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Intraoperative sentinel lymph node mapping of the lung using near-infrared fluorescent quantum dots.

BACKGROUND: The presence of lymph node metastases is an important prognostic marker with regard to non-small-cell lung cancer (NSCLC). Assessment of the sentinel lymph node (SLN) for the presence of tumor may improve staging. Our objective was to develop an optical noninvasive imaging tool that would permit intraoperative SLN mapping and provide real-time visual feedback for image-guided localization and resection. METHODS: Invisible near-infrared (NIR) light penetrates relatively deeply into tissue and background autofluorescence is low. We have developed a NIR fluorescence imaging system that simultaneously displays color video and NIR images of the surgical field. We recently engineered 15 nm nonradioactive NIR fluorescent quantum dots (QDs) as optimal lymphotrophic optical probes. The introduction of these QDs into lung tissue allows real-time visualization of draining lymphatic channels and nodes. RESULTS: In 12 Yorkshire pigs (mean weight 35 kg) we demonstrated that 200 pmol of NIR QDs injected into lobar parenchyma accurately maps lymphatic drainage and the SLN. All SLNs were strongly fluorescent and easily visualized within 5 minutes of injection. In 14 separate injections QDs localized to a mediastinal node, whereas in 2 injections QDs localized to a hilar intraparenchymal node. Histologic analysis in all cases confirmed the presence of nodal tissue. CONCLUSIONS: We report a highly sensitive rapid technique for SLN mapping of the lung. This technique permits precise real-time imaging and therefore overcomes many limitations of currently available techniques.

Animals↗

Biofeedback of slow cortical potentials. I.

An experiment was performed to investigate the self-regulation of slow cortical potentials (SCP) found in a previous study (Elbert et al. 1979). Seventeen subjects received continuous visual feedback of their actual cortical shift perceptible as a rocket moving across a TV-screen during intervals of 6 sec; subjects had to direct the rocket into one of two goals representing more or less cortical negativity, depending on the pitch of two signal tones. Within two identical experimental sessions feedback trials alternated with test trials without feedback. Highly significant differences of SCP between the two required polarities were demonstrated. The most pronounced differences were observed during test trials without feedback of the second session in which a positive shift below baseline level occurred when positivity (or less negativity) was required.

Adult↗

Spatial stability, voluntary action and causal attribution during self-locomotion.

Adaptive changes in locomotory control and perception occur in environments where the normal relationship between effort and body displacement is altered (1,2). We have further investigated this plastic relationship by altering visual feedback during voluntary walking in place on a rotary treadmill. When the velocity of optical flow was increased or reversed relative to normal for the steps being made, subjects reported changes in perceived self-motion, the size, rate, and/or direction of their voluntary steps, the extent of voluntary effort required, and the apparent stability of a hand-held support bar. The floor and the visual environment were perceived as stable. We will show that these perceptual remappings obey "terrestrial constraints."

Adaptation, Physiological↗

The effect of the Ebbinghaus illusion on grasping behaviour of children.

Within the context of the Ebbinghaus illusion, adults regularly misjudge the physical size of a centre disc, yet scale their hand aperture according to its actual size. Separate visual pathways for perception and action are assumed to account for this finding. The dorsal visual stream is said to elaborate on egocentric (visuomotor), while the ventral stream is involved in allocentric transformations (object recognition). This study examines the ontogenetic development of this dissociation between perception and action in 35 children between the ages of 5 and 12 years. We report four major results. First, when children judged object size without grasping the disc, their judgements were deceived by the illusion to the same extent as adults. However, when asked to estimate size and then to grasp the disc, young children's (5-7 years) perceptual judgements became unreliable, while adults were still reliably deceived by the illusion in 80% of their trials. Second, the younger the children, the more their aperture was affected by the illusional surround. Discs of the same size were grasped with a smaller aperture when surrounded by a small annulus, although they were perceived as being larger. Third, young children used the largest safety margin during grasping. Fourth, the reliance on visual feedback decreased with increasing age, which was documented by shorter movement times and earlier maximum hand opening during grasping in the older children (feedforward control). Our results indicate that grasping behaviour in children is subject to an interaction between ventral and dorsal processes. Both pathways seem not to be functionally segregated in early and middle childhood. The data are inconclusive about whether young children predominantly use a specific visual stream for either a perceptual or motor task. However, our data demonstrate that children were relying on both visual processing streams during perceptual as well as visuomotor tasks. We found that children used egocentric cues to make perceptual judgements, while their grasping gestures were not exclusively shaped by viewer-centred but also by object-centred information.

