A Wireless, Bidirectional Interface for <em>In Vivo</em> Recording and Stimulation of Neural Activity in Freely Behaving Rats

In vivo electrophysiology is a powerful technique to investigate the relationship between brain activity and behavior at a millisecond and micrometer ...

Philipps-Universität Marburg

In the posterior parietal cortex (PPC) of the macaque, spatial and motion signals arising from different sensory signals converge. One of the functional subregions within the PPC, the ventral intraparietal area (VIP), is thought to play an important role for the multisensory encoding of self- and object motion. In the present study we analysed the activity of area VIP neurons related to smooth pursuit eye movements (SPEMs). Fifty-three per cent of the neurons (123/234) were selective for the direction of the SPEMs. As evident from control experiments, activity observed during smooth eye movements was more closely related to extraretinal signals than visual parameters. In addition, we examined the sensitivity of area VIP neurons for the velocity of SPEMs. Seventy-four per cent of the pursuit-related neurons had a significant velocity tuning. There was a clear preference for high velocities. Eighty-six per cent of the neurons preferred the highest pursuit velocity (40 deg s-1) employed in our study. In everyday life, high pursuit velocities most frequently occur if the pursuit target is located in near-extrapersonal space, i.e. the action space of the head. Together with previous findings, the current results thus suggest that the information provided by VIP neurons may be used to encode motion in near-extrapersonal space and to guide and co-ordinate smooth eye and head movements within this very part of space.

Selectivity of macaque ventral intraparietal area (area VIP) for smooth pursuit eye movements.

Spatial perception is modulated by eye movements. During smooth pursuit, perceived locations are shifted in the direction of the eye movement. During active fixation, visual space is perceptually compressed towards the fovea. In our present study, we were interested to determine the time course of spatial localization during pursuit initiation, i.e. the transition period from fixation to steady-state pursuit. Human observers had to localize briefly flashed targets around the time of pursuit initiation. Our data clearly show that pursuit-like mislocalization starts well before the onset of the eye movement. Our results point towards corollary-discharge as neural source for the observed perceptual effect.

Spatial perception during pursuit initiation.

Sensitivity to luminance contrast is reduced just before and during saccades (saccadic suppression), whereas sensitivity to color contrast is unimpaired peri-saccadically and enhanced post-saccadically. The exact spatiotemporal map of these perceptual effects is as yet unknown. Here, we measured detection thresholds for briefly flashed Gaussian blobs modulated in either luminance or chromatic contrast, displayed at a range of eccentricities. Sensitivity to luminance contrast was reduced peri-saccadically by a scaling factor, which was almost constant across retinal space. Saccadic suppression followed a similar time course across all tested eccentricities and was maximal shortly after the saccade onset. Sensitivity to chromatic contrast was enhanced post-saccadically at all tested locations. The enhancement was not specifically linked to the execution of saccades, as it was also observed following a displacement of retinal images comparable to that caused by a saccade. We conclude that luminance and chromatic contrast sensitivities are subject to distinct modulations at the time of saccades, resulting from independent neural processes.

Spatiotemporal profile of peri-saccadic contrast sensitivity.

Stimuli flashed briefly around the time of saccadic eye movements are subject to complex distortions: compression of space and time; underestimate of numerosity. Here we show that saccadic distortions extend to abstract quantities, affecting the representation of symbolic numerical magnitude. Subjects consistently underestimated the results of rapidly computed mental additions and subtractions, when the operands were briefly displayed before a saccade. However, the recognition of the number symbols was unimpaired. These results are consistent with the hypothesis of a common, abstract metric encoding magnitude along multiple dimensions. They suggest that a surprising link exists between the preparation of action and the representation of abstract quantities.

Saccadic compression of symbolic numerical magnitude.

