Dorsal Medial Superior Temporal Area Research Articles

Visual-Based Spatial Coordinate Dominates Probabilistic Multisensory Inference in Macaque MST-d Disparity Encoding.

Numerous studies have demonstrated that animal brains accurately infer whether multisensory stimuli are from a common source or separate sources. Previous work proposed that the multisensory neurons in the dorsal medial superior temporal area (MST-d) serve as integration or separation encoders determined by the tuning–response ratio. However, it remains unclear whether MST-d neurons mainly take a sense input as a spatial coordinate reference for carrying out multisensory integration or separation. Our experimental analysis shows that the preferred tuning response to visual input is generally larger than vestibular according to the Macaque MST-d neuronal recordings. This may be crucial to serving as the base of coordinate reference when the subject perceives moving direction information from two senses. By constructing a flexible Monte-Carlo probabilistic sampling (fMCS) model, we validate this hypothesis that the visual and vestibular cues are more likely to be integrated into a visual-based coordinate rather than vestibular. Furthermore, the property of the tuning gradient also affects decision-making regarding whether the cues should be integrated or not. To a dominant modality, an effective decision is produced by a steep response-tuning gradient of the corresponding neurons, while to a subordinate modality a steep tuning gradient produces a rigid decision with a significant bias to either integration or separation. This work proposes that the tuning response amplitude and tuning gradient jointly modulate which modality serves as the base coordinate for the reference frame and the direction change with which modality is decoded effectively.

Unveiling Dynamic System Strategies for Multisensory Processing: From Neuronal Fixed-Criterion Integration to Population Bayesian Inference.

Multisensory processing is of vital importance for survival in the external world. Brain circuits can both integrate and separate visual and vestibular senses to infer self-motion and the motion of other objects. However, it is largely debated how multisensory brain regions process such multisensory information and whether they follow the Bayesian strategy in this process. Here, we combined macaque physiological recordings in the dorsal medial superior temporal area (MST-d) with modeling of synaptically coupled multilayer continuous attractor neural networks (CANNs) to study the underlying neuronal circuit mechanisms. In contrast to previous theoretical studies that focused on unisensory direction preference, our analysis showed that synaptic coupling induced cooperation and competition in the multisensory circuit and caused single MST-d neurons to switch between sensory integration or separation modes based on the fixed-criterion causal strategy, which is determined by the synaptic coupling strength. Furthermore, the prior of sensory reliability was represented by pooling diversified criteria at the MST-d population level, and the Bayesian strategy was achieved in downstream neurons whose causal inference flexibly changed with the prior. The CANN model also showed that synaptic input balance is the dynamic origin of neuronal direction preference formation and further explained the misalignment between direction preference and inference observed in previous studies. This work provides a computational framework for a new brain-inspired algorithm underlying multisensory computation.

Supervised Multisensory Calibration Signals Are Evident in VIP But Not MSTd.

Multisensory plasticity enables our senses to dynamically adapt to each other and the external environment, a fundamental operation that our brain performs continuously. We searched for neural correlates of adult multisensory plasticity in the dorsal medial superior temporal area (MSTd) and the ventral intraparietal area (VIP) in 2 male rhesus macaques using a paradigm of supervised calibration. We report little plasticity in neural responses in the relatively low-level multisensory cortical area MSTd. In contrast, neural correlates of plasticity are found in higher-level multisensory VIP, an area with strong decision-related activity. Accordingly, we observed systematic shifts of VIP tuning curves, which were reflected in the choice-related component of the population response. This is the first demonstration of neuronal calibration, together with behavioral calibration, in single sessions. These results lay the foundation for understanding multisensory neural plasticity, applicable broadly to maintaining accuracy for sensorimotor tasks.SIGNIFICANCE STATEMENT Multisensory plasticity is a fundamental and continual function of the brain that enables our senses to adapt dynamically to each other and to the external environment. Yet, very little is known about the neuronal mechanisms of multisensory plasticity. In this study, we searched for neural correlates of adult multisensory plasticity in the dorsal medial superior temporal area (MSTd) and the ventral intraparietal area (VIP) using a paradigm of supervised calibration. We found little plasticity in neural responses in the relatively low-level multisensory cortical area MSTd. By contrast, neural correlates of plasticity were found in VIP, a higher-level multisensory area with strong decision-related activity. This is the first demonstration of neuronal calibration, together with behavioral calibration, in single sessions.

Modeling Physiological Sources of Heading Bias from Optic Flow.

