Robust Coding of Eye Position in Posterior Parietal Cortex despite Context-Dependent Tuning.

Neurons in posterior parietal cortex (PPC) encode many aspects of the sensory world (e.g., scene structure), the posture of the body, and plans for action. For a downstream computation, however, only some of these dimensions are relevant; the rest are "nuisance variables" because their influence on neural activity changes with sensory and behavioral context, potentially corrupting the read-out of relevant information. Here we show that a key postural variable for vision (eye position) is represented robustly in male macaque PPC across a range of contexts, although the tuning of single neurons depended strongly on context. Contexts were defined by different stages of a visually guided reaching task, including (1) a visually sparse epoch, (2) a visually rich epoch, (3) a "go" epoch in which the reach was cued, and (4) during the reach itself. Eye position was constant within trials but varied across trials in a 3 × 3 grid spanning 24° × 24°. Using demixed principal component analysis of neural spike-counts, we found that the subspace of the population response encoding eye position is orthogonal to that encoding task context. Accordingly, a context-naive (fixed-parameter) decoder was nevertheless able to estimate eye position reliably across contexts. Errors were small given the sample size (∼1.78°) and would likely be even smaller with larger populations. Moreover, they were comparable to that of decoders that were optimized for each context. Our results suggest that population codes in PPC shield encoded signals from crosstalk to support robust sensorimotor transformations across contexts.SIGNIFICANCE STATEMENT Neurons in posterior parietal cortex (PPC) which are sensitive to gaze direction are thought to play a key role in spatial perception and behavior (e.g., reaching, navigation), and provide a potential substrate for brain-controlled prosthetics. Many, however, change their tuning under different sensory and behavioral contexts, raising the prospect that they provide unreliable representations of egocentric space. Here, we analyze the structure of encoding dimensions for gaze direction and context in PPC during different stages of a visually guided reaching task. We use demixed dimensionality reduction and decoding techniques to show that the coding of gaze direction in PPC is mostly invariant to context. This suggests that PPC can provide reliable spatial information across sensory and behavioral contexts.

Spatial effects of shifting prisms on properties of posterior parietal cortex neurons.

The posterior parietal cortex contains neurons that respond to visual stimulation and motor behaviour. The objective of the current study was to test short-term adaptation in neurons in macaque area 7a and the dorsal prelunate during visually guided reaching using Fresnel prisms that displaced the visual field. The visual perturbation shifted the eye position and created a mismatch between perceived and actual reach location. Two non-human primates were trained to reach to visual targets before, during and after prism exposure while fixating the reach target in different locations. They were required to reach to the physical location of the reach target and not the perceived, displaced location. While behavioural adaptation to the prisms occurred within a few trials, the majority of neurons responded to the distortion either with substantial changes in spatial eye position tuning or changes in overall firing rate. These changes persisted even after prism removal. The spatial changes were not correlated with the direction of induced prism shift. The transformation of gain fields between conditions was estimated by calculating the translation and rotation in Euler angles. Rotations and translations of the horizontal and vertical spatial components occurred in a systematic manner for the population of neurons suggesting that the posterior parietal cortex retains a constant representation of the visual field remapping between experimental conditions.

Optical imaging of visually guided reaching in macaque posterior parietal cortex.

Sensorimotor transformation for reaching movements in primates requires a large network of visual, parietal, and frontal cortical areas. We performed intrinsic optical imaging over posterior parietal cortex including areas 7a and the dorsal perilunate in macaque monkeys during visually guided hand movements. Reaching was performed while foveating one of nine static reach targets; thus eye-position-varied concurrently with reach position. The hemodynamic reflectance signal was analyzed during specific phases of the task including pre-reach, reach, and touch epochs. The eye position maps changed substantially as the task progressed: First, direction of spatial tuning shifted from a weak preference close to the center to the lower eye positions in both cortical areas. Overall tuning strength was greater in area 7a. Second, strength of spatial tuning increased from the early pre-reach to the later touch epoch. These consistent temporal changes suggest that dynamic properties of the reflectance signal were modulated by task parameters. The peak amplitude and peak delay of the reflectance signal showed considerable differences between eye position but were similar between areas. Compared with a detection task using a lever response, the reach task yielded higher amplitudes and longer delays. These findings demonstrate a spatially tuned topographical representation for reaching in both areas and suggest a strong synergistic combination of various feedback signals that result in a spatially tuned amplification of the hemodynamic response in posterior parietal cortex.

