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Introduction: Underlying mechanisms of speech perception masked by background speakers, a common daily listening condition, are often investigated using various and lengthy psychophysical tests. The presence of a social agent, such as an interactive humanoid NAO robot, may help maintain engagement and attention. However, such robots potentially have limited sound quality or processing speed., Methods: As a first step toward the use of NAO in psychophysical testing of speech- in-speech perception, we compared normal-hearing young adults' performance when using the standard computer interface to that when using a NAO robot to introduce the test and present all corresponding stimuli. Target sentences were presented with colour and number keywords in the presence of competing masker speech at varying target-to-masker ratios. Sentences were produced by the same speaker, but voice differences between the target and masker were introduced using speech synthesis methods. To assess test performance, speech intelligibility and data collection duration were compared between the computer and NAO setups. Human-robot interaction was assessed using the Negative Attitude Toward Robot Scale (NARS) and quantification of behavioural cues (backchannels)., Results: Speech intelligibility results showed functional similarity between the computer and NAO setups. Data collection durations were longer when using NAO. NARS results showed participants had a relatively positive attitude toward "situations of interactions" with robots prior to the experiment, but otherwise showed neutral attitudes toward the "social influence" of and "emotions in interaction" with robots. The presence of more positive backchannels when using NAO suggest higher engagement with the robot in comparison to the computer., Discussion: Overall, the study presents the potential of the NAO for presenting speech materials and collecting psychophysical measurements for speech-in-speech perception., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Meyer, Araiza-Illan, Rachman, Gaudrain and Başkent.)

Background: Interactions between the somatosensory and motor cortices are of fundamental importance for motor control. Although physically distant, face and hand representations are side by side in the sensorimotor cortex and interact functionally. Traumatic brachial plexus injury (TBPI) interferes with upper limb sensorimotor function, causes bilateral cortical reorganization, and is associated with chronic pain. Thus, TBPI may affect sensorimotor interactions between face and hand representations., Objective: The aim of this study was to investigate changes in hand-hand and face-hand sensorimotor integration in TBPI patients using an afferent inhibition (AI) paradigm., Method: The experimental design consisted of electrical stimulation (ES) applied to the hand or face followed by transcranial magnetic stimulation (TMS) to the primary motor cortex to activate a hand muscle representation. In the AI paradigm, the motor evoked potential (MEP) in a target muscle is significantly reduced when preceded by an ES at short-latency (SAI) or long-latency (LAI) interstimulus intervals. We tested 18 healthy adults (control group, CG), evaluated on the dominant upper limb, and nine TBPI patients, evaluated on the injured or the uninjured limb. A detailed clinical evaluation complemented the physiological investigation., Results: Although hand-hand SAI was present in both the CG and the TBPI groups, hand-hand LAI was present in the CG only. Moreover, less AI was observed in TBPI patients than the CG both for face-hand SAI and LAI., Conclusion: Our results indicate that sensorimotor integration involving both hand and face sensorimotor representations is affected by TBPI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Torres, Ramalho, Rodrigues, Schmaedeke, Moraes, Reilly, Carvalho and Vargas.)

Experiencing chronic stress significantly increases the risk for depression. Depression is a complex disorder with varied symptoms across patients. However, feeling of sadness and decreased motivation, and diminished feeling of pleasure (anhedonia) appear to be core to most depressive pathology. Odorants are potent signals that serve a critical role in social interactions, avoiding danger, and consummatory behaviors. Diminished quality of olfactory function is associated with negative effects on quality of life leading to and aggravating the symptoms of depression. Odor hedonic value (I like or I dislike this smell) is a dominant feature of olfaction and guides approach or avoidance behavior of the odor source. The neural representation of the hedonic value of odorants is carried by the granule cells in the olfactory bulb, which functions to modulate the cortical relay of olfactory information. The granule cells of the olfactory bulb and those of the dentate gyrus are the two major populations of cells in the adult brain with continued neurogenesis into adulthood. In hippocampus, decreased neurogenesis has been linked to development or maintenance of depression symptoms. Here, we hypothesize that chronic mild stress can alter olfactory hedonics through effects on the olfactory bulb neurogenesis, contributing to the broader anhedonia phenotype in stress-associated depression. To test this, mice were subjected to chronic unpredictable mild stress and then tested on measures of depressive-like behaviors, odor hedonics, and measures of olfactory neurogenesis. Chronic unpredictable mild stress led to a selective effect on odor hedonics, diminishing attraction to pleasant but not unpleasant odorants, an effect that was accompanied by a specific decrease in adult neurogenesis and of the percentage of adult-born cells responding to pleasant odorants in the olfactory bulb., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Athanassi, Breton, Chalençon, Brunelin, Didier, Bath and Mandairon.)

