Experimental Procedure for the Metrological Characterization of Time-of-Flight Cameras for Human Body 3D Measurements.

Time-of-flight cameras are widely adopted in a variety of indoor applications ranging from industrial object measurement to human activity recognition. However, the available products may differ in terms of the quality of the acquired point cloud, and the datasheet provided by the constructors may not be enough to guide researchers in the choice of the perfect device for their application. Hence, this work details the experimental procedure to assess time-of-flight cameras' error sources that should be considered when designing an application involving time-of-flight technology, such as the bias correction and the temperature influence on the point cloud stability. This is the first step towards a standardization of the metrological characterization procedure that could ensure the robustness and comparability of the results among tests and different devices. The procedure was conducted on Kinect Azure, Basler Blaze 101, and Basler ToF 640 cameras. Moreover, we compared the devices in the task of 3D reconstruction following a procedure involving the measure of both an object and a human upper-body-shaped mannequin. The experiment highlighted that, despite the results of the previously conducted metrological characterization, some devices showed evident difficulties in reconstructing the target objects. Thus, we proved that performing a rigorous evaluation procedure similar to the one proposed in this paper is always necessary when choosing the right device.

Two Functionally Distinct Serotonergic Projections into Hippocampus.

Hippocampus receives dense serotonergic input specifically from raphe nuclei. However, what information is carried by this input and its impact on behavior has not been fully elucidated. Here we used in vivo two-photon imaging of activity of hippocampal median raphe projection fibers in behaving male and female mice and identified two distinct populations: one linked to reward delivery and the other to locomotion. Local optogenetic manipulation of these fibers confirmed a functional role for these projections in the modulation of reward-induced behavior. The diverse function of serotonergic inputs suggests a key role in integrating locomotion and reward information into the hippocampal CA1.SIGNIFICANCE STATEMENT Information constantly flows in the hippocampus, but only some of it is captured as a memory. One potential process that discriminates which information should be remembered is concomitance with reward. In this work, we report a neuromodulatory pathway, which delivers reward signal as well as locomotion signal to the hippocampal CA1. We found that the serotonergic system delivers heterogeneous input that may be integrated by the hippocampus to support its mnemonic functions. It is dynamically involved in regulating behavior through interaction with the hippocampus. Our results suggest that the serotonergic system interacts with the hippocampus in a dynamic and behaviorally specific manner to regulate reward-related information processing.

Validation of Marker-Less System for the Assessment of Upper Joints Reaction Forces in Exoskeleton Users.

This paper presents the validation of a marker-less motion capture system used to evaluate the upper limb stress of subjects using exoskeletons for locomotion. The system fuses the human skeletonization provided by commercial 3D cameras with forces exchanged by the user to the ground through upper limbs utilizing instrumented crutches. The aim is to provide a low cost, accurate, and reliable technology useful to provide the trainer a quantitative evaluation of the impact of assisted gait on the subject without the need to use an instrumented gait lab. The reaction forces at the upper limbs' joints are measured to provide a validation focused on clinically relevant quantities for this application. The system was used simultaneously with a reference motion capture system inside a clinical gait analysis lab. An expert user performed 20 walking tests using instrumented crutches and force platforms inside the observed volume. The mechanical model was applied to data from the system and the reference motion capture, and numerical simulations were performed to assess the internal joint reaction of the subject's upper limbs. A comparison between the two results shows a root mean square error of less than 2% of the subject's body weight.

Self-Weighted Multilateration for Indoor Positioning Systems.

The paper proposes an improved method for calculating the position of a movable tag whose distance to a (redundant) set of fixed beacons is measured by some suitable physical principle (typically ultra wide band or ultrasound propagation). The method is based on the multilateration technique, where the contribution of each individual beacon is weighed on the basis of a recurring, self-supported calibration of the measurement repeatability of each beacon at a given distance range. The work outlines the method and its implementation, and shows the improvement in measurement quality with respect to the results of a commercial Ultra-Wide-Band (UWB) system when tested on the same set of raw beacon-to-tag distances. Two versions of the algorithm are proposed: one-dimensional, or isotropic, and 3D. With respect to the standard approach, the isotropic solution managed to reduce the maximum localization error by around 25%, with a maximum error of 0.60 m, while the 3D version manages to improve even further the localization accuracy, with a maximum error of 0.45 m.

Early Post-Natal Immune Activation Leads to Object Memory Deficits in Female Tsc2+/- Mice: The Importance of Including Both Sexes in Neuroscience Research.

