When fear is near: threat imminence elicits prefrontal-periaqueductal gray shifts in humans.

Humans, like other animals, alter their behavior depending on whether a threat is close or distant. We investigated spatial imminence of threat by developing an active avoidance paradigm in which volunteers were pursued through a maze by a virtual predator endowed with an ability to chase, capture, and inflict pain. Using functional magnetic resonance imaging, we found that as the virtual predator grew closer, brain activity shifted from the ventromedial prefrontal cortex to the periaqueductal gray. This shift showed maximal expression when a high degree of pain was anticipated. Moreover, imminence-driven periaqueductal gray activity correlated with increased subjective degree of dread and decreased confidence of escape. Our findings cast light on the neural dynamics of threat anticipation and have implications for the neurobiology of human anxiety-related disorders.

Dopamine-dependent prediction errors underpin reward-seeking behaviour in humans.

Theories of instrumental learning are centred on understanding how success and failure are used to improve future decisions. These theories highlight a central role for reward prediction errors in updating the values associated with available actions. In animals, substantial evidence indicates that the neurotransmitter dopamine might have a key function in this type of learning, through its ability to modulate cortico-striatal synaptic efficacy. However, no direct evidence links dopamine, striatal activity and behavioural choice in humans. Here we show that, during instrumental learning, the magnitude of reward prediction error expressed in the striatum is modulated by the administration of drugs enhancing (3,4-dihydroxy-L-phenylalanine; L-DOPA) or reducing (haloperidol) dopaminergic function. Accordingly, subjects treated with L-DOPA have a greater propensity to choose the most rewarding action relative to subjects treated with haloperidol. Furthermore, incorporating the magnitude of the prediction errors into a standard action-value learning algorithm accurately reproduced subjects' behavioural choices under the different drug conditions. We conclude that dopamine-dependent modulation of striatal activity can account for how the human brain uses reward prediction errors to improve future decisions.

Cortical substrates for exploratory decisions in humans.

Decision making in an uncertain environment poses a conflict between the opposing demands of gathering and exploiting information. In a classic illustration of this 'exploration-exploitation' dilemma, a gambler choosing between multiple slot machines balances the desire to select what seems, on the basis of accumulated experience, the richest option, against the desire to choose a less familiar option that might turn out more advantageous (and thereby provide information for improving future decisions). Far from representing idle curiosity, such exploration is often critical for organisms to discover how best to harvest resources such as food and water. In appetitive choice, substantial experimental evidence, underpinned by computational reinforcement learning (RL) theory, indicates that a dopaminergic, striatal and medial prefrontal network mediates learning to exploit. In contrast, although exploration has been well studied from both theoretical and ethological perspectives, its neural substrates are much less clear. Here we show, in a gambling task, that human subjects' choices can be characterized by a computationally well-regarded strategy for addressing the explore/exploit dilemma. Furthermore, using this characterization to classify decisions as exploratory or exploitative, we employ functional magnetic resonance imaging to show that the frontopolar cortex and intraparietal sulcus are preferentially active during exploratory decisions. In contrast, regions of striatum and ventromedial prefrontal cortex exhibit activity characteristic of an involvement in value-based exploitative decision making. The results suggest a model of action selection under uncertainty that involves switching between exploratory and exploitative behavioural modes, and provide a computationally precise characterization of the contribution of key decision-related brain systems to each of these functions.

Temporal difference models describe higher-order learning in humans.

The ability to use environmental stimuli to predict impending harm is critical for survival. Such predictions should be available as early as they are reliable. In pavlovian conditioning, chains of successively earlier predictors are studied in terms of higher-order relationships, and have inspired computational theories such as temporal difference learning. However, there is at present no adequate neurobiological account of how this learning occurs. Here, in a functional magnetic resonance imaging (fMRI) study of higher-order aversive conditioning, we describe a key computational strategy that humans use to learn predictions about pain. We show that neural activity in the ventral striatum and the anterior insula displays a marked correspondence to the signals for sequential learning predicted by temporal difference models. This result reveals a flexible aversive learning process ideally suited to the changing and uncertain nature of real-world environments. Taken with existing data on reward learning, our results suggest a critical role for the ventral striatum in integrating complex appetitive and aversive predictions to coordinate behaviour.

The neural signature of escalating frustration in humans.

Mammalian studies show that frustration is experienced when goal-directed activity is blocked. Despite frustration's strongly negative role in health, aggression and social relationships, the neural mechanisms are not well understood. To address this we developed a task in which participants were blocked from obtaining a reward, an established method of producing frustration. Levels of experienced frustration were parametrically varied by manipulating the participants' motivation to obtain the reward prior to blocking. This was achieved by varying the participants' proximity to a reward and the amount of effort expended in attempting to acquire it. In experiment 1, we confirmed that proximity and expended effort independently enhanced participants' self-reported desire to obtain the reward, and their self-reported frustration and response vigor (key-press force) following blocking. In experiment 2, we used functional magnetic resonance imaging (fMRI) to show that both proximity and expended effort modulated brain responses to blocked reward in regions implicated in animal models of reactive aggression, including the amygdala, midbrain periaqueductal grey (PAG), insula and prefrontal cortex. Our findings suggest that frustration may serve an energizing function, translating unfulfilled motivation into aggressive-like surges via a cortical, amygdala and PAG network.

