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Background & Aims: Transmural healing is a long-term target for patients with Crohn's disease. Factors contributing to its promotion are poorly understood. This study assessed factors correlating with transmural healing based on intestinal ultrasound, in patients in long-term clinical remission on anti-TNF., Methods: 68 consecutive Crohn's patients on adalimumab (50) or infliximab (18) therapy with clinical remission ≥1 year were recruited and assessed for clinical features, trough serum levels of anti-TNF and intestinal ultrasound findings. Univariate analysis and multivariate binary logistic regression analysis identified variables independently associated with bowel wall thickening behavior., Results: Sixty eight patients were in remission for a mean of 4.1 years. Thirty-six patients (52.9 %) showed anti-TNF trough levels below the normal threshold. Twenty-two patients (38.4 %) showed transmural healing, 32 (47.1 %) transmural response, and 26 (38.2 %) no treatment response. Transmural healing correlated with higher BMI and lower baseline bowel wall thickening; transmural response correlated with short Crohn's disease duration, high drug levels, and with non-stricturing phenotype. Treatment non-response correlated with lower BMI, lower drug levels, higher baseline bowel wall thickening, and stricturing phenotype., Conclusions: Lack of transmural healing in stable remission Crohn's patients on anti-TNF therapy is multifactorial, mainly due to low anti-TNFs trough levels, development of strictures, and higher baseline bowel wall thickening at treatment initiation., Competing Interests: Declaration of competing interest Giovanni Maconi consulted for Alfa Sigma, Arena Pharmaceuticals, Fresenius Kabi, Galapaos, Janssen Cilag, Gilead, Riche, Takeda. Simone Saibeni received lecture fees and was an advisory board member for Takeda and Janssen. Cristina Bezzio received lecture fees from Takeda, AbbVie, and Janssen. Sandro Ardizzone served as a speaker, consultant, and/or advisory board member for the following organizations: AbbVie, MSD, Takeda, Janssen, Pfizer, Sandoz, and Enthera. Bincy Abraham has received research funding from Takeda; consulted for AbbVie, Bristol Myers Squibb, Eli Lilly, Janssen, Medtronic, Pfizer, Samsung Bioepis, Celltrion, and Takeda; lectured for AbbVie, Bristol Myers Squibb, Eli Lilly, Janssen, Pfizer, and Takeda. 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 © 2024. Published by Elsevier Ltd.)

Pancreatic ductal adenocarcinoma (PDAC) still has a poor response to therapies, partly due to their cancer-associated fibroblasts (CAFs). Here, we investigate the synergistic impact of a combinatory approach between a known chemotherapy agent, such as gemcitabine (GEM), and gene-modified human mesenchymal stromal/stem cells (MSCs) secreting the pro-apoptotic soluble (s)TRAIL (sTRAIL MSCs) on both PDAC cells and CAFs. The combo significantly impacts on PDAC survival in 2D and 3D models. In orthotopic xenograft models, GEM and sTRAIL MSCs induce tumor architecture shredding with a reduction of CK7- and CK8/18-positive cancer cells and the abrogation of spleen metastases. A cytotoxic effect on primary human CAFs is also observed along with an alteration of their transcriptome and a reduction of the related desmoplasia. Collectively, we demonstrate a promising therapeutic profile of combining GEM and sTRAIL MSCs to target both tumoral and stromal compartments in PDAC., Competing Interests: Declaration of interests M. Dominici and G.G. hold patents in the field of cell and gene therapy. EIR Biotherapies srl holds patents related to the presented technologies. M. Dall’Ora and O.C. are employees of EVOTEC Modena Srl., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Our goal was to evaluate persisting deficits in gait and executive functioning in asymptomatic athletes with a history of concussion using a novel approach combining a dual-task paradigm and post-exercise exertion. Thirty-eight athletes aged 17 to 25 years old participated in the study, including 18 with a history of concussion. The dual-task paradigm required walking continuously at a predetermined self-paced target speed of 6.5 km/h while executing a complex switch task. Athletes completed two conditions, each on separate days: (1) dual task alone and (2) dual task following 20 min of running on a non-motorized treadmill. The statistical analyses revealed a significant reduction in gait speed exclusively for athletes with a history of concussion and only following the post-exercise condition ( p = 0.008). These findings suggest that although asymptomatic concussed athletes maintain a cognitive performance comparable to non-concussed athletes, this appears to be achieved at the expense of gait speed. Our results underscore the importance of incorporating gait assessments and post-exercise exertion into concussion evaluation protocols in both research and clinical settings.

Background: The number of accidents due to distracted pedestrian is on the rise and many governments and institutions are enacting public policies which restrict texting while walking. However, pedestrians do more than just texting when they use their mobile devices on the go., Objective: Exploring pedestrian multitasking, this paper aims to examine the effects of mobile device task type on pedestrian performance outcomes., Method: We performed two studies in lab simulations where 78 participants were asked to perform different tasks on a mobile device (playing a game, reading, writing an email, texting one person, group texting) while performing a pedestrian visual discrimination task while either standing or walking on a treadmill. Behavioral performance as well as neurophysiological data are collected., Results: Results show that compared to a no-phone control, multitasking with any of the tasks on a mobile device leads to poor performance on a pedestrian visual discrimination task. Playing a game is the most cognitively demanding task and leads to the greatest performance degradation., Conclusion: Our studies show that multitasking with a mobile device has the potential to negatively impact pedestrian safety, regardless of task type. However, the impacts of different mobile device tasks are not all equivalent. More research is needed to tease out the different effects of these various tasks and to design mobile applications which effectively and safely capture pedestrians' attention., Application: Public policy, infrastructure, and smart technologies can be used to mitigate the negative effects of mobile multitasking. A more thorough understanding of mobile device task-specific factors at play can help tailor these counter-measures to better aid distracted pedestrians.

Purpose: Colonic pseudopolyps are a frequent finding in inflammatory bowel disease (IBD). Yet there are no published data describing the characteristics of pseudopolyposis in intestinal ultrasound (IUS). This study aimed at identifying the key features of pseudopolyposis in IUS., Methods: This case-control study included 12 patients with ulcerative colitis or Crohn's colitis with extensive left colon pseudopolyposis and 18 matched IBD patients without pseudopolyps at colonoscopy. Luminal (diameters, thickening, stratification, margins, and vascularity) and intraluminal (vascular signals at color Doppler), and extraluminal (mesenteric fat) parameters of the left colon were compared. Anonymized still images and videos of these patients were blindly reviewed to estimate the accuracy in detecting this condition., Results: Among the IUS parameters assessed, the anteroposterior diameter ≥ 12 mm and the presence of luminal vascular signals were significantly correlated with pseudopolyposis. The detection of both these findings were able to detect extensive pseudopolyposis a sensitivity of 75% (CI 95%: 42.8-94.5%) and a specificity of 100% (CI 95%: 81.5-100%)., Conclusion: This is the first study describing the IUS features of pseudopolyposis in IBD. The potential use of IUS to assess pseudopolyposis might have an impact on IUS monitoring and surveillance of IBD patients with condition., (© 2024. The Author(s).)

