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Eye position signals in the dorsal pulvinar during fixation and goal-directed saccades
Abstract
Most sensorimotor cortical areas contain eye position information thought to ensure perceptual stability across saccades and underlie spatial transformations supporting goal-directed actions. One pathway by which eye position signals could be relayed to and across cortical areas is via the dorsal pulvinar. Several studies demonstrated saccade-related activity in the dorsal pulvinar and we have recently shown that many neurons exhibit post-saccadic spatial preference long after the saccade execution. In addition, dorsal pulvinar lesions lead to gaze-holding deficits expressed as nystagmus or ipsilesional gaze bias, prompting us to investigate the effects of eye position. We tested three starting eye positions (−15°/0°/15°) in monkeys performing a visually-cued memory saccade task. We found two main types of gaze dependence. First, ∼50% of neurons showed an effect of static gaze direction during initial and post-saccadic fixation. Eccentric gaze preference was more common than straight ahead. Some of these neurons were not visually-responsive and might be primarily signaling the position of the eyes in the orbit, or coding foveal targets in a head/body/world-centered reference frame. Second, many neurons showed a combination of eye-centered and gaze-dependent modulation of visual, memory and saccadic responses to a peripheral target. A small subset showed effects consistent with eye position-dependent gain modulation. Analysis of reference frames across task epochs from visual cue to post-saccadic target fixation indicated a transition from predominantly eye-centered encoding to representation of final gaze or foveated locations in non-retinocentric coordinates. These results show that dorsal pulvinar neurons carry information about eye position, which could contribute to steady gaze during postural changes and to reference frame transformations for visually-guided eye and limb movements.
New & Noteworthy
Work on the pulvinar focused on eye-centered visuospatial representations, but position of the eyes in the orbit is also an important factor that needs to be taken into account during spatial orienting and goal-directed reaching. Here we show that dorsal pulvinar neurons are influenced by eye position. Gaze direction modulated ongoing firing during stable fixation, as well as visual and saccade responses to peripheral targets, suggesting involvement of the dorsal pulvinar in spatial coordinate transformations.
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Spatial attention is discontinuous, sampling behaviorally relevant locations in theta-rhythmic cycles (3–6 Hz). Underlying this rhythmic sampling are intrinsic theta oscillations in frontal and parietal cortices that provide a clocking mechanism for two alternating attentional states that are associated with either engagement at the presently attended location (and enhanced perceptual sensitivity) or disengagement (and diminished perceptual sensitivity). It has remained unclear, however, how these theta-dependent states are coordinated across the large-scale network that directs spatial attention. The pulvinar is a candidate for such coordination, having been previously shown to regulate cortical activity. Here, we examined pulvino-cortical interactions during theta-rhythmic sampling by simultaneously recording from macaque frontal eye fields (FEF), lateral intraparietal area (LIP), and pulvinar. Neural activity propagated from pulvinar to cortex during periods of engagement, and from cortex to pulvinar during periods of disengagement. A rhythmic reweighting of pulvino-cortical interactions thus defines functional dissociations in the attention network.
The pulvinar influences communication between cortical areas. We use fMRI to characterize the functional organization of the human pulvinar and its coupling with cortex. The ventral pulvinar is sensitive to spatial position and moment-to-moment transitions in visual statistics, but also differentiates visual categories such as faces and scenes. The dorsal pulvinar is modulated by spatial attention and is sensitive to the temporal structure of visual input. Cortical areas are functionally coupled with discrete pulvinar regions. The spatial organization of this coupling reflects the functional specializations and anatomical distances between cortical areas. The ventral pulvinar is functionally coupled with occipital-temporal cortices. The dorsal pulvinar is functionally coupled with frontal, parietal, and cingulate cortices, including the attention, default mode, and human-specific tool networks. These differences mirror the principles governing cortical organization of dorsal and ventral cortical visual streams. These results provide a functional framework for how the pulvinar facilitates and regulates cortical processing.
Expansion of the dorsal pulvinar in humans and its anatomical connectivity suggests its involvement in higher-order cognitive and visuomotor functions. We investigated visuomotor performance in a 31 year old patient with a lesion centered on the medial portion of the dorsal pulvinar (left > right) due to an atypical Sarcoidosis manifestation. Unlike lesions with a vascular etiology, the lesion of M.B. did not include primary sensory or motor thalamic nuclei. Thus, this patient gave us the exceedingly rare opportunity to study the contribution of the dorsal pulvinar to visuomotor behavior in a human without confounding losses in primary sensory or motor domains. We investigated reaching, saccade and visual decision making performance. Patient data in each task was compared to at least seven age matched healthy controls. While saccades were hypometric towards both hemifields, the patient did not show any spatial choice or perceptual deficits. At the same time, he exhibited reach and grasp difficulties, which shared features with both, parietal and cerebellar damage. In particular, he had problems to form a precision grip and exhibited reach deficits expressed in decreased accuracy, delayed initiation and prolonged movement durations. Reach deficits were similar in foveal and extrafoveal viewing conditions and in both visual hemifields but were stronger with the right hand. These results suggest that dorsal pulvinar function in humans goes beyond its subscribed role in visual cognition and is critical for the programming of voluntary actions with the hands.
Neurosarcoidosis is a rare disease that occurs as a serious complication in about 2-26% of cases with a systemic sarcoidosis. It typically manifests as cranial neuropathy, peripheral neuropathy or meningitis, often accompanied by headache but also affects cortical, subcortical and spinal cord structures. [1]
Ocular fixation is a dynamic process that is actively controlled by many of the same brain structures involved in the control of eye movements, including the superior colliculus, cerebellum and reticular formation. In this article, we review several aspects of this active control. First, the decision to move the eyes not only depends on target-related signals from the peripheral visual field, but also on signals from the currently fixated target at the fovea, and involves mechanisms that are shared between saccades and smooth pursuit. Second, eye position during fixation is actively controlled and depends on bilateral activity in the superior colliculi and medio-posterior cerebellum; disruption of activity in these circuits causes systematic deviations in eye position during both fixation and smooth pursuit eye movements. Third, the eyes are not completely still during fixation but make continuous miniature movements, including ocular drift and microsaccades, which are controlled by the same neuronal mechanisms that generate larger saccades. Finally, fixational eye movements have large effects on visual perception. Ocular drift transforms the visual input in ways that increase spatial acuity; microsaccades not only improve vision by relocating the fovea but also cause momentary changes in vision analogous to those caused by larger saccades.
