Safety and efficacy of tenalisib in combination with romidepsin in patients with relapsed/refractory T-cell lymphoma: results from a phase I/II open-label multicenter study.

Tenalisib, a selective phosphoinositide-3-kinase δ/γ, and salt-inducible-kinase-3 inhibitor has shown efficacy and was well-tolerated in patients with T-cell lymphoma (TCL). In vitro studies suggest a synergistic anti-tumor potential for the combination of tenalisib with the histone-deacetylase inhibitor, romidepsin. This multicenter, open-label, phase I/II study was designed to characterize the safety, efficacy and pharmacokinetics of oral tenalisib twice-daily and intravenous romidepsin administered on days 1, 8 and 15 in 28-day cycles in adults with relapsed/refractory TCL. Phase I/dose escalation determined the maximum tolerated dose (MTD)/optimal doses of tenalisib and romidepsin. The phase II/dose expansion assessed the safety and anti-tumor activity of the combination at MTD/optimal dose. Overall, 33 patients were enrolled. In dose escalation, no dose-limiting toxicity was identified. Hence, the recommended doses for dose expansion were tenalisib 800 mg twice daily orally, and romidepsin 14 mg/m2 intravenous. Overall treatment-emergent adverse events of any grade reported in >15% of patients were nausea, thrombocytopenia, increased aspartate aminotransferase, increased alanine aminotransferase, decreased appetite, neutropenia, vomiting, fatigue, anemia, dysgeusia, weight loss, diarrhea, and hypokalemia. Twenty-three patients (69.7%) had related grade ≥3 treatment-emergent adverse events. The overall objective response rate in evaluable patients was 63.0% (peripheral TCL: 75% and cutaneous TCL: 53.3%), with a complete response and partial response of 25.9% and 37.0% respectively. The median duration of response was 5.03 months. Co-administration of tenalisib and romidepsin did not significantly alter the pharmacokinetics of romidepsin. Overall, tenalisib and romidepsin combination demonstrated a favorable safety and efficacy profile supporting its further development for relapsed/refractory TCL (clinicaltrials gov. Identifier: NCT03770000).

A phase 2, multicentre, open-label trial (ACE-LY-003) of acalabrutinib in patients with relapsed or refractory marginal zone lymphoma.

Acalabrutinib, a Bruton tyrosine kinase inhibitor, demonstrated greater selectivity and improved safety versus ibrutinib in a head-to-head trial in relapsed/refractory (R/R) chronic lymphocytic leukaemia. In the R/R marginal zone lymphoma (MZL) cohort (phase 2) of a phase 1b/2 trial (NCT02180711), 43 patients with MZL and at least one prior therapy received acalabrutinib 100 mg twice daily until disease progression or unacceptable toxicity [median age 69 years (range 42-84); median one (1-4) prior systemic regimens]. Median follow-up was 13.3 months (range 0.5-45.5). Among 40 patients evaluable for response, investigator-assessed overall response rate was 53% [95% confidence interval (CI) 36%-69%] with five (13%) complete responses. Tumour reduction occurred in 40 (93%) of the treated patients. Median time to response was 2.9 months (median duration of response not estimable). Estimated median progression-free survival (PFS) was 27.4 months (12-month PFS rate, 67%). Five patients died (disease progression, n = 4; septic shock, n = 1). Seventeen patients (40%) had grade 3 or higher adverse events (AEs), most commonly neutropenia (14%), anaemia, dyspnoea (7% each), fatigue and thrombocytopenia (5% each). Hypertension occurred in 5%; atrial fibrillation/flutter and major haemorrhage were not reported. AEs led to treatment discontinuation in three (7%) patients. Acalabrutinib was active and well tolerated in patients with R/R MZL.

Lisocabtagene maraleucel as second-line therapy in adults with relapsed or refractory large B-cell lymphoma who were not intended for haematopoietic stem cell transplantation (PILOT): an open-label, phase 2 study.

