Breath-hold BOLD fMRI without CO2 sampling enables estimation of venous cerebral blood volume: potential use in normalization of stimulus-evoked BOLD fMRI data.

BOLD fMRI signal has been used in conjunction with vasodilatory stimulation as a marker of cerebrovascular reactivity (CVR): the relative change in cerebral blood flow (CBF) arising from a unit change in the vasodilatory stimulus. Using numerical simulations, we demonstrate that the variability in the relative BOLD signal change induced by vasodilation is strongly influenced by the variability in deoxyhemoglobin-containing cerebral blood volume (CBV), as this source of variability is likely to be more prominent than that of CVR. It may, therefore, be more appropriate to describe the relative BOLD signal change induced by an isometabolic vasodilation as a proxy of deoxygenated CBV (CBVdHb) rather than CVR. With this in mind, a new method was implemented to map a marker of CBVdHb, termed BOLD-CBV, based on the normalization of voxel-wise BOLD signal variation by an estimate of the intravascular venous BOLD signal from voxels filled with venous blood. The intravascular venous BOLD signal variation, recorded during repeated breath-holding, was extracted from the superior sagittal sinus in a cohort of 27 healthy volunteers and used as a regressor across the whole brain, yielding maps of BOLD-CBV. In the same cohort, we demonstrated the potential use of BOLD-CBV for the normalization of stimulus-evoked BOLD fMRI by comparing group-level BOLD fMRI responses to a visuomotor learning task with and without the inclusion of voxel-wise vascular covariates of BOLD-CBV and the BOLD signal change per mmHg variation in end-tidal carbon dioxide (BOLD-CVR). The empirical measure of BOLD-CBV accounted for more between-subject variability in the motor task-induced BOLD responses than BOLD-CVR estimated from end-tidal carbon dioxide recordings. The new method can potentially increase the power of group fMRI studies by including a measure of vascular characteristics and has the strong practical advantage of not requiring experimental measurement of end-tidal carbon dioxide, unlike traditional methods to estimate BOLD-CVR. It also more closely represents a specific physiological characteristic of brain vasculature than BOLD-CVR, namely blood volume.

Changes of brain parenchyma free water fraction reflect tissue damage and impaired processing speed in multiple sclerosis.

Free water fraction (FWF) represents the amount of water per unit volume of brain parenchyma, which is not bound to macromolecules. Its excess in multiple sclerosis (MS) is related to increased tissue loss. The use of mcDESPOT (multicomponent driven single pulse observation of T1 and T2), a 3D imaging method which exploits both the T1 and T2 contrasts, allows FWF to be derived in clinically feasible times. However, this method has not been used to quantify changes of FWF and their potential clinical impact in MS. The aim of this study is to investigate the changes in FWF in MS patients and their relationship with tissue damage and cognition, under the hypothesis that FWF is a proxy of clinically meaningful tissue loss. To this aim, we tested the relationship between FWF, MS lesion burden and information processing speed, evaluated via the Symbol Digit Modalities Test (SDMT). In addition to standard sequences, used for T1- and T2-weighted lesion delineation, the mcDESPOT sequence with 1.7 mm isotropic resolution and a diffusion weighted imaging protocol (b = 0, 1200 s/mm2, 40 diffusion directions) were employed at 3 T. The fractional anisotropy map derived from diffusion data was used to define a subject-specific white matter (WM) atlas. Brain parenchyma segmentation returned masks of gray matter (GM) and WM, and normal-appearing WM (NAWM), in addition to the T1 and T2 lesion masks (T1L and T2L, respectively). Ninety-nine relapsing-remitting MS patients (age = 43.3 ± 9.9 years, disease duration 12.3 ± 7.7 years) were studied, together with twenty-five healthy controls (HC, age = 38.8 ± 11.0 years). FWF was higher in GM and NAWM of MS patients, compared to GM and WM of HC (both p < .001). In MS patients, FWF was the highest in the T1L and GM, followed by T2L and NAWM, respectively. FWF increased significantly with T1L and T2L volume (ρ ranging from 0.40 to 0.58, p < .001). FWF in T2L was strongly related to both T1L volume and the volume ratio T1L/T2L (ρ = 0.73, p < .001). MS patients performed worse than HC in the processing speed test (mean ± SD: 54.1 ± 10.3 for MS, 63.8 ± 10.8 for HC). FWF in GM, T2L, perilesional tissue and NAWM increased with SDMT score reduction (ρ = -0.30, -0.29, -0.33 respectively and r = -.30 for T2L, all with p < .005). A regional analysis, conducted to determine which NAWM regions were of particular importance to explain the relationship between FWF and cognitive impairment, revealed that FWF spatial variance was negatively related to SDMT score in the corpus callosum and the superior longitudinal fasciculus, WM structures known to be associated with cognitive impairment, in addition to the left corticospinal tract, the sagittal stratum, the right anterior limb of internal capsule. In conclusion, we found excess free water in brain parenchyma of MS patients, an alteration that involved not only MS lesions, but also the GM and NAWM, impinging on brain function and negatively associated with cognitive processing speed. We suggest that the FWF metric, derived from noninvasive, rapid MRI acquisitions and bearing good biological interpretability, may prove valuable as an MRI biomarker of tissue damage and associated cognitive impairment in MS.