Introduction: Ketamine, a glutamate NMDA receptor antagonist, is suggested to act very rapidly and durably on the depressive symptoms including treatment-resistant patients but its mechanisms of action remain unclear. There is a requirement for non-invasive biomarkers, such as imaging techniques, which hold promise in monitoring and elucidating its therapeutic impact., Methods: We explored the glucose metabolism with [ 18 F]FDG positron emission tomography (PET) in ten male rats in a longitudinal study designed to compare imaging patterns immediately after acute subanaesthetic ketamine injection (i.p. 10 mg/kg) with its sustained effects, 5 days later. Changes in [ 18 F]FDG uptake following ketamine administration were estimated using a voxel-based analysis with SPM12 software, and a region of interest (ROI) analysis. A metabolic connectivity analysis was also conducted to estimate the immediate and delayed effects of ketamine on the inter-individual metabolic covariance between the ROIs., Results: No significant difference was observed in brain glucose metabolism immediately following acute subanaesthetic ketamine injection. However, a significant decrease of glucose uptake appeared 5 days later, reflecting a sustained and delayed effect of ketamine in the frontal and the cingulate cortex. An increase in the raphe, caudate and cerebellum was also measured. Moreover, metabolic connectivity analyses revealed a significant decrease between the hippocampus and the thalamus at day 5 compared to the baseline., Discussion: This study showed that the differences in metabolic profiles appeared belatedly, 5 days after ketamine administration, particularly in the cortical regions. Finally, this methodology will help to characterize the effects of future molecules for the treatment of treatment resistant depression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chaib, Bouillot, Bouvard, Vidal, Zimmer and Levigoureux.)

Attention-Deficit hyperactivity disorder (ADHD) is a central nervous system (CNS) disorder frequently associated with other psychiatric disorders. Pathophysiology processes at stake in ADHD are still under investigation and interestingly neuroimaging data points to modulated brain connectivity in patients. The genetic spontaneously hypertensive rat (SHR) model has been widely used to study pathophysiological underpinnings of ADHD and resting-state brain connectivity using functional magnetic resonance imaging. Here, functional ultrasound imaging, a new technique enabling fast measurement of cerebral blood volume (CBV), was used to further characterize resting-state functional connectivity - at both local and long-range - and visual response in SHR. We demonstrated that response to visual stimulation was increased in SHR in the visual cortex and the superior colliculus. They displayed altered long-range functional connectivity between spatially distinct regions. SHR also displayed modulated local connectivity, with strong increases of regional homogeneity in parts of the motor and visual cortex, along with decreases in the secondary cingulate cortex, the superior colliculus and the pretectal area. As CBV is intricately coupled to cerebral activity, these results suggest an abnormal neural activity in the SHR animal model, consistent with previous clinical studies and demonstrate the potential of functional ultrasound imaging as a translational tool in ADHD., Competing Interests: MD, BV, FM, and MC are full-time employees of Theranexus company. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Droguerre, Vidal, Valdebenito, Mouthon, Zimmer and Charvériat.)

The left hemisphere preference for verbal stimuli is well known, with a right ear (RE) advantage obtained when competing verbal stimuli are presented simultaneously, at comfortable intensities, to both ears. Speech perception involves not only the processing of acoustic peripheral information but also top-down contextual influences, filling the gaps in the incoming information that is particularly degraded in hearing-impaired individuals. This study aimed to analyze the potential asymmetry of those contextual influences on a simple speech perception task in hearing-impaired patients in light of hemispheric asymmetry. Contextual influences on disyllabic word perception scores of 60 hearing-impaired patients were compared between left ear (LE) and RE, in a balanced design, involving two repetitions of the same task. Results showed a significantly greater contextual influence on the RE versus the LE and, for the second repetition versus the first one, without any interaction between the two. Furthermore, the difference in contextual influences between RE and LE increased significantly with the RE advantage measured by a dichotic listening test in the absence of any significant correlation with hearing threshold asymmetry. Lastly, the contextual influence asymmetry decreased significantly as age increased, which was mainly due to a greater increase, with age, of contextual influences on the LE versus the RE. Those results agree with the literature reporting a relative right-shift of hemispheric asymmetry observed with age in speech in noise perception tasks in normal hearing subjects and the clinical reports of generally better audiometric speech scores obtained in RE versus LE., Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Moulin.)