Many neurons in the macaque ventral intraparietal area (VIP) are multimodal, i.e., they respond not only to visual but also to tactile, auditory and vestibular stimulation. Anatomical studies have shown distinct projections between area VIP and a region of premotor cortex controlling head movements. A specific function of area VIP could be to guide movements in order to head for and/or to avoid objects in near extrapersonal space. This behavioral role would require a consistent representation of visual motion within 3-D space and enhanced activity for nearby motion signals. Accordingly, in our present study we investigated whether neurons in area VIP are sensitive to moving visual stimuli containing depth signals from horizontal disparity. We recorded single unit activity from area VIP of two awake behaving monkeys (Macaca mulatta) fixating a central target on a projection screen. Sensitivity of neurons to horizontal disparity was assessed by presenting large field moving images (random dot fields) stereoscopically to the two eyes by means of LCD shutter goggles synchronized with the stimulus computer. During an individual trial, stimuli had one of seven different disparity values ranging from 3° uncrossed- (far) to 3° crossed- (near) disparity in 1° steps. Stimuli moved at constant speed in all simulated depth planes. Different disparity values were presented across trials in pseudo-randomized order. Sixty-one percent of the motion sensitive cells had a statistically significant selectivity for the horizontal disparity of the stimulus (p < 0.05, distribution free ANOVA). Seventy-five percent of them preferred crossed-disparity values, i.e., moving stimuli in near space, with the highest mean activity for the nearest stimulus. At the population level, preferred direction of visual stimulus motion was not affected by horizontal disparity. Thus, our findings are in agreement with the behavioral role of area VIP in the representation of movement in near extrapersonal space.

Encoding of movement in near extrapersonal space in primate area VIP.

Rapid eye movements (saccades) induce visual misperceptions. A number of studies in recent years have investigated the spatio-temporal profiles of effects like saccadic suppression or perisaccadic mislocalization and revealed substantial functional similarities. Saccade induced chronostasis describes the subjective overestimation of stimulus duration when the stimulus onset falls within a saccade. In this study we aimed to functionally characterize saccade induced chronostasis in greater detail. Specifically we tested if chronostasis is influenced by or functionally related to saccadic suppression. In a first set of experiments, we measured the perceived duration of visual stimuli presented at different spatial positions as a function of presentation time relative to the saccade. We further compared perceived duration during saccades for isoluminant and luminant stimuli. Finally, we investigated whether or not saccade induced chronostasis is dependent on the execution of a saccade itself. We show that chronostasis occurs across the visual field with a clear spatio-temporal tuning. Furthermore, we report chronostasis during simulated saccades, indicating that spurious retinal motion induced by the saccade is a prime origin of the phenomenon.

Spatio-temporal topography of saccadic overestimation of time.

Self-motion through space generates a visual pattern called optic flow. It can be used to determine one's direction of self-motion (heading). Previous studies have already shown that this perceptual ability, which is of critical importance during everyday life, changes with age. In most of these studies subjects were asked to judge whether they appeared to be heading to the left or right of a target. Thresholds were found to increase continuously with age. In our current study, we were interested in absolute rather than relative heading judgments and in the question about a potential neural correlate of an age-related deterioration of heading perception. Two groups, older test subjects and younger controls, were shown optic flow stimuli in a virtual-reality setup. Visual stimuli simulated self-motion through a 3-D cloud of dots and subjects had to indicate their perceived heading direction after each trial. In different subsets of experiments we varied individually relevant stimulus parameters: presentation time, number of dots in the display, stereoscopic vs. non-stereoscopic stimulation, and motion coherence. We found decrements in heading performance with age for each stimulus parameter. In a final step we aimed to determine a putative neural basis of this behavioral decline. To this end we modified a neural network model which previously has proven to be capable of reproduce and predict certain aspects of heading perception. We show that the observed data can be modeled by implementing an age related neuronal cell loss in this neural network. We conclude that a continuous decline of certain aspects of motion perception, among them heading, might be based on an age-related progressive loss of groups of neurons being activated by visual motion.

Self-motion perception in the elderly.

