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Little is known about the genetic factors modulating the progression of Huntington's disease (HD). Dopamine levels are affected in HD and modulate executive functions, the main cognitive disorder of HD. We investigated whether the Val158Met polymorphism of the catechol-O-methyltransferase (COMT) gene, which influences dopamine (DA) degradation, affects clinical progression in HD. We carried out a prospective longitudinal multicenter study from 1994 to 2011, on 438 HD gene carriers at different stages of the disease (34 pre-manifest; 172 stage 1; 130 stage 2; 80 stage 3; 17 stage 4; and 5 stage 5), according to Total Functional Capacity (TFC) score. We used the Unified Huntington's Disease Rating Scale to evaluate motor, cognitive, behavioral and functional decline. We genotyped participants for COMT polymorphism (107 Met-homozygous, 114 Val-homozygous and 217 heterozygous). 367 controls of similar ancestry were also genotyped. We compared clinical progression, on each domain, between groups of COMT polymorphisms, using latent-class mixed models accounting for disease duration and number of CAG (cytosine adenine guanine) repeats. We show that HD gene carriers with fewer CAG repeats and with the Val allele in COMT polymorphism displayed slower cognitive decline. The rate of cognitive decline was greater for Met/Met homozygotes, which displayed a better maintenance of cognitive capacity in earlier stages of the disease, but had a worse performance than Val allele carriers later on. COMT polymorphism did not significantly impact functional and behavioral performance. Since COMT polymorphism influences progression in HD, it could be used for stratification in future clinical trials. Moreover, DA treatments based on the specific COMT polymorphism and adapted according to disease duration could potentially slow HD progression., Competing Interests: R. de Diego-Balaguer, C. Schramm, I. Rebeix, E. Dupoux, A. Durr, A. Brice, P. Charles, L. Cleret de Langavant, K. Youssov, G. Fénelon, C. Verny, V. Damotte, JP Azulay, C. Simonin, C. Tranchant, P. Maison, A. Rialland, D. Schmitz, C. Jacquemot, B. Fontaine have nothing to disclose. A.C. Bachoud-Lévi acted as a consultant once for Teva in 2014 and reports grants from the National Reference Center for Huntington’s Disease from the Ministry of Health and from the clinical research directorate (AP-HP). C. Goizet reports grants from the European Huntington Disease Network and the Programme Hospitalier de Recherche Clinique (PHRC) during the duration of the study; personal fees came from Raptor Pharmaceutical France, Genzyme, and Actelion; grants from Genzyme, Association Française contre les myopathies (AFM), Association Strumpell-Lorrain (ASL), Connaître les Syndromes Cérébelleux (CSC), Union Nationale des Aveugles et Déficients Visuels (UNADEV), Conseil Régional d’Aquitaine (CRA), Agence Nationale pour la Recherche (ANR), Programme Hospitalier de Recherche Clinique (PHRC), Genzyme, Actelion, and Biomarin, not covering the work submitted here. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

In the adult brain, speech can recruit a brain network that is overlapping with, but not identical to, that involved in perceiving non-linguistic vocalizations. Using the same stimuli that had been presented to human 4-month-olds and adults, as well as adult macaques, we sought to shed light on the cortical networks engaged when human newborns process diverse vocalization types. Near infrared spectroscopy was used to register the response of 40 newborns' perisylvian regions when stimulated with speech, human and macaque emotional vocalizations, as well as auditory controls where the formant structure was destroyed but the long-term spectrum was retained. Left fronto-temporal and parietal regions were significantly activated in the comparison of stimulation versus rest, with unclear selectivity in cortical activation. These results for the newborn brain are qualitatively and quantitatively compared with previous work on newborns, older human infants, adult humans, and adult macaques reported in previous work.

We report evidence that 29-month-old toddlers and 10-month-old preverbal infants discriminate between two agents: a pro-social agent, who performs a positive (comforting) action on a human patient and a negative (harmful) action on an inanimate object, and an anti-social agent, who does the converse. The evidence shows that they prefer the former to the latter even though the agents perform the same bodily movements. Given that humans can cause physical harm to their conspecifics, we discuss this finding in light of the likely adaptive value of the ability to detect harmful human agents.

Until recently, imaging the infant brain was very challenging. Functional Near InfraRed Spectroscopy (fNIRS) is a promising, relatively novel technique, whose use is rapidly expanding. As an emergent field, it is particularly important to share methodological knowledge to ensure replicable and robust results. In this paper, we present a community-augmented database which will facilitate precisely this exchange. We tabulated articles and theses reporting empirical fNIRS research carried out on infants below three years of age along several methodological variables. The resulting spreadsheet has been uploaded in a format allowing individuals to continue adding new results, and download the most recent version of the table. Thus, this database is ideal to carry out systematic reviews. We illustrate its academic utility by focusing on the factors affecting three key variables: infant attrition, the reliability of oxygenated and deoxygenated responses, and signal-to-noise ratios. We then discuss strengths and weaknesses of the DBIfNIRS, and conclude by suggesting a set of simple guidelines aimed to facilitate methodological convergence through the standardization of reports.

Communicative pointing is a human specific gesture which allows sharing information about a visual item with another person. It sets up a three-way relationship between a subject who points, an addressee and an object. Yet psychophysical and neuroimaging studies have focused on non-communicative pointing, which implies a two-way relationship between a subject and an object without the involvement of an addressee, and makes such gesture comparable to touching or grasping. Thus, experimental data on the communicating function of pointing remain scarce. Here, we examine whether the communicative value of pointing modifies both its behavioral and neural correlates by comparing pointing with or without communication. We found that when healthy participants pointed repeatedly at the same object, the communicative interaction with an addressee induced a spatial reshaping of both the pointing trajectories and the endpoint variability. Our finding supports the hypothesis that a change in reference frame occurs when pointing conveys a communicative intention. In addition, measurement of regional cerebral blood flow using H(2)O(15) PET-scan showed that pointing when communicating with an addressee activated the right posterior superior temporal sulcus and the right medial prefrontal cortex, in contrast to pointing without communication. Such a right hemisphere network suggests that the communicative value of pointing is related to processes involved in taking another person's perspective. This study brings to light the need for future studies on communicative pointing and its neural correlates by unraveling the three-way relationship between subject, object and an addressee.