The development of reliable assistive devices for patients that suffer from motor impairments following central nervous system lesions remains a major challenge in the field of non-invasive Brain-Computer Interfaces (BCIs). These approaches are predominated by electroencephalography and rely on advanced signal processing and machine learning methods to extract neural correlates of motor activity. However, despite tremendous and still ongoing efforts, their value as effective clinical tools remains limited. We advocate that a rather overlooked research avenue lies in efforts to question neurophysiological markers traditionally targeted in non-invasive motor BCIs. We propose an alternative approach grounded by recent fundamental advances in non-invasive neurophysiology, specifically subject-specific feature extraction of sensorimotor bursts of activity recorded via (possibly magnetoencephalography-optimized) electroencephalography. This path holds promise in overcoming a significant proportion of existing limitations, and could foster the wider adoption of online BCIs in rehabilitation protocols., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Papadopoulos, Bonaiuto and Mattout.)

During the past decade, several studies have identified electroencephalographic (EEG) correlates of selective auditory attention to speech. In these studies, typically, listeners are instructed to focus on one of two concurrent speech streams (the "target"), while ignoring the other (the "masker"). EEG signals are recorded while participants are performing this task, and subsequently analyzed to recover the attended stream. An assumption often made in these studies is that the participant's attention can remain focused on the target throughout the test. To check this assumption, and assess when a participant's attention in a concurrent speech listening task was directed toward the target, the masker, or neither, we designed a behavioral listen-then-recall task (the Long-SWoRD test). After listening to two simultaneous short stories, participants had to identify keywords from the target story, randomly interspersed among words from the masker story and words from neither story, on a computer screen. To modulate task difficulty, and hence, the likelihood of attentional switches, masker stories were originally uttered by the same talker as the target stories. The masker voice parameters were then manipulated to parametrically control the similarity of the two streams, from clearly dissimilar to almost identical. While participants listened to the stories, EEG signals were measured and subsequently, analyzed using a temporal response function (TRF) model to reconstruct the speech stimuli. Responses in the behavioral recall task were used to infer, retrospectively, when attention was directed toward the target, the masker, or neither. During the model-training phase, the results of these behavioral-data-driven inferences were used as inputs to the model in addition to the EEG signals, to determine if this additional information would improve stimulus reconstruction accuracy, relative to performance of models trained under the assumption that the listener's attention was unwaveringly focused on the target. Results from 21 participants show that information regarding the actual - as opposed to, assumed - attentional focus can be used advantageously during model training, to enhance subsequent (test phase) accuracy of auditory stimulus-reconstruction based on EEG signals. This is the case, especially, in challenging listening situations, where the participants' attention is less likely to remain focused entirely on the target talker. In situations where the two competing voices are clearly distinct and easily separated perceptually, the assumption that listeners are able to stay focused on the target is reasonable. The behavioral recall protocol introduced here provides experimenters with a means to behaviorally track fluctuations in auditory selective attention, including, in combined behavioral/neurophysiological studies., Competing Interests: CM was employed by the company Starkey France, S.a.r.l. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Huet, Micheyl, Parizet and Gaudrain.)

The interactions between epilepsy and sleep are numerous and the impact of epilepsy on cognition is well documented. Epilepsy is therefore likely to influence dreaming as one sleep-related cognitive activity. The frequency of dream recall is indeed decreased in patients with epilepsy, especially in those with primary generalized seizures. The content of dreams is also disturbed in epilepsy patients, being more negative and with more familiar settings. While several confounding factors (anti-seizure medications, depression and anxiety disorders, cognitive impairment) may partly account for these changes, some observations suggest an effect of seizures themselves on dreams. Indeed, the incorporation of seizure symptoms in dream content has been described, concomitant or not with a focal epileptic discharge during sleep, suggesting that epilepsy might directly or indirectly interfere with dreaming. These observations, together with current knowledge on dream neurophysiology and the links between epilepsy and sleep, suggest that epilepsy may impact not only wake- but also sleep-related cognition., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 de la Chapelle, Frauscher, Valomon, Ruby and Peter-Derex.)