Aging↗

Haptic subjective vertical shows context dependence: task and vision play a role during dynamic tilt stimulation.

Perceiving one's vertical is an integral part of efficiently functioning in an environment physically polarized along that dimension. How one determines the direction of gravity is not a task left only to inertial sensors, such as the vestibular organs, rather as numerous studies have shown, this task is influenced visually and somatosensorily. In addition, there is evidence that higher order cognitive effects such as expectancies and context are critical in perception of the vertical. One's ability to integrate these various inputs during normal activity is not generally questioned, one's doubts being satisfied by observing a waiter navigating a crowded restaurant with a tray balanced on one hand, neither tripping or dropping an entree. But how these various sources are integrated is still debated. Most research focuses on subjective vertical perception used visual matching/alignment tasks, verbal reports, or saccadic eye movements as a dependent measure. Although a motor task involving a joystick or indicator to be aligned with gravity without visual feedback is used much less frequently, there is good evidence that individuals easily orient limbs to an external gravity-aligned coordinate axis while being statically tilted. By exposure to a dynamic situation, the central nervous system should be no more challenged by the task of determining the subjective vertical than during static conditions, because our spatial orientation systems were likely selected for just that. In addition, the sensitive calibration between visual and other sensory input also must have been key to its selection. This sensory interaction can be tested by changing the relation between the various sources. With the advent of virtual reality technology, a complex and "natural" visual stimulus is achievable and is easily manipulable. How one tests perception of verticality is also a pertinent question when researching spatial orientation systems. The system's performance may be better indicated by a task of higher relevance to its normal function. In other words, the dependent measure can be made more or less relevant to real-world tasks. With an experimental design that attempts to mimic natural conditions, the current study focuses on two main topics. First, how does manipulation of the visual inputs during passive roll-tilt affect one's sense of body orientation? And second, how does changing the task used to measure subjective vertical affect one's performance?

Darkness↗

Preferential representation of instructed target location versus limb trajectory in dorsal premotor area.

The dorsal premotor area (PMd) of monkeys has been implicated in processes relating to movement preparation and movement selection. In the present study, we sought to determine whether PMd neurons that are activated during a delayed reaching task have directional responses that reflect either the target (i.e., the goal) of an intended movement or the physical properties of the movement itself. Two macaque monkeys were trained to perform a visually instructed, delayed reaching task with indirect visual feedback. The subjects and methods were identical to those described in the preceding paper. In the behavioral task, each subject moved a two-dimensional joystick with the right forelimb to align a cursor with targets presented on a video display. The paradigm dissociated the direction of forelimb movement from the spatial location of the target. This was accomplished by varying the spatial mappings between joystick and cursor. A variable delay separated the visual stimulus that instructed the target location (IS) from the visual stimulus that triggered the instructed movement (TS). Task-related activity was recorded from a total of 181 PMd neurons. The focus of this study was on directionally tuned neuronal responses that included 1) stimulus-related activity (phasic, following IS); 2) set-related activity (phasic, following IS and TS); and 3) movement-related activity (phasic, following TS). Of the entire sample of PMd neurons with directionally tuned activity, 114 were tested with two joystick/cursor mappings, permitting dissociation of directional responses that depended on limb trajectory from those that depended on target location. Task-related neuronal activity was classified as target-dependent if it covaried exclusively with target location across both conditions, and as limb-dependent if it covaried exclusively with limb trajectory. Directional activity that changed significantly across rotation conditions was classified as complex. Approximately one half of the sample of PMd neurons showed stimulus-related activity that was directionally tuned (56%, 64 of 114). Nearly all of the directionally classifiable stimulus-related activity was target dependent (94%, 44 of 47 responses), and none was limb dependent. A small proportion was classified as complex (6%, 3 of 47 responses). More than two thirds of the PMd neurons showed set-related activity that was directionally tuned (69%, 79 of 114). Among cells with set-related activity that was directionally classifiable, there were approximately 9 times as many target-dependent responses (76%, 48 of 63) as there were limb-dependent responses (8%, 5 of 63), with the remainder being complex (16%, 10 of 63). Approximately three quarters of the sample of PMd neurons showed early movement-related activity (before movement onset) that was directionally tuned (78%, 89 of 114). Among those cells whose early movement-related activity was directionally classifiable, there were > 3 times as many target-dependent responses ((51%, 34 of 66) as limb-dependent responses (14%, 9 of 66), with the remainder being complex (35%, 23 of 66). Approximately two thirds of the sample showed late movement-related responses (after movement onset) that were directionally tuned (68%, 78 of 114). Among those cells whose late movement-related activity was directionally classifiable, there were comparable numbers of target-dependent (25%, 15 of 61) and limb-dependent responses (28%, 17 of 61), with the remainder being complex (47%, 29 of 61). These results indicate a preferential representation of target location rather than limb trajectory among PMd neurons. Over the extended interval from IS to motor response, there was a gradual decline in the frequency of target-dependent activity and corresponding increases in the frequencies of both limb-dependent and complex activity. These findings suggest that PMd neurons may participate in mediating the sensory-to-motor transformation required by the delayed reaching

Animals↗

Accurate real-time feedback of surface EMG during fMRI.

