Responses to visual motion of neurons in the extrastriate visual cortex of macaque monkeys with experimental amblyopia.

Amblyopia is a developmental disorder that results from abnormal visual experience in early life. Amblyopia typically reduces visual performance in one eye. We studied the representation of visual motion information in area MT and nearby extrastriate visual areas in two monkeys made amblyopic by creating an artificial strabismus in early life, and in a single age-matched control monkey. Tested monocularly, cortical responses to moving dot patterns, gratings, and plaids were qualitatively normal in awake, fixating amblyopic monkeys, with primarily subtle differences between the eyes. However, the number of binocularly driven neurons was substantially lower than normal; of the neurons driven predominantly by one eye, the great majority responded only to stimuli presented to the fellow eye. The small population driven by the amblyopic eye showed reduced coherence sensitivity and a preference for faster speeds in much the same way as behavioral deficits. We conclude that, while we do find important differences between neurons driven by the two eyes, amblyopia does not lead to a large scale reorganization of visual receptive fields in the dorsal stream when tested through the amblyopic eye, but rather creates a substantial shift in eye preference toward the fellow eye.

Development of visual cortical function in infant macaques: A BOLD fMRI study.

Functional brain development is not well understood. In the visual system, neurophysiological studies in nonhuman primates show quite mature neuronal properties near birth although visual function is itself quite immature and continues to develop over many months or years after birth. Our goal was to assess the relative development of two main visual processing streams, dorsal and ventral, using BOLD fMRI in an attempt to understand the global mechanisms that support the maturation of visual behavior. Seven infant macaque monkeys (Macaca mulatta) were repeatedly scanned, while anesthetized, over an age range of 102 to 1431 days. Large rotating checkerboard stimuli induced BOLD activation in visual cortices at early ages. Additionally we used static and dynamic Glass pattern stimuli to probe BOLD responses in primary visual cortex and two extrastriate areas: V4 and MT-V5. The resulting activations were analyzed with standard GLM and multivoxel pattern analysis (MVPA) approaches. We analyzed three contrasts: Glass pattern present/absent, static/dynamic Glass pattern presentation, and structured/random Glass pattern form. For both GLM and MVPA approaches, robust coherent BOLD activation appeared relatively late in comparison to the maturation of known neuronal properties and the development of behavioral sensitivity to Glass patterns. Robust differential activity to Glass pattern present/absent and dynamic/static stimulus presentation appeared first in V1, followed by V4 and MT-V5 at older ages; there was no reliable distinction between the two extrastriate areas. A similar pattern of results was obtained with the two analysis methods, although MVPA analysis showed reliable differential responses emerging at later ages than GLM. Although BOLD responses to large visual stimuli are detectable, our results with more refined stimuli indicate that global BOLD activity changes as behavioral performance matures. This reflects an hierarchical development of the visual pathways. Since fMRI BOLD reflects neural activity on a population level, our results indicate that, although individual neurons might be adult-like, a longer maturation process takes place on a population level.

Experimental test of spatial updating models for monkey eye-head gaze shifts.

How the brain maintains an accurate and stable representation of visual target locations despite the occurrence of saccadic gaze shifts is a classical problem in oculomotor research. Here we test and dissociate the predictions of different conceptual models for head-unrestrained gaze-localization behavior of macaque monkeys. We adopted the double-step paradigm with rapid eye-head gaze shifts to measure localization accuracy in response to flashed visual stimuli in darkness. We presented the second target flash either before (static), or during (dynamic) the first gaze displacement. In the dynamic case the brief visual flash induced a small retinal streak of up to about 20 deg at an unpredictable moment and retinal location during the eye-head gaze shift, which provides serious challenges for the gaze-control system. However, for both stimulus conditions, monkeys localized the flashed targets with accurate gaze shifts, which rules out several models of visuomotor control. First, these findings exclude the possibility that gaze-shift programming relies on retinal inputs only. Instead, they support the notion that accurate eye-head motor feedback updates the gaze-saccade coordinates. Second, in dynamic trials the visuomotor system cannot rely on the coordinates of the planned first eye-head saccade either, which rules out remapping on the basis of a predictive corollary gaze-displacement signal. Finally, because gaze-related head movements were also goal-directed, requiring continuous access to eye-in-head position, we propose that our results best support a dynamic feedback scheme for spatial updating in which visuomotor control incorporates accurate signals about instantaneous eye- and head positions rather than relative eye- and head displacements.

