Het in kaart brengen van de verwerking van 3D vormen in de makaak aap: een gecombineerde fMRI en single-cell studie

By combining fMRI and electrophysiological recordings within the same monkeys we tried to obtain more insight in the parietal cortical areas sensitive to depth structure. In particular, awake monkey fMRI revealed that anterior IPS is activated more for curved surfaces compared to flat surfaces at different disparities. However, using the same stimuli set and fMRI experimental design, two separate activations in the IPS were observed in humans by Georgieva et al. (2009), namely DIPSA and DIPSM. This difference between monkeys and humans could be due to low spatial resolution in the monkey fMRI study, or genuine interspecies differences in the organization of anterior IPS. We targeted the activated fMRI voxels within this area with single-cell recordings and observed two patches of higher-order disparity selective neurons, one more anterior and one more posterior in AIP. These results reconcile previous observations of human and monkey fMRI studies concerning sensitivity to depth structure. Furthermore the results of this study show that with awake monkey fMRI the patchy distribution of the 3D structure selective neurons could not be detected, although fMRI generally localizes the neurons correctly. Accordingly, the relation between fMRI responses and neural activity remains complex and awake monkey fMRI in combination with electrophysiology can be a valuable technique for gaining more insight. Thanks to technological improvements, i.e. higher signal-to-noise ratio, higher spatial resolution and solid behavioral control we could define a more extensive stereo network (activated more to curved surfaces compared to flat surfaces at different disparities) compared to previous studies. New (besides the anterior IPS and F5a) robust activations were found in caudal IPS, PIT and more consistent and extended activations were observed in AIT. We reversibly inactivated area CIP, one of the early stages of the dorsal stream in the stereo network, while performing the same fMRI experiment to investigate the causal influence it exerts on other components of the stereo network. We found causal contributions of CIP on the depth structure related activations in the anterior IPS and surprisingly also to those in AIT in the ventral visual stream. In addition, CIP inactivation reduces the performance of the monkeys on a depth structure categorization task. We argue that the CIP inactivation effects in anterior IPS and AIT are caused indirectly since electrical microstimulation of area CIP and PIP did not activate anterior IPS nor AIT. These results designate a key role to area CIP in processing depth structure information for both the dorsal and the ventral visual stream.Table of Contents List of abbreviations iii Acknowledgements v Chapter 1: General Introduction 1 1.1 Processing of visual information 1 1.2 Seeing in depth 3 1.2.1 Binocular disparity 3 1.3 Flow of 3D information from early visual areas to higher-order visual areas 5 1.3.1 Evidence coming from single cell studies 5 1.3.2 Evidence coming from fMRI 11 1.3.3 Anatomical connections between ventral and dorsal stream 14 1.4 Methodology 15 1.4.1 Function magnetic resonance imaging 15 1.4.2 Relation between single-cell studies and fMRI 16 1.4.3 Reversible inactivation 19 Objectives 21 Chapter 2: The Relationship between functional magnetic resonance imaging and single-cell selectivity in the intra-parietal sulcus 25 2.1 Abstract 25 2.2 Introduction 26 2.3 Materials and Methods 28 2.3.1 Subjects, surgery and training procedures 28 2.3.2 Stimuli 31 2.3.3 fMRI scanning procedures 32 2.3.4 Single-cell recording procedures 34 2.3.5 Data analysis 38 2.4 Results 42 2.4.1 fMRI results: curvature x disparity interaction effect in the IPS 42 2.4.2 Assessment of higher-order disparity-selectivity 45 2.4.3 Patches of higher-order disparity-selective neurons 47 2.4.4 Population spiking responses 54 2.4.5 Local field potential responses 58 2.4.6 Localizer experiments 60 2.5 Discussion 65 2.6 Supplemental figures 72 Chapter 3: Functional interactions between dorsal and ventral visual stream during three-dimensional objects vision 75 3.1 Abstract 75 3.2 Introduction 76 3.3 Methods 77 3.3.1 Subjects, surgery and stimuli 77 3.3.2 Training in depth-structure categorization 79 3.3.3 Scanning procedures 80 3.3.4 Reversible inactivation procedures 82 3.3.5 Electrical Microstimulation 83 3.3.6 Data Analysis 84 3.4 Results 88 3.4.1 The network of depth structure-sensitive cortical areas 89 3.4.2 The effect of reversible inactivation of CIP during fMRI (ipsilateral results) 93 3.4.3 The effect of reversible inactivation of area CIP on depth structure categorization 101 3.4.4 CIP microstimulation during fMRI activates a distinct network of cortical areas 103 3.5 Discussion 106 3.6 Supplemental figures 115 Chapter 4: General Discussion 121 4.1 Summary of findings 121 4.2 Limitations 123 4.2.1 Limitations of fMRI 123 4.2.2 Limitations of electrophysiology 125 4.2.3 Limitations of the stimuli 125 4.2.4 What did we inactivate? 126 4.2.5 Near future experiments 127 4.2.6 Future perspectives 128 4.2.7 Relation to human studies 129 4.2.8 Conclusion 130 Summary 133 Samenvatting 135 Reference List 137 Curriculum Vitae 153nrpages: 156status: publishe