Donepezil is a potent acetylcholinesterase inhibitor, largely used worldwide to alleviate cognitive symptoms in Alzheimer's disease (AD). Beyond the widely described neuronal impact of donepezil, it was recently shown that targeting connexins, the proteins involved in astrocyte network organization, potentiates donepezil efficacy profile using behavioral tests in AD rodent models. We herein present data demonstrating the potential of functional ultrasound imaging to monitor cerebral activity changes after pharmacological challenge in mice. As an example, we showed that although administration of donepezil or mefloquine alone at low dose had only very limited effects on the signal compared to the baseline, their combination produced marked hemodynamic effects in the hippocampus, in line with previously published behavioral data demonstrating a synergic interaction between both drugs. Thus, the present study provides new perspectives, (i) through the use of pharmaco-fUS, a new non-clinical imaging modality, to move forward drug discovery in AD and (ii) by the profiling of two drug treatments on brain dynamics, one used in AD: donepezil, and the other in development: donepezil combined with mefloquine (THN201) as a modulator of astrocyte network., (Copyright © 2020 Vidal, Droguerre, Valdebenito, Zimmer, Hamon, Mouthon and Charvériat.)

Machine learning classification techniques are frequently applied to structural and resting-state fMRI data to identify brain-based biomarkers for developmental disorders. However, task-related fMRI has rarely been used as a diagnostic tool. Here, we used structural MRI, resting-state connectivity and task-based fMRI data to detect congenital amusia, a pitch-specific developmental disorder. All approaches discriminated amusics from controls in meaningful brain networks at similar levels of accuracy. Interestingly, the classifier outcome was specific to deficit-related neural circuits, as the group classification failed for fMRI data acquired during a verbal task for which amusics were unimpaired. Most importantly, classifier outputs of task-related fMRI data predicted individual behavioral performance on an independent pitch-based task, while this relationship was not observed for structural or resting-state data. These results suggest that task-related imaging data can potentially be used as a powerful diagnostic tool to identify developmental disorders as they allow for the prediction of symptom severity., (Copyright © 2019 Albouy, Caclin, Norman-Haignere, Lévêque, Peretz, Tillmann and Zatorre.)

Background: The accurate assessment of patients with disorders of consciousness (DOC) is a challenge to most experienced clinicians. As a potential clinical tool, functional magnetic resonance imaging (fMRI) could detect residual awareness without the need for the patients' actual motor responses., Methods: We adopted a simple active fMRI motor paradigm (hand raising) to detect residual awareness in these patients. Twenty-nine patients were recruited. They met the diagnosis of minimally conscious state (MCS) (male = 6, female = 2; n = 8), vegetative state/unresponsive wakefulness syndrome (VS/UWS) (male = 17, female = 4; n = 21)., Results: We analyzed the command-following responses for robust evidence of statistically reliable markers of motor execution, similar to those found in 15 healthy controls. Of the 29 patients, four (two MCS, two VS/UWS) could adjust their brain activity to the "hand-raising" command, and they showed activation in motor-related regions (which could not be discovered in the own-name task)., Conclusion: Longitudinal behavioral assessments showed that, of these four patients, two in a VS/UWS recovered to MCS and one from MCS recovered to MCS+ (i.e., showed command following). In patients with no response to hand raising task, six VS/UWS and three MCS ones showed recovery in follow-up procedure. The simple active fMRI "hand-raising" task can elicit brain activation in patients with DOC, similar to those observed in healthy volunteers. Activity of the motor-related network may be taken as an indicator of high-level cognition that cannot be discerned through conventional behavioral assessment., (Copyright © 2019 Wang, Hu, Hu, Jing, Heine, Thibaut, Huang, Yan, Wang, Schnakers, Laureys and Di.)