Multi-omics staging of locally advanced rectal cancer predicts treatment response: a pilot study.

Treatment response assessment of rectal cancer patients is a critical component of personalized cancer care and it allows to identify suitable candidates for organ-preserving strategies. This pilot study employed a novel multi-omics approach combining MRI-based radiomic features and untargeted metabolomics to infer treatment response at staging. The metabolic signature highlighted how tumor cell viability is predictively down-regulated, while the response to oxidative stress was up-regulated in responder patients, showing significantly reduced oxoproline values at baseline compared to non-responder patients (p-value < 10-4). Tumors with a high degree of texture homogeneity, as assessed by radiomics, were more likely to achieve a major pathological response (p-value < 10-3). A machine learning classifier was implemented to summarize the multi-omics information and discriminate responders and non-responders. Combining all available radiomic and metabolomic features, the classifier delivered an AUC of 0.864 (± 0.083, p-value < 10-3) with a best-point sensitivity of 90.9% and a specificity of 81.8%. Our results suggest that a multi-omics approach, integrating radiomics and metabolomic data, can enhance the predictive value of standard MRI and could help to avoid unnecessary surgical treatments and their associated long-term complications.

MRI-Based Radiomics Approach Predicts Tumor Recurrence in ER + /HER2 - Early Breast Cancer Patients.

Oncotype Dx Recurrence Score (RS) has been validated in patients with ER + /HER2 - invasive breast carcinoma to estimate patient risk of recurrence and guide the use of adjuvant chemotherapy. We investigated the role of MRI-based radiomics features extracted from the tumor and the peritumoral tissues to predict the risk of tumor recurrence. A total of 62 patients with biopsy-proved ER + /HER2 - breast cancer who underwent pre-treatment MRI and Oncotype Dx were included. An RS > 25 was considered discriminant between low-intermediate and high risk of tumor recurrence. Two readers segmented each tumor. Radiomics features were extracted from the tumor and the peritumoral tissues. Partial least square (PLS) regression was used as the multivariate machine learning algorithm. PLS ß-weights of radiomics features included the 5% features with the largest ß-weights in magnitude (top 5%). Leave-one-out nested cross-validation (nCV) was used to achieve hyperparameter optimization and evaluate the generalizable performance of the procedure. The diagnostic performance of the radiomics model was assessed through receiver operating characteristic (ROC) analysis. A null hypothesis probability threshold of 5% was chosen (p < 0.05). The exploratory analysis for the complete dataset revealed an average absolute correlation among features of 0.51. The nCV framework delivered an AUC of 0.76 (p = 1.1∙10-3). When combining "early" and "peak" DCE images of only T or TST, a tendency toward statistical significance was obtained for TST with an AUC of 0.61 (p = 0.05). The 47 features included in the top 5% were balanced between T and TST (23 and 24, respectively). Moreover, 33/47 (70%) were texture-related, and 25/47 (53%) were derived from high-resolution images (1 mm). A radiomics-based machine learning approach shows the potential to accurately predict the recurrence risk in early ER + /HER2 - breast cancer patients.

