ERRα attenuated PGC-1α-mediated induction of mitochondrial and synaptic genes in cell culture. Localization in the mouse brain revealed enrichment of ERRα expression in parvalbumin-expressing neurons with tight correlation of expression with PGC-1α across brain regions. In ERRα null mice, PGC-1α-dependent genes were reduced in multiple regions, including neocortex, hippocampus, and cerebellum, though not to the extent observed in PGC-1α null mice. Behavioral assessment revealed ambulatory hyperactivity in response to amphetamine and impairments in sensorimotor gating without the overt motor impairment characteristic of PGC-1α null mice. These data suggest that ERRα is required for normal levels of expression of PGC-1α-dependent genes in neurons but that additional factors may be involved in their regulation.

Prophylactic mesh augmentation using permanent synthetic mesh: outcomes of keyhole and Stapled Ostomy Reinforcement with Retromuscular Mesh techniques.

INTRODUCTION: Parastomal hernias (PSH) are the most common complication of stoma creation and can cause significant morbidity. We present a consecutive series of patients receiving prophylactic mesh augmentation (PMA) for prevention of PSH. METHODS: This retrospective review evaluates the efficacy and outcomes of PMA for PSH prevention, and retrospectively compares traditional keyhole PMA (tPMA) (n = 28) with a prophylactic Stapled Ostomy Reinforcement with Retromuscular Mesh technique (pSTORRM) (n = 24). RESULTS: PMA was performed in 52 cases between January 2015 and July 2018. All cases used a large-pore, non-coated, mid-weight polypropylene mesh placed in the retrorectus space. With a median follow-up of 16 mos, parastomal hernia was confirmed in 11.5% (n = 6), 5 of whom were symptomatic. patient-reported outcomes (PRO) indicated 6 additional patients with symptoms associated with PSH without clinical or radiographic confirmation. Patients had similar comorbidities and operative characteristics between tPMA and pSTORRM techniques, and no difference in a median follow-up. pSTORRM patients had fewer surgical site infections (8.3 vs 32.1%; p = 0.046) and occurrences (12.5 vs 46.4%; p = 0.015), and lower rate of PSH, though not statistically significant (4.2 vs 17.9%; p = 0.195). CONCLUSION: Permanent synthetic mesh placed as a sublay in the retromuscular space is safe and appears to decrease the risk of PSH formation after the creation of permanent stomas. A stapled technique may provide advantages over a traditional keyhole technique.

Early COVID-19 pandemic modeling: Three compartmental model case studies from Texas, USA.

The novel coronavirus (SARS-CoV-2) emerged in late 2019 and spread globally in early 2020. Initial reports suggested the associated disease, COVID-19, produced rapid epidemic growth and caused high mortality. As the virus sparked local epidemics in new communities, health systems and policy makers were forced to make decisions with limited information about the spread of the disease. We developed a compartmental model to project COVID-19 healthcare demands that combined information regarding SARS-CoV-2 transmission dynamics from international reports with local COVID-19 hospital census data to support response efforts in three Metropolitan Statistical Areas (MSAs) in Texas, USA: Austin-Round Rock, Houston-The Woodlands-Sugar Land, and Beaumont-Port Arthur. Our model projects that strict stay-home orders and other social distancing measures could suppress the spread of the pandemic. Our capacity to provide rapid decision-support in response to emerging threats depends on access to data, validated modeling approaches, careful uncertainty quantification, and adequate computational resources.

The selective 5-HT1A receptor agonist, NLX-112, exerts anti-dyskinetic effects in MPTP-treated macaques.