Sensory deprivation, especially hearing loss (HL), offers a valuable model for studying neuroplasticity in the human brain and adaptive behaviours that support the daily lives of those with limited or absent sensory input. The study of olfactory function is particularly important as it is an understudied aspect of sensory deprivation. This study aimed to compare the effects of congenital HL on olfactory capacity by using psychophysical tasks. Methodological concerns from previous studies regarding the onset of HL and cognitive assessments were addressed. We recruited 11 individuals with severe-to-profound sensorineural HL (SNHL) since birth and 11 age- and sex-matched typical hearing non-signers. We used standardized neuropsychological tests to assess typical cognition among participants with SNHL. We evaluated olfactory functions by assessing olfactory detection threshold, odour discrimination and odour identification. Hearing-impaired participants outperformed their typical hearing counterparts in olfactory tasks. We further evaluated the accuracy and response time in identifying and localizing odours to disentangle olfactory sensitivity from trigeminal system sensitivity. Participants with SNHL demonstrated higher sensitivity to both the identification and localization tasks. These findings suggest that congenital SNHL is associated with enhanced higher-level olfactory processing and increased trigeminal sensitivity., (© 2023 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Animal models are currently used in several fields of biomedical research as useful alternatives to human-based studies. However, the obtained results do not always effectively translate into clinical applications, due to interspecies anatomical and physiological differences. Detailed comparability studies are therefore required to verify whether the selected animal species could be a representative model for the disease or for cellular process under investigation. This has proven to be fundamental to obtaining reliable data from preclinical studies. Among the different species, swine is deemed an excellent animal model in many fields of biological research, and has been largely used in respiratory medicine, considering the high homology between human and swine airways. In the context of in vitro studies, the validation of porcine airway epithelial cells as an alternative to human epithelial cells is crucial. In this paper, porcine and human tracheal and bronchial epithelial cells are compared in terms of in vivo tissue architecture and in vitro cell behaviour under standard and airlifted conditions, analyzing the regenerative, proliferative and differentiative potentials of these cells. We report multiple analogies between the two species, validating the employment of porcine airway epithelial cells for most in vitro preclinical studies, although with some limitations due to species-related divergences., (© 2023. Springer Nature Limited.)

Our ability to consciously perceive information from the visual scene relies on a myriad of intrinsic neural mechanisms. Functional neuroimaging studies have sought to identify the neural correlates of conscious visual processing and to further dissociate from those pertaining to preconscious and unconscious visual processing. However, delineating what core brain regions are involved in eliciting a conscious percept remains a challenge, particularly regarding the role of prefrontal-parietal regions. We performed a systematic search of the literature that yielded a total of 54 functional neuroimaging studies. We conducted two quantitative meta-analyses using activation likelihood estimation to identify reliable patterns of activation engaged by i. conscious (n = 45 studies, comprising 704 participants) and ii. unconscious (n = 16 studies, comprising 262 participants) visual processing during various task performances. Results of the meta-analysis specific to conscious percepts quantitatively revealed reliable activations across a constellation of regions comprising the bilateral inferior frontal junction, intraparietal sulcus, dorsal anterior cingulate, angular gyrus, temporo-occipital cortex and anterior insula. Neurosynth reverse inference revealed conscious visual processing to be intertwined with cognitive terms related to attention, cognitive control and working memory. Results of the meta-analysis on unconscious percepts revealed consistent activations in the lateral occipital complex, intraparietal sulcus and precuneus. These findings highlight the notion that conscious visual processing readily engages higher-level regions including the inferior frontal junction and unconscious processing reliably recruits posterior regions, mainly the lateral occipital complex., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier Inc.)

Childhood adversity and anxiety have been associated with increased risk for internalizing disorders later in life and with a range of brain structural abnormalities. However, few studies have examined the link between harsh parenting practices and brain anatomy, outside of severe maltreatment or psychopathology. Moreover, to our knowledge, there has been no research on parenting and subclinical anxiety symptoms which remain persistent over time during childhood (i.e., between 2.5 and 9 years old). Here, we examined data in 94 youth, divided into four cells based on their levels of coercive parenting (high / low) and of anxiety (high / low) between 2.5 and 9 years old. Anatomical images were analyzed using voxel-based morphometry (VBM) and FreeSurfer. Smaller gray matter volumes in the prefrontal cortex regions and in the amygdala were observed in youth with high versus low levels of harsh parenting over time. In addition, we observed significant interaction effects between parenting practices and subclinical anxiety symptoms in rostral anterior cingulate cortical thickness and in amygdala volume. These youth should be followed further in time to identify which youth will or will not go on to develop an anxiety disorder, and to understand factors associated with the development of sustained anxiety psychopathology.

It is well documented that early sensory loss typically alters brain morphology in the areas associated with the lost sense. However, much less is known about the impact of early sensory loss on the remainder of the sensory regions. Therefore, we investigated whether congenitally blind (CB) individuals show brain alterations in the olfactory system by comparing cortical morphology and olfactory bulb (OB) volume between 16 congenitally blind individuals and 16 sighted matched controls. Our results showed that not only CB blind individuals exhibited smaller OB but also alterations of cortical density in some higher olfactory processing centres, but unchanged cortical thickness. Our current findings suggest that a lifelong absence of visual input leads to morphological alterations in olfactory processing areas., (© 2022 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

The brain operates through the synaptic interaction of distant neurons within flexible, often heterogeneous, distributed systems. Histological studies have detailed the connections between distant neurons, but their functional characterization deserves further exploration. Studies performed on the corpus callosum in animals and humans are unique in that they capitalize on results obtained from several neuroscience disciplines. Such data inspire a new interpretation of the function of callosal connections and delineate a novel road map, thus paving the way toward a general theory of cortico-cortical connectivity. Here we suggest that callosal axons can drive their post-synaptic targets preferentially when coupled to other inputs endowing the cortical network with a high degree of conditionality. This might depend on several factors, such as their pattern of convergence-divergence, the excitatory and inhibitory operation mode, the range of conduction velocities, the variety of homotopic and heterotopic projections and, finally, the state-dependency of their firing. We propose that, in addition to direct stimulation of post-synaptic targets, callosal axons often play a conditional driving or modulatory role, which depends on task contingencies, as documented by several recent studies., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can generate severe pneumonia associated with high mortality. A bedside lung ultrasound (LUS) examination has been shown to have a potential role in this setting. The purpose of this study was to evaluate the potential prognostic value of a new LUS protocol (evaluation of 14 anatomic landmarks, with graded scores of 0-3) in patients with SARS-CoV-2 pneumonia and the association of LUS patterns with clinical or laboratory findings., Methods: A cohort of 52 consecutive patients with laboratory-confirmed SARS-CoV-2 underwent LUS examinations on admission in an internal medicine ward and before their discharge. A total LUS score as the sum of the scores at each explored area was computed. We investigated the association between the LUS score and clinical worsening, defined as a combination of high-flow oxygen support, intensive care unit admission, or 30-day mortality as the primary end point., Results: Twenty (39%) patients showed a worse outcome during the observation period; the mean LUS scores ± SDs were 20.4 ± 8.5 and 29.2 ± 7.3 in patients without and with worsening, respectively (P < .001). In a multivariable analysis, adjusted for comorbidities (>2), age (>65 years), sex (male), and body mass index (≥25 kg/m 2 ), the association between the LUS score and worsening (odds ratio, 1.17; 95% confidence interval, 1.05 to 1.29; P = .003) was confirmed, with good discrimination of the model (area under the receiver operating characteristic curve, 0.82). A median LUS score higher than 24 was associated with an almost 6-fold increase in the odds of worsening (odds ratio, 5.67; 95% confidence interval, 1.29 to 24.8; P = .021)., Conclusions: Lung ultrasound can represent an effective tool for monitoring and stratifying the prognosis of patients with SARS-CoV-2 pulmonary involvement., (© 2020 American Institute of Ultrasound in Medicine.)