Study of nonperfusion area changes after ranibizumab intravitreal injection for diabetic macular edema by means of widefield OCT angiography.

INTRODUCTION: To evaluate changes of retinal capillary non-perfusion areas (RCNPA) and the retinal capillary vessel density (RCVD) of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) using widefield optical coherence tomography angiography (WFOCTA) in patients with diabetic retinopathy (DR) and diabetic macular edema (DME) treated with intravitreal ranibizumab injection (IRI). MATERIALS AND METHODS: 24 eyes of 24 patients with DR and DME candidates to a loading dose of IRI were enrolled. All patients underwent WFOCTA with the PLEX Elite 9000 device with 15 × 9 mm scans centered on the foveal center at baseline (T0) and 1 month after each intravitreal injection at 30 days (T1), 60 days (T2), and 90 days (T3). In all patients, the variation of RCNPA and the RCVD of the of the SCP and DCP were calculated using automatic software written in Matlab (MathWorks, Natick, MA). RESULTS: The SCP showed a significant longitudinal variation of RCNPA (p = 0.04). Post-hoc analysis revealed a statistically significant reduction of RCNPA at T1 (p = 0.04) and a not significant reduction at T2 (p=0.18) and T3 (p=0.96). The DCP showed longitudinal changes of the RCNPA that tended to statistical significance (p = 0.09). Post-hoc analysis revealed a trend towards a statistically significant reduction of RCNPA at T3 (p = 0.09) not statistically significant, at T1 (p=0.17) and T2 (p=0.75). The RCVD of SCP and DCP showed no significant changes in any of the time points. CONCLUSIONS: Widefield OCT angiography showed a decrease of RCNPA after IRI, probably related to the reperfusion of retinal capillaries.

A Motion Artifact Correction Procedure for fNIRS Signals Based on Wavelet Transform and Infrared Thermography Video Tracking.

Functional near infrared spectroscopy (fNIRS) is a neuroimaging technique that allows to monitor the functional hemoglobin oscillations related to cortical activity. One of the main issues related to fNIRS applications is the motion artefact removal, since a corrupted physiological signal is not correctly indicative of the underlying biological process. A novel procedure for motion artifact correction for fNIRS signals based on wavelet transform and video tracking developed for infrared thermography (IRT) is presented. In detail, fNIRS and IRT were concurrently recorded and the optodes' movement was estimated employing a video tracking procedure developed for IRT recordings. The wavelet transform of the fNIRS signal and of the optodes' movement, together with their wavelet coherence, were computed. Then, the inverse wavelet transform was evaluated for the fNIRS signal excluding the frequency content corresponding to the optdes' movement and to the coherence in the epochs where they were higher with respect to an established threshold. The method was tested using simulated functional hemodynamic responses added to real resting-state fNIRS recordings corrupted by movement artifacts. The results demonstrated the effectiveness of the procedure in eliminating noise, producing results with higher signal to noise ratio with respect to another validated method.

Mismatch between Tissue Partial Oxygen Pressure and Near-Infrared Spectroscopy Neuromonitoring of Tissue Respiration in Acute Brain Trauma: The Rationale for Implementing a Multimodal Monitoring Strategy.

The brain tissue partial oxygen pressure (PbtO2) and near-infrared spectroscopy (NIRS) neuromonitoring are frequently compared in the management of acute moderate and severe traumatic brain injury patients; however, the relationship between their respective output parameters flows from the complex pathogenesis of tissue respiration after brain trauma. NIRS neuromonitoring overcomes certain limitations related to the heterogeneity of the pathology across the brain that cannot be adequately addressed by local-sample invasive neuromonitoring (e.g., PbtO2 neuromonitoring, microdialysis), and it allows clinicians to assess parameters that cannot otherwise be scanned. The anatomical co-registration of an NIRS signal with axial imaging (e.g., computerized tomography scan) enhances the optical signal, which can be changed by the anatomy of the lesions and the significance of the radiological assessment. These arguments led us to conclude that rather than aiming to substitute PbtO2 with tissue saturation, multiple types of NIRS should be included via multimodal systemic- and neuro-monitoring, whose values then are incorporated into biosignatures linked to patient status and prognosis. Discussion on the abnormalities in tissue respiration due to brain trauma and how they affect the PbtO2 and NIRS neuromonitoring is given.