BACKGROUND: Patients with relapsed or refractory large B-cell lymphoma after first-line treatment who are not intended for haematopoietic stem-cell transplantation (HSCT) have poor outcomes and limited treatment options. We assessed the antitumour activity and safety of lisocabtagene maraleucel, an autologous, CD19-directed chimeric antigen receptor (CAR) T-cell product, as second-line treatment in adults with relapsed or refractory large B-cell lymphoma not intended for HSCT. METHODS: PILOT, an open-label, phase 2 trial done at 18 clinical sites in the USA, included adults aged 18 years or older who had relapsed or refractory large B-cell lymphoma and PET-positive disease, had received first-line therapy containing an anthracycline and a CD20-targeted agent, were not intended for HSCT by their physician, and met at least one prespecified transplantation not intended criterion. Patients received lymphodepleting chemotherapy (intravenous fludarabine 30 mg/m2 and intravenous cyclophosphamide 300 mg/m2 daily for 3 days) followed 2-7 days later by two sequential lisocabtagene maraleucel infusions (equal target doses of CD8+ and CD4+ CAR+ T cells for a total target dose of 100 × 106 CAR+ T cells). The primary endpoint was the overall response rate and was assessed in all patients who received lisocabtagene maraleucel and had confirmed PET-positive disease before lisocabtagene maraleucel administration based on an independent review committee according to the Lugano 2014 criteria. Safety was assessed in all patients who received lisocabtagene maraleucel. Patient follow-up is ongoing. This study is registered with ClinicalTrials.gov, NCT03483103. FINDINGS: Between July 26, 2018, and Sept 24, 2021 (data cutoff for the primary analysis), 74 patients underwent leukapheresis and 61 received lisocabtagene maraleucel (efficacy and safety sets); median age was 74 years (IQR 70-78), 24 (39%) patients were women versus 37 (61%) men, and 54 (89%) patients were White. 16 (26%) of 61 patients had an Eastern Cooperative Oncology Group performance status of 2, 33 (54%) had refractory disease, 13 (21%) relapsed within 1 year of first-line therapy, and 15 (25%) relapsed after 12 months of first-line therapy. Median on-study follow-up was 12·3 months (IQR 6·1-18·0). 49 (80% [95% CI 68-89]; p<0·0001) patients had an overall response. The most common grade 3 or worse treatment-emergent adverse events were neutropenia (29 [48%] patients), leukopenia (13 [21%]), and thrombocytopenia (12 [20%]). Lisocabtagene maraleucel-related serious treatment-emergent adverse events were reported in 13 (21%) patients. There were no treatment-related deaths. Cytokine release syndrome occurred in 23 (38%; grade 3 in one) patients and neurological events in 19 (31%; grade 3 in three) patients, with no grade 4 events or deaths. INTERPRETATION: These results support lisocabtagene maraleucel as a potential second-line treatment in patients with large B-cell lymphoma for whom HSCT is not intended. FUNDING: Juno Therapeutics, a Bristol-Myers Squibb company.

Brief psychological screening for trapeziectomy: Identifying patients at high risk of a poor functional outcome.

Introduction: This study investigates if the psychological subscale from the STarT Back Screening Tool (STarT Psych-sub) identifies patients at high risk of a poor functional outcome after a trapeziectomy based on modifiable psychological factors. Methods: A total of 83 patients completed the STarT Psych-sub, QuickDASH (Quick Disabilities of the Arm, Shoulder and Hand), Patient Evaluation Measure (PEM) and a numeric pain rating scale (NPRS) before trapeziectomy. QuickDASH, PEM and NPRS were completed at 6 weeks, 16 weeks and 1 year after the trapeziectomy. Results: The STarT Psych-sub stratified 24 patients (29%) as 'high-risk' and 59 (71%) as 'not high-risk' of a poor outcome. The 'high-risk' group reported worse function and pain (QuickDASH = 72.7, PEM = 81.1, NPRS = 8.3) at baseline than the 'not high-risk' group (QuickDASH = 56.1, PEM = 66.4, NPRS = 7.2). This difference remained constant at all time points after the trapeziectomy with 1-year scores on the QuickDASH = 39.6; PEM = 47.1 and NPRS = 3.7 for the 'high-risk' group and QuickDASH = 24.3; PEM = 33.3 and NPRS = 1.9 for the 'not high-risk' group. Conclusions: Brief psychological screening shows that patients with psychological risk factors experience improved pain and function outcomes following trapeziectomy, however their outcomes are significantly worse than patients who do not have psychological risk factors.

The effect of eccentricity on the linear-radial speed bias: Testing the motion-in-depth model.