This article is part of the themed issue ‘Movement suppression: brain mechanisms for stopping and stillness’.
Significance statement:
Despite a recent surge of interest, the core function of the pulvinar, the largest thalamic complex in primates, remains elusive. This understanding is crucial given the central role of the pulvinar in current theories of integrative brain functions supporting cognition and goal-directed behaviors, but electrophysiological and causal interference studies of dorsal pulvinar are rare. Building on our previous studies that pharmacologically suppressed dorsal pulvinar activity for several hours, here we used transient electrical microstimulation at different periods while monkeys performed instructed and choice eye movement tasks, to determine time-specific contributions of pulvinar to saccade generation and decision-making. We show that stimulation effects depend on timing and behavioral state, and that effects on choices can be dissociated from motor effects.
The frontal eye fields (FEFs) participate in both working memory and sensorimotor transformations for saccades, but their role in integrating these functions through time remains unclear. Here, we tracked FEF spatial codes through time using a novel analytic method applied to the classic memory-delay saccade task. Three-dimensional recordings of head-unrestrained gaze shifts were made in two monkeys trained to make gaze shifts toward briefly flashed targets after a variable delay (450-1500 ms). A preliminary analysis of visual and motor response fields in 74 FEF neurons eliminated most potential models for spatial coding at the neuron population level, as in our previous study (Sajad et al., 2015). We then focused on the spatiotemporal transition from an eye-centered target code (T; preferred in the visual response) to an eye-centered intended gaze position code (G; preferred in the movement response) during the memory delay interval. We treated neural population codes as a continuous spatiotemporal variable by dividing the space spanning T and G into intermediate T–G models and dividing the task into discrete steps through time. We found that FEF delay activity, especially in visuomovement cells, progressively transitions from T through intermediate T–G codes that approach, but do not reach, G. This was followed by a final discrete transition from these intermediate T–G delay codes to a “pure” G code in movement cells without delay activity. These results demonstrate that FEF activity undergoes a series of sensory–memory–motor transformations, including a dynamically evolving spatial memory signal and an imperfect memory-to-motor transformation.
The pulvinar is the largest thalamic nucleus in primates and one of the most mysterious. Endeavors to understand its role in vision have focused on its abundant connections with the visual cortex. While its connectivity mapping in the cortex displays a broad topographic organization, its projections are also marked by considerable convergence and divergence. As a result, the pulvinar is often regarded as a central forebrain hub. Moreover, new evidence suggests that its comparatively modest input from structures such as the retina and superior colliculus may critically shape the functional organization of the visual cortex, particularly during early development. Here we review recent studies that cast fresh light on how the many convergent pathways through the pulvinar contribute to visual cognition.
Although neuronal responses in behaving monkeys are typically studied while the monkey fixates straight ahead, it is known that eye position modulates responses of visual neurons. The modulation has been found to enhance neuronal responses when the receptive field is placed in the straight-ahead position for neurons receiving input from the peripheral but not the central retina. We studied the effect of eye position on the responses of V1 complex cells receiving input from the central retina (1.1-5.7° eccentricity) while minimizing the effect of fixational eye movements. Contrast response functions were obtained separately with drifting light and dark bars. Data were fit with the Naka-Rushton equation: r(c)=Rmax×c/(c+c50)+s, where r(c) is mean spike rate at contrast c, Rmax is the maximum response, c50 is the contrast that elicits half of Rmax, and s is the spontaneous activity. Contrast sensitivity as measured by c50 was not affected by eye position. For dark bars, there was a statistically significant decline in the normalized Rmax with increasing deviation from straight ahead. Data for bright bars showed a similar trend with a less rapid decline. Our results indicate that neurons representing the central retina show a bias for the straight-ahead position resulting from modulation of the response gain without an accompanying modulation of contrast sensitivity. The modulation is especially obvious for dark stimuli, which might be useful for directing attention to hazardous situations such as dark holes or shadows concealing important objects (Supplement 1: Video Abstract, Supplemental digital content 1, http://links.lww.com/WNR/A295).
The Scalable Brain Atlas (SBA) is a collection of web services that provide unified access to a large collection of brain atlas templates for different species. Its main component is an atlas viewer that displays brain atlas data as a stack of slices in which stereotaxic coordinates and brain regions can be selected. These are subsequently used to launch web queries to resources that require coordinates or region names as input. It supports plugins which run inside the viewer and respond when a new slice, coordinate or region is selected. It contains 20 atlas templates in six species, and plugins to compute coordinate transformations, display anatomical connectivity and fiducial points, and retrieve properties, descriptions, definitions and 3d reconstructions of brain regions. The ambition of SBA is to provide a unified representation of all publicly available brain atlases directly in the web browser, while remaining a responsive and light weight resource that specializes in atlas comparisons, searches, coordinate transformations and interactive displays.
Electronic supplementary material
The online version of this article (doi:10.1007/s12021-014-9258-x) contains supplementary material, which is available to authorized users.