Exposure to mercury, lead and polychlorinated biphenyls (PCBs) have been associated with emotional dysregulation, but their neuronal correlates have yet to be examined. Inuit from Nunavik (Northern Quebec, Canada) face internalizing problems and are among the most exposed individuals to these environmental contaminants in the world. The aim of this study was to examine the link between pre- and postnatal exposure to these contaminants and brain fear-circuitry in Inuit adolescents. Facial expression stimuli were presented to participants (mean age = 18.3 years) in a magnetic resonance imaging (MRI) scanner. Fear conditioning and extinction tasks included neutral faces as the conditioned threat and safety cues and a fearful face paired with a shrieking scream as the unconditioned stimulus. Functional MRI data were gathered at the conditioning phase (n = 71) and at the extinction phase (n = 62). Mercury, lead and PCB 153 concentrations were measured in blood samples at birth (cord blood) and at the time of the adolescent testing to estimate pre- and postnatal exposure, respectively. For each time point, exposures were categorized in tertiles (low, moderate and high exposed groups). Mixed analyses of variance were conducted for each contaminant of interest controlling for sex, age, socioeconomic status, drug/alcohol use, food insecurity and contaminant co-exposure. Results revealed greater differential activation during the conditioning phase in the right orbitofrontal cortex in participants with moderate and high concentrations of cord blood PCB 153 compared to those in the low exposure group. During the extinction phase, the high prenatal mercury exposed group showed a lower differential activation in the right and left anterior cingulate cortex compared to those in the low-exposed group; whereas there was a higher differential activation in right dorsolateral prefrontal cortex in the high postnatal lead exposed group compared to the moderate- and low-exposed groups. Our study is the first to show alterations in the prefrontal brain areas in fear conditioning and extinction tasks in relation to environmental contaminant exposures. The observed brain correlates may advance our understanding of the emotional problems associated with environmental chemical toxicity., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Although often considered a nondominant sense for spatial perception, chemosensory perception can be used to localize the source of an event and potentially help us navigate through our environment. Would blind people who lack the dominant spatial sense-vision-develop enhanced spatial chemosensation or suffer from the lack of visual calibration on spatial chemosensory perception? To investigate this question, we tested odorant localization abilities across nostrils in blind people compared to sighted controls and if the time of vision loss onset modulates those abilities. We observed that congenitally blind individuals (10 subjects) outperformed sighted (20 subjects) and late-blind subjects (10 subjects) in a birhinal localization task using mixed olfactory-trigeminal stimuli. This advantage in congenitally blind people was selective to olfactory localization but not observed for odorant detection or identification. We, therefore, showed that congenital blindness but not blindness acquired late in life is linked to enhanced localization of chemosensory stimuli across nostrils, most probably of the trigeminal component. In addition to previous studies highlighting enhanced localization abilities in auditory and tactile modalities, our current results extend such enhanced abilities to chemosensory localization., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Speech perception relies on auditory and visual cues and there are strong links between speech perception and production. We aimed to evaluate the role of auditory and visual modalities on speech perception and production in adults with impaired hearing or sight versus those with normal hearing and sight. We examined speech perception and production of three isolated vowels (/i/, /y/, /u/), which were selected based on their different auditory and visual perceptual saliencies, in 12 deaf adults who used one or two cochlear implants (CIs), 14 congenitally blind adults, and 16 adults with normal sight and hearing. The results showed that the deaf adults who used a CI had worse vowel identification and discrimination perception and they also produced vowels that were less typical or precise than other participants. They had different tongue positions in speech production, which possibly partly explains the poorer quality of their spoken vowels. Blind individuals had larger lip openings and smaller lip protrusions for the rounded vowel and unrounded vowels, compared to the other participants, but they still produced vowels that were similar to those produced by the adults with normal sight and hearing. In summary, the deaf adults, even though they used CIs, had greater difficulty in producing accurate vowel targets than the blind adults, whereas the blind adults were still able to produce accurate vowel targets, even though they used different articulatory strategies.

Deafness leads to brain modifications that are generally associated with a cross-modal activity of the auditory cortex, particularly for visual stimulations. In the present study, we explore the cortical processing of biological motion that conveyed either non-communicative (pantomimes) or communicative (emblems) information, in early-deaf and hearing individuals, using fMRI analyses. Behaviorally, deaf individuals showed an advantage in detecting communicative gestures relative to hearing individuals. Deaf individuals also showed significantly greater activation in the superior temporal cortex (including the planum temporale and primary auditory cortex) than hearing individuals. The activation levels in this region were correlated with deaf individuals' response times. This study provides neural and behavioral evidence that cross-modal plasticity leads to functional advantages in the processing of biological motion following lifelong auditory deprivation., Competing Interests: The authors have declared that no competing interests exist.

The exact contribution of the insula to risky decision making remains unclear, as are the specific outcome parameters and inter-individual characteristics that modulate insular activity prior to a risky choice. This fMRI study examines the contributions of outcome valence, magnitude, probability, and expected value (EV) to insular activity during risky decision making, and explores the influence of sensitivity to reward and to punishment, and anxiety, to insular activity. Participants (N = 31) performed a gambling task requiring choice between two roulettes with different outcome magnitude, probability and EV, under gain and loss conditions separately, and filled questionnaires assessing sensitivity to punishment/reward, and state/trait anxiety. Parametric analyses were conducted to examine the modulation of brain activity during decision making in relation to each task parameter. Correlations were examined between insular activity and psychometric questionnaires. EV of the selected roulette was associated with right posterior insula activation during decision making. Higher sensitivity to punishment was associated with lower bilateral insular activation. These findings suggest that the right posterior insula is involved in tracking the EV of a risky option during decision making. The involvement of the insula when making risky decisions also appears to be influenced by inter-individual differences in sensitivity to punishment.