Human heading perception from optic flow is accurate for directions close to the straight-ahead and systematic biases emerge in the periphery (Cuturi and Macneilage, 2013; Sun et al., 2020). In pursuit of the underlying neural mechanisms, primate brain dorsal medial superior temporal (MSTd) area has been a focus because of its causal link with heading perception (Gu et al., 2012). Computational models generally explain heading sensitivity in individual MSTd neurons as a feedforward integration of motion signals from medial temporal (MT) area that resemble full-field optic flow patterns consistent with the preferred heading direction (Britten, 2008; Mineault et al., 2012). In the present simulation study, we quantified within the structure of this feedforward model how physiological properties of MT and MSTd shape heading signals. We found that known physiological tuning characteristics generally supported the accuracy of heading estimation, but not always. A weak-to-moderate overrepresentation of peripheral headings in MSTd garnered the highest accuracy and precision out of the models that we tested. The model also performed well when noise corrupted high proportions of the optic flow vectors. Such a peripheral MSTd model performed well when units possessed a range of receptive field (RF) sizes and were strongly direction tuned. Physiological biases in MT direction tuning toward the radial direction also supported heading estimation, but the tendency for MT preferred speed and RF size to scale with eccentricity did not. Our findings help elucidate the extent to which different physiological tuning properties influence the accuracy and precision of neural heading signals.

Encoding of vestibular and optic flow cues to self-motion in the posterior superior temporal polysensory area.

Neurons in the posterior superior temporal polysensory area (STPp) showed significant directional selectivity in response to vestibular, optic flow and combined visual-vestibular stimuli. By comparison to the dorsal medial superior temporal area, the visual latency was slower in STPp but the vestibular latency was faster. Heading preferences under combined stimulation in STPp were usually dominated by visual signals. Cross-modal enhancement was observed in STPp when both vestibular and visual cues were presented together at their heading preferences. Human neuroimaging data implicated that the superior temporal polysensory area (STP) might be involved in vestibular-visual interaction during heading computations, but the heading selectivity has not been examined in the macaque. Here, we investigated the convergence of optic flow and vestibular signals in macaque STP by using a virtual-reality system and found that 6.3% of STP neurons showed multisensory responses, with visual and vestibular direction preferences either congruent or opposite in roughly equal proportion. The percentage of vestibular-tuned cells (18.3%) was much smaller than that of visual-tuned cells (30.4%) in STP. The vestibular tuning strength was usually weaker than the visual condition. The visual latency was significantly slower in STPp than in the dorsal medial superior temporal area (MSTd), but the vestibular latency was significantly faster than in MSTd. During the bimodal condition, STP cells' response was dominated by visual signals, with the visual heading preference not affected by the vestibular signals but the response amplitudes modulated by vestibular signals in a subadditive way.

Retinal Stabilization Reveals Limited Influence of Extraretinal Signals on Heading Tuning in the Medial Superior Temporal Area.

Heading perception in primates depends heavily on visual optic-flow cues. Yet during self-motion, heading percepts remain stable, even though smooth-pursuit eye movements often distort optic flow. According to theoretical work, self-motion can be represented accurately by compensating for these distortions in two ways: via retinal mechanisms or via extraretinal efference-copy signals, which predict the sensory consequences of movement. Psychophysical evidence strongly supports the efference-copy hypothesis, but physiological evidence remains inconclusive. Neurons that signal the true heading direction during pursuit are found in visual areas of monkey cortex, including the dorsal medial superior temporal area (MSTd). Here we measured heading tuning in MSTd using a novel stimulus paradigm, in which we stabilize the optic-flow stimulus on the retina during pursuit. This approach isolates the effects on neuronal heading preferences of extraretinal signals, which remain active while the retinal stimulus is prevented from changing. Our results from 3 female monkeys demonstrate a significant but small influence of extraretinal signals on the preferred heading directions of MSTd neurons. Under our stimulus conditions, which are rich in retinal cues, we find that retinal mechanisms dominate physiological corrections for pursuit eye movements, suggesting that extraretinal cues, such as predictive efference-copy mechanisms, have a limited role under naturalistic conditions.SIGNIFICANCE STATEMENT Sensory systems discount stimulation caused by an animal's own behavior. For example, eye movements cause irrelevant retinal signals that could interfere with motion perception. The visual system compensates for such self-generated motion, but how this happens is unclear. Two theoretical possibilities are a purely visual calculation or one using an internal signal of eye movements to compensate for their effects. The latter can be isolated by experimentally stabilizing the image on a moving retina, but this approach has never been adopted to study motion physiology. Using this method, we find that extraretinal signals have little influence on activity in visual cortex, whereas visually based corrections for ongoing eye movements have stronger effects and are likely most important under real-world conditions.