Radial motion is perceived as faster than linear motion when local spatiotemporal properties are matched. This radial speed bias (RSB) is thought to occur because radial motion is partly interpreted as motion-in-depth. Geometry dictates that a fixed amount of radial expansion at increasing eccentricities is consistent with smaller motion in depth, so it is perhaps surprising that the impact of eccentricity on RSB has not been examined. With this issue in mind, across 3 experiments we investigated the RSB as a function of eccentricity. In a 2IFC task, participants judged which of a linear (test - variable speed) or radial (reference - 2 or 4°/s) stimulus appeared to move faster. Linear and radial stimuli comprised 4 Gabor patches arranged left, right, above and below fixation at varying eccentricities (3.5°-14°). For linear stimuli, Gabors all drifted left or right, whereas for radial stimuli Gabors drifted towards or away from the centre. The RSB (difference in perceived speeds between matched linear and radial stimuli) was recovered from fitted psychometric functions. Across all 3 experiments we found that the RSB decreased with eccentricity but this tendency was less marked beyond 7° - i.e. at odds with the geometry, the effect did not continue to decrease as a function of eccentricity. This was true irrespective of whether stimuli were fixed in size (Experiment 1) or varied in size to account for changes in spatial scale across the retina (Experiment 2). It was also true when we removed conflicting stereo cues via monocular viewing (Experiment 3). To further investigate our data, we extended a previous model of speed perception, which suggests perceived motion for such stimuli reflects a balance between two opposing perceptual interpretations, one for motion in depth and the other for object deformation. We propose, in the context of this model, that our data are consistent with placing greater weight on the motion in depth interpretation with increasing eccentricity and this is why the RSB does not continue to reduce in line with purely geometric constraints.

Detection of scene-relative object movement and optic flow parsing across the adult lifespan.

Moving around safely relies critically on our ability to detect object movement. This is made difficult because retinal motion can arise from object movement or our own movement. Here we investigate ability to detect scene-relative object movement using a neural mechanism called optic flow parsing. This mechanism acts to subtract retinal motion caused by self-movement. Because older observers exhibit marked changes in visual motion processing, we consider performance across a broad age range (N = 30, range: 20-76 years). In Experiment 1 we measured thresholds for reliably discriminating the scene-relative movement direction of a probe presented among three-dimensional objects moving onscreen to simulate observer movement. Performance in this task did not correlate with age, suggesting that ability to detect scene-relative object movement from retinal information is preserved in ageing. In Experiment 2 we investigated changes in the underlying optic flow parsing mechanism that supports this ability, using a well-established task that measures the magnitude of globally subtracted optic flow. We found strong evidence for a positive correlation between age and global flow subtraction. These data suggest that the ability to identify object movement during self-movement from visual information is preserved in ageing, but that there are changes in the flow parsing mechanism that underpins this ability. We suggest that these changes reflect compensatory processing required to counteract other impairments in the ageing visual system.

The Effect of Ageing on Optimal Integration of Conflicting and Non-Conflicting Visual-Haptic Stimuli.

Multisensory integration typically follows the predictions of a statistically optimal model whereby the contribution of each sensory modality is weighted according to its reliability. Previous research has shown that multisensory integration is affected by ageing, however it is less certain whether older adults follow this statistically optimal model. Additionally, previous studies often present multisensory cues which are conflicting in size, shape or location, yet naturally occurring multisensory cues are usually non-conflicting. Therefore, the mechanisms of integration in older adults might differ depending on whether the multisensory cues are consistent or conflicting. In the current experiment, young ( n = 21) and older ( n = 30) adults were asked to make judgements regarding the height of wooden blocks using visual, haptic or combined visual-haptic information. Dual modality visual-haptic blocks could be presented as equal or conflicting in size. Young and older adults' size discrimination thresholds (i.e., precision) were not significantly different for visual, haptic or visual-haptic cues. In addition, both young and older adults' discrimination thresholds and points of subjective equality did not follow model predictions of optimal integration, for both conflicting and non-conflicting cues. Instead, there was considerable between subject variability as to how visual and haptic cues were processed when presented simultaneously. This finding has implications for the development of multisensory therapeutic aids and interventions to assist older adults with everyday activities, where these should be tailored to the needs of each individual.

Contrast effects on speed perception for linear and radial motion.