There is evidence that viral infections during pre-natal development constitute a risk factor for neuropsychiatric disorders and lead to learning and memory deficits. However, little is known about why viral infections during early post-natal development have a different impact on learning and memory depending on the sex of the subject. We previously showed that early post-natal immune activation induces hippocampal-dependent social memory deficits in a male, but not in a female, mouse model of tuberous sclerosis complex (TSC; Tsc2+/- mice). Here, we explored the impact of a viral-like immune challenge in object memory. We demonstrate that early post-natal immune activation (during the first 2 weeks of life) leads to object memory deficits in female, but not male, mice that are heterozygous for a gene responsible for tuberous sclerosis complex (Tsc2+/- mice), while no effect was observed in wild type (WT) mice. Moreover, we found that the same immune activation in Tsc2+/- adult mice was not able to cause object memory deficits in females, which suggests that the early post-natal development stage constitutes a critical window for the effects of immune challenge on adult memory. Also, our results suggest that mTOR plays a critical role in the observed deficit in object memory in female Tsc2+/- mice. These results, together with previous results published by our laboratory, showing sex-specific memory deficits due to early post-natal immune activation, reinforce the necessity of using both males and females for research studies. This is especially true for studies related to immune activation, since the higher levels of estrogens in females are known to affect inflammation and to provide neuroprotection.

Excitability mediates allocation of pre-configured ensembles to a hippocampal engram supporting contextual conditioned threat in mice.

Little is understood about how engrams, sparse groups of neurons that store memories, are formed endogenously. Here, we combined calcium imaging, activity tagging, and optogenetics to examine the role of neuronal excitability and pre-existing functional connectivity on the allocation of mouse cornu ammonis area 1 (CA1) hippocampal neurons to an engram ensemble supporting a contextual threat memory. Engram neurons (high activity during recall or TRAP2-tagged during training) were more active than non-engram neurons 3 h (but not 24 h to 5 days) before training. Consistent with this, optogenetically inhibiting scFLARE2-tagged neurons active in homecage 3 h, but not 24 h, before conditioning disrupted memory retrieval, indicating that neurons with higher pre-training excitability were allocated to the engram. We also observed stable pre-configured functionally connected sub-ensembles of neurons whose activity cycled over days. Sub-ensembles that were more active before training were allocated to the engram, and their functional connectivity increased at training. Therefore, both neuronal excitability and pre-configured functional connectivity mediate allocation to an engram ensemble.

Wheelchair driving strategies: A comparison between standard joystick and gaze-based control.

This paper aims to evaluate and compare the driving performances achieved with a power wheelchair using a standard joystick versus a novel gaze-based technology. The gaze-based interface, called RoboEYE, involves a novel paradigm of computer interaction that handles the receipt of information from an eye tracker, using it as a continuous input for wheelchair navigation. A pool of 36 subjects has tested both technologies in a circuit designed considering the Wheelchair Skill Test. The experimental analysis involved evaluations of specific metrics of motion and the submission of questionnaires to collect required information about perceived feelings and mental workload. The joystick proved to be the best driving interface. It turned out to be more accurate and efficient than the gaze-based solution. However, the latter achieved only small differences in driving kinematics. These differences can be considered negligible from an operational point of view, offering a driving experience similar to that achievable with the joystick. Testers reported no particular stress, fatigue, or frustration when switching from one interface to another. These elements suggest that the proposed gaze-based solution is an appropriate alternative for a technology transition driven by a pathological change in the user's condition.

Local memory allocation recruits memory ensembles across brain regions.

Memories are thought to be stored in ensembles of neurons across multiple brain regions. However, whether and how these ensembles are coordinated at the time of learning remains largely unknown. Here, we combined CREB-mediated memory allocation with transsynaptic retrograde tracing to demonstrate that the allocation of aversive memories to a group of neurons in one brain region directly affects the allocation of interconnected neurons in upstream brain regions in a behavioral- and brain region-specific manner in mice. Our analysis suggests that this cross-regional recruitment of presynaptic neurons is initiated by downstream memory neurons through a retrograde mechanism. Together with statistical modeling, our results indicate that in addition to the anterograde flow of information between brain regions, the establishment of interconnected, brain-wide memory traces relies on a retrograde mechanism that coordinates memory ensembles at the time of learning.

Monoclonal antibodies conjugated with superparamagnetic iron oxide particles allow magnetic resonance imaging detection of lymphocytes in the mouse brain.

