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Biomedical subjects

L S Stone

Publications and source records attributed to L S Stone.

At least 37 records · Page 2Linked to original sources

Immunofluorescence analysis of antisense oligodeoxynucleotide-mediated 'knock-down' of the mouse delta opioid receptor in vitro and in vivo.

We have previously used antisense oligodeoxynucleotides (ODN) to the cloned delta opioid receptor (DOR) to inhibit the antinociceptive response to spinally administered delta opioid receptor selective agonists in mice. Here we have examined the effect of DOR antisense ODN treatment on the level of DOR expressed in NG 108-15 cells and the spinal cord, through immuno-fluorescence microscopy, to determine the efficiency and selectivity of the antisense ODN-mediated "knock-down' of the DOR in these tissues. Antisense ODN, but not mismatch control, treatment resulted in a significant reduction in DOR immunoreactivity (-ir) in NG 108-15 cells and spinal cord. Thus, the inhibition of antinociceptive response to intrathecal delta selective agonists by DOR antisense ODN correlates with the loss of DOR-ir in the superficial layers of the dorsal horn of the spinal cord.

Animals↗

Perceived visual speed constrained by image segmentation.

Little is known about how or where the visual system parses the visual scene into objects or surfaces. However, it is generally assumed that the segmentation and grouping of pieces of the image into discrete entities is due to 'later' processing stages, after the 'early' processing of the visual image by local mechanisms selective for attributes such as colour, orientation, depth, and motion. Speed perception is also thought to be mediated by early mechanisms tuned for speed. Here we show that manipulating the way in which an image is parsed changes the way in which local speed information is processed. Manipulations that cause multiple stimuli to appear as parts of a single patch degrade speed discrimination, whereas manipulations that perceptually divide a single large stimulus into parts improve discrimination. These results indicate that processes as early as speed perception may be constrained by the parsing of the visual image into discrete entities.

Humans↗

Speed estimates from grating patches are not contrast-normalized.

We have previously shown that the perceived speed of a moving grating depends upon its contrast, with lower-contrast patterns appearing to move more slowly than otherwise identical higher-contrast patterns. To explain this finding while remaining consistent with the findings of McKee, Silverman and Nakayama [(1986) Vision Research, 26, 609-619], we proposed that this misperception might arise from a modified version of the contrast-normalization procedure, envisaged by Adelson and Bergen [(1986) The extraction of spatio-temporal energy in human and machine vision (pp. 135-139). Charleston, S.C.: IEEE Computer Society] as a necessary second stage of motion-energy models of human motion processing. Specifically, our previous results might be explained if the two gratings to be compared interfered with each other's normalization. To test this hypothesis we performed two experiments. Experiment 1 demonstrates that the contrast effects persist even when two grating patches to be compared are presented up to 5 sec apart so that they would not be expected to bias each other's normalization. Experiment 2 shows that the contrast effects are unchanged when the two grating patches are surrounded by a range of patterns whose contrast would be expected to interfere with any normalization process. These two results allow the rejection of the contrast-normalized motion-energy hypothesis as an explanation of human speed perception. We discuss the consequences of these results on models of speed processing in the human visual system.

Contrast Sensitivity↗

The barberplaid illusion: plaid motion is biased by elongated apertures.

The perceived direction of motion of plaids windowed by elongated spatial Gaussians is biased toward the window's long axis. The bias increases as the relative angle between the plaid motion and the long axis of the window increases, peaks at a relative angle of approximately 45 deg, and then decreases. The bias increases as the window is made narrower (at fixed height) and decreases as the component spatial frequency increases (at fixed aperture size). We examine several models of human motion processing (cross-correlation, motion-energy, intersection-of-constraints, and vector-sum), and show that none of these standard models can predict our data. We conclude that spatial integration of motion signals plays a crucial role in plaid motion perception and that current models must be explicitly expanded to include such spatial interactions.

Adult↗

Screening for depression in pregnancy: characteristics of the Beck Depression Inventory.

OBJECTIVE: To determine the test characteristics of a self-report questionnaire, the Beck Depression Inventory, when used as a screening test for depression in a population of ambulatory pregnant women. METHODS: One hundred five pregnant women completed the Beck Depression Inventory and underwent a structured interview using the National Institute of Mental Health Diagnostic Interview Schedule-version III. Current depression was diagnosed according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders-III-R. A receiver operating characteristic curve was constructed for the Beck Depression Inventory score as a predictor of current depression. A table of sensitivities, specificities, predictive values, and likelihood ratios was created for various cutoff values. RESULTS: For the 105 women enrolled, the median Beck Depression Inventory score was 8.0. Twelve women (11%) were diagnosed with current depression and had a median Beck Depression Inventory score of 25.5, compared with those without current depression, who had a median score of 8.0 (P = .001). The area under the receiver operating characteristic curve was 0.9940. Using a cutoff range of greater than 16, the sensitivity of the Beck Depression Inventory to detect current depression was 0.83, the specificity was 0.89, the positive predictive value was 0.50, and the negative predictive value was 0.98. CONCLUSIONS: The Beck Depression Inventory can serve as a rapid screening test for depression during pregnancy. A higher cutoff value is required for pregnant women than is customarily used outside of pregnancy.

