Electrophysiological responses of audiovisual integration from infancy to adulthood.

Our ability to merge information from different senses into a unified percept is a crucial perceptual process for efficient interaction with our multisensory environment. Yet, the developmental process underlying how the brain implements multisensory integration (MSI) remains poorly known. This cross-sectional study aims to characterize the developmental patterns of audiovisual events in 131 individuals aged from 3 months to 30 years. Electroencephalography (EEG) was recorded during a passive task, including simple auditory, visual, and audiovisual stimuli. In addition to examining age-related variations in MSI responses, we investigated Event-Related Potentials (ERPs) linked with auditory and visual stimulation alone. This was done to depict the typical developmental trajectory of unisensory processing from infancy to adulthood within our sample and to contextualize the maturation effects of MSI in relation to unisensory development. Comparing the neural response to audiovisual stimuli to the sum of the unisensory responses revealed signs of MSI in the ERPs, more specifically between the P2 and N2 components (P2 effect). Furthermore, adult-like MSI responses emerge relatively late in the development, around 8 years old. The automatic integration of simple audiovisual stimuli is a long developmental process that emerges during childhood and continues to mature during adolescence with ERP latencies decreasing with age.

Multichannel wearable fNIRS-EEG system for long-term clinical monitoring.

Continuous brain imaging techniques can be beneficial for the monitoring of neurological pathologies (such as epilepsy or stroke) and neuroimaging protocols involving movement. Among existing ones, functional near-infrared spectroscopy (fNIRS) and electroencephalography (EEG) have the advantage of being noninvasive, nonobstructive, inexpensive, yield portable solutions, and offer complementary monitoring of electrical and local hemodynamic activities. This article presents a novel system with 128 fNIRS channels and 32 EEG channels with the potential to cover a larger fraction of the adult superficial cortex than earlier works, is integrated with 32 EEG channels, is light and battery-powered to improve portability, and can transmit data wirelessly to an interface for real-time display of electrical and hemodynamic activities. A novel fNIRS-EEG stretchable cap, two analog channels for auxiliary data (e.g., electrocardiogram), eight digital triggers for event-related protocols and an internal accelerometer for movement artifacts removal contribute to improve data acquisition quality. The system can run continuously for 24 h. Following instrumentation validation and reliability on a solid phantom, performance was evaluated on (1) 12 healthy participants during either a visual (checkerboard) task at rest or while pedalling on a stationary bicycle or a cognitive (language) task and (2) 4 patients admitted either to the epilepsy (n = 3) or stroke (n = 1) units. Data analysis confirmed expected hemodynamic variations during validation recordings and useful clinical information during in-hospital testing. To the best of our knowledge, this is the first demonstration of a wearable wireless multichannel fNIRS-EEG monitoring system in patients with neurological conditions. Hum Brain Mapp 39:7-23, 2018. © 2017 Wiley Periodicals, Inc.

Using patient-specific hemodynamic response function in epileptic spike analysis of human epilepsy: a study based on EEG-fNIRS.

Functional near-infrared spectroscopy (fNIRS) can be combined with electroencephalography (EEG) to continuously monitor the hemodynamic signal evoked by epileptic events such as seizures or interictal epileptiform discharges (IEDs, aka spikes). As estimation methods assuming a canonical shape of the hemodynamic response function (HRF) might not be optimal, we sought to model patient-specific HRF (sHRF) with a simple deconvolution approach for IED-related analysis with EEG-fNIRS data. Furthermore, a quadratic term was added to the model to account for the nonlinearity in the response when IEDs are frequent. Prior to analyzing clinical data, simulations were carried out to show that the HRF was estimable by the proposed deconvolution methods under proper conditions. EEG-fNIRS data of five patients with refractory focal epilepsy were selected due to the presence of frequent clear IEDs and their unambiguous focus localization. For each patient, both the linear sHRF and the nonlinear sHRF were estimated at each channel. Variability of the estimated sHRFs was seen across brain regions and different patients. Compared with the SPM8 canonical HRF (cHRF), including these sHRFs in the general linear model (GLM) analysis led to hemoglobin activations with higher statistical scores as well as larger spatial extents on all five patients. In particular, for patients with frequent IEDs, nonlinear sHRFs were seen to provide higher sensitivity in activation detection than linear sHRFs. These observations support using sHRFs in the analysis of IEDs with EEG-fNIRS data.