Real-time acquisition of EMG during functional MRI (fMRI) provides a novel method of controlling motor experiments in the scanner using feedback of EMG. Because of the redundancy in the human muscle system, this is not possible from recordings of joint torque and kinematics alone, because these provide no information about individual muscle activation. This is particularly critical during brain imaging because brain activations are not only related to joint torques and kinematics but are also related to individual muscle activation. However, EMG collected during imaging is corrupted by large artifacts induced by the varying magnetic fields and radio frequency (RF) pulses in the scanner. Methods proposed in literature for artifact removal are complex, computationally expensive, and difficult to implement for real-time noise removal. We describe an acquisition system and algorithm that enables real-time acquisition for the first time. The algorithm removes particular frequencies from the EMG spectrum in which the noise is concentrated. Although this decreases the power content of the EMG, this method provides excellent estimates of EMG with good resolution. Comparisons show that the cleaned EMG obtained with the algorithm is, like actual EMG, very well correlated with joint torque and can thus be used for real-time visual feedback during functional studies.

Adult↗

The effect of pictorial illusion on prehension and perception.

The present study examined the effect of a size-contrast illusion (Ebbinghaus or Titchener Circles Illusion) on visual perception and the visual control of grasping movements. Seventeen right-handed participants picked up and, on other trials, estimated the size of "poker-chip" disks, which functioned as the target circles in a three-dimensional version of the illusion. In the estimation condition, subjects indicated how big they thought the target was by separating their thumb and forefinger to match the target's size. After initial viewing, no visual feedback from the hand or the target was available. Scaling of grip aperture was found to be strongly correlated with the physical size of the disks, while manual estimations of disk size were biased in the direction of the illusion. Evidently, grip aperture is calibrated to the true size of an object, even when perception of object size is distorted by a pictorial illusion, a result that is consistent with recent suggestions that visually guided prehension and visual perception are mediated by separate visual pathways.

Adult↗

Drug delivery as control task: improving performance in a common anesthetic task.

OBJECTIVE: To conceptualize delivery of anesthesia as a control task, similar to control tasks in nonmedical domains, and to evaluate how presentation of new information and feedback affects task performance. BACKGROUND: In anesthesia, integrated monitors that show intravenous drug and effect-site concentrations in a patient currently do not exist. However, using real-time displays of intravenous anesthetic concentrations and effects could significantly enhance intraoperative clinical performance. Pharmacological models are available to estimate past, present, and future drug concentrations in the brain and to predict the drug's physiological effects. A display that integrates pharmacological models and visualizes drug concentrations was developed and tested to see if this drug display significantly improved clinical performance. METHOD: Thirty-three anesthesiologists with different levels of expertise administered anesthesia to simulated patients in a high-fidelity patient simulator. The experimental group used a drug display that visualized drug concentrations in real time, whereas the control group administered drugs without this information. RESULTS: Anesthesiologists using the drug display achieved better hemodynamic control of the simulated patient than did the control group. Similarly, the drug display enabled anesthesiologists to wake up and reanimate the patient faster. CONCLUSION: Visual feedback of drug concentrations leads to superior performance in the delivery of anesthesia. Drug delivery can be conceptualized within a control theoretical framework. Finally, the drug display has significant clinical potential to increase patient safety. APPLICATION: Clinical performance in delivering anesthesia depends on feedback. By providing this feedback, the drug display supports clinicians' ability to more precisely and safely administer anesthesia.

Anesthetics↗

Sensorimotor adaptation to visual distortions with different kinematic coupling.

We investigated the mechanisms of sensorimotor adaptation by sequentially exposing human subjects to different visual distortions. Subjects performed a manual tracking task, while the relationship between their actual finger movement and its visual feedback was manipulated either by a position-to-position (PP), or by a position-to-velocity (PV) transformation. The outcome confirmed previous findings, in that adaptation to PP facilitated the subsequent adaptation to a second, additional PP. More importantly, our present data documented that pre-exposure to PP interferes with the subsequent adaptation to PV, and vice versa. Thus, we observed anterograde interference between two transformations of common physical nature (i.e., visual), but different kinematic coupling. When previous work on sequential adaptation to visual and mechanical transformations is reconsidered in light of this finding, converging evidence is yielded in favor of a distributed adaptive mechanism, where the magnitude of interference between two successive adaptation sessions depends on the overlap of the involved neural structures.