Influence of static eye and head position on tone-evoked gaze shifts.

The auditory system represents sound-source directions initially in head-centered coordinates. To program eye-head gaze shifts to sounds, the orientation of eyes and head should be incorporated to specify the target relative to the eyes. Here we test (1) whether this transformation involves a stage in which sounds are represented in a world- or a head-centered reference frame, and (2) whether acoustic spatial updating occurs at a topographically organized motor level representing gaze shifts, or within the tonotopically organized auditory system. Human listeners generated head-unrestrained gaze shifts from a large range of initial eye and head positions toward brief broadband sound bursts, and to tones at different center frequencies, presented in the midsagittal plane. Tones were heard at a fixed illusory elevation, regardless of their actual location, that depended in an idiosyncratic way on initial head and eye position, as well as on the tone's frequency. Gaze shifts to broadband sounds were accurate, fully incorporating initial eye and head positions. The results support the hypothesis that the auditory system represents sounds in a supramodal reference frame, and that signals about eye and head orientation are incorporated at a tonotopic stage.

The effect of head roll on perceived auditory zenith.

We studied the influence of static head roll on the perceived auditory zenith in head-centred and world-centred coordinates. Subjects sat either upright, or with their head left/right rolled sideways by about 35° relative to gravity, whilst judging whether a broadband sound was heard left or right from the head-centred or world-centred zenith. When upright, these reference frames coincide. Results show that subjects judged the zenith accurately within different planes, although response variability increased for the midsagittal plane. With the head rolled, head-centred auditory zenith shifted by the same amount and was located as accurately as for upright, indicating unaltered localisation cues by head-on-body roll. Interestingly, when judging world-centred zenith subjects made large systematic errors (10-15°) in the direction of head roll, and response variability increased, which resembles the visual Aubert effect. These results demonstrate a significant influence of the vestibular-collic system on auditory spatial awareness, which sheds new light on the mechanisms underlying multisensory integration and spatial updating in sound localisation behaviour.

Applying double-magnetic induction to measure head-unrestrained gaze shifts: calibration and validation in monkey.

The double magnetic induction (DMI) method has successfully been used to record head-unrestrained gaze shifts in human subjects (Bremen et al., J Neurosci Methods 160:75-84, 2007a, J Neurophysiol, 98:3759-3769, 2007b). This method employs a small golden ring placed on the eye that, when positioned within oscillating magnetic fields, induces orientation-dependent voltages in a pickup coil in front of the eye. Here we develop and test a streamlined calibration routine for use with experimental animals, in particular, with monkeys. The calibration routine requires the animal solely to accurately follow visual targets presented at random locations in the visual field. Animals can readily learn this task. In addition, we use the fact that the pickup coil can be fixed rigidly and reproducibly on implants on the animal's skull. Therefore, accumulation of calibration data leads to increasing accuracy. As a first step, we simulated gaze shifts and the resulting DMI signals. Our simulations showed that the complex DMI signals can be effectively calibrated with the use of random target sequences, which elicit substantial decoupling of eye- and head orientations in a natural way. Subsequently, we tested our paradigm on three macaque monkeys. Our results show that the data for a successful calibration can be collected in a single recording session, in which the monkey makes about 1,500-2,000 goal-directed saccades. We obtained a resolution of 30 arc minutes (measurement range [-60,+60]°). This resolution compares to the fixation resolution of the monkey's oculomotor system, and to the standard scleral search-coil method.

Human sound-localization behavior accounts for ocular drift.

To generate an accurate saccade toward a sound in darkness requires a transformation of the head-centered sound location into an oculocentric motor command, which necessitates the use of an eye-in-head position signal. We tested whether this transformation uses a continuous representation of eye position by exploiting the property that the oculomotor neural integrator is leaky with a time constant of ∼20 s. Hence in complete darkness, the eyes tend to drift toward a neutral position. Alternatively, the spatial mapping stage could employ a sampled eye-position signal in which case drift will not be accounted for. Our data show that the sound location is accurately represented and that the transformation uses a dynamic eye-position signal. This signal, however, is slightly underestimated, leading to small systematic localization errors that tend to covary with the direction of eye position.

