Fast Compensatory Functional Network Changes Caused by Reversible Inactivation of Monkey Parietal Cortex.

The brain has a remarkable capacity to recover after lesions. However, little is known about compensatory neural adaptations at the systems level. We addressed this question by investigating behavioral and (correlated) functional changes throughout the cortex that are induced by focal, reversible inactivations. Specifically, monkeys performed a demanding covert spatial attention task while the lateral intraparietal area (LIP) was inactivated with muscimol and whole-brain fMRI activity was recorded. The inactivation caused LIP-specific decreases in task-related fMRI activity. In addition, these local effects triggered large-scale network changes. Unlike most studies in which animals were mainly passive relative to the stimuli, we observed heterogeneous effects with more profound muscimol-induced increases of task-related fMRI activity in areas connected to LIP, especially FEF. Furthermore, in areas such as FEF and V4, muscimol-induced changes in fMRI activity correlated with changes in behavioral performance. Notably, the activity changes in remote areas did not correlate with the decreased activity at the site of the inactivation, suggesting that such changes arise via neuronal mechanisms lying in the intact portion of the functional task network, with FEF a likely key player. The excitation-inhibition dynamics unmasking existing excitatory connections across the functional network might initiate these rapid adaptive changes.

The retinotopic organization of macaque occipitotemporal cortex anterior to V4 and caudoventral to the middle temporal (MT) cluster.

The retinotopic organization of macaque occipitotemporal cortex rostral to area V4 and caudorostral to the recently described middle temporal (MT) cluster of the monkey (Kolster et al., 2009) is not well established. The proposed number of areas within this region varies from one to four, underscoring the ambiguity concerning the functional organization in this region of extrastriate cortex. We used phase-encoded retinotopic functional MRI mapping methods to reveal the functional topography of this cortical domain. Polar-angle maps showed one complete hemifield representation bordering area V4 anteriorly, split into dorsal and ventral counterparts corresponding to the lower and upper visual field quadrants, respectively. The location of this hemifield representation corresponds to area V4A. More rostroventrally, we identified three other complete hemifield representations. Two of these correspond to the dorsal and the ventral posterior inferotemporal areas (PITd and PITv, respectively) as identified in the Felleman and Van Essen (1991) scheme. The third representation has been tentatively named dorsal occipitotemporal area (OTd). Areas V4A, PITd, PITv, and OTd share a central visual field representation, similar to the areas constituting the MT cluster. Furthermore, they vary widely in size and represent the complete contralateral visual field. Functionally, these four areas show little motion sensitivity, unlike those of the MT cluster, and two of them, OTd and PITd, displayed pronounced two-dimensional shape sensitivity. In general, these results suggest that retinotopically organized tissue extends farther into rostral occipitotemporal cortex of the monkey than generally assumed.

Correspondences between retinotopic areas and myelin maps in human visual cortex.

We generated probabilistic area maps and maximum probability maps (MPMs) for a set of 18 retinotopic areas previously mapped in individual subjects (Georgieva et al., 2009 and Kolster et al., 2010) using four different inter-subject registration methods. The best results were obtained using a recently developed multimodal surface matching method. The best set of MPMs had relatively smooth borders between visual areas and group average area sizes that matched the typical size in individual subjects. Comparisons between retinotopic areas and maps of estimated cortical myelin content revealed the following correspondences: (i) areas V1, V2, and V3 are heavily myelinated; (ii) the MT cluster is heavily myelinated, with a peak near the MT/pMSTv border; (iii) a dorsal myelin density peak corresponds to area V3D; (iv) the phPIT cluster is lightly myelinated; and (v) myelin density differs across the four areas of the V3A complex. Comparison of the retinotopic MPM with cytoarchitectonic areas, including those previously mapped to the fs_LR cortical surface atlas, revealed a correspondence between areas V1-3 and hOc1-3, respectively, but little correspondence beyond V3. These results indicate that architectonic and retinotopic areal boundaries are in agreement in some regions, and that retinotopy provides a finer-grained parcellation in other regions. The atlas datasets from this analysis are freely available as a resource for other studies that will benefit from retinotopic and myelin density map landmarks in human visual cortex.