Two-photon scanning microscopy of in vivo sensory responses of cortical neurons genetically encoded with a fluorescent voltage sensor in rat.

A fluorescent voltage sensor protein "Flare" was created from a Kv1.4 potassium channel with YFP situated to report voltage-induced conformational changes in vivo. The RNA virus Sindbis introduced Flare into neurons in the binocular region of visual cortex in rat. Injection sites were selected based on intrinsic optical imaging. Expression of Flare occurred in the cell bodies and dendritic processes. Neurons imaged in vivo using two-photon scanning microscopy typically revealed the soma best, discernable against the background labeling of the neuropil. Somatic fluorescence changes were correlated with flashed visual stimuli; however, averaging was essential to observe these changes. This study demonstrates that the genetic modification of single neurons to express a fluorescent voltage sensor can be used to assess neuronal activity in vivo.

Two-photon imaging of calcium in virally transfected striate cortical neurons of behaving monkey.

Two-photon scanning microscopy has advanced our understanding of neural signaling in non-mammalian species and mammals. Various developments are needed to perform two-photon scanning microscopy over prolonged periods in non-human primates performing a behavioral task. In striate cortex in two macaque monkeys, cortical neurons were transfected with a genetically encoded fluorescent calcium sensor, memTNXL, using AAV1 as a viral vector. By constructing an extremely rigid and stable apparatus holding both the two-photon scanning microscope and the monkey's head, single neurons were imaged at high magnification for prolonged periods with minimal motion artifacts for up to ten months. Structural images of single neurons were obtained at high magnification. Changes in calcium during visual stimulation were measured as the monkeys performed a fixation task. Overall, functional responses and orientation tuning curves were obtained in 18.8% of the 234 labeled and imaged neurons. This demonstrated that the two-photon scanning microscopy can be successfully obtained in behaving primates.

Neural representation during visually guided reaching in macaque posterior parietal cortex.

Visually guided hand movements in primates require an interconnected network of various cortical areas. Single unit firing rate from area 7a and dorsal prelunate (DP) neurons of macaque posterior parietal cortex (PPC) was recorded during reaching movements to targets at variable locations and under different eye position conditions. In the eye position-varied task, the reach target was always foveated; thus eye position varied with reach target location. In the retinal-varied task, the monkey reached to targets at variable retinotopic locations while eye position was kept constant in the center. Spatial tuning was examined with respect to temporal (task epoch) and contextual (task condition) aspects, and response fields were compared. The analysis showed distinct tuning types. The majority of neurons changed their gain field tuning and retinotopic tuning between different phases of the task. Between the onset of visual stimulation and the preparatory phase (before the go signal), about one half the neurons altered their firing rate significantly. Spatial response fields during preparation and initiation epochs were strongly influenced by the task condition (eye position varied vs. retinal varied), supporting a strong role of eye position during visually guided reaching. DP neurons, classically considered visual, showed reach related modulation similar to 7a neurons. This study shows that both area 7a and DP are modulated during reaching behavior in primates. The various tuning types in both areas suggest distinct populations recruiting different circuits during visually guided reaching.

Attentional modulation of receptive field structure in area 7a of the behaving monkey.