BACKGROUND: Long-term treatment of Parkinson's disease (PD) with l-DOPA typically leads to development of l-DOPA induced dyskinesia (LID). Amantadine, an NMDA antagonist, attenuates LID, but with limited efficacy and considerable side-effects. NLX-112 (also known as befiradol or F13640), a highly selective and efficacious 5-HT1A receptor agonist, reduced LID when tested in rodent and marmoset models of PD. METHODS: The effects of NLX-112 (0.03, 0.1 and 0.3 mg/kg PO) on established LID evoked by acute challenge with l-DOPA (27.5 ± 3.8 mg/kg PO) were assessed in MPTP-treated cynomolgus macaques. Amantadine (10 mg/kg PO) was tested as a positive control. Plasma exposure of NLX-112 (0.1 mg/kg PO) was determined. RESULTS: NLX-112 significantly and dose-dependently reduced median LID levels by up to 96% during the first hour post-administration (0.3 mg/kg). Moreover, NLX-112 reduced the duration of 'bad on-time' associated with disabling LID by up to 48% (0.3 mg/kg). In contrast, NLX-112 had negligible impact on the anti-parkinsonian benefit of l-DOPA. NLX-112 exposure peaked at ~50 ng/ml at 30 min post-administration but decreased to ~15 ng/ml at 2h. Amantadine reduced by 42% 'bad on-time' associated with l-DOPA, thereby validating the model. CONCLUSION: These data show that, in MPTP-lesioned cynomolgus macaques, NLX-112 exerts robust anti-dyskinetic effects, without reducing the anti-parkinsonian benefit of l-DOPA. These observations complement previous findings and suggest that selective and high efficacy activation of 5-HT1A receptors by NLX-112 may constitute a promising approach to combat LID in PD, providing an alternative for patients in whom amantadine is poorly tolerated or without useful effect.

A Role for PGC-1α in Transcription and Excitability of Neocortical and Hippocampal Excitatory Neurons.

The transcriptional coactivator peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) is a critical regulator of genes involved in neuronal metabolism, neurotransmission, and morphology. Reduced PGC-1α expression has been implicated in several neurological and psychiatric disorders. An understanding of PGC-1α's roles in different cell types will help determine the functional consequences of PGC-1α dysfunction and/or deficiency in disease. Reports from our laboratory and others suggest a critical role for PGC-1α in inhibitory neurons with high metabolic demand such as fast-spiking interneurons. Here, we document a previously unrecognized role for PGC-1α in maintenance of gene expression programs for synchronous neurotransmitter release, structure, and metabolism in neocortical and hippocampal excitatory neurons. Deletion of PGC-1α from these neurons caused ambulatory hyperactivity in response to a novel environment and enhanced glutamatergic transmission in neocortex and hippocampus, along with reductions in mRNA levels from several PGC-1α neuron-specific target genes. Given the potential role for a reduction in PGC-1α expression or activity in Huntington Disease (HD), we compared reductions in transcripts found in the neocortex and hippocampus of these mice to that of an HD knock-in model; few of these transcripts were reduced in this HD model. These data provide novel insight into the function of PGC-1α in glutamatergic neurons and suggest that it is required for the regulation of structural, neurosecretory, and metabolic genes in both glutamatergic neuron and fast-spiking interneuron populations in a region-specific manner. These findings should be considered when inferring the functional relevance of changes in PGC-1α gene expression in the context of disease.

Management of the axilla in breast cancer: outcome analysis in a series of ductal versus lobular invasive cancers.

INTRODUCTION: Axillary lymph node dissection (ALND) has been considered essential for the staging of breast cancer (BC). As the impact of tumor biology on clinical outcomes is recognized, a surgical de-escalation approach is being implemented. We performed a retrospective study focused on surgical management of the axilla in invasive lobular carcinoma (ILC) versus invasive ductal carcinoma (IDC). MATERIALS AND METHODS: 1151 newly diagnosed BCs, IDCs (79.6%) or ILCs (20.4%), were selected among patients treated at our Breast Cancer Unit from 2012 to 2018. Tumor characteristics and clinical information were collected and predictors of further metastasis after positive sentinel lymph node biopsy (SLNB) analyzed in relation to disease-free survival (DFS) and overall survival (OS). RESULTS: 27.5% of patients with ILC had ≥ 3 metastatic lymph nodes at ALND after positive SLNB versus 11.48% of IDCs (p = 0.04). Risk predictors of further metastasis at ALND were the presence of > 2 positive lymph nodes at SLNB (OR = 4.72, 95% CI 1.15-19.5 p = 0.03), T3-T4 tumors (OR = 4.93, 95% CI 1.10-22.2, p = 0.03) and Non-Luminal BC (OR = 2.74, 95% CI 1.16-6.50, p = 0.02). The lobular histotype was not associated with the risk of further metastasis at ALND (OR = 1.62, 95% CI 0.77-3.41, p = 0.20). CONCLUSIONS: ILC histology is not associated with higher risk of further metastasis at ALND in our analysis. However, surgical management decisions should be taken considering tumor histotype, biology and expected sensitivity to adjuvant therapies.

Fabrication of Bioengineered Skin by Injection Molding: A Feasibility Study on Automation.