The eye drives non-visual (NV) responses to light, including circadian resetting, pupillary reflex and alerting effects. Initially thought to depend on melanopsin-expressing retinal ganglion cells (ipRGCs), classical photopigments play a modulatory role in some of these responses. As most studies have investigated only a limited number of NV functions, generally under conditions of relatively high light levels and long duration of exposure, whether NV functions share similar irradiance sensitivities and response dynamics during light exposure is unknown. We addressed this issue using light exposure paradigms spectrally and spatially tuned to target mainly cones or ipRGCs, and by measuring longitudinally (50 min) several NV responses in 28 men. We demonstrate that the response dynamics of NV functions are faster than previously thought. We find that the brain, the heart, and thermoregulation are activated within 1 to 5 min of light exposure. Further, we show that NV functions do not share the same response sensitivities. While the half-maximum response is only ∼48 s for the tonic pupil diameter, it is ∼12 min for EEG gamma activity. Most NV responses seem to be saturated by low light levels, as low as 90 melanopic lux. Our results also reveal that it is possible to maintain optimal visual performance while modulating NV responses. Our findings have real-life implications. On one hand, light therapy paradigms should be re-evaluated with lower intensities and shorter durations, with the potential of improving patients' compliance. On the other hand, the significant impact of low intensity and short duration light exposures on NV physiology should make us reconsider the potential health consequences of light exposure before bedtime, in particular on sleep and circadian physiology.

Introduction: Changes in the autonomic nervous system due to Obstructive Sleep Apnea (OSA) during the life span have been described. Some pediatric studies have shown cardiovascular effects in children who do not fit the criteria for OSA; namely children with mild sleep disordered breathing. Objective: We investigated heart rate variability (HRV) during sleep in children with chronic snoring and flow limitation events during sleep. Methods: Ten children and adolescents with chronic snoring and an apnea hypopnea index < 1, associated to high Respiratory Index, and 10 controls matched for age, gender, and Tanner stage were monitored following one night of habituation in the sleep laboratory. HRV was studied at each sleep stage. The time and frequency domains were calculated for each 5-min period. Results: All patients were chronic heavy snorers. They presented an apnea hypopnea index = 0.8, respiratory disturbance index = 10.2/h with lowest O2 saturation 96.1 ± 2.4%. The total power of HRV was decreased in all stages ( p < 0.05). There was also a decrease in NN50 and pNN50 during all sleep stages compared to healthy controls ( p = 0.0003 and p = 0.03, respectively). Conclusion: A reduction in parasympathetic tone was found in the patient group. This may represent an autonomic impairment during sleep in children with mild SDB. A reduction in HRV in children with habitual snoring could be associated with possible increases in cardiovascular risk in adulthood. Significance: The study indicates that children with habitual snoring have important parasympathetic tone changes during sleep.

According to contemporary views, the lateral frontal cortex is organized along a rostro-caudal functional axis with increasingly complex cognitive/behavioral control implemented rostrally, and increasingly detailed motor control implemented caudally. Whether the medial frontal cortex follows the same organization remains to be elucidated. To address this issue, the functional connectivity of the 3 cingulate motor areas (CMAs) in the human brain with the lateral frontal cortex was investigated. First, the CMAs and their representations of hand, tongue, and eye movements were mapped via task-related functional magnetic resonance imaging (fMRI). Second, using resting-state fMRI, their functional connectivity with lateral prefrontal and lateral motor cortical regions of interest (ROIs) were examined. Importantly, the above analyses were conducted at the single-subject level to account for variability in individual cingulate morphology. The results demonstrated a rostro-caudal functional organization of the CMAs in the human brain that parallels that in the lateral frontal cortex: the rostral CMA has stronger functional connectivity with prefrontal regions and weaker connectivity with motor regions; conversely, the more caudal CMAs have weaker prefrontal and stronger motor connectivity. Connectivity patterns of the hand, tongue and eye representations within the CMAs are consistent with that of their parent CMAs. The parallel rostral-to-caudal functional organization observed in the medial and lateral frontal cortex could likely contribute to different hierarchies of cognitive-motor control.