Spatial attention modulates the activity of inferior parietal neurons. A statistically rigorous approach to classical retinotopic mapping was used to quantify the receptive fields of area 7a neurons under 2 attentional conditions. Measurements were made with retinal stimulation held constant and the locus of attention manipulated covertly. Both tasks required central fixation but differed in the locus of covert attention (either on the center fixation point or on a peripheral square target in one of 25 locations). The neuron's identity over the recording session was confirmed using chaos theory to characterize unique temporal patterns. Sixty-six percent of the neurons changed prestimulus activity based on task state. Retinotopic mapping showed no evidence for foveal sparing. Attentional factors influenced visual responses for approximately 30% of the neurons. Two types of modulation were equally observed. One group of cells had a multiplicative scaling of response, with equal instances of enhancement and suppression. A second group of cells had a complex interaction of visual and attentional signals, such that spatial tuning was subject to a nonlinear modulation across the visual field based on attentional constraints. These 2 cell groups may have different roles in the shift of attention preceding motor behaviors and may underlie shifts in parietal retinotopic maps observed with intrinsic optical imaging.

Functional architecture of retinotopy in visual association cortex of behaving monkey.

While the receptive field properties of single neurons in the inferior parietal cortex have been quantitatively described from numerous electrical measurements, the visual topography of area 7a and the adjacent dorsal prelunate area (DP) remains unknown. This lacuna may be a technical byproduct of the difficulty of reconstructing tens to hundreds of penetrations, or may be the result of varying functional retinotopic architectures. Intrinsic optical imaging, performed in behaving monkey for extended periods of time, was used to evaluate retinotopy simultaneously at multiple positions across the cortical surface. As electrical recordings through an implanted artificial dura are difficult, the measurement and quantification of retinotopy with long-term recordings was validated by imaging early visual cortex (areas V1 and V2). Retinotopic topography was found in each of the three other areas studied within a single day's experiment. However, the ventral portion of DP (DPv) had a retinotopic topography that varied from day to day, while the more dorsal aspects (DPd) exhibited consistent retinotopy. This suggests that the dorsal prelunate gyrus may consist of more than one visual area. The retinotopy of area 7a also varied from day to day. Possible mechanisms for this variability across days are discussed as well as its impact upon our understanding of the representation of extrapersonal space in the inferior parietal cortex.

Stereoscopic illusory contours--cortical neuron responses and human perception.

In human perception, figure-ground segregation suggests that stereoscopic cues are grouped over wide areas of the visual field. For example, two abutting rectangles of equal luminance and size are seen as a uniform surface when presented at the same depth, but appear as two surfaces separated by an illusory contour and a step in depth when presented with different retinal disparities. Here, we describe neurons in the monkey visual cortex that signal such illusory contours and can be selective for certain figure-ground directions that human observers perceive at these contours. The results suggest that these neurons group stereoscopic cues over distances up to 8 degrees. In addition, we compare these results with human perception and show that the mean stimulus parameters required by these neurons also induce optimal percepts of illusory contours in human observers.

A chamber and artificial dura method for long-term optical imaging in the monkey.

Optical imaging over extended periods of time in non-human primates presents serious challenges because the dura mater must be removed to expose the cortical surface. We present a novel nylon imaging chamber with a transparent artificial dura implant, which allows repeated, long-term optical recordings from the cortex. The cylinder of the chamber is inserted into a cranial trephination and held in place with a minimum of screws and acrylic cement. A round patch of artificial dura with a perpendicular wall protects the cortical surface and slows re-growth of dural tissue within the chamber. A cap, manufactured from the same material as the cylinder, is screwed into the chamber and seals it completely. Over a period of 1-4 months, the chamber required a minimum of maintenance and stayed infection-free without local antibiotic application. We repeatedly performed optical imaging in the same animal with the advantages of shortened preparation time. To permit precise alignment and comparison of maps obtained from different imaging sessions, we developed a program that calculated a 2-dimensional spatial transformation between maps of different magnifications, translations, and distortions. We suggest that these methods provide a practical solution to long-term optical imaging in the anesthetized or alert monkey. The exclusive use of non-metallic materials offers the benefit of a lighter and more compact implant, and the possibility to perform MRI scans after chamber implantation.