Neural activity in the dorsal medial superior temporal area of monkeys represents retinal error during adaptive motor learning

To adapt to variable environments, humans regulate their behavior by modulating gains in sensory-to-motor processing. In this study, we measured a simple eye movement, the ocular following response (OFR), in monkeys to study the neuronal basis of adaptive motor learning in the visuomotor processing stream. The medial superior temporal (MST) area of the cerebral cortex is a critical site for contextual gain modulation of the OFR. However, the role of MST neurons in adaptive gain modulation of the OFR remains unknown. We adopted a velocity step-down sequence paradigm that was designed to promote adaptive gain modulation of the OFR to investigate the role of the dorsal MST (MSTd) in adaptive motor learning. In the initial learning stage, we observed a reduction in the OFR but no significant change in the “open-loop” responses for the majority of the MSTd neurons. However, in the late learning stage, some MSTd neurons exhibited significantly enhanced “closed-loop” responses in association with increases in retinal error velocity. These results indicate that the MSTd area primarily encodes visual motion, suggesting that MSTd neurons function upstream of the motor learning site to provide sensory signals to the downstream structures involved in adaptive motor learning.

A neural model of MST and MT explains perceived object motion during self-motion

When a moving object cuts in front of a moving observer at a 90° angle, the observer correctly perceives that the object is traveling along a perpendicular path just as if viewing the moving object from a stationary vantage point. Although the observer9s own (self-)motion affects the object9s pattern of motion on the retina, the visual system is able to factor out the influence of self-motion and recover the world-relative motion of the object (Matsumiya and Ando, 2009). This is achieved by using information in global optic flow (Rushton and Warren, 2005; Warren and Rushton, 2009; Fajen and Matthis, 2013) and other sensory arrays (Dupin and Wexler, 2013; Fajen et al., 2013; Dokka et al., 2015) to estimate and deduct the component of the object9s local retinal motion that is due to self-motion. However, this account (known as “flow parsing”) is qualitative and does not shed light on mechanisms in the visual system that recover object motion during self-motion. We present a simple computational account that makes explicit possible mechanisms in visual cortex by which self-motion signals in the medial superior temporal area interact with object motion signals in the middle temporal area to transform object motion into a world-relative reference frame. The model (1) relies on two mechanisms (MST-MT feedback and disinhibition of opponent motion signals in MT) to explain existing data, (2) clarifies how pathways for self-motion and object-motion perception interact, and (3) unifies the existing flow parsing hypothesis with established neurophysiological mechanisms. SIGNIFICANCE STATEMENT To intercept targets, we must perceive the motion of objects that move independently from us as we move through the environment. Although our self-motion substantially alters the motion of objects on the retina, compelling evidence indicates that the visual system at least partially compensates for self-motion such that object motion relative to the stationary environment can be more accurately perceived. We have developed a model that sheds light on plausible mechanisms within the visual system that transform retinal motion into a world-relative reference frame. Our model reveals how local motion signals (generated through interactions within the middle temporal area) and global motion signals (feedback from the dorsal medial superior temporal area) contribute and offers a new hypothesis about the connection between pathways for heading and object motion perception.

A Neural Model of MST and MT Explains Perceived Object Motion during Self-Motion.