Children with developmental language disorders have been shown to be also impaired in rhythm and meter perception. Temporal processing and its link to language processing can be understood within the dynamic attending theory. An external stimulus can stimulate internal oscillators, which orient attention over time and drive speech signal segmentation to provide benefits for syntax processing, which is impaired in various patient populations. For children with Specific Language Impairment (SLI) and dyslexia, previous research has shown the influence of an external rhythmic stimulation on subsequent language processing by comparing the influence of a temporally regular musical prime to that of a temporally irregular prime. Here we tested whether the observed rhythmic stimulation effect is indeed due to a benefit provided by the regular musical prime (rather than a cost subsequent to the temporally irregular prime). Sixteen children with SLI and 16 age-matched controls listened to either a regular musical prime sequence or an environmental sound scene (without temporal regularities in event occurrence; i.e., referred to as "baseline condition") followed by grammatically correct and incorrect sentences. They were required to perform grammaticality judgments for each auditorily presented sentence. Results revealed that performance for the grammaticality judgments was better after the regular prime sequences than after the baseline sequences. Our findings are interpreted in the theoretical framework of the dynamic attending theory (Jones, 1976) and the temporal sampling (oscillatory) framework for developmental language disorders (Goswami, 2011). Furthermore, they encourage the use of rhythmic structures (even in non-verbal materials) to boost linguistic structure processing and outline perspectives for rehabilitation.

Top-down contextual influences play a major part in speech understanding, especially in hearing-impaired patients with deteriorated auditory input. Those influences are most obvious in difficult listening situations, such as listening to sentences in noise but can also be observed at the word level under more favorable conditions, as in one of the most commonly used tasks in audiology, i.e., repeating isolated words in silence. This study aimed to explore the role of top-down contextual influences and their dependence on lexical factors and patient-specific factors using standard clinical linguistic material. Spondaic word perception was tested in 160 hearing-impaired patients aged 23-88 years with a four-frequency average pure-tone threshold ranging from 21 to 88 dB HL. Sixty spondaic words were randomly presented at a level adjusted to correspond to a speech perception score ranging between 40 and 70% of the performance intensity function obtained using monosyllabic words. Phoneme and whole-word recognition scores were used to calculate two context-influence indices (the j factor and the ratio of word scores to phonemic scores) and were correlated with linguistic factors, such as the phonological neighborhood density and several indices of word occurrence frequencies. Contextual influence was greater for spondaic words than in similar studies using monosyllabic words, with an overall j factor of 2.07 (SD = 0.5). For both indices, context use decreased with increasing hearing loss once the average hearing loss exceeded 55 dB HL. In right-handed patients, significantly greater context influence was observed for words presented in the right ears than for words presented in the left, especially in patients with many years of education. The correlations between raw word scores (and context influence indices) and word occurrence frequencies showed a significant age-dependent effect, with a stronger correlation between perception scores and word occurrence frequencies when the occurrence frequencies were based on the years corresponding to the patients' youth, showing a "historic" word frequency effect. This effect was still observed for patients with few years of formal education, but recent occurrence frequencies based on current word exposure had a stronger influence for those patients, especially for younger ones.

The transcriptome of embryonic and adult rat lateral ventricular choroid plexus, using a combination of RNA-Sequencing and microarray data, was analyzed by functional groups of influx transporters, particularly solute carrier (SLC) transporters. RNA-Seq was performed at embryonic day (E) 15 and adult with additional data obtained at intermediate ages from microarray analysis. The largest represented functional group in the embryo was amino acid transporters (twelve) with expression levels 2-98 times greater than in the adult. In contrast, in the adult only six amino acid transporters were up-regulated compared to the embryo and at more modest enrichment levels (<5-fold enrichment above E15). In E15 plexus five glucose transporters, in particular Glut-1, and only one monocarboxylate transporter were enriched compared to the adult, whereas only two glucose transporters but six monocarboxylate transporters in the adult plexus were expressed at higher levels than in embryos. These results are compared with earlier published physiological studies of amino acid and monocarboxylate transport in developing rodents. This comparison shows correlation of high expression of some transporters in the developing brain with higher amino acid transport activity reported previously. Data for divalent metal transporters are also considered. Immunohistochemistry of several transporters (e.g., Slc16a10, a thyroid hormone transporter) gene products was carried out to confirm translational activity and to define cellular distribution of the proteins. Overall the results show that there is substantial expression of numerous influx transporters in the embryonic choroid plexus, many at higher levels than in the adult. This, together with immunohistochemical evidence and data from published physiological transport studies suggests that the choroid plexus in embryonic brain plays a major role in supplying the developing brain with essential nutrients.