The SNARC (spatial numerical association of response codes) effect, indicating that subjects react faster to the left for small numbers and to the right for large numbers, is used as evidence for the idea that humans use space to organize number representations. Previous studies compared the SNARC effect across sensory modalities within participants and concluded modality independence. So far, it is unknown what sensory-to-motor mappings are involved in generating the SNARC effect and whether these mappings are identical for different effectors within subjects. Hence, we tested whether the SNARC effect is effector specific. Participants performed an auditory parity judgment task and responded with three different effectors: finger (button release), eyes (saccades), and arm (pointing). The SNARC effect occurred in each effector but varied in strength across the effectors. Across subjects, we found a significant correlation of SNARC strength for finger and arm responses suggesting the use of a shared sensory-to-motor mapping. SNARC strength did not correlate, however, between finger and eyes or arm and eyes. An additional statistical analysis based on conditional probabilities provided further evidence for SNARC-effector specificity. Taken together, our results suggest that the sensory-to-motor mapping is not as tight as it would be expected if the SNARC effect was effector independent.

SNARC Effect in Different Effectors.

Eye movements are essential to primate vision but introduce potentially disruptive displacements of the retinal image. To maintain stable vision, the brain is thought to rely on neurons that carry both visual signals and information about the current direction of gaze in their firing rates. We have shown previously that these neurons provide an accurate representation of eye position during fixation, but whether they are updated fast enough during saccadic eye movements to support real-time vision remains controversial. Here we show that not only do these neurons carry a fast and accurate eye-position signal, but also that they support in parallel a range of time-lagged variants, including predictive and post dictive signals. We recorded extracellular activity in four areas of the macaque dorsal visual cortex during a saccade task, including the lateral and ventral intraparietal areas (LIP, VIP), and the middle temporal (MT) and medial superior temporal (MST) areas. As reported previously, neurons showed tonic eye-position-related activity during fixation. In addition, they showed a variety of transient changes in activity around the time of saccades, including relative suppression, enhancement, and pre-saccadic bursts for one saccade direction over another. We show that a hypothetical neuron that pools this rich population activity through a weighted sum can produce an output that mimics the true spatiotemporal dynamics of the eye. Further, with different pooling weights, this downstream eye position signal (EPS) could be updated long before (<100 ms) or after (<200 ms) an eye movement. The results suggest a flexible coding scheme in which downstream computations have access to past, current, and future eye positions simultaneously, providing a basis for visual stability and delay-free visually-guided behavior.

The Dorsal Visual System Predicts Future and Remembers Past Eye Position.

Primates perform saccadic eye movements in order to bring the image of an interesting target onto the fovea. Compared to stationary targets, saccades toward moving targets are computationally more demanding since the oculomotor system must use speed and direction information about the target as well as knowledge about its own processing latency to program an adequate, predictive saccade vector. In monkeys, different brain regions have been implicated in the control of voluntary saccades, among them the lateral intraparietal area (LIP). Here we asked, if activity in area LIP reflects the distance between fovea and saccade target, or the amplitude of an upcoming saccade, or both. We recorded single unit activity in area LIP of two macaque monkeys. First, we determined for each neuron its preferred saccade direction. Then, monkeys performed visually guided saccades along the preferred direction toward either stationary or moving targets in pseudo-randomized order. LIP population activity allowed to decode both, the distance between fovea and saccade target as well as the size of an upcoming saccade. Previous work has shown comparable results for saccade direction (Graf and Andersen, 2014a,b). Hence, LIP population activity allows to predict any two-dimensional saccade vector. Functional equivalents of macaque area LIP have been identified in humans. Accordingly, our results provide further support for the concept of activity from area LIP as neural basis for the control of an oculomotor brain-machine interface.

Decoding Target Distance and Saccade Amplitude from Population Activity in the Macaque Lateral Intraparietal Area (LIP).