Spatiotemporal dynamics of affective picture processing revealed by intracranial high-gamma modulations.

Our comprehension of the neural mechanisms underlying emotional information processing has largely benefited from noninvasive electrophysiological and functional neuroimaging techniques in recent years. However, the spatiotemporal dynamics of the neural events occurring during emotional processing remain imprecise due to the limited combination of spatial and temporal resolution provided by these techniques. This study examines the modulations of high-frequency activity of intracranial electroencephalography recordings associated with affective picture valence, in epileptic patients awaiting neurosurgery. Recordings were obtained from subdural grids and depth electrodes in eight patients while they viewed a series of unpleasant, pleasant and neutral pictures from the International Affective Picture System. Broadband high-gamma (70-150 Hz) power was computed for separate 100-ms time windows and compared according to ratings of emotional valence. Compared to emotionally neutral or pleasant pictures, unpleasant stimuli were associated with an early and long-lasting (≈200-1,000 ms) bilateral increase in high-gamma activity in visual areas of the occipital and temporal lobes, together with a late and transient (≈500-800 ms) decrease found bilaterally in the lateral prefrontal cortex (PFC). Pleasant pictures were associated with increased gamma activity in the occipital cortex, compared to the emotionally neutral stimuli. Consistent with previous studies, our results provide direct evidence of emotion-related modulations in the visual ventral pathway during picture processing. Results in the lateral PFC also shed light on the neural mechanisms underlying its role in negative emotions processing. This study demonstrates the utility of intracranial high-gamma modulations to study emotional process with a high spatiotemporal precision.

Recognizing an object from the sum of its parts: an intracranial study on alpha rhythms.

Little is known about the relation of alpha rhythms and object recognition. Alpha has been generally proposed to be associated with attention and memory and to be particularly important for the mediation of long-distance communication between neuronal populations. However, how these apply to object recognition is still unclear. This study aimed at describing the spatiotemporal dynamics of alpha rhythms while recognizing fragmented images of objects presented for the first time and presented again 24 hr later. Intracranial electroencephalography was performed in six epileptic patients undergoing presurgical evaluation. Time-frequency analysis revealed a strong alpha activity, mainly of the evoked type, propagating from posterior cerebral areas to anterior regions, which was similar whether the objects were recognized or not. Phase coherence analysis, however, showed clear phase synchronization specific for the moment of recognition. Twenty-four hr later, frontal regions displayed stronger alpha activity and more distributed phase synchronization than when images were presented for the first time. In conclusion, alpha amplitude seems to be related to nonspecific mechanism. Phase coherence analysis suggests a communicational role of alpha activity in object recognition, which may be important for the comparison between bottom-up representations and memory templates.

Language brain responses and neurodevelopmental outcome in preschoolers with congenital heart disease: A fNIRS study.

Neurodevelopmental disabilities affect up to 50% of survivors of congenital heart disease (CHD). Language difficulties are frequently identified during preschool period and can lead to academic, social, behavioral, and emotional difficulties. Structural brain alterations are associated with poorer neurodevelopmental outcomes in patients with CHD during infancy, childhood, and adolescence. However, evidence is lacking about the functional brain activity in children with CHD and its relationship with neurodevelopment. This study therefore aimed to characterize brain responses during a passive story-listening task in 3-year-old children with CHD, and to investigate the relationship between functional brain patterns of language processing and neurodevelopmental outcomes. To do so, we assessed hemodynamic concentration changes, using functional near-infrared spectroscopy (fNIRS), and neurodevelopmental outcomes, using the Wechsler Preschool and Primary Scale of Intelligence - 4th Edition (WPPSI-IV), in children with CHD (n = 19) and healthy controls (n = 23). Compared to their healthy peers, children with CHD had significantly lower scores on the Verbal comprehension index (VCI), the Vocabulary acquisition index (VAI), the General ability index (GAI), and the Information and the Picture Naming subtests of the WPPSI-IV. During the passive story-listening task, healthy controls showed significant hemodynamic brain responses in the temporal and the temporal posterior regions, with stronger activation in the temporal posterior than in the temporal regions. In contrast, children with CHD showed reduced activation in the temporal posterior regions compared to controls, with no difference of activation between regions. Reduced brain responses in the temporal posterior regions were also correlated with lower neurodevelopmental outcomes in both groups. This is the first study that reveals reduced brain functional responses in preschoolers with CHD during a receptive language task. It also suggests that the temporal posterior activation could be a potential brain marker of cognitive development. These findings provide support for the feasibility of identifying brain correlates of neurodevelopmental vulnerabilities in children with CHD.