When a moving object cuts in front of a moving observer at a 90° angle, the observer correctly perceives that the object is traveling along a perpendicular path just as if viewing the moving object from a stationary vantage point. Although the observer's own (self-)motion affects the object's pattern of motion on the retina, the visual system is able to factor out the influence of self-motion and recover the world-relative motion of the object (Matsumiya and Ando, 2009). This is achieved by using information in global optic flow (Rushton and Warren, 2005; Warren and Rushton, 2009; Fajen and Matthis, 2013) and other sensory arrays (Dupin and Wexler, 2013; Fajen et al., 2013; Dokka et al., 2015) to estimate and deduct the component of the object's local retinal motion that is due to self-motion. However, this account (known as "flow parsing") is qualitative and does not shed light on mechanisms in the visual system that recover object motion during self-motion. We present a simple computational account that makes explicit possible mechanisms in visual cortex by which self-motion signals in the medial superior temporal area interact with object motion signals in the middle temporal area to transform object motion into a world-relative reference frame. The model (1) relies on two mechanisms (MST-MT feedback and disinhibition of opponent motion signals in MT) to explain existing data, (2) clarifies how pathways for self-motion and object-motion perception interact, and (3) unifies the existing flow parsing hypothesis with established neurophysiological mechanisms. To intercept targets, we must perceive the motion of objects that move independently from us as we move through the environment. Although our self-motion substantially alters the motion of objects on the retina, compelling evidence indicates that the visual system at least partially compensates for self-motion such that object motion relative to the stationary environment can be more accurately perceived. We have developed a model that sheds light on plausible mechanisms within the visual system that transform retinal motion into a world-relative reference frame. Our model reveals how local motion signals (generated through interactions within the middle temporal area) and global motion signals (feedback from the dorsal medial superior temporal area) contribute and offers a new hypothesis about the connection between pathways for heading and object motion perception.

Evidence for a Causal Contribution of Macaque Vestibular, But Not Intraparietal, Cortex to Heading Perception.

Multisensory vestibular and visual signals are found in multiple cortical areas, but their causal contribution to self-motion perception has been previously tested only in the dorsal medial superior temporal (MSTd) area. In these experiments, we show that inactivation of the parietoinsular vestibular cortex (PIVC) also results in causal deficits during heading discrimination for both visual and vestibular cues. In contrast, ventral intraparietal (VIP) area inactivation led to no behavioral deficits, despite the fact that VIP neurons show much stronger choice-related activity than MSTd or PIVC neurons. These results demonstrate that choice-related activity does not always imply a causal role in sensory perception.

Steering Transforms the Cortical Representation of Self-Movement from Direction to Destination.

Unplanned heading changes trigger lifesaving steering back to a goal. Conventionally, such behaviors are thought of as cortical sensory-motor reflex arcs. We find that a more reciprocal process underlies such cycles of perception and action, rapidly transforming visual processing to suit each stage of the task. When monkeys monitor their simulated self-movement, dorsal medial superior temporal area (MSTd) neurons represent their current heading direction. When monkeys steer to recover from an unplanned change in heading direction, MSTd shifts toward representing the goal location. We hypothesize that this transformation reflects the reweighting of bottom-up visual motion signals and top-down spatial location signals, reshaping MSTd's response properties through task-dependent interactions with adjacent cortical areas.

The temporal dynamics of heading perception in the presence of moving objects.

Many forms of locomotion rely on the ability to accurately perceive one's direction of locomotion (i.e., heading) based on optic flow. Although accurate in rigid environments, heading judgments may be biased when independently moving objects are present. The aim of this study was to systematically investigate the conditions in which moving objects influence heading perception, with a focus on the temporal dynamics and the mechanisms underlying this bias. Subjects viewed stimuli simulating linear self-motion in the presence of a moving object and judged their direction of heading. Experiments 1 and 2 revealed that heading perception is biased when the object crosses or almost crosses the observer's future path toward the end of the trial, but not when the object crosses earlier in the trial. Nonetheless, heading perception is not based entirely on the instantaneous optic flow toward the end of the trial. This was demonstrated in Experiment 3 by varying the portion of the earlier part of the trial leading up to the last frame that was presented to subjects. When the stimulus duration was long enough to include the part of the trial before the moving object crossed the observer's path, heading judgments were less biased. The findings suggest that heading perception is affected by the temporal evolution of optic flow. The time course of dorsal medial superior temporal area (MSTd) neuron responses may play a crucial role in perceiving heading in the presence of moving objects, a property not captured by many existing models.

Saccade-induced image motion cannot account for post-saccadic enhancement of visual processing in primate MST.

Primates use saccadic eye movements to make gaze changes. In many visual areas, including the dorsal medial superior temporal area (MSTd) of macaques, neural responses to visual stimuli are reduced during saccades but enhanced afterwards. How does this enhancement arise—from an internal mechanism associated with saccade generation or through visual mechanisms activated by the saccade sweeping the image of the visual scene across the retina? Spontaneous activity in MSTd is elevated even after saccades made in darkness, suggesting a central mechanism for post-saccadic enhancement. However, based on the timing of this effect, it may arise from a different mechanism than occurs in normal vision. Like neural responses in MSTd, initial ocular following eye speed is enhanced after saccades, with evidence suggesting both internal and visually mediated mechanisms. Here we recorded from visual neurons in MSTd and measured responses to motion stimuli presented soon after saccades and soon after simulated saccades—saccade-like displacements of the background image during fixation. We found that neural responses in MSTd were enhanced when preceded by real saccades but not when preceded by simulated saccades. Furthermore, we also observed enhancement following real saccades made across a blank screen that generated no motion signal within the recorded neurons' receptive fields. We conclude that in MSTd the mechanism leading to post-saccadic enhancement has internal origins.

