Context-dependent place-selective responses of the neurons in the medial parietal region of macaque monkeys.

To investigate the role of the medial parietal region (MPR), comprising area 7 m and the retrosplenial and posterior cingulate cortices, in spatial navigation, we analyzed the spatial aspect of the responses of the MPR neurons in monkeys while they actively performed a navigation task in a virtual environment. One-third of the analyzed MPR neurons were activated depending on the location of the monkeys in the environment, that is, showed place-selective responses. Some neurons showed varying responses based on the starting point (SP) or destination. We further investigated the responses of the place-selective neurons when the monkeys were shown animations of the entire navigation route, including the preferred field, and a segment of the route, including an area around the preferred field, and a still image of the preferred field. We observed that the responses of some place-selective neurons reduced when the monkeys viewed the preferred field in the segmented animation or in the still image compared with when they viewed the entire animation. These results suggested that the knowledge about the SP or destination, that is, context, is necessary to activate place-selective neurons. The effect of such contextual information suggests that the MPR plays decisive roles in spatial processing such as navigation.

[Clinical study of one-day fentanyl patch in patients with cancer pain--evaluation of the efficacy and safety in relation to treatment switch from opioid analgesic therapy].

BACKGROUND: In patients with moderate to severe cancer pain receiving treatment with opioid analgesics, the treatment was switched from the existing opioid analgesic to the 1-day fentanyl patch (the "1-day formulation"), and the efficacy and safety of the 1-day formulation were evaluated. METHODS: The preceding opioid analgesic therapy was switched to therapy with the 1-day formulation, at a dose level corresponding to the daily dose level of the preceding opioid analgesic. The pain control rate was evaluated 10 days after the treatment switch. The dose level of the 1-day formulation was kept unchanged for the first 2 days after the treatment switch. RESULTS: The pain control rate with the 1-day formulation was 81.8% (54/66 patients). In 57.6% (38/66) of patients, the treatment switch to a low-dose 1-day formulation (0.3 or 0.6 mg x day(-1)) yielded sustained pain control. The adverse reactions to the 1-day formulation observed in this study were similar to those previously reported for the Durotep MT Patch (the "3-day formulation"). No severe adverse reactions, such as respiratory depression, were noted in the present study. Thus, the 1-day formulation was well-tolerated. CONCLUSIONS: In patients with moderate to severe cancer pain, switching of opioid analgesic therapy to 1-day formulation therapy has been shown to be safe and useful, following rotation from other opioids, for controlling cancer pain. The demonstrated utility was similar to that associated with the 3-day formulation.

[Double-blind parallel-group dose-titration study comparing a fentanyl-containing patch formulated for 1-day application for the treatment of cancer pain with Durotep MT Patch].

BACKGROUND: The efficacy and safety of a fentanyl-containing patch formulated for 1-day application at the initiation and during continuous treatment of cancer pain were evaluated in patients previously untreated with opioid analgesics. METHODS: In the dose-titration period (Period I), the 1-day formulation (0.84 mg x day(-1)) was applied for 2 days. If pain relief was insufficient, the dose was titrated, and the success rate was evaluated. In the double-blind period (Period II), the efficacies of the 1-day and the 3-day formulations for pain control were compared. RESULTS: The dose-titration success rate of the 1-day formulation was 80.6%, and its analgesic effect was comparable to that of the 3-day formulation. Moreover, tolerability of the 1-day formulation was good. Adverse events occurring in the patients were those generally seen after treatments with opioid analgesics, and severe symptoms were also reported. CONCLUSIONS: Dose titration of the 1-day formulation was accomplished in a short period in patients with cancer pain who had been previously untreated with opioid analgesics; the efficacy of the formulation for pain control after repeated dosing was comparable to that of the 3-day formulation, and its tolerability was good. However, it was considered that the 1-day formulation should be used in patients with good tolerability to opioid analgesics. Further, for safety reasons, the dose should not be increased for at least 2 days after the initial application and the last dose increase.

Short-term memory and perceptual decision for three-dimensional visual features in the caudal intraparietal sulcus (Area CIP).

The purpose of the present study was to examine whether neurons in the caudolateral part of the intraparietal sulcus (area CIP), a part of the posterior parietal cortex, contribute to short-term memory and perceptual decision of three-dimensional (3D) surface orientation, in addition to its purely visual nature of responding selectively to 3D surface orientation. Activities of CIP neurons were recorded while monkeys performed a modified delayed matching-to-sample (DMTS) task using stereoscopic stimuli. Seventy-seven neurons were examined with a routine of the DMTS task, and 94% (72 of 77) of them showed selectivity to surface orientation. Furthermore, 82% (63 of 77) of the examined neurons showed sustained activity during delay, and 60% (38 of 63) of them showed selective delay activity depending on the sample stimulus, suggesting that they contribute to short-term memory of 3D visual features. On the other hand, 53% (41 of 77) of the examined neurons showed modulation of visual response depending on whether a stimulus appeared as a sample, match, or nonmatch stimulus (contextual modulation). The majority (73%, 30 of 41) of these neurons with contextual modulation showed activity change depending on whether the test stimuli did or did not match the sample stimuli (match-nonmatch modulation), suggesting their involvement in matching, or perceptual decision, concerning 3D visual features. These findings suggest that CIP neurons play important roles not only in the perception of 3D visual features but also in cognitive functions such as short-term memory and perceptual decision of 3D visual information.