Speed perception is vital for safe activity in the environment. However, considerable evidence suggests that perceived speed changes as a function of stimulus contrast, with some investigators suggesting that this might have meaningful real-world consequences (e.g. driving in fog). In the present study we investigate whether the neural effects of contrast on speed perception occur at the level of local or global motion processing. To do this we examine both speed discrimination thresholds and contrast-dependent speed perception for two global motion configurations that have matched local spatio-temporal structure. Specifically we compare linear and radial configurations, the latter of which arises very commonly due to self-movement. In experiment 1 the stimuli comprised circular grating patches. In experiment 2, to match stimuli even more closely, motion was presented in multiple local Gabor patches equidistant from central fixation. Each patch contained identical linear motion but the global configuration was either consistent with linear or radial motion. In both experiments 1 and 2, discrimination thresholds and contrast-induced speed biases were similar in linear and radial conditions. These results suggest that contrast-based speed effects occur only at the level of local motion processing, irrespective of global structure. This result is interpreted in the context of previous models of speed perception and evidence suggesting differences in perceived speed of locally matched linear and radial stimuli.

Similarities in Autistic and Neurotypical Visual-Haptic Perception When Making Judgements About Conflicting Sensory Stimuli.

A number of studies have shown that multisensory performance is well predicted by a statistically optimal maximum likelihood estimation (MLE) model. Under this model unisensory estimates are combined additively and weighted according to relative reliability. Recent theories have proposed that atypical sensation and perception commonly reported in autism spectrum condition (ASC) may result from differences in the use of reliability information. Furthermore, experimental studies have indicated that multisensory processing is less effective in those with the condition in comparison to neurotypical (NT) controls. In the present study, adults with ASC (n=13) and a matched NT group (n=13) completed a visual-haptic size judgement task (cf. Gori et al., 2008) in which participants compared the height of wooden blocks using either vision or haptics, and in a dual modality condition in which visual-haptic stimuli were presented in size conflict. Participants with ASC tended to produce more reliable estimates than the NT group. However, dual modality performance was not well predicted by the MLE model for either group. Performance was subsequently compared to alternative models in which the participant either switched between modalities trial to trial (rather than integrating) and a model of non-optimal integration. Performance of both groups was statistically comparable to the cue-switching model. These findings suggest that adults with ASC adopted a similar strategy to NTs when processing conflicting visual-haptic information. Findings are discussed in relation to multisensory perception in ASC and methodological considerations associated with multisensory conflict paradigms.

Visual extrapolation under risk: human observers estimate and compensate for exogenous uncertainty.

Humans commonly face choices between multiple options with uncertain outcomes. Such situations occur in many contexts, from purely financial decisions (which shares should I buy?) to perceptuo-motor decisions between different actions (where should I aim my shot at goal?). Regardless of context, successful decision-making requires that the uncertainty at the heart of the decision-making problem is taken into account. Here, we ask whether humans can recover an estimate of exogenous uncertainty and then use it to make good decisions. Observers viewed a small dot that moved erratically until it disappeared behind an occluder. We varied the size of the occluder and the unpredictability of the dot's path. The observer attempted to capture the dot as it emerged from behind the occluded region by setting the location and extent of a 'catcher' along the edge of the occluder. The reward for successfully catching the dot was reduced as the size of the catcher increased. We compared human performance with that of an agent maximizing expected gain and found that observers consistently selected catcher size close to this theoretical solution. These results suggest that humans are finely tuned to exogenous uncertainty information and can exploit it to guide action.

Discrimination contours for the perception of head-centered velocity.

There is little direct psychophysical evidence that the visual system contains mechanisms tuned to head-centered velocity when observers make a smooth pursuit eye movement. Much of the evidence is implicit, relying on measurements of bias (e.g., matching and nulling). We therefore measured discrimination contours in a space dimensioned by pursuit target motion and relative motion between target and background. Within this space, lines of constant head-centered motion are parallel to the main negative diagonal, so judgments dominated by mechanisms that combine individual components should produce contours with a similar orientation. Conversely, contours oriented parallel to the cardinal axes of the space indicate judgments based on individual components. The results provided evidence for mechanisms tuned to head-centered velocity-discrimination ellipses were significantly oriented away from the cardinal axes, toward the main negative diagonal. However, ellipse orientation was considerably less steep than predicted by a pure combination of components. This suggests that observers used a mixture of two strategies across trials, one based on individual components and another based on their sum. We provide a model that simulates this type of behavior and is able to reproduce the ellipse orientations we found.

Ground-plane influences on size estimation in early visual processing.