The existence of an association between numbers and space is known for a long time. The most prominent demonstration of this relationship is the spatial numerical association of response codes (SNARC) effect, describing the fact that participants' reaction times are shorter with the left hand for small numbers and with the right hand for large numbers, when being asked to judge the parity of a number (Dehaene et al., J. Exp. Psychol., 122, 371-396, 1993). The SNARC effect is commonly seen as support for the concept of a mental number line, i.e. a mentally conceived line where small numbers are represented more on the left and large numbers are represented more on the right. The SNARC effect has been demonstrated for all three cardinal axes and recently a transverse SNARC plane has been reported (Chen et al., Exp. Brain Res., 233(5), 1519-1528, 2015). Here, by employing saccadic responses induced by auditory or visual stimuli, we measured the SNARC effect within the same subjects along the horizontal (HM) and vertical meridian (VM) and along the two interspersed diagonals. We found a SNARC effect along HM and VM, which allowed predicting the occurrence of a SNARC effect along the two diagonals by means of linear regression. Importantly, significant differences in SNARC strength were found between modalities. Our results suggest the existence of a frontoparallel mental number plane, where small numbers are represented left and down, while large numbers are represented right and up. Together with the recently described transverse mental number plane our findings provide further evidence for the existence of a three-dimensional mental number space.

The SNARC effect in two dimensions: Evidence for a frontoparallel mental number plane.

Humans can perceive and estimate approximate numerical information, even when accurate counting is impossible e.g., due to short presentation time. If the number of objects to be estimated is small, typically around 1-4 items, observers are able to give very fast and precise judgments with high confidence-an effect that is called subitizing. Due to its speed and effortless nature subitizing has usually been assumed to be preattentive, putting it into the same category as other low level visual features like color or orientation. More recently, however, a number of studies have suggested that subitizing might be dependent on attentional resources. In our current study we investigated the potentially preattentive nature of visual numerical perception in the subitizing range by means of EEG. We presented peripheral, task irrelevant sequences of stimuli consisting of a certain number of circular patches while participants were engaged in a demanding, non-numerical detection task at the fixation point drawing attention away from the number stimuli. Within a sequence of stimuli of a given number of patches (called "standards") we interspersed some stimuli of different numerosity ("oddballs"). We compared the evoked responses to visually identical stimuli that had been presented in two different conditions, serving as standard in one condition and as oddball in the other. We found significant visual mismatch negativity (vMMN) responses over parieto-occipital electrodes. In addition to the event-related potential (ERP) analysis, we performed a time-frequency analysis (TFA) to investigate whether the vMMN was accompanied by additional oscillatory processes. We found a concurrent increase in evoked theta power of similar strength over both hemispheres. Our results provide clear evidence for a preattentive processing of numerical visual information in the subitizing range.

Preattentive Processing of Numerical Visual Information.

Perceptual illusions help to understand how sensory signals are decoded in the brain. Here we report that the opposite approach is also applicable, i.e., results from decoding neural activity from monkey extrastriate visual cortex correctly predict a hitherto unknown perceptual illusion in humans. We record neural activity from monkey medial superior temporal (MST) and ventral intraparietal (VIP) area during presentation of self-motion stimuli and concurrent reflexive eye movements. A heading-decoder performs veridically during slow eye movements. During fast eye movements (saccades), however, the decoder erroneously reports compression of heading toward straight ahead. Functional equivalents of macaque areas MST and VIP have been identified in humans, implying a perceptual correlate (illusion) of this perisaccadic decoding error. Indeed, a behavioral experiment in humans shows that perceived heading is perisaccadically compressed toward the direction of gaze. Response properties of primate areas MST and VIP are consistent with being the substrate of the newly described visual illusion.Macaque higher visual areas MST and VIP encode heading direction based on self-motion stimuli. Here the authors show that, while making saccades, the heading direction decoded from the neural responses is compressed toward straight-ahead, and independently demonstrate a perceptual illusion in humans based on this perisaccadic decoding error.

Frank Bremmer

Department of Neurophysics

Philipps-Universität Marburg

A Wireless, Bidirectional Interface for In Vivo Recording and Stimulation of Neural Activity in Freely Behaving Rats

Frank Bremmer

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Department of Neurophysics

Philipps-Universität Marburg

A Wireless, Bidirectional Interface for In Vivo Recording and Stimulation of Neural Activity in Freely Behaving Rats

Department of Neurophysics