Multisensory Convergence of Visual and Vestibular Heading Cues in the Pursuit Area of the Frontal Eye Field.

Both visual and vestibular sensory cues are important for perceiving one's direction of heading during self-motion. Previous studies have identified multisensory, heading-selective neurons in the dorsal medial superior temporal area (MSTd) and the ventral intraparietal area (VIP). Both MSTd and VIP have strong recurrent connections with the pursuit area of the frontal eye field (FEFsem), but whether FEFsem neurons may contribute to multisensory heading perception remain unknown. We characterized the tuning of macaque FEFsem neurons to visual, vestibular, and multisensory heading stimuli. About two-thirds of FEFsem neurons exhibited significant heading selectivity based on either vestibular or visual stimulation. These multisensory neurons shared many properties, including distributions of tuning strength and heading preferences, with MSTd and VIP neurons. Fisher information analysis also revealed that the average FEFsem neuron was almost as sensitive as MSTd or VIP cells. Visual and vestibular heading preferences in FEFsem tended to be either matched (congruent cells) or discrepant (opposite cells), such that combined stimulation strengthened heading selectivity for congruent cells but weakened heading selectivity for opposite cells. These findings demonstrate that, in addition to oculomotor functions, FEFsem neurons also exhibit properties that may allow them to contribute to a cortical network that processes multisensory heading cues.

How Can Single Sensory Neurons Predict Behavior?

Single sensory neurons can be surprisingly predictive of behavior in discrimination tasks. We propose this is possible because sensory information extracted from neural populations is severely restricted, either by near-optimal decoding of a population with information-limiting correlations or by suboptimal decoding that is blind to correlations. These have different consequences for choice correlations, the correlations between neural responses and behavioral choices. In the vestibular and cerebellar nuclei and the dorsal medial superior temporal area, we found that choice correlations during heading discrimination are consistent with near-optimal decoding of neuronal responses corrupted by information-limiting correlations. In the ventral intraparietal area, the choice correlations are also consistent with the presence of information-limiting correlations, but this area does not appear to influence behavior, although the choice correlations are particularly large. These findings demonstrate how choice correlations can be used to assess the efficiency of the downstream readout and detect the presence of information-limiting correlations.

Neural mechanisms for discounting head-roll-induced retinal motion.

An extensive series of physiological studies in macaques shows the existence of neurons in three multisensory cortical regions, dorsal medial superior temporal area (MSTd), ventral intraparietal area (VIP), and visual posterior sylvian area (VPS), that are tuned for direction of self-motion in both visual and vestibular modalities. Some neurons have congruent direction preferences, suggesting integration of signals for optimum encoding of self-motion trajectory; others have opposite preferences and could be used for discounting retinal motion that arises from perceptually irrelevant head motion. Whether such a system exists in humans is unknown. Here, artificial vestibular stimulation was administered to human participants during fMRI scanning in conjunction with carefully calibrated visual stimulation that emulated either congruent or opposite stimulation conditions. Direction and speed varied sinusoidally, such that the two conditions contained identical vestibular stimulation and identical retinal stimulation, differing only in the relative phase of the two components. In human MST and putative VIP, multivoxel pattern analysis permitted classification of stimulus phase based on fMRI time-series data, consistent with the existence of separate neuron populations responsive to congruent and opposite cue combinations. Decoding was also possible in the vicinity of parieto-insular vestibular cortex, possibly in a homolog of macaque VPS.