The use of bioengineered skin has facilitated fundamental and applied research because it enables the investigation of complex interactions between various cell types as well as the extracellular matrix. The predominantly manual fabrication of these living tissues means, however, that their quality, standardization, and production volume are extremely dependent on the technician's experience. Simple laboratory automation could facilitate the use of living tissues by a greater number of research groups. We developed and present here an injection molding technique for the fabrication of bilayered skin equivalents. The tissue was formed automatically by two separate injections into a customized mold to produce the dermal and epidermal skin layers. We demonstrated the biocompatibility of this fabrication process and confirmed the resulting bilayered morphology of the bioengineered skin using histology and immunohistochemistry. Our findings highlight the possibility of fabricating multilayered living tissue by injection molding, suggesting that further investigation into this automation method could result in the rapid and low-cost fabrication of standardized bioengineered skin.

A simplified fabrication technique for cellularized high-collagen dermal equivalents.

Human autologous bioengineered skin has been successfully developed and used to treat skin injuries in a growing number of cases. In current clinical studies, the biomaterial used is fabricated via plastic compression of collagen hydrogel to increase the density and stability of the tissue. To further facilitate clinical adoption of bioengineered skin, the fabrication technique needs to be improved in terms of standardization and automation. Here, we present a one-step mixing technique using highly concentrated collagen and human fibroblasts to simplify fabrication of stable dermal equivalents. As controls, we prepared cellularized dermal equivalents with three varying collagen compositions. We found that the dermal equivalents produced using the simplified mixing technique were stable and pliable, showed viable fibroblast distribution throughout the tissue, and were comparable to highly concentrated manually produced collagen gels. Because no subsequent plastic compression of collagen is required in the simplified mixing technique, the fabrication steps and production time for dermal equivalents are consistently reduced. The present study provides a basis for further investigations to optimize the technique, which has significant promise in enabling efficient clinical production of bioengineered skin in the future.

Psychometric evaluation of a measure of factors influencing hand hygiene behaviour to inform intervention.

BACKGROUND: Although the hand hygiene (HH) procedure is simple, the related behaviour is complex and is not readily understood, explained or changed. There is a need for practical tools to provide data that can guide healthcare managers and practitioners not only on the 'what' (the standards that must be met), but also the 'how' (guidance on how to achieve the standards). AIM: To develop a valid questionnaire to evaluate attitudes to the factors that influence engagement in HH behaviour that can be readily completed, administered and analysed by healthcare professionals to identify appropriate intervention strategies. Construct validity was assessed using confirmatory factor analysis, predictive validity was assessed through comparison with self-reported HH behaviour, and convergent validity was assessed through direct unit-level observation of HH behaviour. METHODS: The Capability, Opportunity, Motivation-Behaviour (COM-B) model was used to design a 25-item questionnaire that was distributed to intensive care unit (ICU) personnel in Ireland. Direct observation of HH behaviour was carried out at two ICUs. FINDINGS: In total, 292 responses to the survey (response rate 41.0%) were included in the analysis. Confirmatory factor analysis resulted in a 17-item questionnaire. Multiple regression revealed that a model including capability, opportunity and motivation was a significant predictor of self-reported behavioural intention [F(3,209)=22.58, P<0.001]. However, the opportunity factor was not found to make a significant contribution to the regression model. CONCLUSION: The COM-B HH questionnaire is reliable and valid, and provides data to support the development and evaluation of HH interventions that meet the needs of specific healthcare units.

Cumulative live birth rates and perinatal outcomes with the use of time-lapse imaging incubators for embryo culture: a retrospective cohort study of 1882 ART cycles.