Ground-planes have an important influence on the perception of 3D space (Gibson, 1950) and it has been shown that the assumption that a ground-plane is present in the scene plays a role in the perception of object distance (Bruno & Cutting, 1988). Here, we investigate whether this influence is exerted at an early stage of processing, to affect the rapid estimation of 3D size. Participants performed a visual search task in which they searched for a target object that was larger or smaller than distracter objects. Objects were presented against a background that contained either a frontoparallel or slanted 3D surface, defined by texture gradient cues. We measured the effect on search performance of target location within the scene (near vs. far) and how this was influenced by scene orientation (which, e.g., might be consistent with a ground or ceiling plane, etc.). In addition, we investigated how scene orientation interacted with texture gradient information (indicating surface slant), to determine how these separate cues to scene layout were combined. We found that the difference in target detection performance between targets at the front and rear of the simulated scene was maximal when the scene was consistent with a ground-plane - consistent with the use of an elevation cue to object distance. In addition, we found a significant increase in the size of this effect when texture gradient information (indicating surface slant) was present, but no interaction between texture gradient and scene orientation information. We conclude that scene orientation plays an important role in the estimation of 3D size at an early stage of processing, and suggest that elevation information is linearly combined with texture gradient information for the rapid estimation of 3D size.

A Bayesian model of perceived head-centered velocity during smooth pursuit eye movement.

During smooth pursuit eye movement, observers often misperceive velocity. Pursued stimuli appear slower (Aubert-Fleishl phenomenon [1, 2]), stationary objects appear to move (Filehne illusion [3]), the perceived direction of moving objects is distorted (trajectory misperception [4]), and self-motion veers away from its true path (e.g., the slalom illusion [5]). Each illusion demonstrates that eye speed is underestimated with respect to image speed, a finding that has been taken as evidence of early sensory signals that differ in accuracy [4, 6-11]. Here we present an alternative Bayesian account, based on the idea that perceptual estimates are increasingly influenced by prior expectations as signals become more uncertain [12-15]. We show that the speeds of pursued stimuli are more difficult to discriminate than fixated stimuli. Observers are therefore less certain about motion signals encoding the speed of pursued stimuli, a finding we use to quantify the Aubert-Fleischl phenomenon based on the assumption that the prior for motion is centered on zero [16-20]. In doing so, we reveal an important property currently overlooked by Bayesian models of motion perception. Two Bayes estimates are needed at a relatively early stage in processing, one for pursued targets and one for image motion.

Do we have direct access to retinal image motion during smooth pursuit eye movements?

One way the visual system estimates object motion during pursuit is to combine estimates of eye velocity and retinal motion. This questions whether observers need direct access to retinal motion during pursuit. We tested this idea by varying the correlation between retinal motion and objective motion in a two-interval speed discrimination task. Responses were classified according to three motion cues: retinal speed (based on measured eye movements), objective speed, and the relative motion between pursuit target and stimulus. In the first experiment, feedback was based on relative motion and this cue fit the response curves best. In the second experiment, simultaneous relative motion was removed but observers still used the sequential relative motion between pursuit target and dot pattern to make their judgements. In a final experiment, feedback was given explicitly on the retinal motion, using online measurements of eye movements. Nevertheless, sequential relative motion still provided the best account of the data. The results suggest that observers do not have direct access to retinal motion when making perceptual judgements about movement during pursuit.

Rapid size scaling in visual search.

In order to compute a representation of an object's size within a 3D scene, the visual system must scale retinal size by an estimate of the distance to the object. Evidence from size discrimination and visual search studies suggests that we have no access to the representation of retinal size when performing such tasks. In this study we investigate whether observers have early access to retinal size prior to scene size. Observer performance was assessed in a visual search task (requiring search within a 3D scene) in which processing was interrupted at a range of short presentation times. If observers have access to retinal size then we might expect to find a presentation time before which observers behave as if using retinal size and after which they behave as if using scene size. Observers searched for a larger or smaller target object within a group of objects viewed against a textured plane slanted at 0 degrees or 60 degrees . Stimuli were presented for 100, 200, 400 or 800ms and immediately followed by a mask. We measured the effect of target location within a stimulus (near vs. far) on task performance and how this was influenced by the background slant. The results of experiments 1 and 2 suggest that background slant had a significant influence on performance at all presentation times consistent with the use of scene size and not retinal size. Experiment 3 shows that this finding cannot be explained by a 2D texture contrast effect. Experiment 4 indicates that contextual information learned across a block of trials could be an important factor in such visual search experiments. In spite of this finding, our results suggest that distance scaling may occur prior to 100ms and we find no clear evidence for explicit access to a retinal representation of size.