The relation between functional magnetic resonance imaging activations and single-cell selectivity in the macaque intraparietal sulcus

Previous functional magnetic resonance (fMRI) studies in humans and monkeys have demonstrated that the anterior intraparietal sulcus (IPS) is sensitive to the depth structure defined by binocular disparity. However, in the macaque monkey, a single large activation was measured in the anterior lateral bank of the IPS, whereas in human subjects two separate regions were sensitive to depth structure from disparity. We performed fMRI and single-cell experiments in the same animals, in a large number of recording sites in the lateral bank of the IPS. The fMRI interaction effect between the factors curvature (curved or flat) and disparity (stereo or control) correctly predicted the location of higher-order disparity selective neurons that encoded the depth structure of objects. However the large region in the IPS activated by depth structure consisted of two patches of higher-order disparity-selective neurons, one in the anterior IPS and one located more posteriorly, surrounded by regions lacking such selectivity. Thus the IPS region activated by curved surfaces consists of at least two patches of higher-order disparity selective neurons, which may reconcile previous fMRI studies in monkeys and humans.publisher: Elsevier articletitle: The relation between functional magnetic resonance imaging activations and single-cell selectivity in the macaque intraparietal sulcus journaltitle: NeuroImage articlelink: http://dx.doi.org/10.1016/j.neuroimage.2015.03.023 content_type: article copyright: Copyright © 2015 Elsevier Inc. All rights reserved.status: publishe

The effect of reversible inactivation of the caudal intraparietal area on 3D structure categorization

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The relation between single-cell activity and fMRI activations in posterior parietal cortex

To investigate the relation between fMRI activations and single-cell responses in parietal cortex we recorded single-unit (SUA), multi-unit (MUA) and local field potential (LFP) activity in the Anterior Intraparietal area (AIP) in voxels that were significantly more activated by curved surfaces than by flat surfaces at different disparities. We scanned two macaque monkeys in a 3T Siemens MR scanner with an 8-channel phased-array coil (MION, 1.25 mm isotropic voxels). Depth structure sensitivity was assessed by the interaction between the factors binocular disparity (disparity vs. no-disparity control condition) and depth order (zero-order disparity vs. second-order disparity). The region in AIP and part of the Lateral Intraparietal area (LIP) that was significantly more activated (corrected FWE=0,05) by curved surfaces than by flat surfaces at different disparities extended 9 mm in both the anterior-posterior and the medio-lateral direction. With the same stimulus set we recorded extracellular responses (48% SUA, 52% MUA) and LFPs in 315 AIP sites in two monkeys and in 14 grid positions (spacing 1 mm), covering 5 mm from posterior to anterior and 4 mm from medial to lateral. Eighty-nine percent (262 sites) of the recording sites was responsive, either early (0-450 ms after stimulus onset) excitatory (50%), early inhibitory (10%) or late (450-1000 ms after stimulus onset) responsive (29%). Averaged across all recording sites and all grid positions, both spiking activity and high gamma power (80-150 Hz) were significantly stronger for curved surfaces than for flat surfaces at different disparities. However, merely 18% of the responsive sites (48/262) preserved their 3D-shape selectivity across positions in depth indicating higher-order disparity selectivity. These higher-order disparity selective sites were mainly concentrated in 2 grid positions in monkey K. and 3 grid positions in monkey M. The main effect of binocular disparity was significant in 33% of the responsive sites in 13 out of 14 grid positions. We measured significantly stronger LFP responses to curved compared to flat surfaces in the gamma (7/14 sites), beta (4/14 sites) and alpha bands (4/14 sites). The magnitude of the interaction between depth order and binocular disparity in the spiking or LFP activity did not correlate with the interaction effect in percent signal change of the fMRI study. Thus in AIP, unlike in premotor cortex (Theys et al., 2009. Program No. 852.9. Neuroscience 2009. Online), the region activated (fMRI) by curved surfaces consists of a heterogeneous population of neurons and is much more extensive than the 3D-shape selective area as measured with single-cell recordings.status: publishe