Distracted walking is an ever-increasing problem. Studies have already shown that using a smartphone while walking impairs attention and increases the risk of accidents. This study seeks to determine if smartphone-addiction proneness magnifies the risks of using a smartphone while walking. In an experimental design, participants, while walking on a treadmill and engaged in a smartphone task, were required to switch tasks by responding to an external stimulus, i.e., determining the direction of movement of a point-light walker. Participants were chosen to cover a range of smartphone-addiction proneness. Four smartphone-use conditions were simulated: a control condition with no smartphone-use, an individual conversation condition, a gaming condition, and a group conversation condition. Our results show that using a smartphone while walking decreases accuracy and increases the number of missed stimuli. Moreover, participants with higher smartphone-addiction proneness scores were also prone to missing more stimuli, and this effect was found regardless of experimental condition. The effect of the smartphone task on accuracy and the number of missed stimuli was mediated by the emotional arousal caused by the smartphone task. Smartphone-addiction proneness was positively correlated with a declared frequency of smartphone use while walking. Furthermore, of all the smartphone tasks, the gaming condition was found to be the most distracting., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Functional neuroimaging studies using auditory stimuli consistently show activation of the insular cortex. However, due to the limited temporal resolution of non-invasive neuroimaging techniques, the role(s) of the insula in auditory processing remains unclear. As the anterior insula (aI) and the posterior insula (pI) have different connections and are thought to be functionally distinct, it is likely that these two areas contribute differently to auditory processing. Our study examines the spatiotemporal dynamics of auditory processing in the insula using intracranial electroencephalography (EEG). Eight epileptic patients completed two passive listening tasks and one three-stimulus auditory oddball detection task during the intracranial EEG monitoring of their drug-resistant seizures. Recordings were obtained from depth electrodes implanted in 11 insulae. Event-related potentials (ERPs) were analyzed using permutation analyses during the N100 and the P300 intervals, and modulations of alpha, theta, and gamma band responses were compared using Wilcoxon/Mann-Whitney analyses. N100 responses to auditory stimuli were mostly observed in the pI and were little affected by task conditions. Auditory target detection was associated with P300 ERPs, and alpha, theta, high- and low-gamma responses, preferentially at aI contacts. Results suggest that the aI is involved in voluntary attentional processing of task-relevant information, whereas the pI is involved in automatic auditory processing.

This paper presents a study protocol to measure the task-switching cost of using a smartphone while walking. This method involves having participants walk on a treadmill under two experimental conditions: a control condition (i.e., simply walking) and a multitasking condition (i.e., texting while walking). During these conditions, the participants must switch between the tasks related to the experimental condition and a direction determining task. This direction task is done with a point-light walker figure, seemingly walking towards the left or the right of the participant. Performance on the direction task represents the participant's task-switching costs. There were two performance measures: 1) correct identification of the direction and 2) response time. EEG data are recorded in order to measure the alpha oscillations and cognitive engagement occurring during the task switch. This method is limited in its ecological validity: pedestrian environments have many stimuli occurring simultaneously and competing for attention. Nonetheless, this method is appropriate for pinpointing task-switching costs. The EEG data allow the study of the underlying mechanisms in the brain that are related to differing task-switching costs. This design allows the comparison between task switching when doing one task at a time, as compared to task switching when multitasking, prior to the stimulus presentation. This allows understanding and pinpointing both the behavioral and neurophysiological impact of these two different task-switching conditions. Furthermore, by correlating the task-switching costs with the brain activity, we can learn more about what causes these behavioral effects. This protocol is an appropriate base for studying the switching cost of different smartphone uses. Different tasks, questionnaires, and other measures can be added to it in order to understand the different factors involved in the task-switching cost of smartphone use while walking.

Although impairment in sensory integration is suggested in the autism spectrum (AS), empirical evidences remain equivocal. We assessed the integration of low-level visual and tactile information within and across modalities in AS and typically developing (TD) individuals. TD individuals demonstrated increased redundancy gain for cross-modal relative to double tactile or visual stimulation, while AS individuals showed similar redundancy gain between cross-modal and double tactile conditions. We further observed that violation of the race model inequality for cross-modal conditions was observed over a wider proportion of the reaction times distribution in TD than AS individuals. Importantly, the reduced cross-modal integration in AS individuals was not related to atypical attentional shift between modalities. We conclude that AS individuals displays selective decrease of cross-modal integration of low-level information.

The primary objective of this chapter is to describe the consequences of central deficiencies on the neurodevelopment of children. We approach this topic from the standpoint of congenital deafness. Thus we first present the current state of knowledge on cortical reorganization following congenital deafness. The allocation of auditory cortices to other sensory systems can enhance sensory processing and therefore the cognitive functions related to them. Second, we explore the linguistic development of deaf children. Given that the English written system is speech-based, its acquisition is complex and atypical for deaf children, usually leading to poorer achievements. Next, we explore the impact of a neural prosthesis named the cochlear implant on the neurocognitive and linguistic development of deaf children. In some cases, it allows the individuals to, at least partially, regain access to the lost sense. We also comment on the specific needs of the deaf population when it comes to neuropsychological assessment. Finally, we touch on the specific context of deaf children born of deaf parents, and therefore naturally exposed to sign language as the only means of communication., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Functional neuroimaging studies suggest that the insular cortex-and more especially the anterior insula (aI)-is involved in attentional processes and plays a crucial role in the "salience network". However, its specific role in attentional processing remains unclear, which is partly attributable to the low temporal resolution of non-invasive neuroimaging techniques. This study aims to examine the spatio-temporal dynamics of visual target processing using intracranial EEG recorded directly from the insula. Eight epileptic patients (four women, age 18-44 years) completed a three-stimulus visual oddball task during the extraoperative invasive intracranial EEG (iEEG) monitoring of their drug-resistant seizures. Depth electrodes were implanted in ten insular lobes (5 left and 5 right) and provided a total of 59 recording contacts in the insula. Event-related potentials (ERPs) and high-gamma-band responses (GBRs) were processed offline. Permutation analyses were performed to compare ERP signals across conditions during the P300 (225-400) interval, and modulations of GBRs (70-150 Hz) were computed for separate 100 ms time windows (from 0 to 1000 ms post-stimulus) and compared across conditions using non-parametric Wilcoxon test. Target stimuli were associated with a P300 (250-338 ms) component for 39% of contacts implanted in the aI, most probably reflecting voluntary attentional processing. Amplitude was significantly greater for target than for standard stimuli for all of these contacts, and was greater than for novel stimuli for 72%. In the posterior insula (pI), 16% of contacts showed preferential responses to target stimulus in the P300 interval. Increased GBRs in response to targets were observed in 53% of aI contacts (from ≈ 200 to 300 ms) and in 43% of pI contacts (from ≈ 400 to 500 ms). This study is the first to characterize the spatio-temporal dynamics of visual target processing in the insula using iEEG. Results suggest that visual targets elicit a P300 in the aI which corresponds in latency to the P3b component, suggesting that this region is involved in top-down processing of task-relevant information. GBRs to visual targets occur earlier in the aI than in the pI, further characterizing their respective roles in voluntary attentional processing.