OBJECTIVE: Comparison of live birth rates and the perinatal outcomes after fresh and frozen embryo transfer between time-lapse imaging (TLI) and standard culture (SC) incubators. DESIGN: Retrospective cohort study. SETTING: A single tertiary level IVF unit. POPULATION: Women undergoing IVF between January 2014 and October 2015. METHODS: Comparison was done between 1064 IVF cycles using TLI (TLI cycles) and 818 IVF cycles using SC (SC cycles). MAIN OUTCOME MEASURES: Cumulative live birth rate per oocyte retrieval and perinatal outcomes including birthweight, gestational age, preterm birth (PTB) (<37 weeks), early preterm birth (PTB; <32 weeks), low birthweight (LBW; <2500 g), very LBW (<1500 g) and macrosomia (>4500 g). RESULTS: The fresh embryo transfer live birth rate was noted to be higher for TLI cycles [TLI 36.8 versus SC 33.9%, adjusted odds ratio (aOR) 1.28, 95% CI 1.05-1.57], but the frozen embryo transfer live birth rates were not significantly different. The mean birthweight was higher in the TLI group after both fresh [adjusted mean difference (aMD) 174.78 g, 95% CI 64.80-284.77] and frozen embryo transfers (aMD 175.91 g, 95% CI 16.98-334.84). After a fresh embryo transfer, there was a lower risk of early PTB and very LBW in the TLI group. Among frozen embryo transfers, there was a lower risk of early PTB and LBW in the TLI group. CONCLUSIONS: TLI incubators are associated with improved perinatal outcomes and higher mean birthweight after fresh and frozen embryo transfer. TWEETABLE ABSTRACT: Time-lapse imaging incubators in IVF improve perinatal outcomes after both fresh and frozen embryo transfers.

Hand or spoon? Exploring the neural basis of affective touch in 5-month-old infants.

In adults, affective touch leads to widespread activation of cortical areas including posterior Superior Temporal Sulcus (pSTS) and Inferior Frontal Gyrus (IFG). Using functional Near Infrared Spectroscopy (fNIRS), we asked whether similar areas are activated in 5-month-old infants, by comparing affective to non-affective touch. We contrasted a human touch stroke to strokes performed with a cold metallic spoon. The hypothesis that adult-like activation of cortical areas would be seen only in response to the human touch stroke was not confirmed. Similar patterns of activation were seen in both conditions. We conclude that either the posterior STS and IFG have not yet developed selective responses to affective touch, or that additional social cues are needed to be able to identify this type of touch.

Changes in Cytochrome-C-Oxidase Account for Changes in Attenuation of Near-Infrared Light in the Healthy Infant Brain.

A novel multi-wavelength broadband near infrared spectroscopy (NIRS) system has been employed to simultaneously measure haemodynamic changes alongside changes in cellular oxygen utilization by measurement of oxidation state of mitochondrial enzyme cytochrome-c-oxidase (oxCCO). The aim of this study was to investigate the role of oxCCO in neural responses to functional activation in infants. Studies were performed using a NIRS broadband system in 33 typically developing infants aged between 4 and 6 months. Responses were recorded over the right temporal lobe while infants were presented with engaging videos containing social and non-social content. Changes in the concentration of oxyhaemoglobin (Δ[HbO2]), deoxyhaemoglobin (Δ[HHb]) and Δ[oxCCO] were calculated using changes in attenuation of light at 120 wavelengths between 780 and 900 nm using the UCLn algorithm. The algorithm was also used to fit (a) HbO2 and HHb spectra (2 component fit) and (b) HbO2, HHb and oxCCO (3 component fit) to the change in attenuation occurring within an experimental block in different participants. Residuals resulting from these two fits were compared with oxidized-minus reduced CCO spectrum, calculated using the CCO specific extinction coefficient. A significant increase in oxCCO was found in response to the social stimuli (maximum increase 0.238 ± 0.13 µM). Residuals analysis showed that the best fits were achieved when oxCCO was included as a tissue chromophore. These results are the first reported significant change in oxCCO to stimulus-evoked activation in infants and may reveal vital information about oxygen metabolism during functional activation in the developing human brain.

A Remote Assay for Measuring Canine Platelet Activation and the Inhibitory Effects of Antiplatelet Agents.

BACKGROUND: Antiplatelet medications are increasingly used in dogs. Remote analysis of platelet activity is challenging, limiting assessment of antiplatelet drug efficacy. HYPOTHESIS/OBJECTIVES: To evaluate a method used in humans for stimulation and remote analysis of canine platelet activity. ANIMALS: Forty-five dogs of various ages without a coagulopathy or thrombocytopenia. Six were receiving antiplatelet medication. METHODS: Prospective observational study. Platelets were stimulated with combinations of arachidonic acid (AA) and epinephrine (Epi) or adenosine diphosphate (ADP) and the thromboxane A2 -mimetic U46619 (U4). PAMFix was added to the blood samples to facilitate delayed analysis of platelet activity. Activity was assessed by flow cytometric measurement of surface P-selectin (CD62P) expression. RESULTS: Canine platelets could be stimulated with both AA/Epi and ADP/U4. The levels of P-selectin were significantly greater than paired, unstimulated samples (P < 0.001). Inhibition of P-selectin expression occurred after this stimulation by adding antiplatelet drugs in vitro. The efficacy of antiplatelet drugs in samples from treated dogs was also measurable ex vivo using this method. Delayed analysis of platelet activity at time points up to 22 days demonstrated excellent correlation between respective mf values at each time point (r2  = 0.92, P < 0.0001). CONCLUSIONS AND CLINICAL IMPORTANCE: This study evaluated a new method to remotely assess canine platelet activity. It shows that PAMFix can be used for this purpose. This provides opportunities to interrogate the inhibitory action of antiplatelet drugs in clinical settings.