A Unified Model of Heading and Path Perception in Primate MSTd

Self-motion, steering, and obstacle avoidance during navigation in the real world require humans to travel along curved paths. Many perceptual models have been proposed that focus on heading, which specifies the direction of travel along straight paths, but not on path curvature, which humans accurately perceive and is critical to everyday locomotion. In primates, including humans, dorsal medial superior temporal area (MSTd) has been implicated in heading perception. However, the majority of MSTd neurons respond optimally to spiral patterns, rather than to the radial expansion patterns associated with heading. No existing theory of curved path perception explains the neural mechanisms by which humans accurately assess path and no functional role for spiral-tuned cells has yet been proposed. Here we present a computational model that demonstrates how the continuum of observed cells (radial to circular) in MSTd can simultaneously code curvature and heading across the neural population. Curvature is encoded through the spirality of the most active cell, and heading is encoded through the visuotopic location of the center of the most active cell's receptive field. Model curvature and heading errors fit those made by humans. Our model challenges the view that the function of MSTd is heading estimation, based on our analysis we claim that it is primarily concerned with trajectory estimation and the simultaneous representation of both curvature and heading. In our model, temporal dynamics afford time-history in the neural representation of optic flow, which may modulate its structure. This has far-reaching implications for the interpretation of studies that assume that optic flow is, and should be, represented as an instantaneous vector field. Our results suggest that spiral motion patterns that emerge in spatio-temporal optic flow are essential for guiding self-motion along complex trajectories, and that cells in MSTd are specifically tuned to extract complex trajectory estimation from flow.

Eye Velocity Gain Fields in MSTd During Optokinetic Stimulation

Lesion studies argue for an involvement of cortical area dorsal medial superior temporal area (MSTd) in the control of optokinetic response (OKR) eye movements to planar visual stimulation. Neural recordings during OKR suggested that MSTd neurons directly encode stimulus velocity. On the other hand, studies using radial visual flow together with voluntary smooth pursuit eye movements showed that visual motion responses were modulated by eye movement-related signals. Here, we investigated neural responses in MSTd during continuous optokinetic stimulation using an information-theoretic approach for characterizing neural tuning with high resolution. We show that the majority of MSTd neurons exhibit gain-field-like tuning functions rather than directly encoding one variable. Neural responses showed a large diversity of tuning to combinations of retinal and extraretinal input. Eye velocity-related activity was observed prior to the actual eye movements, reflecting an efference copy. The observed tuning functions resembled those emerging in a network model trained to perform summation of 2 population-coded signals. Together, our findings support the hypothesis that MSTd implements the visuomotor transformation from retinal to head-centered stimulus velocity signals for the control of OKR.

Diverse Spatial Reference Frames of Vestibular Signals in Parietal Cortex

Reference frames are important for understanding how sensory cues from different modalities are coordinated to guide behavior, and the parietal cortex is critical to these functions. We compare reference frames of vestibular self-motion signals in the ventral intraparietal area (VIP), parietoinsular vestibular cortex (PIVC), and dorsal medial superior temporal area (MSTd). Vestibular heading tuning in VIP is invariant to changes in both eye and head positions, indicating a body (or world)-centered reference frame. Vestibular signals in PIVC have reference frames that are intermediate between head and body centered. In contrast, MSTd neurons show reference frames between head and eye centered but not body centered. Eye and head position gain fields were strongest in MSTd and weakest in PIVC. Our findings reveal distinct spatial reference frames for representing vestibular signals and pose new challenges for understanding the respective roles of these areas in potentially diverse vestibular functions.

Causal Links between Dorsal Medial Superior Temporal Area Neurons and Multisensory Heading Perception

The dorsal medial superior temporal area (MSTd) in the extrastriate visual cortex is thought to play an important role in heading perception because neurons in this area are tuned to both optic flow and vestibular signals. MSTd neurons also show significant correlations with perceptual judgments during a fine heading direction discrimination task. To test for a causal link with heading perception, we used microstimulation and reversible inactivation techniques to artificially perturb MSTd activity while monitoring behavioral performance. Electrical microstimulation significantly biased monkeys' heading percepts based on optic flow, but did not significantly impact vestibular heading judgments. The latter result may be due to the fact that vestibular heading preferences in MSTd are more weakly clustered than visual preferences and multiunit tuning for vestibular stimuli is weak. Reversible chemical inactivation, however, increased behavioral thresholds when heading judgments were based on either optic flow or vestibular cues, although the magnitude of the effects was substantially stronger for optic flow. Behavioral deficits in a combined visual/vestibular stimulus condition were intermediate between the single-cue effects. Despite deficits in discrimination thresholds, animals were able to combine visual and vestibular cues near optimally, even after large bilateral muscimol injections into MSTd. Simulations show that the overall pattern of results following inactivation is consistent with a mixture of contributions from MSTd and other areas with vestibular-dominant tuning for heading. Our results support a causal link between MSTd neurons and multisensory heading perception but suggest that other multisensory brain areas also contribute.