Introduction: Humeral shaft is a common site of fracture non-union. Biology and bone quality represent some of the problems that the orthopaedic surgeon has to face up in the elderly. The goals of treatment of humeral shaft non-union are the achievement of mechanical stability and creation of a favourable biologic environment. Bone graft and stem cells are some of the augmentation techniques available to reach these goals., Purpose: Evaluation of the outcomes of humeral shaft non-union in elderly population treated with cortical allograft and stem cells., Material and Methods: A cohort of 21 patients with humeral shaft non-union was reviewed. Inclusion criteria were patients aged more than 65 years, with a diagnosis of humeral shaft non-union treated with cortical allograft and stem cells. Primary endpoints were 'bone healing' and 'time-to-union'. Secondary endpoints were shoulder and elbow function and patients' quality of life with Oxford Shoulder Score (OSS), Constant score and EuroQol-5D (EQ-5D)., Results: 6 patients met the inclusion criteria. In 5 of them, the cortical allograft was opposite to a plate, whereas in the other one a "Sandwich" technique was chosen because of large osteolysis. 'Bone healing' occurred in all patients after a mean of 3.3 months (range 2-5). In all but two patients, the elbow range of motion was in almost normal range (15-130). The mean OSS was 35.8 (+/- 6.4), whereas the mean Constant was 53.3 (+/- 2.2). The mean EQ-5D index was 0.451 (+/- 0.21)., Discussion: Bone healing occurred in all patients, with a time-to-union comparable or even better compared with other series. The use of cortical bone graft provide both stability and biological benefit, whereas stem cells improve the non-union environmental biology. Functional outcomes were lower than other series and patients' quality of life was similar to Italian elderly women., Conclusion: The use cortical allograft with stem cells is a viable strategy to treat humeral shaft non-union in the elderly., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Previous studies have reported altered fear circuitry function during fear conditioning in highly anxious individuals and in adults with a history of severe childhood adversity; less is known regarding younger populations and more common forms of adversity. We investigated fear circuitry functioning in healthy youths with histories of high (HH) or low (LH) chronic harsh parenting and high (HA) or low (LA) anxiety levels. 84 youths aged 13-16 performed an fMRI fear conditioning task. HH displayed decreased selective medial temporal lobe deactivations to CS+> CS- relative to LH. In addition, we found less amygdala-insula connectivity in HH vs LH. Interestingly, we observed distinct patterns of anxiety differences in amygdala-rostral ACC connectivity and subjective fear ratings depending on harsh parenting levels, suggesting a history of harsh parenting is linked with unique neural and behavioral anxious manifestations, which are different from anxiety manifestations in a context of low adversity., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Brain imaging offers a valuable tool to observe functional brain plasticity by showing how sensory inputs reshape cortical activations after a visual impairment. Following a unilateral post-chiasmatic lesion affecting the visual cortex, patients may suffer a contralateral visual loss referred to homonymous hemianopia. Nevertheless, these patients preserve the ability to unconsciously detect, localize and discriminate visual stimuli presented in their impaired visual field. To investigate this paradox, known as blindsight, we conducted a study using functional magnetic resonance imaging (fMRI) to evaluate the structural and functional impact of such lesion in a 33-year old patient (ML), who suffers a complete right hemianopia without macular sparing and showing strong evidences of blindsight. We thus performed whole brain and sliced thalamic fMRI scan sequences during an event-related motion detection task. We provided evidence of the neuronal fingerprint of blindsight by acquiring and associating neural correlates, specific structures and functional networks of the midbrain during blindsight performances which may help to better understand this condition. Accurate performance demonstrated the presence of residual vision and the ability to unconsciously perceive motion presented in the blind hemifield, although her reaction time was significantly higher in her blind-field. When the normal hemifield was stimulated, we observed significant contralateral activations in primary and secondary visual areas as well as motion specific areas, such as the supramarginal gyrus and middle temporal area. We also demonstrated sub-thalamic activations within the superior colliculi (SC) and the pulvinar. These results suggest a role of secondary subcortical structures in normal spontaneous motion detection. In a similar way, when the lesioned hemifield was stimulated, we observed contralateral activity in extrastriate areas with no activation of the primary lesioned visual cortex. Moreover, we observed activations within the SC when the blind hemifield was stimulated. However, we observed unexpected ipsilateral activations within the same motion specific areas, as well as bilateral frontal activations. These results highlight the importance of abnormal secondary pathways bypassing the primary visual area (V1) in residual vision. This reorganization in the structure and function of the visual pathways correlates with behavioral changes, thus offering a plausible explanation for the blindsight phenomenon. Our results may potentially impact the development of rehabilitation strategies to target subcortical pathways., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Having a parent with an anxiety disorder increases the risk of anxiety symptoms and anxiety disorders during the lifespan. Moreover, childhood and adolescence anxiety disorders and symptoms have been linked to a range of brain structure abnormalities. However, to date, no study has investigated brain anatomy in adolescents at high risk based on parental anxiety disorders and in adolescents with an anxiety disorder but without any treatment or therapy., Methods: Anatomical images from magnetic resonance imaging of 68 adolescents with anxiety disorders without any treatment (N = 20), at risk for anxiety because of their parents' anxiety disorders (N = 21), and comparison youths (N = 27), were analyzed using Freesurfer., Results: Compared to comparison group, smaller cortical thickness of the rostral anterior cingulate cortex and of the insula was observed in anxious and at-risk groups; smaller amygdala volume was observed in the anxious group only., Limitations: The age range studied is large (10 to 17 years old). Moreover, this study is cross-sectional. Since adolescence is one of the biggest periods of cerebral reorganization, longitudinal follow-up of these youths would be necessary., Conclusions: Smaller rostral anterior cingulate cortex and insula cortical thickness appear to be cerebral markers of the risk of developing an anxiety disorder in adolescence. The reduction of the amygdala volume seems to be linked to the onset of the disorder., (Copyright © 2019. Published by Elsevier B.V.)

Objective: The increasing number of total knee arthroplasties performed yearly worldwide has resulted in a concomitant rise in bacterial infections. Two-stage reimplantation has been reported as the most successful method of treating periprosthetic knee infections. The purpose of this study was to describe all the phases of the two-stage reimplantation and to review the literature regarding the topic., Materials and Methods: Most significant and recent papers about the management of periprosthetic knee infection through a two-stage reimplantation protocol were carefully analysed and reviewed. Our personal experience, previously published, with two-stage-reimplantation protocol was also briefly reported., Results: Two-stage reimplantation has been reported as the most successful method of treating periprosthetic knee infections. The strategy of using an antibiotic-loaded cement spacer and intravenous antibiotics with delayed exchange arthroplasty is actually considered the state-of-the-art, with a reported success rate of 88-96%. The two-stage protocol has been reported as a viable option also for patients with a periprosthetic knee infection by multidrug-resistant organisms. On the other hand, open debridement with polyethylene exchange and single-stage reimplantation have been reported effective only in selective case series involving acute infections by low-virulence organisms., Conclusions: The strategy that involves the use of cement spacer, intravenous antibiotic therapy, and successive revision total knee implantation is nowadays considered the gold standard for the management of the periprosthetic knee infection. This treatment is actually considered the first choice not only for chronic but also for acute infections, especially in the presence of resistant bacteria.

Aging is associated with cognitive decline and decreased capacity to inhibit distracting information. Video game training holds promise to increase inhibitory mechanisms in older adults. In the current study, we tested the impact of 3D-platform video game training on performance in an antisaccade task and on related changes in grey matter within the frontal eye fields (FEFs) of older adults. An experimental group (VID group) engaged in 3D-platform video game training over a period of 6 months, while an active control group was trained on piano lessons (MUS group), and a no-contact control group did not participate in any intervention (CON group). Increased performance in oculomotor inhibition, as measured by the antisaccade task, and increased grey matter in the right FEF was observed uniquely in the VID group. These results demonstrate that 3D-platform video game training can improve inhibitory control known to decline with age.