Modification of the convexity prior but not the light-from-above prior in visual search with shaded objects.

Studies of visual search performance with shaded stimuli, in which the target is rotated by 180 degrees relative to the distracters, typically demonstrate more efficient performance in stimuli with vertical compared to horizontal shading gradients. In addition, performance is usually better for vertically shaded stimuli with top-light (seen as convex) distracters compared to those with bottom-light (seen as concave) distracters. These findings have been cited as evidence for the use of the prior assumptions of overhead lighting and convexity in the interpretation of shaded stimuli and suggest that these priors affect preattentive processing. Here we attempt to modify these priors by providing observers with visual-haptic training in an environment inconsistent with their priors. Observers' performance was measured in a visual search task and a shape judgment task before and after training. Following training, we found a reduced asymmetry between visual search performance with convex and concave distracters, suggesting a modification of the convexity prior. However, although evidence of a change in the light-from-above prior was found in the shape judgment task, no change was found in the visual search task. We conclude that experience can modify the convexity prior at a preattentive stage in processing; however, our training did not modify the light-from-above prior that is measured via visual search.

Perceptual distortions of speed at low luminance: evidence inconsistent with a Bayesian account of speed encoding.

Our perception of speed has been shown to be distorted under a number of viewing conditions. Recently the well-known reduction of perceived speed at low contrast has led to Bayesian models of speed perception that account for these distortions with a slow speed 'prior'. To test the predictive, rather than the descriptive, power of the Bayesian approach we have investigated perceived speed at low luminance. Our results indicate that, for the mesopic and photopic range (0.13-30 cd m(-2)) the perceived speed of lower luminance patterns is virtually unaffected at low speeds (<4 deg s(-1)) but is over-estimated at higher speeds (>4 deg s(-1)). We show here that the results can be accounted for by an extension to a simple ratio model of speed encoding [Hammett, S. T., Champion, R. A., Morland, A. & Thompson, P. G. (2005). A ratio model of perceived speed in the human visual system. Proceedings of Royal Society B, 262, 2351-2356.] that takes account of known changes in neural responses as a function of luminance, contrast and temporal frequency. The results are not consistent with current Bayesian approaches to modelling speed encoding that postulate a slow speed prior.

Perceived direction of plaid motion is not predicted by component speeds.

It has been shown that the perceived direction of a plaid with components of unequal contrast is biased towards the direction of the higher-contrast component [Stone, L. S., Watson, A. B., & Mulligan, J. B. (1990). Effect of contrast on the perceived direction of a moving plaid. Vision Research 30, 1049-1067]. It was proposed that this effect is due to the influence of contrast on the perceived speed of the plaid components. This led to the conclusion that perceived plaid direction is computed by the intersection of constraints (IOC) of the perceived speed of the components rather than their physical speeds. We tested this proposal at a wider range of component speeds (2-16deg/s) than used previously, across which the effect of contrast on perceived speed is seen to reverse. We find that across this range, perceived plaid direction cannot be predicted either by a model which takes the IOC of physical or perceived component speed. Our results are consistent with an explanation of 2D motion perception proposed by [Bowns, L. (1996). Evidence for a feature tracking explanation of why Type II plaids move in the vector sum direction at short durations. Vision Research, 36, 3685-3694.] in which the motion of the zero-crossing edges of the features in the stimulus contribute to the perceived direction of motion.

A ratio model of perceived speed in the human visual system.

The perceived speed of moving images changes over time. Prolonged viewing of a pattern (adaptation) leads to an exponential decrease in its perceived speed. Similarly, responses of neurones tuned to motion reduce exponentially over time. It is tempting to link these phenomena. However, under certain conditions, perceived speed increases after adaptation and the time course of these perceptual effects varies widely. We propose a model that comprises two temporally tuned mechanisms whose sensitivities reduce exponentially over time. Perceived speed is taken as the ratio of these filters' outputs. The model captures increases and decreases in perceived speed following adaptation and describes our data well with just four free parameters. Whilst the model captures perceptual time courses that vary widely, parameter estimates for the time constants of the underlying filters are in good agreement with estimates of the time course of adaptation of direction selective neurones in the mammalian visual system.