Adult↗

Combining speed information across space.

We used speed discrimination tasks to measure the ability of observers to combine speed information from multiple stimuli distributed across space. We compared speed discrimination thresholds in a classical discrimination paradigm to those in an uncertainty/search paradigm. Thresholds were measured using a temporal two-interval forced-choice design. In the discrimination paradigm, the n gratings in each interval all moved at the same speed and observers were asked to choose the interval with the faster gratings. Discrimination thresholds for this paradigm decreased as the number of gratings increased. This decrease was not due to increasing the effective stimulus area as a control experiment that increased the area of a single grating did not show a similar improvement in thresholds. Adding independent speed noise to each of the n gratings caused thresholds to decrease at a rate similar to the original no-noise case, consistent with observers combining an independent sample of speed from each grating in both the added- and no-noise cases. In the search paradigm, observers were asked to choose the interval in which one of the n gratings moved faster. Thresholds in this case increased with the number of gratings, behavior traditionally attributed to an input bottleneck. However, results from the discrimination paradigm showed that the increase was not due to observers' inability to process these gratings. We have also shown that the opposite trends of the data in the two paradigms can be predicted by a decision theory model that combines independent samples of speed information across space. This demonstrates that models typically used in classical detection and discrimination paradigms are also applicable to search paradigms. As our model does not distinguish between samples in space and time, it predicts that discrimination performance should be the same regardless of whether the gratings are presented in two spatial intervals or two temporal intervals. Our last experiment largely confirmed this prediction.

Decision Theory↗

A model of self-motion estimation within primate extrastriate visual cortex.

Perrone [(1992) Journal of the Optical Society of America A, 9, 177-194] recently proposed a template-based model of self-motion estimation which uses direction- and speed-tuned input sensors similar to neurons in area MT of primate visual cortex. Such an approach would generally require an unrealistically large number of templates (five continuous dimensions). However, because primates, including humans, have a number of oculomotor mechanisms which stabilize gaze during locomotion, we can greatly reduce the number of templates required (two continuous dimensions and one compressed and bounded dimension). We therefore refined the model to deal with the gaze-stabilization case and extended it to extract heading and relative depth simultaneously. The new model is consistent with previous human psychophysics and has the emergent property that its output detectors have similar response properties to neurons in area MST.

Depth Perception↗

Neural basis for motor learning in the vestibuloocular reflex of primates. II. Changes in the responses of horizontal gaze velocity Purkinje cells in the cerebellar flocculus and ventral paraflocculus.

1. We made extracellular recordings from Purkinje cells in the flocculus and ventral paraflocculus of awake monkeys before and after motor learning in the vestibuloocular reflex (VOR). Three samples were recorded 1) after miniaturizing spectacles had reduced the gain of the VOR (eye speed divided by head speed) to 0.4; 2) when the gain of the VOR was near 1.0; and 3) after magnifying spectacles had increased the gain of the VOR to 1.6. 2. We studied Purkinje cells that showed stronger modulation of simple-spike firing rate during horizontal than during vertical pursuit. These cells corresponded to the previously identified "horizontal gaze velocity Purkinje cells" or HGVP-cells. During pursuit of smooth target motion with the head stationary, HGVP-cells showed strong modulation of firing rate with increases for ipsiversive eye motion (toward the side of recording). When the monkey canceled his VOR by tracking a target that moved exactly with him during sinusoidal head rotation in the horizontal plane, HGVP-cells again showed strong modulation of firing rate with increases for ipsiversive head motion. 3. The responses of HGVP-cells during pursuit with the head stationary and during cancellation of the VOR reveal separate components of firing rate related to eye and head velocity. We used these two behavioral conditions to test for effects of motor learning on the head and eye velocity components of the simple-spike firing of HGVP-cells. Our data confirm the previous observation that motor learning causes the sensitivity to head velocity to be larger when the gain of the VOR is high and smaller when the gain of the VOR is low. Thus we agree with the previous conclusion that changes in the vestibular sensitivity of HGVP-cells, measured during sinusoidal head motion at low frequencies, are in the wrong direction to cause changes in the gain of the VOR. 4. To determine whether the simple-spike output from the HGVP-cells plays a role in the VOR after motor learning, we recorded simple-spike firing during the VOR evoked by transient, rapid changes in head velocity in darkness. When the gain of the VOR was low, firing rate increased during the VOR evoked by ipsiversive head motion and decreased during the VOR evoked by contraversive head motion. When the gain of the VOR was high, the direction selectivity of the responses was reversed.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Human speed perception is contrast dependent.