Relationship between EEG spectral power and dysglycemia with neurodevelopmental outcomes after neonatal encephalopathy.

OBJECTIVE: We investigated how electroencephalography (EEG) quantitative measures and dysglycemia relate to neurodevelopmental outcomes following neonatal encephalopathy (NE). METHODS: This retrospective study included 90 neonates with encephalopathy who received therapeutic hypothermia. EEG absolute spectral power was calculated during post-rewarming and 2-month follow-up. Measures of dysglycemia (hypoglycemia, hyperglycemia, and glycemic lability) and glucose variability were computed for the first 48 h of life. We evaluated the ability of EEG and glucose measures to predict neurodevelopmental outcomes at ≥ 18 months, using logistic regressions (with area under the receiver operating characteristic [AUROC] curves). RESULTS: The post-rewarming global delta power (average all electrodes), hyperglycemia and glycemic lability predicted moderate/severe neurodevelopmental outcome separately (AUROC = 0.8, 95%CI [0.7,0.9], p < .001) and even more so when combined (AUROC = 0.9, 95%CI [0.8,0.9], p < .001). After adjusting for NE severity and magnetic resonance imaging (MRI) brain injury, only global delta power remained significantly associated with moderate/severe neurodevelopmental outcome (odds ratio [OR] = 0.9, 95%CI [0.8,1.0], p = .04), gross motor delay (OR = 0.9, 95%CI [0.8,1.0], p = .04), global developmental delay (OR = 0.9, 95%CI [0.8,1.0], p = .04), and auditory deficits (OR = 0.9, 95%CI [0.8,1.0], p = .03). CONCLUSIONS: In NE, global delta power post-rewarming was predictive of outcomes at ≥ 18 months. SIGNIFICANCE: EEG markers post-rewarming can aid prediction of neurodevelopmental outcomes following NE.

Noninvasive continuous functional near-infrared spectroscopy combined with electroencephalography recording of frontal lobe seizures.

PURPOSE: To investigate spatial and metabolic changes associated with frontal lobe seizures. METHODS: Functional near-infrared spectroscopy combined with electroencephalography (EEG-fNIRS) recordings of patients with confirmed nonlesional refractory frontal lobe epilepsy (FLE). KEY FINDINGS: Eighteen seizures from nine patients (seven male, mean age 27 years, range 13-46 years) with drug-refractory FLE were captured during EEG-fNIRS recordings. All seizures were coupled with significant hemodynamic variations that were greater with electroclinical than with electrical seizures. fNIRS helped in the identification of seizures in three patients with more subtle ictal EEG abnormalities. Hemodynamic changes consisted of local increases in oxygenated (HbO) and total hemoglobin (HbT) but heterogeneous deoxygenated hemoglobin (HbR) behavior. Furthermore, rapid hemodynamic alterations were observed in the homologous contralateral region, even in the absence of obvious propagated epileptic activity. The extent of HbO activation adequately lateralized the epileptogenic side in the majority of patients. SIGNIFICANCE: EEG-fNIRS reveals complex spatial and metabolic changes during focal frontal lobe seizures. Further characterization of these changes could improve seizure detection, localization, and understanding of the impact of focal seizures.

Neurometabolic and microstructural alterations following a sports-related concussion in female athletes.

BACKGROUND: Sports-related concussions are a major public health concern affecting millions of individuals annually. Neurometabolic and microstructural alterations have been reported in the chronic phase following a concussion in male athletes, while no study has investigated these alterations in female athletes. METHODS: Neurometabolic and microstructural alterations following a concussion were investigated by comparing 10 female athletes with a concussion and 10 control female athletes, using magnetic resonance spectroscopy (MRS) and diffusion tensor imaging (DTI). Athletes with concussion were scanned at least 7 months post-concussion (mean = 18.9 months). RESULTS: MRS revealed a significant lower level of myo-inositol in the hippocampus and the primary motor cortices (M1) bilaterally. DTI analysis using Tract-Based Spatial Statistics (TBSS) showed no difference in fractional anisotropy (FA) while higher level of mean diffusivity (MD) in athletes with concussion was detected in large white matter tracts including the forceps minors, inferior/superior longitudinal fasciculi, inferior fronto-occipital fasciculus, cingulum, uncinate fasciculus, anterior thalamic radiations and corticospinal tract. Moreover, a region of interest approach for the corpus callosum revealed a significant lower level of FA in the segment containing fibres projecting to M1. CONCLUSIONS: This study demonstrates persistent neurometabolic and microstructural alterations in female athletes suffering a sports-related concussion.