The effect of reversible inactivation of the caudal intraparietal area on 3D structure categorization

Previous monkey fMRI-studies have revealed an extensive network involved in processing disparity-defined three-dimensional (3D) shapes in both the dorsal and ventral visual stream, (Durand et al., 2007. Neuron 55, 493-505). In contrast to what was previously reported, however, we recently found that also the caudal intraparietal area (CIP) is activated by disparity-defined 3D curved surfaces (Van Dromme et al., 2010. Program No. 19.7. Neuroscience 2010. Online). Moreover, reversible inactivation of area CIP in one hemisphere during contrast-agent enhanced fMRI caused a significant reduction of the activations related to depth structure (the interaction between the factors disparity and depth order) in the anterior intraparietal area (AIP), the premotor area F5 and in the anterior part of the superior temporal sulcus (anterior TE) (Van Dromme et al., 2013. Program No. 161.80 Neuroscience 2010. Online). Therefore, area CIP may play an essential role as input stage of higher-order disparity information for both the dorsal and the ventral stream. However, the role of CIP in the perception of 3D curved shapes remains unclear. Therefore, we reversibly inactivated area CIP while the monkeys performed a 3D structure discrimination task. Two monkeys were trained to discriminate convex and concave curved surfaces by means of an eye movement. All stimuli were presented for 800 ms at the fixation point and at one of three positions in depth. Task difficulty was manipulated by changing the percentage of dots defining the surface (between 10 and 100% disparity coherence). The monkeys were trained until above chance performance was reached for the most difficult disparity coherence condition, i.e. at 10% disparity coherence. Inactivation sessions (N = 3 for monkey 1 and N = 4 for monkey 2) were alternated with sessions without inactivations (N = 6 and N = 8, respectively). In inactivation sessions we injected 4-6μl muscimol solution (10mg/ml) unilaterally in area CIP. Subsequently, the monkeys were tested with 4 different disparity coherence levels: 10%, 20%, 30% and 50%. In both monkeys, reversible inactivation of area CIP caused a significant reduction in 3D structure discrimination performance, with the most consistent effects in the 10 and 20% coherence conditions. However, even in the latter conditions the maximal reduction in discrimination performance was 6%. These results suggest that area CIP could play a role in the discrimination of 3D structure in disparity-defined curved surfaces.status: publishe

Single-cell responses to three-dimensional structure in a functionally defined patch in macaque area TEO

Both dorsal and ventral visual pathways harbor several areas sensitive to gradients of binocular disparity (i.e., higher-order disparity). Although a wealth of information exists about disparity processing in early visual (V1, V2, and V3) and end-stage areas, TE in the ventral stream, and the anterior intraparietal area (AIP) in the dorsal stream, little is known about midlevel area TEO in the ventral pathway. We recorded single-unit responses to disparity-defined curved stimuli in a functional magnetic resonance imaging (fMRI) activation elicited by curved surfaces compared with flat surfaces in the macaque area TEO. This fMRI activation contained a small proportion of disparity-selective neurons, with very few of them second-order disparity selective. Overall, this population of TEO neurons did not preserve its three-dimensional structure selectivity across positions in depth, indicating a lack of higher-order disparity selectivity, but showed stronger responses to flat surfaces than to curved surfaces, as predicted by the fMRI experiment. The receptive fields of the responsive TEO cells were relatively small and generally foveal. A linear support vector machine classifier showed that this population of disparity-selective TEO neurons contains reliable information about the sign of curvature and the position in depth of the stimulus. NEW & NOTEWORTHY We recorded in a part of the macaque area TEO that is activated more by curved surfaces than by flat surfaces at different disparities using the same stimuli. In contrast to previous studies, this functional magnetic resonance imaging-defined patch did not contain a large number of higher-order disparity-selective neurons. However, a linear support vector machine could reliably classify both the sign of the disparity gradient and the position in depth of the stimuli.status: publishe