When two parallel gratings moving at the same speed are presented simultaneously, the lower-contrast grating appears slower. This misperception is evident across a wide range of contrasts (2.5-50%) and does not appear to saturate (e.g. a 50% contrast grating appears slower than a 70% contrast grating moving at the same speed). On average, a 70% contrast grating must be slowed by 35% to match a 10% contrast grating moving at 2 degrees/sec (N = 6). Furthermore, the effect is largely independent of the absolute contrast level and is a quasi-linear function of log contrast ratio. A preliminary parametric study shows that, although spatial frequency has little effect, relative orientation is important. Finally, the misperception of relative speed appears lessened when the stimuli to be matched are presented sequentially.

Adolescent↗

Effect of contrast on the perceived direction of a moving plaid.

We performed a series of experiments examining the effect of contrast on the perception of moving plaids. This was done to test the hypothesis put forth by Adelson and Movshon (1982) that the human visual system determines the direction of a moving plaid in a two-staged process: decomposition into component motion followed by application of the intersection of constraints rule. Although there is recent evidence that the first tenet of their hypothesis is correct, i.e. that plaid motion is initially decomposed into the motion of the individual grating components (Movshon, Adelson, Gizzi & Newsome, 1986; Welch, 1989), the nature of the second-stage combination rule has not as yet been established. We found that when the gratings within the plaid are of different contrast, the perceived direction is not predicted by the intersection of constraints rule. There is a strong (up to 20 deg) bias in the direction of the higher-contrast grating. A revised model, which incorporates a contrast-dependent weighting of perceived grating speed as observed for 1-D patterns (Thompson, 1982), can quantitatively predict most of our results. We discuss our results in the context of various models of human visual motion processing and of physiological responses of neurons in the primate visual system.

Adolescent↗

Visual responses of Purkinje cells in the cerebellar flocculus during smooth-pursuit eye movements in monkeys. I. Simple spikes.

1. We have identified a visually driven output from the flocculus of the monkey by studying the simple-spike responses of Purkinje cells (P-cells) during the initiation of smooth-pursuit eye movements. We report on two groups of P-cells that appear to be the horizontal and vertical gaze-velocity P-cells (GVP-cells) studied previously during periodic target and head motion. 2. During pursuit of periodic target motion, one group of P-cells prefers downward motion (down GVP-cells), and the other prefers motion toward the side of recording (ipsi GVP-cells). The two groups have mean directional preferences that are nearly orthogonal, but their responses during pursuit of sinusoidal target motion and sinusoidal vestibular stimulation are in other respects quantitatively similar. 3. During the initiation of pursuit to step-ramp target motion, GVP-cells show a large transient change in simple-spike firing rate followed by a sustained change in firing that persists during steady-state pursuit. 4. The transient response is directionally selective, so that GVP-cells show a pulse of simple spikes for pursuit in the ON-direction and a dip in simple-spike firing for pursuit in the OFF-direction. The amplitude of the transient response is too large to be explained by the sensitivity of GVP-cells to eye velocity measured during pursuit of sinusoidal target motion. 5. To test whether the transient change in simple-spike firing was related to a visual input or to an eye-acceleration input to the flocculus, we recorded the firing of ipsi GVP-cells during a rapid eye acceleration caused by a transient vestibular stimulus in darkness. Most GVP-cells showed little or no transient response under these conditions, even though eye acceleration was greater than during the initiation of pursuit. We conclude that the transient response at the initiation of pursuit is probably caused by visual mossy-fiber inputs to the flocculus. 6. The sustained change in simple-spike firing is also directionally selective, with large increases in simple-spike firing for pursuit in the ON-direction and smaller decreases for pursuit in the OFF-direction. For pursuit in the ON-direction, the amplitude of the sustained response is well predicted by the sensitivity of GVP-cells to eye velocity measured during pursuit of sinusoidal target motion. 7. To determine whether the sustained response was driven by visual inputs, we recorded simple-spike firing when image motion was prevented by electronically stabilizing the target image on the fovea during steady-state pursuit.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

Visual responses of Purkinje cells in the cerebellar flocculus during smooth-pursuit eye movements in monkeys. II. Complex spikes.