Early childhood malnutrition impairs adult resting brain function using near-infrared spectroscopy.

Introduction: Early childhood malnutrition affects 200+ million children under 5 years of age worldwide and is associated with persistent cognitive, behavioral and psychiatric impairments in adulthood. However, very few studies have investigated the long-term effects of childhood protein-energy malnutrition (PEM) on brain function using a functional hemodynamic brain imaging technique. Objective and methods: This study aims to investigate functional brain network alterations using near infrared spectroscopy (NIRS) in adults, aged 45-51 years, from the Barbados Nutrition Study (BNS) who suffered from a single episode of malnutrition restricted to their first year of life (n = 26) and controls (n = 29). A total of 55 individuals from the BNS cohort underwent NIRS recording at rest. Results and discussion: Using functional connectivity and permutation analysis, we found patterns of increased Pearson's correlation with a specific vulnerability of the frontal cortex in the PEM group (ps < 0.05). Using a graph theoretical approach, mixed ANCOVAs showed increased segregation (ps = 0.0303 and 0.0441) and decreased integration (p = 0.0498) in previously malnourished participants compared to healthy controls. These results can be interpreted as a compensatory mechanism to preserve cognitive functions, that could also be related to premature or pathological brain aging. To our knowledge, this study is the first NIRS neuroimaging study revealing brain function alterations in middle adulthood following early childhood malnutrition limited to the first year of life.

Functional brain connectivity after corrective cardiac surgery for critical congenital heart disease: a preliminary near-infrared spectroscopy (NIRS) report.

Patients with congenital heart disease (CHD) requiring cardiac surgery in infancy are at high risk for neurodevelopmental impairments. Neonatal imaging studies have reported disruptions of brain functional organization before surgery. Yet, the extent to which functional network alterations are present after cardiac repair remains unexplored. This preliminary study aimed at investigating cortical functional connectivity in 4-month-old infants with repaired CHD, using resting-state functional near-infrared spectroscopy (fNIRS). After fNIRS signal frequency decomposition, we compared values of magnitude-squared coherence as a measure of connectivity strength, between 21 infants with corrected CHD and 31 healthy controls. We identified a subset of connections with differences between groups at an uncorrected statistical level of p < .05 while controlling for sex and maternal socioeconomic status, with most of these connections showing reduced connectivity in infants with CHD. Although none of these differences reach statistical significance after FDR correction, likely due to the small sample size, moderate to large effect sizes were found for group-differences. If replicated, these results would therefore suggest preliminary evidence that alterations of brain functional connectivity are present in the months after cardiac surgery. Additional studies involving larger sample size are needed to replicate our data, and comparisons between pre- and postoperative findings would allow to further delineate alterations of functional brain connectivity in this population.

Brain language networks and cognitive outcomes in children with frontotemporal lobe epilepsy.

Introduction: Pediatric frontal and temporal lobe epilepsies (FLE, TLE) have been associated with language impairments and structural and functional brain alterations. However, there is no clear consensus regarding the specific patterns of cerebral reorganization of language networks in these patients. The current study aims at characterizing the cerebral language networks in children with FLE or TLE, and the association between brain network characteristics and cognitive abilities. Methods: Twenty (20) children with FLE or TLE aged between 6 and 18 years and 29 age- and sex-matched healthy controls underwent a neuropsychological evaluation and a simultaneous functional near-infrared spectroscopy and electroencephalography (fNIRS-EEG) recording at rest and during a receptive language task. EEG was used to identify potential subclinical seizures in patients. We removed these time intervals from the fNIRS signal to investigate language brain networks and not epileptogenic networks. Functional connectivity matrices on fNIRS oxy-hemoglobin concentration changes were computed using cross-correlations between all channels. Results and discussion: Group comparisons of residual matrices (=individual task-based matrix minus individual resting-state matrix) revealed significantly reduced connectivity within the left and between hemispheres, increased connectivity within the right hemisphere and higher right hemispheric local efficiency for the epilepsy group compared to the control group. The epilepsy group had significantly lower cognitive performance in all domains compared to their healthy peers. Epilepsy patients' local network efficiency in the left hemisphere was negatively associated with the estimated IQ (p = 0.014), suggesting that brain reorganization in response to FLE and TLE does not allow for an optimal cognitive development.