Contribution of Metabolomics to Multiple Sclerosis Diagnosis, Prognosis and Treatment.

Metabolomics-based technologies map in vivo biochemical changes that may be used as early indicators of pathological abnormalities prior to the development of clinical symptoms in neurological conditions. Metabolomics may also reveal biochemical pathways implicated in tissue dysfunction and damage and thus assist in the development of novel targeted therapeutics for neuroinflammation and neurodegeneration. Metabolomics holds promise as a non-invasive, high-throughput and cost-effective tool for early diagnosis, follow-up and monitoring of treatment response in multiple sclerosis (MS), in combination with clinical and imaging measures. In this review, we offer evidence in support of the potential of metabolomics as a biomarker and drug discovery tool in MS. We also use pathway analysis of metabolites that are described as potential biomarkers in the literature of MS biofluids to identify the most promising molecules and upstream regulators, and show novel, still unexplored metabolic pathways, whose investigation may open novel avenues of research.

Fiberless, Multi-Channel fNIRS-EEG System Based on Silicon Photomultipliers: Towards Sensitive and Ecological Mapping of Brain Activity and Neurovascular Coupling.

Portable neuroimaging technologies can be employed for long-term monitoring of neurophysiological and neuropathological states. Functional Near-Infrared Spectroscopy (fNIRS) and Electroencephalography (EEG) are highly suited for such a purpose. Their multimodal integration allows the evaluation of hemodynamic and electrical brain activity together with neurovascular coupling. An innovative fNIRS-EEG system is here presented. The system integrated a novel continuous-wave fNIRS component and a modified commercial EEG device. fNIRS probing relied on fiberless technology based on light emitting diodes and silicon photomultipliers (SiPMs). SiPMs are sensitive semiconductor detectors, whose large detection area maximizes photon harvesting from the scalp and overcomes limitations of fiberless technology. To optimize the signal-to-noise ratio and avoid fNIRS-EEG interference, a digital lock-in was implemented for fNIRS signal acquisition. A benchtop characterization of the fNIRS component showed its high performances with a noise equivalent power below 1 pW. Moreover, the fNIRS-EEG device was tested in vivo during tasks stimulating visual, motor and pre-frontal cortices. Finally, the capabilities to perform ecological recordings were assessed in clinical settings on one Alzheimer's Disease patient during long-lasting cognitive tests. The system can pave the way to portable technologies for accurate evaluation of multimodal brain activity, allowing their extensive employment in ecological environments and clinical practice.

Tomographic Task-Related Functional Near-Infrared Spectroscopy in Acute Sport-Related Concussion: An Observational Case Study.

Making decisions regarding return-to-play after sport-related concussion (SRC) based on resolution of symptoms alone can expose contact-sport athletes to further injury before their recovery is complete. Task-related functional near-infrared spectroscopy (fNIRS) could be used to scan for abnormalities in the brain activation patterns of SRC athletes and help clinicians to manage their return-to-play. This study aims to show a proof of concept of mapping brain activation, using tomographic task-related fNIRS, as part of the clinical assessment of acute SRC patients. A high-density frequency-domain optical device was used to scan 2 SRC patients, within 72 h from injury, during the execution of 3 neurocognitive tests used in clinical practice. The optical data were resolved into a tomographic reconstruction of the brain functional activation pattern, using diffuse optical tomography. Moreover, brain activity was inferred using single-subject statistical analyses. The advantages and limitations of the introduction of this optical technique into the clinical assessment of acute SRC patients are discussed.

Working Memory Decline in Alzheimer's Disease Is Detected by Complexity Analysis of Multimodal EEG-fNIRS.