Eye-position signals (EPS) are found throughout the primate visual system and are thought to provide a mechanism for representing spatial locations in a manner that is robust to changes in eye position. It remains unknown, however, whether cortical EPS (also known as "gain fields") have the necessary spatial and temporal characteristics to fulfill their purported computational roles. To quantify these EPS, we combined single-unit recordings in four dorsal visual areas of behaving rhesus macaques (lateral intraparietal area, ventral intraparietal area, middle temporal area, and the medial superior temporal area) with likelihood-based population-decoding techniques. The decoders used knowledge of spiking statistics to estimate eye position during fixation from a set of observed spike counts across neurons. Importantly, these samples were short in duration (100 ms) and from individual trials to mimic the real-time estimation problem faced by the brain. The results suggest that cortical EPS provide an accurate and precise representation of eye position, albeit with unequal signal fidelity across brain areas and a modest underestimation of eye eccentricity. The underestimation of eye eccentricity predicted a pattern of mislocalization that matches the errors made by human observers. In addition, we found that eccentric eye positions were associated with enhanced precision relative to the primary eye position. This predicts that positions in visual space should be represented more reliably during eccentric gaze than while looking straight ahead. Together, these results suggest that cortical eye-position signals provide a useable head-centered representation of visual space on timescales that are compatible with the duration of a typical ocular fixation.
The ability to selectively process visual inputs and to decide between multiple movement options in an adaptive manner is critical for survival. Such decisions are known to be influenced by factors such as reward expectation and visual saliency. The dorsal pulvinar connects to a multitude of cortical areas that are involved in visuospatial memory and integrate information about upcoming eye movements with expected reward values. However, it is unclear whether the dorsal pulvinar is critically involved in spatial memory and reward-based oculomotor decision behavior. To examine this, we reversibly inactivated the dorsal portion of the pulvinar while monkeys performed a delayed memory saccade task that included choices between equally or unequally rewarded options. Pulvinar inactivation resulted in a delay of saccade initiation toward memorized contralesional targets but did not affect spatial memory. Furthermore, pulvinar inactivation caused a pronounced choice bias toward the ipsilesional hemifield when the reward value in the two hemifields was equal. However, this choice bias could be alleviated by placing a high reward target into the contralesional hemifield. The bias was less affected by the manipulation of relative visual saliency between the two competing targets. These results suggest that the dorsal pulvinar is involved in determining the behavioral desirability of movement goals while being less critical for spatial memory and reward processing.
The INIA19 is a new, high-quality template for imaging-based studies of non-human primate brains, created from high-resolution, T(1)-weighted magnetic resonance (MR) images of 19 rhesus macaque (Macaca mulatta) animals. Combined with the comprehensive cortical and sub-cortical label map of the NeuroMaps atlas, the INIA19 is equally suitable for studies requiring both spatial normalization and atlas label propagation. Population-averaged template images are provided for both the brain and the whole head, to allow alignment of the atlas with both skull-stripped and unstripped data, and thus to facilitate its use for skull stripping of new images. This article describes the construction of the template using freely available software tools, as well as the template itself, which is being made available to the scientific community (http://nitrc.org/projects/inia19/).
The activity of thalamocortical neurons is primarily determined by giant excitatory terminals, called drivers. These afferents may arise from neocortex or from subcortical centers; however, their exact distribution, segregation, or putative absence in given thalamic nuclei are unknown. To unravel the nucleus-specific composition of drivers, we mapped the entire macaque thalamus using vesicular glutamate transporters 1 and 2 to label cortical and subcortical afferents, respectively. Large thalamic territories were innervated exclusively by either giant vGLUT2- or vGLUT1-positive boutons. Codistribution of drivers with different origin was not abundant. In several thalamic regions, no giant terminals of any type could be detected at light microscopic level. Electron microscopic observation of these territories revealed either the complete absence of large multisynaptic excitatory terminals (basal ganglia-recipient nuclei) or the presence of both vGLUT1- and vGLUT2-positive terminals, which were significantly smaller than their giant counterparts (intralaminar nuclei, medial pulvinar). In the basal ganglia-recipient thalamus, giant inhibitory terminals replaced the excitatory driver inputs. The pulvinar and the mediodorsal nucleus displayed subnuclear heterogeneity in their driver assemblies. These results show that distinct thalamic territories can be under pure subcortical or cortical control; however, there is significant variability in the composition of major excitatory inputs in several thalamic regions. Because thalamic information transfer depends on the origin and complexity of the excitatory inputs, this suggests that the computations performed by individual thalamic regions display considerable variability. Finally, the map of driver distribution may help to resolve the morphological basis of human diseases involving different parts of the thalamus.
Increasing evidence has implicated the cerebellum in providing forward models of motor plants predicting the sensory consequences of actions. Assuming that cerebellar input to the cerebral cortex contributes to the cerebro-cortical processing by adding forward model signals, we would expect to find projections emphasising motor and sensory cortical areas. However, this expectation is only partially met by studies of cerebello-cerebral connections. Here we show that by electrically stimulating the cerebellar output and imaging responses with functional magnetic resonance imaging, evoked blood oxygen level-dependant activity is observed not only in the classical cerebellar projection target, the primary motor cortex, but also in a number of additional areas in insular, parietal and occipital cortex, including sensory cortical representations. Further probing of the responses reveals a projection system that has been optimized to mediate fast and temporarily precise information. In conclusion, both the topography of the stimulation effects and its emphasis on temporal precision are in full accordance with the concept of cerebellar forward model information modulating cerebro-cortical processing.
Many visual areas of the primate brain contain signals related to the current position of the eyes in the orbit. These cortical eye-position signals are thought to underlie the transformation of retinal input-which changes with every eye movement-into a stable representation of visual space. For this coding scheme to work, such signals would need to be updated fast enough to keep up with the eye during normal exploratory behavior. We examined the dynamics of cortical eye-position signals in four dorsal visual areas of the macaque brain: the lateral and ventral intraparietal areas (LIP; VIP), the middle temporal area (MT), and the medial-superior temporal area (MST). We recorded extracellular activity of single neurons while the animal performed sequences of fixations and saccades in darkness.
The data show that eye-position signals are updated predictively, such that the representation shifts in the direction of a saccade prior to (<100 ms) the actual eye movement. Despite this early start, eye-position signals remain inaccurate until shortly after (10-150 ms) the eye movement. By using simulated behavioral experiments, we show that this brief misrepresentation of eye position provides a neural explanation for the psychophysical phenomenon of perisaccadic mislocalization, in which observers misperceive the positions of visual targets flashed around the time of saccadic eye movements.