The functional connectivity of macaque area AIP. SfN Annual Meeting

A previous electrophysiology study identified two separate locations in monkey area AIP which contained neurons selective for disparity-defined depth structure: one located more anteriorly (aAIP), and a posterior spot (pAIP) neighboring area LIP (Van Dromme et al., SFN 2012, New Orleans, 264.03/Z14). The goal of our current research was to examine the functional connectivity of both stereo-sensitive AIP spots using electrical microstimulation during fMRI. In interleaved blocks, two macaque monkeys performed a memory-guided saccade task and a passive fixation task. Stimulation blocks for both tasks were interleaved with no-stimulation blocks. During stimulation blocks, area AIP was stimulated in every trial, at 200 micro-amperes. Stimulation started together with target or distractor onset, and lasted for 500 ms (pulsewidth: 0.48 ms, frequency: 200 Hz). Both monkeys were injected with a contrast agent and scanned at a 3T Siemens MR scanner with an 8-channel phased-array coil. Before every scan session, a platinum-iridium electrode (impedance: 40-150 kΩ) was inserted in the recording grid, and fixed at a depth which had previously been determined based on single- or multi-unit responses. We analyzed the effects of microstimulation by comparing stimulation blocks with no-stimulation blocks averaged across tasks (memory saccades and passive fixation). Electrical microstimulation of the most anterior part of area AIP (aAIP) caused increased fMRI activations in the stimulated area itself and in a network of areas implicated in reaching and grasping: the medial bank of the intraparietal sulcus corresponding to area MIP (the parietal reach region); somatosensory area S2; parietal areas PFG and 7a and premotor area F5. Similar results were obtained when stimulating aAIP under ketamine/medetomidine anaesthesia (1mA, 250 ms stimulation). A largely different pattern of activations was observed when stimulating more posteriorly located pAIP: we obtained increased fMRI-activation in pAIP, in area TEO and in the Caudal Intraparietal area (CIP), while no stimulation-induced activation was obtained in area MIP, and only modest increased activation in premotor area F5. Similar results were obtained in anaesthetized animals. Furthermore, the results were verified in a third monkey in which pAIP was previously identified by the presence of selective single-unit responses to images of objects. Our results thus suggest that area AIP consists of two subdivisions with different functional connectivity: while aAIP is embedded in a network of areas implicated in reaching and grasping, pAIP is connected with areas typically more implicated in object processing.status: publishe

Responses to two-dimensional shapes in the macaque Anterior Intraparietal area

Neurons in the macaque dorsal visual stream respond to the visual presentation of objects in the context of a grasping task and to three-dimensional (3D) surfaces defined by binocular disparity, but little is known about the neural representation of two-dimensional (2D) shape in the dorsal stream. We recorded the responses of single neurons in the macaque Anterior Intraparietal area, which is known to be crucial for grasping, to images of objects and silhouette -, outline- and line drawing versions of these images (contour stimuli). The vast majority of AIP neurons responding selectively to 2D images were also selective for at least one of the contour stimuli with the same boundary shape, suggesting that the boundary is sufficient for the image selectivity of most AIP neurons. Furthermore a subset of these neurons with foveal receptive fields generally preserved the shape preference across positions, whereas for more than half of the AIP population the center of the receptive field was at a parafoveal location with less tolerance to changes in stimulus position. AIP neurons frequently exhibited shape selectivity across different stimulus sizes. These results demonstrate that AIP neurons encode not only 3D but also 2D shape features.status: publishe

The role of binocular disparity in stereoscopic images of objects in the macaque anterior intraparietal area.

Neurons in the macaque Anterior Intraparietal area (AIP) encode depth structure in random-dot stimuli defined by gradients of binocular disparity, but the importance of binocular disparity in real-world objects for AIP neurons is unknown. We investigated the effect of binocular disparity on the responses of AIP neurons to images of real-world objects during passive fixation. We presented stereoscopic images of natural and man-made objects in which the disparity information was congruent or incongruent with disparity gradients present in the real-world objects, and images of the same objects where such gradients were absent. Although more than half of the AIP neurons were significantly affected by binocular disparity, the great majority of AIP neurons remained image selective even in the absence of binocular disparity. AIP neurons tended to prefer stimuli in which the depth information derived from binocular disparity was congruent with the depth information signaled by monocular depth cues, indicating that these monocular depth cues have an influence upon AIP neurons. Finally, in contrast to neurons in the inferior temporal cortex, AIP neurons do not represent images of objects in terms of categories such as animate-inanimate, but utilize representations based upon simple shape features including aspect ratio