The cerebral microvessel endothelium forming the blood-brain barrier (BBB) and the epithelium of the choroid plexuses forming the blood-CSF barrier (BCSFB) operate as gatekeepers for the central nervous system. Exposure of the vulnerable developing brain to chemical insults can have dramatic consequences for brain maturation and lead to life-long neurological diseases. The ability of blood-brain interfaces to efficiently protect the immature brain is therefore an important pathophysiological issue. This is also key to our understanding of drug entry into the brain of neonatal and pediatric patients. Non-specific paracellular diffusion through barriers is restricted early during development, but other neuroprotective properties of these interfaces differ between the developing and adult brains. This review focuses on the developmental expression and function of various classes of efflux transporters. These include the multispecific transporters of the ATP-binding cassette transporter families ABCB, ABCC, ABCG, the organic anion and cation transporters of the solute carrier families SLC21/SLCO and SLC22, and the peptide transporters of the SLC15 family. These transporters play a key role in preventing brain entry of blood-borne molecules such as drugs, environmental toxicants, and endogenous metabolites, or else in increasing the clearance of potentially harmful organic ions from the brain. The limited data available for laboratory animals and human highlight transporter-specific developmental patterns of expression and function, which differ between blood-brain interfaces. The BCSFB achieves an adult phenotype earlier than BBB. Efflux transporters at the BBB appear to be regulated by various factors subsequently secreted by neural progenitors and astrocytes during development. Their expression is also modulated by oxidative stress, inflammation, and exposure to xenobiotic inducers. A better understanding of these regulatory pathways during development, in particular the signaling pathways triggered by oxidative stress and xenobiotics, may open new opportunities to therapeutic manipulation in view to improve or restore neuroprotective functions of the blood-brain interfaces in the context of perinatal injuries.

Much theoretical attention is currently devoted to social learning. Yet, empirical studies formally comparing its effectiveness relative to individual learning are rare. Here, we focus on free choice, which is at the heart of individual reward-based learning, but absent in social learning. Choosing among two equally valued options is known to create a preference for the selected option in both humans and monkeys. We thus surmised that social learning should be more helpful when choice-induced preferences retard individual learning than when they optimize it. To test this prediction, the same task requiring to find which among two items concealed a reward was applied to rhesus macaques and humans. The initial trial was individual or social, rewarded or unrewarded. Learning was assessed on the second trial. Choice-induced preference strongly affected individual learning. Monkeys and humans performed much more poorly after an initial negative choice than after an initial positive choice. Comparison with social learning verified our prediction. For negative outcome, social learning surpassed or at least equaled individual learning in all subjects. For positive outcome, the predicted superiority of individual learning did occur in a majority of subjects (5/6 monkeys and 6/12 humans). A minority kept learning better socially though, perhaps due to a more dominant/aggressive attitude toward peers. Poor learning from errors due to over-valuation of personal choices is among the decision-making biases shared by humans and animals. The present study suggests that choice-immune social learning may help curbing this potentially harmful tendency. Learning from successes is an easier path. The present data suggest that whether one tends to walk it alone or with a peer's help might depend on the social dynamics within the actor/observer dyad.

Associative olfactory learning increased survival of adult born granule interneurons in the olfactory bulb (OB) at regions which are specific to the learned odorant. However, the mechanism shaping this odor-specific distribution of newborn neurons and its temporal relationship with the learning process are unknown. In the present study, using Bromodeoxyuridine or activated-caspase3 labeling, newborn and apoptotic cells respectively were mapped in the granule cell layer (GCL) of the OB, just before, during, and at the end of odor conditioning or pseudo-conditioning in adult mice. Results indicate that before and during training, when the task is not yet acquired, conditioned and pseudo-conditioned animals displayed the same density of newborn neurons. However, at the end of the conditioning, when the animals mastered the task, the density of newborn cells remained elevated in conditioned animals while it decreased in pseudo-conditioned animals suggesting newborn cell death in that group. Indeed, using Activated-Caspase3/BrdU co-labeling, we found that the proportion of newborn cells among dying cells was reduced in conditioned animals mastering the task compared to non-expert conditioned or pseudo-conditioned animals. The overall level of cell death did not change across training and was similar in conditioned and pseudo-conditioned groups, indicating that BrdU-positive cells were spared to the detriment of non-labeled cells. In addition, a fine analysis of cell distribution showed an uneven distribution of apoptotic cells, with lower densities in the medial part of the GCL where the density of newborn cells is high in conditioned animals. We conclude that acquisition of the task triggered the rescue of newborn neurons by a targeted regulation of cell death.