Together, these results suggest that eye-position signals in the dorsal visual system are updated rapidly across eye movements and play a direct role in perceptual localization, even when they are erroneous.
Focusing gaze on a target helps stabilize upright posture. We investigated how this visual stabilization can be affected by observing a target presented under different gaze and viewing angles. In a series of 10-second trials, participants (N = 20, 29.3 ± 9 years of age) stood on a force plate and fixed their gaze on a figure presented on a screen at a distance of 1 m. The figure changed position (gaze angle: eye level (0°), 25° up or down), vertical body orientation (viewing angle: at eye level but rotated 25° as if leaning toward or away from the participant), or both (gaze and viewing angle: 25° up or down with the rotation equivalent of a natural visual perspective). Amplitude of participants' sagittal displacement, surface area, and angular position of the center of gravity (COG) were compared. Results showed decreased COG velocity and amplitude for up and down gaze angles. Changes in viewing angles resulted in altered body alignment and increased amplitude of COG displacement. No significant changes in postural stability were observed when both gaze and viewing angles were altered. Results suggest that both the gaze angle and viewing perspective may be essential variables of the visuomotor system modulating postural responses.
Spatial perception, the localization of stimuli in space, can rely on visual reference stimuli or on egocentric factors such as a stimulus position relative to eye gaze. In total darkness, only an egocentric reference frame provides sufficient information. When stimuli are briefly flashed around saccades, the localization error reveals potential mechanisms of updating such reference frames as described in several theories and computational models. Recent novel experimental evidence, however, showed that the maximum amount of mislocalization does not scale linearly with saccade amplitude but rather stays below 13° even for long saccades, which is different from predicted by present models. We propose a new model of perisaccadic mislocalization in complete darkness to account for this observation. According to this model, mislocalization arises not on the motor side by comparing a retinal position signal with an extraretinal eye position related signal but by updating stimulus position in visual areas through a combination of proprioceptive eye position and corollary discharge. Simulations with realistic input signals and temporal dynamics show that both signals together are used for spatial updating and in turn bring about perisaccadic mislocalization.
Lesions in the motor thalamus can cause deficits in somatic movements. However, the involvement of the thalamus in the generation of eye movements has only recently been elucidated. In this article, we review recent advances into the role of the thalamus in eye movements. Anatomically, the anterior group of the intralaminar nuclei and paralaminar portion of the ventrolateral, ventroanterior and mediodorsal nuclei of the thalamus send massive projections to the frontal eye field and supplementary eye field. In addition, these parts of the thalamus, collectively known as the 'oculomotor thalamus', receive inputs from the cerebellum, the basal ganglia and virtually all stages of the saccade-generating pathways in the brainstem. In their pioneering work in the 1980s, Schlag and Schlag-Rey found a variety of eye movement-related neurons in the oculomotor thalamus, and proposed that this region might constitute a 'central controller' playing a role in monitoring eye movements and generating self-paced saccades. This hypothesis has been evaluated by recent experiments in non-human primates and by clinical observations of subjects with thalamic lesions. In addition, several recent studies have also addressed the involvement of the oculomotor thalamus in the generation of anti-saccades and the selection of targets for saccades. These studies have revealed the impact of subcortical signals on the higher-order cortical processing underlying saccades, and suggest the possibility of future studies using the oculomotor system as a model to explore the neural mechanisms of global cortico-subcortical loops and the neural basis of a local network between the thalamus and cortex.
The planning and control of sensory-guided movements requires the integration of multiple sensory streams. Although the information conveyed by different sensory modalities is often overlapping, the shared information is represented differently across modalities during the early stages of cortical processing. We ask how these diverse sensory signals are represented in multimodal sensorimotor areas of cortex in macaque monkeys. Although a common modality-independent representation might facilitate downstream readout, previous studies have found that modality-specific representations in multimodal cortex reflect upstream spatial representations. For example, visual signals have a more eye-centered representation. We recorded neural activity from two parietal areas involved in reach planning, area 5 and the medial intraparietal area (MIP), as animals reached to visual, combined visual and proprioceptive, and proprioceptive targets while fixing their gaze on another location. In contrast to other multimodal cortical areas, the same spatial representations are used to represent visual and proprioceptive signals in both area 5 and MIP. However, these representations are heterogeneous. Although we observed a posterior-to-anterior gradient in population responses in parietal cortex, from more eye-centered to more hand- or body-centered representations, we do not observe the simple and discrete reference frame representations suggested by studies that focused on identifying the "best-match" reference frame for a given cortical area. In summary, we find modality-independent representations of spatial information in parietal cortex, although these representations are complex and heterogeneous.
A proprioceptive representation of eye position exists in area 3a of primate somatosensory cortex (Wang X, Zhang M, Cohen IS, Goldberg ME. Nat Neurosci 10: 640-646, 2007). This eye position signal is consistent with a fusimotor response (Taylor A, Durbaba R, Ellaway PH, Rawlinson S. J Physiol 571: 711-723, 2006) and has two components during a visually guided saccade task: a short-latency phasic response followed by a tonic response. While the early phasic response can be excitatory or inhibitory, it does not accurately reflect the eye's orbital position. The late tonic response appears to carry the proprioceptive eye position signal, but it is not clear when this component emerges and whether the onset of this signal is reliable. To test the temporal dynamics of the tonic proprioceptive signal, we used an oculomotor smooth pursuit task in which saccadic eye movements and phasic proprioceptive responses are suppressed. Our results show that the tonic proprioceptive eye position signal consistently lags the actual eye position in the orbit by ~60 ms under a variety of eye movement conditions. To confirm the proprioceptive nature of this signal, we also studied the responses of neurons in a vestibuloocular reflex (VOR) task in which the direction of gaze was held constant; response profiles and delay times were similar in this task, suggesting that this signal does not represent angle of gaze and does not receive visual or vestibular inputs. The length of the delay suggests that the proprioceptive eye position signal is unlikely to be used for online visual processing for action, although it could be used to calibrate an efference copy signal.