Relationship between 4-month functional brain network topology and 24-month neurodevelopmental outcome in children with congenital heart disease.

Survivors of complex forms of congenital heart disease (CHD)∗ are at high risk of neurodevelopmental disabilities. Neuroimaging studies have pointed to brain anomalies and immature networks in infants with CHD, yet less is known about their functional network topology and associations with neurodevelopment. To characterize the functional network topology in 4-month-old infants with repaired CHD, we compared graph theory metrics measured using resting-state functional near-infrared spectroscopy (rs-fNIRS) between infants with CHD (n = 22) and healthy controls (n = 30). We also investigated the moderating effect of graph theory metrics on the relationship between group (CHD vs. Controls) and developmental outcomes at 24 months. At 4 months, both groups presented similar functional brain network topology. At 24 months, children with CHD had lower scores on the language scale and the expressive communication subscale of the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), as well as lower scores on the Grammatical Form scale of the MacArthur-Bates Communicative Development Inventory (MBCDI). The relationship between group and expressive language was moderated by the normalized characteristic path length (λ) and the degree (k). Although infants with CHD have functional brain topology similar to that of healthy controls, our findings suggest that they do not benefit from an optimal functional brain organization in comparison with healthy infants.

Mother and stranger: an electrophysiological study of voice processing in newborns.

In the mature adult brain, there are voice selective regions that are especially tuned to familiar voices. Yet, little is known about how the infant's brain treats such information. Here, we investigated, using electrophysiology and source analyses, how newborns process their mother's voice compared with that of a stranger. Results suggest that, shortly after birth, newborns distinctly process their mother's voice at an early preattentional level and at a later presumably cognitive level. Activation sources revealed that exposure to the maternal voice elicited early language-relevant processing, whereas the stranger's voice elicited more voice-specific responses. A central probably motor response was also observed at a later time, which may reflect an innate auditory-articulatory loop. The singularity of left-dominant brain activation pattern together with its ensuing sustained greater central activation in response to the mother's voice may provide the first neurophysiologic index of the preferential mother's role in language acquisition.

Parallel factor analysis for multidimensional decomposition of functional near-infrared spectroscopy data.

Significance: Current techniques for data analysis in functional near-infrared spectroscopy (fNIRS), such as artifact correction, do not allow to integrate the information originating from both wavelengths, considering only temporal and spatial dimensions of the signal's structure. Parallel factor analysis (PARAFAC) has previously been validated as a multidimensional decomposition technique in other neuroimaging fields. Aim: We aimed to introduce and validate the use of PARAFAC for the analysis of fNIRS data, which is inherently multidimensional (time, space, and wavelength). Approach: We used data acquired in 17 healthy adults during a verbal fluency task to compare the efficacy of PARAFAC for motion artifact correction to traditional two-dimensional decomposition techniques, i.e., target principal (tPCA) and independent component analysis (ICA). Correction performance was further evaluated under controlled conditions with simulated artifacts and hemodynamic response functions. Results: PARAFAC achieved significantly higher improvement in data quality as compared to tPCA and ICA. Correction in several simulated signals further validated its use and promoted it as a robust method independent of the artifact's characteristics. Conclusions: This study describes the first implementation of PARAFAC in fNIRS and provides validation for its use to correct artifacts. PARAFAC is a promising data-driven alternative for multidimensional data analyses in fNIRS and this study paves the way for further applications.

LIONirs: flexible Matlab toolbox for fNIRS data analysis.