Alzheimer's disease (AD) is characterized by working memory (WM) failures that can be assessed at early stages through administering clinical tests. Ecological neuroimaging, such as Electroencephalography (EEG) and functional Near Infrared Spectroscopy (fNIRS), may be employed during these tests to support AD early diagnosis within clinical settings. Multimodal EEG-fNIRS could measure brain activity along with neurovascular coupling (NC) and detect their modifications associated with AD. Data analysis procedures based on signal complexity are suitable to estimate electrical and hemodynamic brain activity or their mutual information (NC) during non-structured experimental paradigms. In this study, sample entropy of whole-head EEG and frontal/prefrontal cortex fNIRS was evaluated to assess brain activity in early AD and healthy controls (HC) during WM tasks (i.e., Rey-Osterrieth complex figure and Raven's progressive matrices). Moreover, conditional entropy between EEG and fNIRS was evaluated as indicative of NC. The findings demonstrated the capability of complexity analysis of multimodal EEG-fNIRS to detect WM decline in AD. Furthermore, a multivariate data-driven analysis, performed on these entropy metrics and based on the General Linear Model, allowed classifying AD and HC with an AUC up to 0.88. EEG-fNIRS may represent a powerful tool for the clinical evaluation of WM decline in early AD.

Modelling Impulse Response Function of Functional Infrared Imaging for General Linear Model Analysis of Autonomic Activity.

Functional infrared imaging (fIRI) is a validated procedure to infer autonomic arousal. Currently, fIRI signals are analysed through descriptive metrics, such as average temperature changes in a region of interest (ROI). However, the employment of mathematical models could provide a powerful tool for the accurate identification of autonomic activity and investigation of the mechanisms underlying autonomic arousal. A linear temporal statistical model such as the general linear model (GLM) is particularly suited for its simplicity and direct interpretation. In order to apply the GLM, the thermal response linearity and time-invariance of fIRI have to be demonstrated, and the thermal impulse response (TIR) needs to be characterized. In this study, the linearity and time-invariance of the thermal response to sympathetic activating stimulation were demonstrated, and the TIR for employment of the GLM was characterized. The performance of the GLM-fIRI was evaluated by comparison with the GLM applied on synchronous measurements of the skin conductance response (SCR). In fact, the GLM-SCR is a validated procedure to estimate autonomic arousal. Assuming the GLM-SCR as the gold standard approach, a GLM-fIRI sensitivity and specificity of 86.4% and 75.9% were obtained. The GLM-fIRI may allow increased performances in the evaluation of autonomic activity and a broader range of application of fIRI in both research and clinical settings for the assessment of psychophysiological and psychopathological states.

Multi-Site Photoplethysmographic and Electrocardiographic System for Arterial Stiffness and Cardiovascular Status Assessment.

The development and validation of a system for multi-site photoplethysmography (PPG) and electrocardiography (ECG) is presented. The system could acquire signals from 8 PPG probes and 10 ECG leads. Each PPG probe was constituted of a light-emitting diode (LED) source at a wavelength of 940 nm and a silicon photomultiplier (SiPM) detector, located in a back-reflection recording configuration. In order to ensure proper optode-to-skin coupling, the probe was equipped with insufflating cuffs. The high number of PPG probes allowed us to simultaneously acquire signals from multiple body locations. The ECG provided a reference for single-pulse PPG evaluation and averaging, allowing the extraction of indices of cardiovascular status with a high signal-to-noise ratio. Firstly, the system was characterized on optical phantoms. Furthermore, in vivo validation was performed by estimating the brachial-ankle pulse wave velocity (baPWV), a metric associated with cardiovascular status. The validation was performed on healthy volunteers to assess the baPWV intra- and extra-operator repeatability and its association with age. Finally, the baPWV, evaluated via the developed instrumentation, was compared to that estimated with a commercial system used in clinical practice (Enverdis Vascular Explorer). The validation demonstrated the system's reliability and its effectiveness in assessing the cardiovascular status in arterial ageing.

Fast optical signals in the sensorimotor cortex: General Linear Convolution Model applied to multiple source-detector distance-based data.