How our vision remains stable in spite of the interruptions produced by saccadic eye movements has been a repeatedly revisited perceptual puzzle. The major hypothesis is that a corollary discharge (CD) or efference copy signal provides information that the eye has moved, and this information is used to compensate for the motion. There has been progress in the search for neuronal correlates of such a CD in the monkey brain, the best animal model of the human visual system. In this article, we briefly summarize the evidence for a CD pathway to frontal cortex, and then consider four questions on the relation of neuronal mechanisms in the monkey brain to stable visual perception. First, how can we determine whether the neuronal activity is related to stable visual perception? Second, is the activity a possible neuronal correlate of the proposed transsaccadic memory hypothesis of visual stability? Third, are the neuronal mechanisms modified by visual attention and does our perceived visual stability actually result from neuronal mechanisms related primarily to the central visual field? Fourth, does the pathway from superior colliculus through the pulvinar nucleus to visual cortex contribute to visual stability through suppression of the visual blur produced by saccades?
We previously established a functional pathway extending from the superficial layers of the superior colliculus (SC) through the inferior pulvinar (PI) to cortical area MT in the primate (Macaca mulatta). Here, we characterized the signals that this pathway conveys to cortex by recording from pulvinar neurons that we identified by microstimulation as receiving input from SC and/or projecting to MT. The basic properties of these ascending-path PI neurons resembled those of SC visual neurons. Namely, they had brisk responses to spots of light, inhibitory surrounds, and relatively large receptive fields that increased with eccentricity, as well as minimal presaccadic activity. Beyond these basic properties, there were two salient results regarding the modulatory and motion signals conveyed by this ascending pathway. First, the PI neurons appeared to convey only a subset of the modulations found in the SC: they exhibited saccadic suppression, the inhibition of activity at the time of the saccade, but did not clearly show the attentional enhancement of the visual response seen in SC. Second, directional selectivity was minimal in PI neurons belonging to the ascending path but was significantly more prominent in PI neurons receiving input from MT. This finding casts doubt on earlier assumptions that PI provides directionally selective signals to MT and instead suggests that PI derives its selectivity from MT. The identification of this pathway and its transmitted activity establishes the first functional pathway from brainstem to cortex through pulvinar and makes it possible to examine its contribution to cortical visual processing, perception, and action.
The coordinated movement of the eyes and hands under visual guidance is an essential part of goal-directed behavior. Several cortical areas known to be involved in this process exchange projections with the dorsal aspect of the thalamic pulvinar nucleus, suggesting that this structure may play a central role in visuomotor behavior. Here, we used reversible inactivation to investigate the role of the dorsal pulvinar in the selection and execution of visually guided manual and saccadic eye movements in macaque monkeys. We found that unilateral pulvinar inactivation resulted in a spatial neglect syndrome accompanied by visuomotor deficits including optic ataxia during visually guided limb movements. Monkeys were severely disrupted in their visually guided behavior regarding space contralateral to the side of the injection in several domains, including the following: (1) target selection in both manual and oculomotor tasks, (2) limb usage in a manual retrieval task, and (3) spontaneous visual exploration. In addition, saccades into the ipsilesional field had abnormally short latencies and tended to overshoot their mark. None of the deficits could be explained by a visual field defect or primary motor deficit. These findings highlight the importance of the dorsal aspect of the pulvinar nucleus as a critical hub for spatial attention and selection of visually guided actions.
The sensorimotor transformations for visually guided reaching were originally thought to take place in a series of discrete transitions from one systematic frame of reference to the next with neurons coding location relative to the fixation position (gaze-centered) in occipital and posterior parietal areas, relative to the shoulder in dorsal premotor cortex, and in muscle- or joint-based coordinates in motor output neurons. Recent empirical and theoretical work has suggested that spatial encodings that use a range of idiosyncratic representations may increase computational power and flexibility. We now show that neurons in the parietal reach region use nonuniform and idiosyncratic frames of reference. We also show that these nonsystematic reference frames coexist with a systematic compound gain field that modulates activity proportional to the distance between the eyes and the hand. Thus, systematic and idiosyncratic signals may coexist within individual neurons.
Extraocular muscles contain two types of muscle fibers according to their innervation pattern: singly innervated muscle fibers (SIFs), similar to most skeletal muscle fibers, and multiply innervated muscle fibers (MIFs). Morphological studies have revealed that SIF and MIF motoneurons are segregated anatomically and receive different proportions of certain afferents, suggesting that while SIF motoneurons would participate in the whole repertoire of eye movements, MIF motoneurons would contribute only to slow eye movements and fixations. We have tested that proposal by performing single-unit recordings, in alert behaving cats, of electrophysiologically identified MIF and SIF motoneurons in the abducens nucleus. Our results show that both types of motoneuron discharge in relation to eye position and velocity, displaying a tonic-phasic firing pattern for different types of eye movement (saccades, vestibulo-ocular reflex, vergence) and gaze-holding. However, MIF motoneurons presented an overall reduced firing rate compared with SIF motoneurons, and had significantly lower recruitment threshold and also lower eye position and velocity sensitivities. Accordingly, MIF motoneurons could control mainly gaze in the off-direction, when less force is needed, whereas SIF motoneurons would contribute to increase muscle tension progressively toward the on-direction as more force is required. Anatomically, MIF and SIF motoneurons distributed intermingled within the abducens nucleus, with MIF motoneurons being smaller and having a lesser somatic synaptic coverage. Our data demonstrate the functional participation of both MIF and SIF motoneurons in fixations and slow and phasic eye movements, although their discharge properties indicate a functional segregation.