BACKGROUND: Functional near-infrared spectroscopy (fNIRS) is a suitable tool for recording brain function in pediatric or challenging populations. As with other neuroimaging techniques, the scientific community is engaged in an evolving debate regarding the most adequate methods for performing fNIRS data analyses. NEW METHOD: We introduce LIONirs, a neuroinformatics toolbox for fNIRS data analysis, designed to follow two main goals: (1) flexibility, to explore several methods in parallel and verify results using 3D visualization; (2) simplicity, to apply a defined processing pipeline to a large dataset of subjects by using the MATLAB Batch System and available on GitHub. RESULTS: Within the graphical user interfaces (DisplayGUI), the user can reject noisy intervals and correct artifacts, while visualizing the topographical projection of the data onto the 3D head representation. Data decomposition methods are available for the identification of relevant signatures, such as brain responses or artifacts. Multimodal data recorded simultaneously to fNIRS, such as physiology, electroencephalography or audio-video, can be visualized using the DisplayGUI. The toolbox includes several functions that allow one to read, preprocess, and analyze fNIRS data, including task-based and functional connectivity measures. COMPARISON WITH EXISTING METHODS: Several good neuroinformatics tools for fNIRS data analysis are currently available. None of them emphasize multimodal visualization of the data throughout the preprocessing steps and multidimensional decomposition, which are essential for understanding challenging data. Furthermore, LIONirs provides compatibility and complementarity with other existing tools by supporting common data format. CONCLUSIONS: LIONirs offers a flexible platform for basic and advanced fNIRS data analysis, shown through real experimental examples.

Impact of Early Childhood Malnutrition on Adult Brain Function: An Evoked-Related Potentials Study.

More than 200 million children under the age of 5 years are affected by malnutrition worldwide according to the World Health Organization. The Barbados Nutrition Study (BNS) is a 55-year longitudinal study on a Barbadian cohort with histories of moderate to severe protein-energy malnutrition (PEM) limited to the first year of life and a healthy comparison group. Using quantitative electroencephalography (EEG), differences in brain function during childhood (lower alpha1 activity and higher theta, alpha2 and beta activity) have previously been highlighted between participants who suffered from early PEM and controls. In order to determine whether similar differences persisted into adulthood, our current study used recordings obtained during a Go-No-Go task in a subsample of the original BNS cohort [population size (N) = 53] at ages 45-51 years. We found that previously malnourished adults [sample size (n) = 24] had a higher rate of omission errors on the task relative to controls (n = 29). Evoked-Related Potentials (ERP) were significantly different in participants with histories of early PEM, who presented with lower N2 amplitudes. These findings are typically associated with impaired conflict monitoring and/or attention deficits and may therefore be linked to the attentional and executive function deficits that have been previously reported in this cohort in childhood and again in middle adulthood.

Spatiotemporal dynamics of auditory information processing in the insular cortex: an intracranial EEG study using an oddball paradigm.

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.

The Z-Profile Study: a multicenter, retrospective cohort study to assess the real-world use and effectiveness of elbasvir/grazoprevir in Canadian adult patients with chronic hepatitis C.

Background: Canada was the first country to approve elbasvir/grazoprevir (EBR/GZR) for the treatment of chronic HCV infection for genotypes 1 and 4 with or without ribavirin and genotype 3 with sofosbuvir, with no recommendation for baseline resistance testing. The aim of this study was to describe the effectiveness of EBR/GZR and the profile of patients selected for treatment in a Canadian real-world setting. Methods: This multicenter retrospective study of HCV-infected patients treated with EBR/GZR took place among selected Canadian health care providers, with no exclusion criteria. Primary outcome measures included parameters associated with patient profile and sustained virologic response at 12 weeks (SVR12) and 24 weeks after treatment. Results: A total of 408 patients were included; 244 had available SVR12 information (per-protocol population [PP]). Genotype distribution included 1a (54.7%), 1b (17.2%), 3 (11.8%), 4 (10.0%), and other (6.4%). The majority (88.7%) of participants were treated for 12 weeks without ribavirin. Fifty-nine (14.5%) participants, predominantly with genotype 1a (49/59) infection, were tested for baseline resistance-associated substitutions (bRAS). SVR12 was achieved by 95.9% of the PP. In an exploratory analysis assessing potential predictors of SVR12, participants who had undergone bRAS testing (OR 0.14, 95% CI 0.03-0.64) and participants who had undergone liver transplant (OR 0.05, 95% CI 0.00-0.68) had significantly lower odds of achieving SVR12. Conclusions: This study supports the real-world effectiveness of EBR/GZR-including a broad range of genotypes and diverse fibrosis stages-in the absence of bRAS testing and in special populations.

Neuronal mechanisms of motion detection underlying blindsight assessed by functional magnetic resonance imaging (fMRI).

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.