In this study, we applied the General Linear Convolution Model to detect fast optical signals (FOS) in the somatosensory cortex, and to study their dependence on the source-detector separation distance (2.0 to 3.5 cm) and irradiated light wavelength (690 and 830 nm). We modeled the impulse response function as a rectangular function that lasted 30 ms, with variable time delay with respect to the stimulus onset. The model was tested in a cohort of 20 healthy volunteers who underwent supra-motor threshold electrical stimulation of the median nerve. The impulse response function quantified the time delay for the maximal response at 70 ms to 110 ms after stimulus onset, in agreement with classical somatosensory-evoked potentials in the literature, previous optical imaging studies based on a grand-average approach, and grand-average based processing. Phase signals at longer wavelength were used to identify FOS for all the source-detector separation distances, but the shortest one. Intensity signals only detected FOS at the greatest distance; i.e., for the largest channel depth. There was no activation for the shorter wavelength light. Correlational analysis between the phase and intensity of FOS further confirmed diffusive rather than optical absorption changes associated with neuronal activity in the activated cortical volume. Our study demonstrates the reliability of our method based on the General Linear Convolution Model for the detection of fast cortical activation through FOS.

Single-Trial Detection and Classification of Event-Related Optical Signals for a Brain-Computer Interface Application.

Event-related optical signals (EROS) measure fast modulations in the brain's optical properties related to neuronal activity. EROS offer a high spatial and temporal resolution and can be used for brain-computer interface (BCI) applications. However, the ability to classify single-trial EROS remains unexplored. This study evaluates the performance of neural network methods for single-trial classification of motor response-related EROS. EROS activity was obtained from a high-density recording montage covering the motor cortex during a two-choice reaction time task involving responses with the left or right hand. This study utilized a convolutional neural network (CNN) approach to extract spatiotemporal features from EROS data and perform classification of left and right motor responses. Subject-specific classifiers trained on EROS phase data outperformed those trained on intensity data, reaching an average single-trial classification accuracy of around 63%. Removing low-frequency noise from intensity data is critical for achieving discriminative classification results with this measure. Our results indicate that deep learning with high-spatial-resolution signals, such as EROS, can be successfully applied to single-trial classifications.

Atrophy of hippocampal subfields and amygdala nuclei in subjects with mild cognitive impairment progressing to Alzheimer's disease.

The hippocampus and amygdala are the first brain regions to show early signs of Alzheimer's Disease (AD) pathology. AD is preceded by a prodromal stage known as Mild Cognitive Impairment (MCI), a crucial crossroad in the clinical progression of the disease. The topographical development of AD has been the subject of extended investigation. However, it is still largely unknown how the transition from MCI to AD affects specific hippocampal and amygdala subregions. The present study is set to answer that question. We analyzed data from 223 subjects: 75 healthy controls, 52 individuals with MCI, and 96 AD patients obtained from the ADNI. The MCI group was further divided into two subgroups depending on whether individuals in the 48 months following the diagnosis either remained stable (N = 21) or progressed to AD (N = 31). A MANCOVA test evaluated group differences in the volume of distinct amygdala and hippocampal subregions obtained from magnetic resonance images. Subsequently, a stepwise linear discriminant analysis (LDA) determined which combination of magnetic resonance imaging parameters was most effective in predicting the conversion from MCI to AD. The predictive performance was assessed through a Receiver Operating Characteristic analysis. AD patients displayed widespread subregional atrophy. MCI individuals who progressed to AD showed selective atrophy of the hippocampal subiculum and tail compared to stable MCI individuals, who were undistinguishable from healthy controls. Converter MCI showed atrophy of the amygdala's accessory basal, central, and cortical nuclei. The LDA identified the hippocampal subiculum and the amygdala's lateral and accessory basal nuclei as significant predictors of MCI conversion to AD. The analysis returned a sensitivity value of 0.78 and a specificity value of 0.62. These findings highlight the importance of targeted assessments of distinct amygdala and hippocampus subregions to help dissect the clinical and pathophysiological development of the MCI to AD transition.

Fast optical signal in visual cortex: Improving detection by General Linear Convolution Model.

In this study we applied the General Linear Convolution Model to fast optical signals (FOS). We modeled the Impulse Response Function (IRF) as a rectangular function lasting 30ms, with variable time delay with respect to the stimulus onset. Simulated data confirmed the feasibility of this approach and its capability of detecting simulated activations in case of very unfavorable Signal to Noise Ratio (SNR), providing better results than the grand average method. The model was tested in a cohort of 10 healthy volunteers who underwent to hemi-field visual stimulation. Experimental data quantified the IRF time delay at 80-100ms after the stimulus onset, in agreement with classical visual evoked potential literature and previous optical imaging studies based on grand average approach and a larger number of trails. FOS confirmed the expected contralateral activation in the occipital region. Correlational analysis between hemodynamic intensity signal, phase and intensity FOS supports diffusive rather than optical absorption changes associated with neuronal activity in the activated cortical volume. Our study provides a feasible method for detecting fast cortical activations by means of FOS.