We accurately perceive the visual scene despite moving our eyes ~3 times per second, an ability that requires incorporation of eye position and retinal information. In this study, we assessed how this neural computation unfolds across three interconnected structures: frontal eye fields (FEF), intraparietal cortex (LIP/MIP), and the superior colliculus (SC). Single-unit activity was assessed in head-restrained monkeys performing visually guided saccades from different initial fixations. As previously shown, the receptive fields of most LIP/MIP neurons shifted to novel positions on the retina for each eye position, and these locations were not clearly related to each other in either eye- or head-centered coordinates (defined as hybrid coordinates). In contrast, the receptive fields of most SC neurons were stable in eye-centered coordinates. In FEF, visual signals were intermediate between those patterns: around 60% were eye-centered, whereas the remainder showed changes in receptive field location, boundaries, or responsiveness that rendered the response patterns hybrid or occasionally head-centered. These results suggest that FEF may act as a transitional step in an evolution of coordinates between LIP/MIP and SC. The persistence across cortical areas of mixed representations that do not provide unequivocal location labels in a consistent reference frame has implications for how these representations must be read out.
NEW & NOTEWORTHY How we perceive the world as stable using mobile retinas is poorly understood. We compared the stability of visual receptive fields across different fixation positions in three visuomotor regions. Irregular changes in receptive field position were ubiquitous in intraparietal cortex, evident but less common in the frontal eye fields, and negligible in the superior colliculus (SC), where receptive fields shifted reliably across fixations. Only the SC provides a stable labeled-line code for stimuli across saccades.
Cognition can be conceptualized as a set of algorithmic control functions whose real-time deployment determines how an organism stores and uses information to guide thought and action. A subset of these functions is required for goal-directed selection and amplification of sensory signals-broadly referred to as attention-and for its flexible control and its interaction with processes such as working memory and decision making. While the contribution of recurrent cortical microcircuits to cognition has been extensively studied, the role of the thalamus is just beginning to be elucidated. Here we highlight recent studies across rodents and primates showing how thalamus contributes to attentional control. In addition to high-fidelity information relay to or between cortical regions, thalamic circuits shift and sustain functional interactions within and across cortical areas. This thalamic process enables rapid coordination of spatially segregated cortical computations, thereby constructing task-relevant functional networks. Because such function may be critical for cognitive flexibility, clarifying its mechanisms will likely expand our basic understanding of cognitive control and its perturbation in disease.
Comparative studies have greatly contributed to our understanding of the organization and function of visual pathways of the brain, including that of humans. This comparative approach is a particularly useful tactic for studying the pulvinar nucleus, an enigmatic structure which comprises the largest territory of the human thalamus. This review focuses on the regions of the mouse pulvinar that receive input from the superior colliculus, and highlights similarities of the tectorecipient pulvinar identified across species. Open questions are discussed, as well as the potential contributions of the mouse model for endeavors to elucidate the function of the pulvinar nucleus.
Although interactions between the thalamus and cortex are critical for cognitive function, the exact contribution of the thalamus to these interactions remains unclear. Recent studies have shown diverse connectivity patterns across the thalamus, but whether this diversity translates to thalamic functions beyond relaying information to or between cortical regions is unknown. Here we show, by investigating the representation of two rules used to guide attention in the mouse prefrontal cortex (PFC), that the mediodorsal thalamus sustains these representations without relaying categorical information. Specifically, mediodorsal input amplifies local PFC connectivity, enabling rule-specific neural sequences to emerge and thereby maintain rule representations. Consistent with this notion, broadly enhancing PFC excitability diminishes rule specificity and behavioural performance, whereas enhancing mediodorsal excitability improves both. Overall, our results define a previously unknown principle in neuroscience; thalamic control of functional cortical connectivity. This function, which is dissociable from categorical information relay, indicates that the thalamus has a much broader role in cognition than previously thought.
There are multiple routes for visual information to reach the neocortex from the retina. The most well studied are those that pass through the lateral geniculate nucleus of the thalamus and arrive at cortex primarily within V1. From V1, visual information is then disseminated onto extrastriate cortical visual areas. However, there are other less well-studied pathways that bypass V1 and directly target extrastriate visual fields. These include pathways that route through the K layers of the lateral geniculate nucleus or the pulvinar, either by direct or indirect retinal input via the superior colliculus. The focus of this chapter is on these alternative visual pathways that project to extrastriate cortical areas, our current understanding of their possible evolution by reviewing comparative data across primates and their close relatives, and the insights these pathways could provide in our understanding of visual perception in the normal and injured brain.
The lateral posterior and pulvinar nuclei can be regarded as parts of a larger nuclear complex. One reason for bringing the two together is that undoubtedly equivalent nuclei have been regarded as part of the lateral posterior nucleus in some species and as parts of a pulvinar in others. The cat, for example, is customarily said to have a lateral posterior nucleus divided into three or more subnuclei and a single pulvinar nucleus (e.g., Berman and Jones, 1982). Monkeys, on the other hand, are usually said-to have a single lateral posterior nucleus and at least four pulvinar nuclei (e.g., Olszewski, 1952). Apart from this idiosyncrasy, however, the lateral posterior and pulvinar nuclei are closely associated topographically and have many morphological and connectional similarities.
As our eyes move, we have a strong percept that the world is stable in space and time; however, the signals in cortex coming from the retina change with each eye movement. It is not known how this changing input produces the visual percept we experience, although the predictive remapping of receptive fields has been described as a likely candidate. To explain how remapping accounts for perceptual stability, we examined responses of neurons in the lateral intraparietal area while animals performed a visual foraging task. When a stimulus was brought into the response field of a neuron that exhibited remapping, the onset of the postsaccadic representation occurred shortly after the saccade ends. Whenever a stimulus was taken out of the response field, the presaccadic representation abruptly ended shortly after the eyes stopped moving. In the 38% (20/52) of neurons that exhibited remapping, there was no more than 30 ms between the end of the presaccadic representation and the start of the postsaccadic representation and, in some neurons, and the population as a whole, it was continuous. We conclude by describing how this seamless shift from a presaccadic to postsaccadic representation could contribute to spatial stability and temporal continuity.