Adaptation, Ocular↗

Initial control component in disparity vergence eye movements.

Recent experimental evidence indicates that a portion of the oculomotor response to disparity stimulation is functionally open-loop; that is, the response occurs without the aid of visual feedback. To investigate the stimulus features that elicit or influence this dynamic movement, convergence responses to a step, a step followed by target disappearance, and a pulse followed by target disappearance were obtained from four subjects using infrared oculography. The target was a thin vertical line (0.25 degrees) either 2 or 10 degrees in height. Stimuli having different amplitudes (1, 2, 4 and 8 degrees) and disappearance times (50, 100 and 200 ms) were selected randomly along with occasional divergent stimuli to minimize prediction and voluntary vergence. Experiments showed that the dynamic characteristics of the initial portion of the response were essentially the same, even when the target disappeared before the movement took place. The magnitude of the initial response depended on the stimulus amplitude, but was not influenced by either stimulus duration or target height. For example, stimulus durations as short as 50 ms elicited responses similar to those caused by standard steps. The initial response was shown to be active over a well-defined time period of about 200 ms, after which the response appears to be mediated by a visually-guided control component. These results support the recently developed dual-mode theory of vergence control in which an initial preprogrammed (open-loop) control component is followed by a feedback (closed-loop) controlled component which reduces any remaining disparity.

Convergence, Ocular↗

Target and hand position information in the online control of goal-directed arm movements.

The present study compared the contribution of visual information of hand and target position to the online control of goal-directed arm movements. Their respective contributions were assessed by examining how human subjects reacted to a change of the position of either their seen hand or the visual target near the onset of the reaching movement. Subjects, seated head-fixed in a dark room, were instructed to look at and reach with a pointer towards visual targets located in the fronto-parallel plane at different distances to the right of the starting position. LEDs mounted on the tip of the pointer were used to provide true or erroneous visual feedback about hand position. In some trials, either the target or the pointer LED that signalled the actual hand position was shifted 4.5 cm to the left or to the right during the ocular saccade towards the target. Because of saccadic suppression, subjects did not perceive these displacements, which occurred near arm movement onset. The results showed that modifications of arm movement amplitude appeared, on average, 150 ms earlier and reached a greater extent (mean difference=2.7 cm) when there was a change of target position than when a change of the seen hand position occurred. These findings highlight the weight of target position information to the online control of arm movements. Visual information relative to hand position may be less contributive because proprioception also provides information about limb position.

Adult↗

Learning-related fMRI activation associated with a rotational visuo-motor transformation.

The unique ability to learn transformed or altered visuo-motor relationships during motor learning (visuo-motor transformation learning) has engaged researchers for over a century. Compared to other forms of motor learning (e.g., sequence learning), little is known about plasticity in the cortical and/or subcortical systems involved. We used fMRI to isolate region-specific activation changes during the learning of a visuo-motor (joystick) task under a simple transformation (90 degree rotation of visual feedback). Distributed brain systems were engaged in the learning process. In particular, we found evidence of a learning-dependent transition from early activation of the posterior parietal cortex to later distributed cortico-subcortical-cerebellar responses (in the temporal and occipital cortices, basal ganglia, cerebellum and thalamus). The role of the posterior parietal cortex may relate specifically to the acquisition of the transformation, while that of the fusiform and superior temporal gyri may reflect higher level visual and visuo-spatial processing underlying consolidation. Learning-related increases in cerebellar responses are consistent with its proposed role in the acquisition of internal models of the motor apparatus. These learning-related changes suggest a role for interacting neural systems involving the co-operation of cortico-cortico, cortico-cerebellar and cortico-basal ganglia loops during visuo-motor transformation learning.

Adult↗

Computerized assessment of voluntary control in the shift of the center of pressure: a pilot study.