Human sound-localization behaviour after multiple changes in eye position.

Orienting the eyes towards a peripheral sound source calls for a transformation of the head-centred sound coordinates into an oculocentric motor command, which requires an estimate of current eye position. Current models of saccadic control explain spatial accuracy by oculocentric transformations that rely on efference copies of relative eye-displacement signals, rather than on absolute eye position in the orbit. In principle, the gaze-control system could keep track of instantaneous eye position by vector addition of intervening eye-displacement commands. However, given that each motor update is endowed with some noise, the neural estimate of eye orientation is then expected to become noisier with increasing number of intervening saccades. As a consequence, the localization response will also be noisier. According to the alternative, in which target updates rely on feedback of the current eye position, such an increase in errors would be absent. In an attempt to dissociate these hypotheses, we studied the influence of the accumulation of oculomotor commands prior to a sound-localization response. Head-restrained subjects generated voluntary eye movements in darkness in random directions for a period between 0.2 and 15 s, after which they rapidly reoriented the eyes towards a brief sound burst. The results demonstrate that the audiomotor system programmes the orienting response on the basis of actual eye position, rather than on an accumulated estimate from intervening eye displacements.

Gaze orienting in dynamic visual double steps.

Visual stimuli are initially represented in a retinotopic reference frame. To maintain spatial accuracy of gaze (i.e., eye in space) despite intervening eye and head movements, the visual input could be combined with dynamic feedback about ongoing gaze shifts. Alternatively, target coordinates could be updated in advance by using the preprogrammed gaze-motor command ("predictive remapping"). So far, previous experiments have not dissociated these possibilities. Here we study whether the visuomotor system accounts for saccadic eye-head movements that occur during target presentation. In this case, the system has to deal with fast dynamic changes of the retinal input and with highly variable changes in relative eye and head movements that cannot be preprogrammed by the gaze control system. We performed visual-visual double-step experiments in which a brief (50-ms) stimulus was presented during a saccadic eye-head gaze shift toward a previously flashed visual target. Our results show that gaze shifts remain accurate under these dynamic conditions, even for stimuli presented near saccade onset, and that eyes and head are driven in oculocentric and craniocentric coordinates, respectively. These results cannot be explained by a predictive remapping scheme. We propose that the visuomotor system adequately processes dynamic changes in visual input that result from self-initiated gaze shifts, to construct a stable representation of visual targets in an absolute, supraretinal (e.g., world) reference frame. Predictive remapping may subserve transsaccadic integration, thus enabling perception of a stable visual scene despite eye movements, whereas dynamic feedback ensures accurate actions (e.g., eye-head orienting) to a selected goal.

Dynamic sound localization during rapid eye-head gaze shifts.

Human sound localization relies on implicit head-centered acoustic cues. However, to create a stable and accurate representation of sounds despite intervening head movements, the acoustic input should be continuously combined with feedback signals about changes in head orientation. Alternatively, the auditory target coordinates could be updated in advance by using either the preprogrammed gaze-motor command or the sensory target coordinates to which the intervening gaze shift is made ("predictive remapping"). So far, previous experiments cannot dissociate these alternatives. Here, we study whether the auditory system compensates for ongoing saccadic eye and head movements in two dimensions that occur during target presentation. In this case, the system has to deal with dynamic changes of the acoustic cues as well as with rapid changes in relative eye and head orientation that cannot be preprogrammed by the audiomotor system. We performed visual-auditory double-step experiments in two dimensions in which a brief sound burst was presented while subjects made a saccadic eye-head gaze shift toward a previously flashed visual target. Our results show that localization responses under these dynamic conditions remain accurate. Multiple linear regression analysis revealed that the intervening eye and head movements are fully accounted for. Moreover, elevation response components were more accurate for longer-duration sounds (50 msec) than for extremely brief sounds (3 msec), for all localization conditions. Taken together, these results cannot be explained by a predictive remapping scheme. Rather, we conclude that the human auditory system adequately processes dynamically varying acoustic cues that result from self-initiated rapid head movements to construct a stable representation of the target in world coordinates. This signal is subsequently used to program accurate eye and head localization responses.