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In this review we discuss several aspects of eye movement control in which the cerebellum is thought to have a key role, but have been relatively ignored. We will focus on the mechanisms underlying certain forms of cerebellar nystagmus, as well as the contributions of the cerebellum to binocular alignment in healthy and diseased states. A contemporary review of our understanding provides a basis for directions of further inquiry to address some of the uncertainties regarding the contributions of the cerebellum to ocular motor control.Eye advance online publication, 14 November 2014; doi:10.1038/eye.2014.271.
During foveal reaching, the activity of neurons in the macaque medial posterior parietal area V6A is modulated by both gaze and arm direction. In the present work, we dissociated the position of gaze and reaching targets, and studied the neural activity of single V6A cells while the eyes and reaching targets were arranged in different spatial configurations (peripheral and foveal combinations). Target position influenced neural activity in all stages of the task, from visual presentation of target and movement planning, through reach execution and holding time. The majority of neurons preferred reaches directed toward peripheral targets, rather than foveal. Most neurons discharged in both premovement and action epochs. In most cases, reaching activity was tuned coherently across action planning and execution. When reaches were planned and executed in different eye/target configurations, multiple analyses revealed that few neurons coded reaching actions according to the absolute position of target, or to the position of target relative to the eye. The majority of cells responded to a combination of both these factors. These data suggest that V6A contains multiple representations of spatial information for reaching, consistent with a role of this area in forming cross-reference frame representations to be used by premotor cortex.
Gain fields, the eye-position modulation of visual responses, are thought to provide a mechanism by which the motor system can accurately calculate target position in space despite a constantly moving eye. Current gain-field models assume that the modulation of visual responses by eye position is accurate at all times, even around the time of a saccade. Here, we show that for at least 150 ms after a saccade, gain fields in the lateral intraparietal area (LIP) are unreliable. The majority of LIP cells with steady-state gain fields reflect the presaccadic eye position. The remainder of the cells have responses that cannot be predicted by their steady-state gain fields. Nonetheless, a monkey's oculomotor performance is accurate during this time. These results suggest that current models built upon a simple gain-field algorithm cannot be used to calculate the position of a target in space that flashes briefly after a saccade.
The parietothalamic projections have been shown to be heterogeneous and appear to be a reflection of the detailed architectonic parcellation of the parietal lobe. In the present study WGA‐HRP injections were placed in the different subdivisions of the posterior parietal cortex of the rhesus monkey to determine whether a similarly complex pattern also exists in the thalamocortical pathway. Additionally, in an attempt to determine whether there is an intranuclear specificity of projections from individual thalamic nuclei to different subdivisions of the parietal lobe, multiple retrograde fluorescent tracers were injected into the rostral to caudal sectors of the parietal lobe of the same animal. Different subdivisions of the parietal lobe appear to receive different sets of thalamic input. Thus the superior parietal lobule (SPL) projections are derived from more lateral regions in the thalamus, arising predominantly from the lateral posterior (LP) and pulvinar oralis (PO) nuclei, with additional contributions from the pulvinar lateralis (PL) and pulvinar medialis (PM) nuclei. The inferior parietal lobule (IPL), by contrast, receives its projections from more medial thalamic regions, its main thalamic input originating from PM, and aided by LP, PL, and PO. Both the SPL and IPL also receive projections from the mediodorsal (MD), ventroposterior, ventrolateral, intralaminar, and limbic nuclei, albeit from different components within these nuclei.
A topographical arrangement also exists in the thalamic projections to the rostral versus the caudal subdivisions of both the SPL and the IPL. Thus, in the SPL, the ventral posterolateral nucleus, pars oralis (VPLo), ventral lateral nucleus, pars oralis (VLo), and ventral lateral nucleus, pars medialis (VLm) project to rostral, whereas the PM and limbic nuclei, anteroventral (AV), and anteromedial (AM), project to area PGm on the medial convexity of the SPL. With respect to projections to the IPL, the ventral posteromedial (VPM) and PO nuclei project to rostral regions, whereas the limbic nuclei lateral dorsal (LD), AM and AV project only to the caudalmost area, Opt. A rostrocaudal difference is reflected also within certain nuclei (LP, PO, and PM) that project to the SPL or IPL. Thus rostral parietal subdivisions receive projections from ventral regions within these thalamic nuclei, whereas caudal parietal afferents arise from the dorsal parts of these nuclei. Intervening cortical levels receive projections from intermediate positions within the nuclei.
It therefore seems that the increasing architectonic and functional complexity as one moves from rostral to caudal in the SPL and IPL appear to be reflected in the thalamic afferents. More rostral areas relate to modality‐specific thalamic nuclei, whereas more caudal regions concerned with complex functions derive their input from multimodal and limbic nuclei.
Numerous studies in both monkey and human provided evidence for multisensory integration at high-level and low-level cortical areas. This chapter focuses on the anatomical pathways contributing to multisensory integration. We first describe the anatomical connections existing between different sensory cortical areas, briefly concerning the well-known connections between associative cortical areas and the more recently described connections targeting low-level sensory cortical areas. Then we focus on the description of the connections of the thalamus with different sensory and motor areas and their potential role in multisensory and sensorimotor integration. Finally, we discuss the several possibilities for the brain to integrate the environmental world with the different senses.
The pulvinar nuclei of the thalamus are proportionately larger in higher mammals, particularly in primates, and account for a quarter of the total mass. Traditionally, these nuclei have been divided into oral (somatosensory), superior and inferior (both visual) and medial (visual, multi-sensory) divisions. With reciprocal connections to vast areas of cerebral cortex, and input from the colliculus and retina, they occupy an analogous position in the extra-striate visual system to the lateral geniculate nucleus in the primary visual pathway, but deal with higher-order visual and visuomotor transduction. With a renewed recent interest in this thalamic nuclear collection, and growth in our knowledge of the cortex with which it communicates, perhaps the time is right to look to new dimensions in the pulvinar code.