The aim of the study was to test a new stabilometric platform (BioGP) designed to provide visual feedback to patients with balance disorders performing sustained voluntary shifts of their center of pressure (COP). Twenty-five outpatients with mild to moderate impairments of balance due to multiple sclerosis (MS) and 23 healthy subjects volunteered for the study. Patients' control of balance in static conditions was first rated on the Ataxia Battery and the Motricity Index; all subjects were then asked to stand on the platform in front of a large screen and try to move a visual target representing the momentary position of their COP along two vertical paths and one horizontal paths by appropriate movements of their hips and ankles along the lateral and antero-posterior planes. To assess the validity of BioGP, clinical scores of static balance were correlated with measures of speed and accuracy on the platform tasks. To assess the sensitivity of the equipment to poor balance control, patients' measures were compared with those of healthy subjects. Pearson's correlation coefficients between the Ataxia Battery scores and BioGP data ranged between -0.4 and - 0.82. As a group, patients performed statistically worse than controls on most BioGP measures. The graphic output of BioGP also contributed to define the dynamic relations between momentary COP position and balance control. These preliminary findings suggest a possible use of the system as both an evaluation and rehabilitation instrument.

Adult↗

Compensatory eye and head movements generated by the cat following stimulation-induced perturbations in gaze position.

It is thought that saccades are controlled by signals representing target and instantaneous eye positions coded with respect to the head. To determine the frame of reference relevant to gaze (= eye + head) control, we extended to the cat whose head is unrestrained the original study of Mays and Sparks (Mays and Sparks 1980). We stimulated the superior colliculus (SC) to perturb initial gaze position before the onset of a gaze shift made in the dark to a flashed target. Gaze shifts compensated for this perturbation and reached the target with normal accuracy, despite the absence of visual feedback. This result indicates that gaze shifts were coded in either a body-centered or spatial frame but we could not distinguish between these two alternatives because the cat's body was fixed.

Animals↗

Visual guidance of the human foot during a step.

When the intended foot placement changes during a step, either due to an obstacle appearing in our path or the sudden shift of a target, visual input can rapidly alter foot trajectory. However, previous studies suggest that when intended foot placement does not change, the path of the foot is fixed after it leaves the floor and vision has no further influence. Here we ask whether visual feedback can be used to improve the accuracy of foot placement during a normal, unperturbed step. To investigate this we measured foot trajectory when subjects made accurate steps, at fast and slow speeds, to stationary floor-mounted targets. Vision was randomly occluded in 50% of trials at the point of foot-off. This caused an increase in foot placement error, reflecting lower accuracy and higher variability. This effect was greatest for slow steps. Trajectory heading analysis revealed that visually guided corrections occurred as the foot neared the target (on average 64 mm away). They occurred closer to the target for the faster movements thus allowing less time and space to execute corrections. However, allowing for a fixed reaction time of 120 ms, movement errors were detected when the foot was approximately halfway to the target. These results suggest that visual information can be used to adjust foot trajectory during the swing phase of a step when stepping onto a stationary target, even for fast movements. Such fine control would be advantageous when environmental constraints place limitations on foot placement, for example when hiking over rough terrain.

Adult↗

Evidence for internal representation of a static nonlinearity in a visual tracking task.

A group of 24 participants was given over 3 h practice at a visual pursuit tracking task with a pronounced static nonlinearity between movement of the joystick and the resulting deflection of the response cursor. The aim was twofold: (1) to determine whether or not participants compensated for the nonlinearity and (2) to show that any such compensation involved the formation of an internal representation of the nonlinear relationship between movement of the joystick as sensed kinaesthetically and/or visually and movement of the response cursor as sensed visually. Results show that participants introduce partial compensation for the static nonlinearity. Furthermore, partial compensation was present even during open-loop tracking when participants were deprived of visual feedback of the position of the response cursor. This implies that participants are able to form an internal representation of the nonlinear relationship between movement of the joystick and the resulting movement of the response cursor.

Adult↗

A specific role for efferent information in self-recognition.

We investigated the specific contribution of efferent information in a self-recognition task. Subjects experienced a passive extension of the right index finger, either as an effect of moving their left hand via a lever ('self-generated action'), or imposed externally by the experimenter ('externally-generated action'). The visual feedback was manipulated so that subjects saw either their own right hand ('view own hand' condition) or someone else's right hand ('view other's hand' condition) during the passive extension of the index finger. Both hands were covered with identical gloves, so that discrimination on the basis of morphological differences was not possible. Participants judged whether the right hand they saw was theirs or not. Self-recognition was significantly more accurate when subjects were themselves the authors of the action, even though visual and proprioceptive information always specified the same posture, and despite the fact that subjects judged the effect and not the action per se. When the passive displacement of the participants right index finger was externally generated, and only afferent information was available, self-recognition performance dropped to near-chance levels. Differences in performance across conditions reflect the distinctive contribution of efferent information to self-recognition, and argue against a dominant role of proprioception in self-recognition.

Adult↗