Cortical responses before 6 months of life associate with later autism.

Autism spectrum disorder (ASD) is a common, highly heritable, developmental disorder and later-born siblings of diagnosed children are at higher risk of developing ASD than the general population. Although the emergence of behavioural symptoms of ASD in toddlerhood is well characterized, far less is known about development during the first months of life of infants at familial risk. In a prospective longitudinal study of infants at familial risk followed to 36 months, we measured functional near-infrared spectroscopy (fNIRS) brain responses to social videos of people (i.e. peek-a-boo) compared to non-social images (vehicles) and human vocalizations compared to non-vocal sounds. At 4-6 months, infants who went on to develop ASD at 3 years (N = 5) evidenced-reduced activation to visual social stimuli relative to low-risk infants (N = 16) across inferior frontal (IFG) and posterior temporal (pSTS-TPJ) regions of the cortex. Furthermore, these infants also showed reduced activation to vocal sounds and enhanced activation to non-vocal sounds within left lateralized temporal (aMTG-STG/pSTS-TPJ) regions compared with low-risk infants and high-risk infants who did not develop ASD (N = 15). The degree of activation to both the visual and auditory stimuli correlated with parent-reported ASD symptomology in toddlerhood. These preliminary findings are consistent with later atypical social brain responses seen in children and adults with ASD, and highlight the need for further work interrogating atypical processing in early infancy and how it may relate to later social interaction and communication difficulties characteristic of ASD.

Molecular classification of autofluorescence excision margins in oral potentially malignant disorders.

OBJECTIVE: To define molecular differences between autofluorescence and white light defined excision margins in oral potentially malignant disorders (OPMD) using transcriptome expression profiles. MATERIALS AND METHODS: Excisional biopsy specimens were taken from 11 patients at three different sites for each lesion: centre, white light margin and autofluorescence margin. The lesions were diagnosed histopathologically as oral epithelial dysplasia, oral lichenoid dysplasia, oral lichen planus or other. Transcriptome analysis was performed by RNA sequencing, hierarchical clustering, differential expression and biological pathway analysis. RESULTS: For hierarchical clustering, the samples broadly clustered according to histology rather than the margins with lichenoid samples clustering together. Differential expression analysis showed that independent of histology, there was greater molecular dysregulation between the lesion centre and autofluorescence margin compared to the lesion centre and white light margin. Furthermore, the autofluorescence and white light margins were molecularly distinct, indicating the white light margins harboured abnormality. CONCLUSION: Our results indicate that the molecular profile of OPMD changes with divergence away from the centre of the lesion, and that autofluorescence determined margins are superior to the white light margin in achieving a clear molecular margin when excising an OPMD.

Cortical specialisation to social stimuli from the first days to the second year of life: A rural Gambian cohort.

Brain and nervous system development in human infants during the first 1000days (conception to two years of age) is critical, and compromised development during this time (such as from under nutrition or poverty) can have life-long effects on physical growth and cognitive function. Cortical mapping of cognitive function during infancy is poorly understood in resource-poor settings due to the lack of transportable and low-cost neuroimaging methods. Having established a signature cortical response to social versus non-social visual and auditory stimuli in infants from 4 to 6 months of age in the UK, here we apply this functional Near Infrared Spectroscopy (fNIRS) paradigm to investigate social responses in infants from the first postnatal days to the second year of life in two contrasting environments: rural Gambian and urban UK. Results reveal robust, localized, socially selective brain responses from 9 to 24 months of life to both the visual and auditory stimuli. In contrast at 0-2 months of age infants exhibit non-social auditory selectivity, an effect that persists until 4-8 months when we observe a transition to greater social stimulus selectivity. These findings reveal a robust developmental curve of cortical specialisation over the first two years of life.