Functional magnetic resonance imaging allows precise localization of brain regions specialized for different perceptual and higher cognitive functions. However, targeting these deep brain structures for electrophysiology still remains a challenging task. Here, we propose a novel framework for MRI-stereotactic registration and chamber placement for precise electrode guidance to recording sites defined in MRI space. The proposed "floating frame" approach can be used without usage of ear bars, greatly reducing pain and discomfort common in standard stereotactic surgeries. Custom pre-surgery planning software was developed to automatically solve the registration problem and report the set of parameters needed to position a stereotactic manipulator to reach a recording site along arbitrary, non-vertical trajectories. Furthermore, the software can automatically identify blood vessels and assist in finding safe trajectories to targets. Our approach was validated by targeting different regions in macaque monkeys and rats. We expect that our method will facilitate recording in new brain areas and provide a valuable tool for electrophysiologists.
The thalamus is classically viewed as passively relaying information to the cortex. However, there is growing evidence that the thalamus actively regulates information transmission to the cortex and between cortical areas using a variety of mechanisms, including the modulation of response magnitude, firing mode, and synchrony of neurons according to behavioral demands. We discuss how the visual thalamus contributes to attention, awareness, and visually guided actions, to present a general role for the thalamus in perception and cognition.
The cerebral cortex must have access to an eye position signal, as humans can report passive changes in eye position in total darkness, and visual responses in many cortical areas are modulated by eye position. The source of this signal is unknown. Here we demonstrate a representation of eye position in monkey primary somatosensory cortex, in the representation of the trigeminal nerve, near cells with a tactile representation of the contralateral brow. The neurons have eye position signals that increase monotonically with increasing orbital eccentricity from near the center of gaze, with directionally selectivity tuned in a Gaussian manner. All directions of eye position are represented in a single hemisphere. The signal is proprioceptive, because it can be obliterated by anesthetizing the contralateral orbit. It is not related to foveal or peripheral visual stimulation, and it represents the position of the eye in the head and not the angle of gaze in space.
The corticothalamic projection includes a main, modulatory projection from cortical layer VI terminating with small endings whereas a less numerous, driving projection from layer V forms giant endings. Such dual pattern of corticothalamic projections is well established in rodents and cats for many cortical areas. In non-human primates (monkeys), it has been reported for the primary sensory cortices (A1, V1, S1), the motor and premotor cortical areas and, in the parietal lobe, also for area 7. The present study aimed first at refining the cytoarchitecture parcellation of area 5 into the sub-areas PE and PEa and, second, establishing whether area 5 also exhibits this dual pattern of corticothalamic projection and what is its precise topography. To this aim, the tracer biotinylated dextran amine (BDA) was injected in area PE in one monkey and in area PEa in a second monkey. Area PE sends a major projection terminating with small endings to the thalamic lateral posterior nucleus (LP), ventral posterior lateral nucleus (VPL), medial pulvinar (PuM) and, but fewer, to ventral lateral posterior nucleus, dorsal division (VLpd), central lateral nucleus (CL) and center median nucleus (CM), whereas giant endings formed restricted terminal fields in LP, VPL and PuM. For area PEa, the corticothalamic projection formed by small endings was found mainly in LP, VPL, anterior pulvinar (PuA), lateral pulvinar (PuL), PuM and, to a lesser extent, in ventral posterior inferior nucleus (VPI), CL, mediodorsal nucleus (MD) and CM. Giant endings originating from area PEa formed restricted terminal fields in LP, VPL, PuA, PuM, MD and PuL. Furthermore, the origin of the thalamocortical projections to areas PE and PEa was established, exhibiting clusters of neurons in the same thalamic nuclei as above, in other words predominantly in the caudal thalamus. Via the giant endings CT projection, areas PE and PEa may send feedforward, transthalamic projections to remote cortical areas in the parietal, temporal and frontal lobes contributing to polysensory and sensorimotor integration, relevant for visual guidance of reaching movements for instance.
Active vision requires the integration of information coming from the retina with that generated internally within the brain, especially by saccadic eye movements. Just as visual information reaches cortex via the lateral geniculate nucleus of the thalamus, this internal information reaches the cerebral cortex through other higher-order nuclei of the thalamus. This review summarizes recent work on four of these thalamic nuclei. The first two pathways convey internal information about upcoming saccades (a corollary discharge) and probably contribute to the neuronal mechanisms that underlie stable visual perception. The second two pathways might contribute to the neuronal mechanisms underlying visual spatial attention in cortex and in the thalamus itself.
The pulvinar nucleus of the thalamus, with its connections to visual areas and to frontal and parietal oculomotor cortex, might serve as a nexus for integrating cortical control of voluntary eye movements with reflexive eye movements generated by the superior colliculus. To investigate this hypothesis, we tested five patients with a unilateral lesion of the pulvinar on the oculomotor capture paradigm. In this task, participants have to ignore a distractor item and make a saccade to a target in a visual search display. Results showed that the interference of the distractor was stronger when it was presented contralateral to their lesion compared to when it was presented in the ipsilesional visual field. These findings were confirmed by an additional single case experiment in which we measured saccade trajectory deviations as evoked by a single distractor. These results show that the pulvinar is involved in the successful influence of higher order signals (like our goals and intentions) on the guidance of our eye movements.
Gaze direction modulates the gain of neurons in most of the visual cortex, including the primary visual (V1) area. These gain modulations are thought to support a mechanism involved in the spatial localization of objects. In the present study, we show that part of them may reflect an additional function: enhancing the visual processing of the objects located straight ahead. Using single- and multiunit recordings in behaving macaques, we found that in peripheral V1, the gain of most neurons increases as their receptive fields (RF) are brought closer to the straight-ahead direction by changing the direction of gaze. No such tendency was observed in central V1, although the influence of gaze direction is similar in term of strength. This previously unknown organization of the gaze-related gain modulations might insure that objects located straight ahead still receive a privileged processing during eccentric fixation, reflecting the ecological importance of this particular egocentric direction.