The body beyond the body: expectation of a sensory event is enough to induce ownership over a fake hand.

More than 100 papers have been published on the rubber hand illusion since its discovery 14 years ago. The illusion has been proposed as a demonstration that the body is distinguished from other objects by its participation in specific forms of intermodal perceptual correlation. Here, we radically challenge this view by claiming that perceptual correlation is not necessary to produce the experience of this body as mine. Each of 15 participants was seated with his/her right arm resting upon a table just below another smaller table. Thus, the real hand was hidden from the participant's view and a life-sized rubber model of a right hand was placed on the small table in front of the participant. The participant observed the experimenter's hand while approaching--without touching--the rubber hand. Phenomenology of the illusion was measured by means of skin conductance response and questionnaire. Both measures indicated that participants experienced the illusion that the experimenter's hand was about to touch their hidden hand rather than the rubber hand, as if the latter replaced their own hand. This did not occur when the rubber hand was rotated by 180° or replaced by a piece of wood. This illusion indicates that our brain does not build a sense of self in a merely reactive way, via perceptual correlations; rather it generates predictions on what may or may not belong to itself.

Fast Optical Signals for Real-Time Retinotopy and Brain Computer Interface.

A brain-computer interface (BCI) allows users to control external devices through brain activity. Portable neuroimaging techniques, such as near-infrared (NIR) imaging, are suitable for this goal. NIR imaging has been used to measure rapid changes in brain optical properties associated with neuronal activation, namely fast optical signals (FOS) with good spatiotemporal resolution. However, FOS have a low signal-to-noise ratio, limiting their BCI application. Here FOS were acquired with a frequency-domain optical system from the visual cortex during visual stimulation consisting of a rotating checkerboard wedge, flickering at 5 Hz. We used measures of photon count (Direct Current, DC light intensity) and time of flight (phase) at two NIR wavelengths (690 nm and 830 nm) combined with a machine learning approach for fast estimation of visual-field quadrant stimulation. The input features of a cross-validated support vector machine classifier were computed as the average modulus of the wavelet coherence between each channel and the average response among all channels in 512 ms time windows. An above chance performance was obtained when differentiating visual stimulation quadrants (left vs. right or top vs. bottom) with the best classification accuracy of ~63% (information transfer rate of ~6 bits/min) when classifying the superior and inferior stimulation quadrants using DC at 830 nm. The method is the first attempt to provide generalizable retinotopy classification relying on FOS, paving the way for the use of FOS in real-time BCI.

Interaction of the salience network, ventral attention network, dorsal attention network and default mode network in neonates and early development of the bottom-up attention system.

The salience network (SN), ventral attention network (VAN), dorsal attention network (DAN) and default mode network (DMN) have shown significant interactions and overlapping functions in bottom-up and top-down mechanisms of attention. In the present study, we tested if the SN, VAN, DAN and DMN connectivity can infer the gestational age (GA) at birth in a study group of 88 healthy neonates, scanned at 40 weeks of post-menstrual age, and with GA at birth ranging from 28 to 40 weeks. We also ascertained whether the connectivity within each of the SN, VAN, DAN and DMN was able to infer the average functional connectivity of the others. The ability to infer GA at birth or another network's connectivity was evaluated using a multivariate data-driven framework. The VAN, DAN and the DMN inferred the GA at birth (p < 0.05). The SN, DMN and VAN were able to infer the average connectivity of the other networks (p < 0.05). Mediation analysis between VAN's and DAN's inference on GA at birth found reciprocal transmittance of change with GA at birth of VAN's and DAN's connectivity (p < 0.05). Our findings suggest that the VAN has a prominent role in bottom-up salience detection in early infancy and that the role of the VAN and the SN may overlap in the bottom-up control of attention.