Objective: Recently identified mutations of the axon guidance molecule receptor gene, DCC, present an opportunity to investigate, in living human brain, mechanisms affecting neural connectivity and the basis of mirror movements, involuntary contralateral responses that mirror voluntary unilateral actions. We hypothesized that haploinsufficient DCC +/- mutation carriers with mirror movements would exhibit decreased DCC mRNA expression, a functional ipsilateral corticospinal tract, greater "mirroring" motor representations, and reduced interhemispheric inhibition. DCC +/- mutation carriers without mirror movements might exhibit some of these features., Methods: The participants (n = 52) included 13 DCC +/- mutation carriers with mirror movements, 7 DCC +/- mutation carriers without mirror movements, 13 relatives without the mutation or mirror movements, and 19 unrelated healthy volunteers. The multimodal approach comprised quantitative real time polymerase chain reaction, transcranial magnetic stimulation (TMS), functional magnetic resonance imaging (fMRI) under resting and task conditions, and measures of white matter integrity., Results: Mirror movements were associated with reduced DCC mRNA expression, increased ipsilateral TMS-induced motor evoked potentials, increased fMRI responses in the mirroring M1 and cerebellum, and markedly reduced interhemispheric inhibition. The DCC +/- mutation, irrespective of mirror movements, was associated with reduced functional connectivity and white matter integrity., Interpretation: Diverse connectivity abnormalities were identified in mutation carriers with and without mirror movements, but corticospinal effects and decreased peripheral DCC mRNA appeared driven by the mirror movement phenotype. ANN NEUROL 2019;85:433-442., (© 2019 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.)

Epidemiological evidence suggests a strict correlation between sudden sensorineural hearing loss (SSNHL) and cerebrovascular disorders. Leukoaraiosis represents a diffuse alteration of the periventricular and subcortical white matter. The aim of our study was to verify if the presence of white matter hyperintensity (WMH) was higher in patients affected by SSNHL compared to controls and evaluate the correlation between WMH and the cardiovascular risk factors, hearing level, and the response to therapy in SSNHL patients. The study group included 36 subjects affected by unilateral SSNHL. Thirty-six age- and sex-matched normal subjects with a negative history of SSNHL were used as controls. All patients underwent magnetic resonance imaging (MRI) (1.5 Tesla GE Signa) and the extent of leukoaraiosis was assessed with the Fazekas scale. The results of the present study demonstrate a high prevalence of WMH in SSNHL patients compared to controls confirming the hypothesis of a vascular impairment in SSNHL patients. The higher recovery rate in patients with greater periventricular white matter hyperintensity (PWMH) may suggest a vascular etiology that is still responsive to medical treatment. We aim to expand both the number of patients and the controls to avoid the limitation of the still small number to warrant solid scientific conclusions.

Arithmetic reasoning activates the occipital cortex of congenitally blind people (CB). This activation of visual areas may highlight the functional flexibility of occipital regions deprived of their dominant inputs or relate to the intrinsic computational role of specific occipital regions. We contrasted these competing hypotheses by characterizing the brain activity of CB and sighted participants while performing subtraction, multiplication and a control letter task. In both groups, subtraction selectively activated a bilateral dorsal network commonly activated during spatial processing. Multiplication triggered activity in temporal regions thought to participate in memory retrieval. No between-group difference was observed for the multiplication task whereas subtraction induced enhanced activity in the right dorsal occipital cortex of the blind individuals only. As this area overlaps with regions showing selective tuning to auditory spatial processing and exhibits increased functional connectivity with a dorsal "spatial" network, our results suggest that the recruitment of occipital regions during high-level cognition in the blind actually relates to the intrinsic computational role of the activated regions., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to report the clinical and functional results of a series of patients with early knee osteoarthritis (KOA) treated with the intra-articular injection of autologous adipose-derived stem cells (aASCs) plus arthroscopic debridement. The hypothesis was that protocol would significantly improve the clinical and functional outcomes in patients with early KOA., Methods: Fifty-two patients with early KOA, who received arthroscopic debridement followed by percutaneous injection of aASCs, were enrolled into the study and retrospectively analyzed with an average follow-up of 15.3 (range, 6 to 24) months. Patients were assessed through the IKS knee and function scores and VAS pain scale., Results: The mean IKS knee score improved from 37.4 (range, 14 to 79) points pre-operatively to 62.6 (range, 27 to 95) points at the latest follow-up (p < < 0.01). The mean IKS function score improved from 57.2 (range, 25 to 100) points pre-operatively to 83.0 (range, 35 to 100) points at the latest follow-up (p < < 0.01). The mean VAS score decreased from 8.5 (range, 3 to 10) pre-operatively to 5.1 (range, 0 to 8) at the latest follow-up (p < < 0.01). Additionally, patients with a pre-operative VAS score greater than 8 were found to show greater clinical and functional benefits compared with patients with VAS score lower than 8., Conclusions: The knee injection of aASCs associated to arthroscopic debridement increased significantly the clinical and functional scores in patients with early KOA at a mid-term follow-up, especially those with higher pre-operative VAS scores.

Microglia are patrolling cells that sense changes in the brain microenvironment and respond acquiring distinct phenotypes that can be either beneficial or detrimental for brain homeostasis. Anti-inflammatory microglia release soluble factors that might promote brain repair; however, in glioma, anti-inflammatory microglia dampen immune response and promote a brain microenvironment that foster tumor growth and invasion. The chemokine CXCL16 is expressed in the brain, where it is neuroprotective against brain ischemia, and it has been found to be over-expressed in glioblastoma (GBM). Considering that CXCL16 specific receptor CXCR6 is diffusely expressed in the brain including in microglia cells, we wanted to investigate the role of CXCL16 in the modulation of microglia cell activity and phenotype, and in the progression of glioma. Here we report that CXCL16 drives microglia polarization toward an anti-inflammatory phenotype, also restraining microglia polarization toward an inflammatory phenotype upon LPS and IFNγ stimulation. In the context of glioma, we demonstrate that CXCL16 released by tumor cells is determinant in promoting glioma associated microglia/macrophages (GAMs) modulation toward an anti-inflammatory/pro-tumor phenotype, and that cxcr6ko mice, orthotopically implanted into the brain with GL261 glioma cells,survive longer compared to wild-type mice. We also describe that CXCL16/CXCR6 signaling acts directly on mouse glioma cells, as well as human primary GBM cells, promoting tumor cell growth, migration and invasion. All together these data suggest that CXCL16 signaling could represent a good target to modulate microglia phenotype in order to restrain inflammation or to limit glioma progression.

The discovery of intrinsically photosensitive retinal ganglion cells (ipRGCs) marked a major shift in our understanding of how light information is processed by the mammalian brain. These ipRGCs influence multiple functions not directly related to image formation such as circadian resetting and entrainment, pupil constriction, enhancement of alertness, as well as the modulation of cognition. More recently, it was demonstrated that ipRGCs may also contribute to basic visual functions. The impact of ipRGCs on visual function, independently of image forming photoreceptors, remains difficult to isolate, however, particularly in humans. We previously showed that exposure to intense monochromatic blue light (465 nm) induced non-conscious light perception in a forced choice task in three rare totally visually blind individuals without detectable rod and cone function, but who retained non-image-forming responses to light, very likely via ipRGCs. The neural foundation of such light perception in the absence of conscious vision is unknown, however. In this study, we characterized the brain activity of these three participants using electroencephalography (EEG), and demonstrate that unconsciously perceived light triggers an early and reliable transient desynchronization (i.e. decreased power) of the alpha EEG rhythm (8-14 Hz) over the occipital cortex. These results provide compelling insight into how ipRGC may contribute to transient changes in ongoing brain activity. They suggest that occipital alpha rhythm synchrony, which is typically linked to the visual system, is modulated by ipRGCs photoreception; a process that may contribute to the non-conscious light perception in those blind individuals.