Parallel Computation of Vernier Offsets, Curvature and Chevrons in Humans

A vernier offset is detected at once among straight lines, and reaction times are almost independent of the number of simultaneously presented stimuli (distractors), indicating parallel processing of vernier offsets. Reaction times for identifying a vernier offset to one side among verniers offset to the opposite side increase with the number of distractors, indicating serial processing. Even deviations below a photoreceptor diameter can be detected at once. The visual system thus attains positional accuracy below the photoreceptor diameter simultaneously at different positions. I conclude that deviation from straightness, or change of orientation, is detected in parallel over the visual field. Discontinuities or gradients in orientation may represent an elementary feature of vision.

How do Humans Determine Reflectance Properties under Unknown Illumination?

Under normal viewing conditions, humans find it easy to distinguish between objects made out of different materials such as plastic, metal, or paper. Untextured materials such as these have different surface reflectance properties, including lightness and gloss. With single isolated images and unknown illumination conditions, the task of estimating surface reflectance is highly underconstrained, because many combinations of reflection and illumination are consistent with a given image. In order to work out how humans estimate surface reflectance properties, we asked subjects to match the appearance of isolated spheres taken out of their original contexts. We found that subjects were able to perform the task accurately and reliably without contextual information to specify the illumination. The spheres were rendered under a variety of artificial illuminations, such as a single point light source, and a number of photographically-captured real-world illuminations from both indoor and outdoor scenes. Subjects performed more accurately for stimuli viewed under real-world patterns of illumination than under artificial illuminations, suggesting that subjects use stored assumptions about the regularities of real-world illuminations to solve the ill-posed problem.

Adapting Home Service Robot Behaviours by Experience Reuse and Interaction with Humans

Meng, Q., Lee, M. (2003). Adapting Home Service Robot Behaviours by Experience Reuse and Interaction with Humans. 673-678. Paper presented at IEEE/ASME International Conference on Advanced Intelligent Mechatronics (AIM 2003), Port Island, Kobe, Japan

Influence of blood donation on O-2 uptake on-kinetics, peak O-2 uptake and time to exhaustion during severe-intensity cycle exercise in humans

Thatcher, Rhys, et al., 'Influence of blood donation on O-2 uptake on-kinetics, peak O-2 uptake and time to exhaustion during severe-intensity cycle exercise in humans', Experimental Physiology (2006) 91(3) pp.499-509 RAE2008

Improved Tracking of Multiple Humans with Trajectory Prediction and Occlusion Modeling

A combined 2D, 3D approach is presented that allows for robust tracking of moving bodies in a given environment as observed via a single, uncalibrated video camera. Tracking is robust even in the presence of occlusions. Low-level features are often insufficient for detection, segmentation, and tracking of non-rigid moving objects. Therefore, an improved mechanism is proposed that combines low-level (image processing) and mid-level (recursive trajectory estimation) information obtained during the tracking process. The resulting system can segment and maintain the tracking of moving objects before, during, and after occlusion. At each frame, the system also extracts a stabilized coordinate frame of the moving objects. This stabilized frame is used to resize and resample the moving blob so that it can be used as input to motion recognition modules. The approach enables robust tracking without constraining the system to know the shape of the objects being tracked beforehand; although, some assumptions are made about the characteristics of the shape of the objects, and how they evolve with time. Experiments in tracking moving people are described.

Antigen-specific responses assessment for the evaluation of Bordetella pertussis T cell immunity in humans.

Measurement of antigen-specific T cell responses is an adjunctive parameter to evaluate protection induced by a previous Bordetella pertussis infection or vaccination. The assessment of T cell responses is technically complex and usually performed on fresh peripheral blood mononuclear cells (PBMC). The objective of this study was to identify simplified methods to assess pertussis specific T cell responses and verify if these assays could be performed using frozen/thawed (frozen) PBMC. Three read-outs to measure proliferation were compared: the fluorescent dye 5,6-carboxylfluorescein diacetate succinimidyl ester (CFSE) dilution test, the number of blast cells defined by physical parameters, and the incorporation of (3)H-thymidine. The results of pertussis-specific assays performed on fresh PBMC were compared to the results on frozen PBMC from the same donor. High concordance was obtained when the results of CFSE and blast read-outs were compared, an encouraging result since blast analysis allows the identification of proliferating cells and does not require any use of radioactive tracer as well as any staining. The results obtained using fresh and frozen PBMC from the same donor in the different T cell assays, including IFNγ and TNFα cytokine production, did not show significant differences, suggesting that a careful cryopreservation process of PBMC would not significantly influence T cell response evaluation. Adopting blast analysis and frozen PBMC, the possibility to test T cell responses is simplified and might be applied in population studies, providing for new instruments to better define correlates of protection still elusive in pertussis.

CD20 deficiency in humans results in impaired T cell-independent antibody responses.

CD20 was the first B cell differentiation antigen identified, and CD20-specific mAbs are commonly used for the treatment of B cell malignancies and autoantibody-mediated autoimmune diseases. Despite this the role of CD20 in human B cell physiology has remained elusive. We describe here a juvenile patient with CD20 deficiency due to a homozygous mutation in a splice junction of the CD20 gene (also known as MS4A1) that results in "cryptic" splicing and nonfunctional mRNA species. Analysis of this patient has led us to conclude that CD20 has a central role in the generation of T cell-independent (TI) antibody responses. Key evidence to support this conclusion was provided by the observation that although antigen-independent B cells developed normally in the absence of CD20 expression, antibody formation, particularly after vaccination with TI antigens, was strongly impaired in the patient. Consistent with this, TI antipolysaccharide B cell responses were severely impeded in CD20-deficient mice. Our study therefore identifies what we believe to be a novel type of humoral immunodeficiency caused by CD20 deficiency and characterized by normal development of antigen-independent B cells, along with a reduced capacity to mount proper antibody responses.