We investigated the potential of antibody-vectorialized superparamagnetic iron oxide (SPIO) particles as cellular specific magnetic resonance contrast agents to image lymphocyte populations within the central nervous system (CNS), with the final goal of obtaining a reliable tool for noninvasively detecting and tracking specific cellular populations in vivo. We used superparamagnetic particles bound to a monoclonal antibody. The particle is the contrast agent, by means of its T2* relaxation properties; the antibody is the targeting vector, responsible for homing the particle to target a surface antigen. To investigate the efficiency of particle vectorialization by these antibodies, we compared two types of antibody-vectorialized CD3-specific particles in vivo. We successfully employed vectorialized SPIO particles to image B220⁺ cells in a murine model of B-cell lymphoma. Likewise, we were able to identify CD3⁺ infiltrates in a murine model of multiple sclerosis. The specificity of the technique was confirmed by immunohistochemistry and electron microscopy of corresponding sections. Our findings suggest that indirect binding of the antibody to a streptavidinated particle allows for enhanced particle vectorialization compared to covalent binding of the antibody to the particle.

The emergence of molecular systems neuroscience.

Systems neuroscience is focused on how ensemble properties in the brain, such as the activity of neuronal circuits, gives rise to internal brain states and behavior. Many of the studies in this field have traditionally involved electrophysiological recordings and computational approaches that attempt to decode how the brain transforms inputs into functional outputs. More recently, systems neuroscience has received an infusion of approaches and techniques that allow the manipulation (e.g., optogenetics, chemogenetics) and imaging (e.g., two-photon imaging, head mounted fluorescent microscopes) of neurons, neurocircuits, their inputs and outputs. Here, we will review novel approaches that allow the manipulation and imaging of specific molecular mechanisms in specific cells (not just neurons), cell ensembles and brain regions. These molecular approaches, with the specificity and temporal resolution appropriate for systems studies, promise to infuse the field with novel ideas, emphases and directions, and are motivating the emergence of a molecularly oriented systems neuroscience, a new discipline that studies how the spatial and temporal patterns of molecular systems modulate circuits and brain networks, and consequently shape the properties of brain states and behavior.

A locus coeruleus-dorsal CA1 dopaminergic circuit modulates memory linking.

Individual memories are often linked so that the recall of one triggers the recall of another. For example, contextual memories acquired close in time can be linked, and this is known to depend on a temporary increase in excitability that drives the overlap between dorsal CA1 (dCA1) hippocampal ensembles that encode the linked memories. Here, we show that locus coeruleus (LC) cells projecting to dCA1 have a key permissive role in contextual memory linking, without affecting contextual memory formation, and that this effect is mediated by dopamine. Additionally, we found that LC-to-dCA1-projecting neurons modulate the excitability of dCA1 neurons and the extent of overlap between dCA1 memory ensembles as well as the stability of coactivity patterns within these ensembles. This discovery of a neuromodulatory system that specifically affects memory linking without affecting memory formation reveals a fundamental separation between the brain mechanisms modulating these two distinct processes.

Within-Trial Persistence of Learned Behavior as a Dissociable Behavioral Component in Hippocampus-Dependent Memory Tasks: A Potential Postlearning Role of Immature Neurons in the Adult Dentate Gyrus.

The term "memory strength" generally refers to how well one remembers something. But more precisely it contains multiple modalities, such as how easily, how accurately, how confidently and how vividly we remember it. In human, these modalities of memory strength are dissociable. In this study, we asked whether we can isolate a behavioral component that is dissociable from others in hippocampus-dependent memory tasks in mice, which potentially reflect a modality of memory strength. Using a virus-mediated inducible method, we ablated immature neurons in the dentate gyrus in mice after we trained the mice with hippocampus-dependent memory tasks normally. In memory retrieval tests, these ablated mice initially showed intact performance. However, the ablated mice ceased learned behavior prematurely within a trial compared with control mice. In addition, the ablated mice showed shorter duration of individual episodes of learned behavior. Both affected behavioral measurements point to persistence of learned behavior. Thus, the effect of the postlearning manipulation showed dissociation between initial performance and persistence of learned behavior. These two behavioral components are likely to reflect different brain functions and be mediated by separate mechanisms, which might represent different modalities of memory strength. These simple dissociable measurements in widely used behavioral paradigms would be useful to understand detailed mechanisms underlying the expression of learned behavior and potentially different modalities of memory strength in mice. We also discuss a potential role that immature neurons in the dentate gyrus may play in persistence of learned behavior.

Getting the full picture.

A combination of old and new techniques has revealed new details about the behavior of individual neurons across the sleep-wake-cycle.