Introduction:: The mechanism that leads to a given fracture pattern is not understood. Heredity could act in this field through the ABO system. We investigated the relationship between ABO blood system and hip fracture pattern in a population from Southern Italy., Methods:: Hip fractures were identified through a registry evaluation of the activity of a level I Hospital, and subsequently classified in 'intracapsular' or 'extracapsular' according to their anatomical location. Information on these patients' ABO blood type was collected and compared with general population data from the report on blood donors of the Salerno division of Italian Blood Volunteers Association (AVIS)., Results:: 590 hip fractures were included (414 extracapsular, 176 intracapsular) and compared with 709 blood donors. Fractured patients presented a blood group A more often and blood group O less often than the AVIS population ( p A vs. non-A = 0.0033; p O vs. non-O = 0.0024). None of the ABO blood groups were associated with fracture pattern ( p O vs. non-O = 0.5858, p A vs. non-A = 0.409; p B vs. non-B = 0.253; p AB vs. non-AB = 0.212). The rhesus factor was not associated the fracture pattern ( p = 0.34)., Conclusions:: The ABO blood type could play a role as a risk factor for proximal femoral fractures, but in our population its relevance in influencing the fracture pattern is unclear.

Blind individuals display superior sensory abilities in other modalities, yet results remain contradictory regarding their performance on olfactory tasks. Using complex ecological olfactory tasks, we evaluated the impact of blindness on olfactory performance. We tested 12 early-blind individuals (M = 49, SD = 13.09) and 12 sighted controls (M = 49, SD = 14.31) who were all blindfolded. Based solely on the wine odors, participants evaluated 24 pairs of wine and determined if both samples belonged to the same category (red wine, white wine, or rosé wine) or not (odor categorization), and if so, whether they were identical or not (odor differentiation). Then, they had to classify 15 different wines (5 red, 5 white and 5 rosé) into red, white, and rosé wines (odor classification). Blind individuals (d': M = 1.3, SD = 1.2) presented lower scores compared to sighted controls (M = 2.2 SD = 0.8; p < .05) in the odor categorization task, but no group difference was observed for the other tasks. For all participants, red wine odors were the easiest to classify (1.8 ± 1.0), followed by white wine odors (0.5 ± 0.6) and finally rosé wine odors (blind and sighted; F[2; 44] = 11.9, p < .001). In summary, early-blind individuals had a harder time to categorize wine odors. This could be explained by a different construction of internal reference categories for wine in early-blind individuals. Finally, this research is in line with the notion of the absence of higher olfactory sensitivity in blind individuals., (Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.)

The hippocampus is critical to healthy cognition, yet results in the current study show that action video game players have reduced grey matter within the hippocampus. A subsequent randomised longitudinal training experiment demonstrated that first-person shooting games reduce grey matter within the hippocampus in participants using non-spatial memory strategies. Conversely, participants who use hippocampus-dependent spatial strategies showed increased grey matter in the hippocampus after training. A control group that trained on 3D-platform games displayed growth in either the hippocampus or the functionally connected entorhinal cortex. A third study replicated the effect of action video game training on grey matter in the hippocampus. These results show that video games can be beneficial or detrimental to the hippocampal system depending on the navigation strategy that a person employs and the genre of the game.

Functional near-infrared spectroscopy (fNIRS) is a non-invasive imaging technique that elicits growing interest for research and clinical applications. In the last decade, efforts have been made to develop a mathematical framework in order to image the effective sources of hemoglobin variations in brain tissues. Different approaches can be used to impose additional information or constraints when reconstructing the cerebral images of an ill-posed problem. The goal of this study is to compare the performance and limitations of several source localization techniques in the context of fNIRS tomography using individual anatomical magnetic resonance imaging (MRI) to model light propagation. The forward problem is solved using a Monte Carlo simulation of light propagation in the tissues. The inverse problem has been linearized using the Rytov approximation. Then, Tikhonov regularization applied to least squares, truncated singular value decomposition, back-projection, L1-norm regularization, minimum norm estimates, low resolution electromagnetic tomography and Bayesian model averaging techniques are compared using a receiver operating characteristic analysis, blurring and localization error measures. Using realistic simulations (n = 450) and data acquired from a human participant, this study depicts how these source localization techniques behave in a human head fNIRS tomography. When compared to other methods, Bayesian model averaging is proposed as a promising method in DOT and shows great potential to improve specificity, accuracy, as well as to reduce blurring and localization error even in presence of noise and deep sources. Classical reconstruction methods, such as regularized least squares, offer better sensitivity but higher blurring; while more novel L1-based method provides sparse solutions with small blurring and high specificity but lower sensitivity. The application of these methods is also demonstrated experimentally using visual fNIRS experiment with adult participant., Competing Interests: The authors declare that there are no conflicts of interest related to this article.

The axon guidance cue receptor DCC (deleted in colorectal cancer) plays a critical role in the organization of mesocorticolimbic pathways in rodents. To investigate whether this occurs in humans, we measured (1) anatomical connectivity between the substantia nigra/ventral tegmental area (SN/VTA) and forebrain targets, (2) striatal and cortical volumes, and (3) putatively associated traits and behaviors. To assess translatability, morphometric data were also collected in Dcc -haploinsufficient mice. The human volunteers were 20 DCC +/- mutation carriers, 16 DCC +/+ relatives, and 20 DCC +/+ unrelated healthy volunteers (UHVs; 28 females). The mice were 11 Dcc +/- and 16 wild-type C57BL/6J animals assessed during adolescence and adulthood. Compared with both control groups, the human DCC +/- carriers exhibited the following: (1) reduced anatomical connectivity from the SN/VTA to the ventral striatum [ DCC +/+ : p = 0.0005, r ( effect size ) = 0.60; UHV: p = 0.0029, r = 0.48] and ventral medial prefrontal cortex ( DCC +/+ : p = 0.0031, r = 0.53; UHV: p = 0.034, r = 0.35); (2) lower novelty-seeking scores ( DCC +/+ : p = 0.034, d = 0.82; UHV: p = 0.019, d = 0.84); and (3) reduced striatal volume ( DCC +/+ : p = 0.0009, d = 1.37; UHV: p = 0.0054, d = 0.93). Striatal volumetric reductions were also present in Dcc +/- mice, and these were seen during adolescence ( p = 0.0058, d = 1.09) and adulthood ( p = 0.003, d = 1.26). Together these findings provide the first evidence in humans that an axon guidance gene is involved in the formation of mesocorticolimbic circuitry and related behavioral traits, providing mechanisms through which DCC mutations might affect susceptibility to diverse neuropsychiatric disorders. SIGNIFICANCE STATEMENT Opportunities to study the effects of axon guidance molecules on human brain development have been rare. Here, the identification of a large four-generational family that carries a mutation to the axon guidance molecule receptor gene, DCC , enabled us to demonstrate effects on mesocorticolimbic anatomical connectivity, striatal volumes, and personality traits. Reductions in striatal volumes were replicated in DCC -haploinsufficient mice. Together, these processes might influence mesocorticolimbic function and susceptibility to diverse neuropsychiatric disorders., (Copyright © 2018 the authors 0270-6474/18/384655-11$15.00/0.)