Toward an understanding of the neural processing for 3D shape perception.

In this article we address the major issue of space vision, how the brain represents the 3D shape of objects in the real world, on the basis of psychophysics and neurophysiology. In psychophysics, Gibson found texture gradients and width gradients, as well as the gradient of binocular disparity, as the major cues for surface orientation in depth. Marr proposed that a surface-based representation is the main step towards 3D shape representation. In our neurophysiological studies of the monkey parietal cortex, we have found visual-dominant neurons in area AIP with selectivity in 3D shape of the objects, and also surface-orientation-selective (SOS) neurons in the caudal intraparietal (CIP) area. SOS neurons responded selectively to surface orientation in depth presented in random dot stereograms with a disparity gradient. Many of the SOS neurons responded selectively also to texture gradients and linear perspective, and their responses were enhanced by the combination of these cues. We also found axis-orientation-selective (AOS) neurons in area CIP, responding selectively to the orientation of the longitudinal axis of elongated objects in depth. We present preliminary data here to demonstrate that some of AOS neurons that prefer intermediate thickness are shape-selective, and they are likely to discriminate surface curvature. These data suggest that neurons in and around area CIP may have the capacity to represent 3D shape.

Neural mechanisms of three-dimensional vision.

We can see things in three dimensions because the visual system re-constructs the three-dimensional (3D) configurations of objects from their two-dimensional (2D) images projected onto the retinas. The purpose of this paper is to give an overview of the psychological background and recent physiological findings concerning three-dimensional vision. Psychophysical and computational studies have suggested that in the visual system the 3D surface orientation is first estimated independently from individual depth cues--such as binocular disparity, as well as various monocular cues including texture gradients--and then the information from these different depth cues is integrated to construct a generalized representation of the 3D surface geometry. Neurons involved in low-level disparity processing, or the detection of local absolute disparity, were found mainly in the occipital cortex, whereas neurons involved in high-level disparity processing, or the reconstruction of 3D surface orientation through the computation of disparity gradients, were found mainly in the parietal area caudal intraparietal sulcus (CIP). Neurons sensitive to texture gradients, which is one of the major monocular cues, were also found in CIP. The majority of these neurons were sensitive to disparity gradients as well, suggesting their involvement in the computation of 3D surface orientation. In CIP, neurons sensitive to multiple depth cues were widely distributed together with those sensitive to a specific depth cue, suggesting CIP's involvement in the integration of depth information from different sources. In addition, human and monkey imaging studies have indicated convergence of multiple depth cues in CIP. These neurophysiological findings suggest that CIP plays a critical role in 3D vision by constructing a generalized representation of the 3D surface geometry of objects.

Navigation in virtual environment by the macaque monkey.

To determine whether monkeys can navigate a virtual environment, and whether they can represent a virtual environment in their brain, we trained two macaque monkeys to perform a navigation task in a virtual building and conducted behavioral analyses. After learning the task from the first starting point, they were trained to perform the navigation task from a second starting point which is already familiar to them during the first training session. The second training was completed faster than the first one. Furthermore, we found that the time required for a free-way-finding test from a novel starting point was shortened after the second training. These results suggest that monkeys can navigate a virtual environment and can construct a flexible representation of a virtual environment in their brain.

Navigation-associated medial parietal neurons in monkeys.

To examine the neural basis of route knowledge by which one can reach one's destination, we recorded the activity of 580 neurons in the monkey medial parietal region (MPR) while monkeys actively navigated through a virtual environment. One hundred eighty of these neurons (31%) showed significant responses to the monkeys' movements in the virtual environment. Of these responsive neurons, 77% (139/180) showed responses associated with a specific movement at a specific location (navigation neurons), 8% (14/180) showed responses associated with a specific movement (movement-selective neurons), and the remaining 27 neurons (15%) were nonselective. We found navigation neurons whose responses to the same movement at the same location were modulated depending on the route that the monkey was currently taking, that is, in a route-selective manner (32 of 59 tested neurons among 139 navigation neurons, route-selective navigation neurons). The reversible inactivation of MPR neurons by muscimol resulted in a monkey becoming lost during the navigation task trial. These results suggest that MPR plays a critical role in route-based navigation by integrating location information and self-movement information.

Neural correlates for perception of 3D surface orientation from texture gradient.

A goal in visual neuroscience is to reveal how the visual system reconstructs the three-dimensional (3D) representation of the world from two-dimensional retinal images. Although the importance of texture gradient cues in the process of 3D vision has been pointed out, most studies concentrate on the neural process based on binocular disparity. We report the neural correlates of depth perception from texture gradient in the cortex. In the caudal part of the lateral bank of intraparietal sulcus, many neurons were selective to 3D surface orientation defined by texture gradient, and their response was invariant over different types of texture pattern. Most of these neurons were also sensitive to a disparity gradient, suggesting that they integrate texture and disparity gradient signals to construct a generalized representation of 3D surface orientation.