1. We report the complex-spike responses of two groups of Purkinje cells (P-cells). The cell were classified according to their simple-spike firing during smooth eye movements evoked by visual and vestibular stimuli with the use of established criteria (Lisberger and Fuchs 1978; Stone and Lisberger 1990). During pursuit with the head fixed, ipsi gaze-velocity P-cells (GVP-cells) showed increased simple-spike firing when gaze moved toward the side of the recording, whereas down GVP-cells showed increased simple-spike firing when gaze moved downward. 2. During pursuit of sinusoidal target motion, the complex-spike firing rate was modulated out-of-phase with the simple-spike firing rate. Ipsi GVP-cells showed increased complex-spike firing during pursuit away from the side of the recording, and down GVP-cells showed increased complex-spike firing during upward pursuit. The strength of the complex-spike response increased as a function of the frequency of sinusoidal target motion. 3. GVP-cells showed directionally selective complex-spike responses during the initiation of pursuit to ramp target motion. Ipsi GVP-cells had increased complex-spike firing 100 ms after the onset of contralaterally directed target motion and decreased complex-spike activity after the onset of ipsilaterally directed target motion. Down GVP-cells had increased complex-spike firing 100 ms after the onset of upward target motion and decreased firing after the onset of downward target motion. As during sinusoidal target motion, each cell's simple- and complex-spike responses had the opposite directional preferences. 4. When the monkeys fixated a stationary target during a transient vestibular stimulus, the retinal slip caused by the 14-ms latency of the vestibuloocular reflex (VOR) affected the complex-spike firing rate. For ipsi GVP-cells, ipsilateral head motion caused transient contralateral image motion and an increase in complex-spike firing. The same vestibular stimulus in darkness caused an almost identical eye movement but had no effect on complex-spike firing. We conclude that complex spikes in ipsi GVP-cells are driven by contralaterally directed image motion. 5. To determine the events surrounding complex-spike firing during pursuit, we triggered averages of eye and target velocity on the occurrence of complex spikes during pursuit of sine-wave target motion. The averages revealed a transient pulse of retinal image motion that peaked approximately 100 ms before the complex spike. We conclude that complex spikes during steady-state pursuit are driven by the retinal slip associated with imperfect pursuit.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

Detection of tracking errors by visual climbing fiber inputs to monkey cerebellar flocculus during pursuit eye movements.

The activity of cerebellar Purkinje cells was monitored in alert monkeys during visually guided smooth pursuit eye movements. The climbing fiber input evokes 'complex-spikes' which show increased firing during the contralateral phase of sinusoidal pursuit. 'Complex-spike triggered averaging' revealed that the increased firing is a visual response to the retina slip which results from inaccurate tracking. The complex-spikes in turn cause a transient reduction in the simple-spike pursuit command signal that emanates from the flocculus and this may contribute to the corrective eye movement. We postulate that the detection (and possibly the correction) of small errors in motor performance may be a general function of climbing fiber inputs to the cerebellum.

Action Potentials↗

Intraocular lenses and anticoagulation and antiplatelet therapy.

Questionnaires were sent to 200 members of the American Intra-Ocular Implant Society to assess the preoperative, intraoperative, and postoperative management trends with intraocular lens implant patients on warfarin sodium and aspirin therapy. Responses were received from 135 members. A sizable majority of practitioners (75%) withhold warfarin sodium both prior to and following surgery. In many cases, the medicine is withheld for longer than is necessary, increasing the risk of medical complications. Respondents slightly favored (53%) discontinuing aspirin, which is perceived to be less harmful than warfarin sodium, preoperatively. Although management decisions must be individualized, according to both the surgeon's technique and the particular patient, certain general guidelines are applicable.

Anticoagulants↗

Bilateral nodular sarcoid choroiditis with vitreous haemorrhage.

A 21-year-old black man with presumed systemic sarcoidosis had bilateral choroidal nodules, unilateral retinal neovascularisation and vitreous haemorrhage, and non-caseating granulomas on percutaneous liver biopsy. The choroidal nodules were serially documented by fundus photography and fluorescein angiography over a 22-month period. Fluorescein angiography was more accurate than ophthalmoscopy in demonstrating choroidal inflammation. The choroidal nodules resolved after systemic corticosteroid therapy. A vitreous haemorrhage occurred probably secondary to neovascularisation related to occlusion of an inferotemporal branch vein. The non-resolving vitreous haemorrhage and associated traction retinal detachment were treated with vitrectomy and membrane sectioning.

Adult↗

Behavioral disturbance following intraocular lens implantation.

A 26-year-old man with mycosis fungoides and dense bilateral cataracts underwent cataract extraction and intraocular lens implantation. The first day postoperatively, the patient attained 20/100 visual acuity with the intraocular implant, without additional visual corrections. On seeing himself in the mirror for the first time in several months, thereby becoming aware of his distorted facial features and unsightly skin, he became transiently depressed. Simple reassurance and emotional support helped ameliorate his symptoms. Previous reports of behavioral disturbances following cataract extraction have emphasized the role of sensory deprivation in triggering aberrant behavior patterns. In this reported case, the rapid visual rehabilitation afforded by an intraocular lens implant resulted in a transiently depressed state in a patient with severe eczematous mycosis fungoides.

Adolescent↗