Sounds activate occipital regions in early blind individuals. However, how different sound categories map onto specific regions of the occipital cortex remains a matter of debate. We used fMRI to characterize brain responses of early blind and sighted individuals to familiar object sounds, human voices, and their respective low-level control sounds. In addition, sighted participants were tested while viewing pictures of faces, objects, and phase-scrambled control pictures. In both early blind and sighted, a double dissociation was evidenced in bilateral auditory cortices between responses to voices and object sounds: Voices elicited categorical responses in bilateral superior temporal sulci, whereas object sounds elicited categorical responses along the lateral fissure bilaterally, including the primary auditory cortex and planum temporale. Outside the auditory regions, object sounds also elicited categorical responses in the left lateral and in the ventral occipitotemporal regions in both groups. These regions also showed response preference for images of objects in the sighted group, thus suggesting a functional specialization that is independent of sensory input and visual experience. Between-group comparisons revealed that, only in the blind group, categorical responses to object sounds extended more posteriorly into the occipital cortex. Functional connectivity analyses evidenced a selective increase in the functional coupling between these reorganized regions and regions of the ventral occipitotemporal cortex in the blind group. In contrast, vocal sounds did not elicit preferential responses in the occipital cortex in either group. Nevertheless, enhanced voice-selective connectivity between the left temporal voice area and the right fusiform gyrus were found in the blind group. Altogether, these findings suggest that, in the absence of developmental vision, separate auditory categories are not equipotent in driving selective auditory recruitment of occipitotemporal regions and highlight the presence of domain-selective constraints on the expression of cross-modal plasticity.

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Localizing touch relies on the activation of skin-based and externally defined spatial frames of reference. Psychophysical studies have demonstrated that early visual deprivation prevents the automatic remapping of touch into external space. We used fMRI to characterize how visual experience impacts the brain circuits dedicated to the spatial processing of touch. Sighted and congenitally blind humans performed a tactile temporal order judgment (TOJ) task, either with the hands uncrossed or crossed over the body midline. Behavioral data confirmed that crossing the hands has a detrimental effect on TOJ judgments in sighted but not in early blind people. Crucially, the crossed hand posture elicited enhanced activity, when compared with the uncrossed posture, in a frontoparietal network in the sighted group only. Psychophysiological interaction analysis revealed, however, that the congenitally blind showed enhanced functional connectivity between parietal and frontal regions in the crossed versus uncrossed hand postures. Our results demonstrate that visual experience scaffolds the neural implementation of the location of touch in space. SIGNIFICANCE STATEMENT In daily life, we seamlessly localize touch in external space for action planning toward a stimulus making contact with the body. For efficient sensorimotor integration, the brain has therefore to compute the current position of our limbs in the external world. In the present study, we demonstrate that early visual deprivation alters the brain activity in a dorsal parietofrontal network typically supporting touch localization in the sighted. Our results therefore conclusively demonstrate the intrinsic role that developmental vision plays in scaffolding the neural implementation of touch perception., (Copyright © 2017 the authors 0270-6474/17/3710097-07$15.00/0.)

The insula is now regarded as a potential site of epileptogenesis in drug-resistant epilepsy, and the advent of microsurgical techniques has allowed insular cortectomy to become a treatment of choice when the insular cortex is involved in the seizure focus. However, considering the evidence of an insular role in socio-emotional processing, it remains unknown whether these cortical resections disturb personality and social behavior as experienced in daily life. We examined such changes in a group of patients (n=19) who underwent epilepsy surgery involving partial or complete resection of the insula, and compared them to a group of patients who underwent standard temporal lobe epilepsy (TLE) surgery (n=19) as a lesion-control group. Participants were assessed on the Iowa Scales of Personality Change, filled by a close relative at least six months after surgery. While postoperative changes did not significantly differ between groups on any of the ISPC items, insular resections were associated with mild but significant increases in irritability, emotional lability, anxiety, and frugality postoperatively, which, apart from anxiety, were not significant among TLE patients. Our results are congruent with the idea that the insula contributes to emotion processing. To our knowledge, this study is the first to systematically assess personality changes in a consecutive sample of patients with insular resections., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Presbyacusis reflects dysfunctions present along the central auditory pathway. Given that the topographic representation of the auditory directional spatial map is deteriorated in the superior colliculus of aged animals, therefore, are spectral and temporal auditory processes altered with aging in the rat's superior colliculus? Extracellular single-unit recordings were conducted in the superior colliculus of anesthetized Sprague-Dawley adult (10 months) and aged (22 months) rats. In the spectral domain, level thresholds in aged rats were significantly increased when superior colliculus auditory neurons were stimulated with pure tones or Gaussian noise bursts. The sharpness of the frequency response tuning curve at 10 dB SPL above threshold was also significantly broader among the aged rats. Furthermore, in the temporal domain, the minimal silent gap thresholds to Gaussian noises were significantly longer in aged rats. Hence, these results highlight that spectral and temporal auditory processing in the superior colliculus are impaired during aging., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Homonymous hemianopia (HH) is the most common cortical visual impairment leading to blindness in the contralateral hemifield. It is associated with many inconveniences and daily restrictions such as exploration and visual orientation difficulties. However, patients with HH can preserve the remarkable ability to unconsciously perceive visual stimuli presented in their blindfield, a phenomenon known as blindsight. Unfortunately, the nature of this captivating residual ability is still misunderstood and the rehabilitation strategies in terms of visual training have been insufficiently exploited. This article discusses type I and type II blindsight in a neuronal framework of altered global workspace, resulting from inefficient perception, attention and conscious networks. To enhance synchronization and create global availability for residual abilities to reach visual consciousness, rehabilitation tools need to stimulate subcortical extrastriate pathways through V5/MT. Multisensory bottom-up compensation combined with top-down restitution training could target pre-existing and new neuronal mechanisms to recreate a framework for potential functionality.

We used BrainVisa software in an exploratory analysis measuring the depth and sulcal profile of the central sulci of congenitally blind and sighted individuals. We found the greatest differences between the groups at locations on the central sulcus corresponding with the pli de passage fronto-parietal moyen (PPFM), suggesting a cortical reorganization of the primary sensorimotor area of the hand within the central sulcus. This may be in response to the congenitally blind individuals' mastery of Braille or general increase of hand use in everyday life.

Tactile perception and motor production share the use of internally- and externally-defined coordinates. In order to examine how visual experience affects the internal/external coding of space for touch and movement, early blind (EB) and sighted controls (SC) took part in two experiments. In experiment 1, participants were required to perform a Temporal Order Judgment task (TOJ), either with their hands in parallel or crossed over the body midline. Confirming previous demonstration, crossing the hands led to a significant decrement in performance in SC but did not affect EB. In experiment 2, participants were trained to perform a sequence of five-finger movements. They were tested on their ability to produce, with the same hand but with the keypad turned upside down, the learned (internal) or the mirror (external) sequence. We observed significant transfer of motor sequence knowledge in both EB and SC irrespective of whether the representation of the sequence was internal or external. Together, these results demonstrate that visual experience differentially impacts the automatic weight attributed to internal versus external coordinates depending on task-specific spatial requirements.