The retinotopic organization of the human middle temporal area MT/V5 and its cortical neighbors.

Although there is general agreement that the human middle temporal (MT)/V5+ complex corresponds to monkey area MT/V5 proper plus a number of neighboring motion-sensitive areas, the identification of human MT/V5 within the complex has proven difficult. Here, we have used functional magnetic resonance imaging and the retinotopic mapping technique, which has very recently disclosed the organization of the visual field maps within the monkey MT/V5 cluster. We observed a retinotopic organization in humans very similar to that documented in monkeys: an MT/V5 cluster that includes areas MT/V5, pMSTv (putative ventral part of the medial superior temporal area), pFST (putative fundus of the superior temporal area), and pV4t (putative V4 transitional zone), and neighbors a more ventral putative human posterior inferior temporal area (phPIT) cluster. The four areas in the MT/V5 cluster and the two areas in the phPIT cluster each represent the complete contralateral hemifield. The complete MT/V5 cluster comprises 70% of the motion localizer activation. Human MT/V5 is located in the region bound by lateral, anterior, and inferior occipital sulci and occupies only one-fifth of the motion complex. It shares the basic functional properties of its monkey homolog: receptive field size relative to other areas, response to moving and static stimuli, as well as sensitivity to three-dimensional structure from motion. Functional properties sharply distinguish the MT/V5 cluster from its immediate neighbors in the phPIT cluster and the LO (lateral occipital) regions. Together with similarities in retinotopic organization and topological neighborhood, the functional properties suggest that MT/V5 in human and macaque cortex are homologous.

Direct visualization of non-human primate subcortical nuclei with contrast-enhanced high field MRI.

Subcortical nuclei are increasingly targeted for deep brain stimulation (DBS) and for gene transfer to treat neurological and psychiatric disorders. For a successful outcome in patients, it is critical to place DBS electrodes or infuse viral vectors accurately within targeted nuclei. However current MRI approaches are still limited to localize brainstem and basal ganglia nuclei accurately. By combining ultra-high resolution structural MRI and contrast-enhanced MRI using iron oxide nanoparticles at high field (3T and 7T), we could precisely locate the subcortical nuclei, in particular the subthalamic nucleus in macaques, and validate this location by intracranial electrophysiological mapping. The present data pave the way to a clinical application.

Modulation of the contrast response function by electrical microstimulation of the macaque frontal eye field.

Spatial attention influences representations in visual cortical areas as well as perception. Some models predict a contrast gain, whereas others a response or activity gain when attention is directed to a contrast-varying stimulus. Recent evidence has indicated that microstimulating the frontal eye field (FEF) can produce modulations of cortical area V4 neuronal firing rates that resemble spatial attention-like effects, and we have shown similar modulations of functional magnetic resonance imaging (fMRI) activity throughout the visual system. Here, we used fMRI in awake, fixating monkeys to first measure the response in 12 visual cortical areas to stimuli of varying luminance contrast. Next, we simultaneously microstimulated subregions of the FEF with movement fields that overlapped the stimulus locations and measured how microstimulation modulated these contrast response functions (CRFs) throughout visual cortex. In general, we found evidence for a nonproportional scaling of the CRF under these conditions, resembling a contrast gain effect. Representations of low-contrast stimuli were enhanced by stimulation of the FEF below the threshold needed to evoke saccades, whereas high-contrast stimuli were unaffected or in some areas even suppressed. Furthermore, we measured a characteristic spatial pattern of enhancement and suppression across the cortical surface, from which we propose a simple schematic of this contrast-dependent fMRI response.

The processing of three-dimensional shape from disparity in the human brain.

Three-dimensional (3D) shape is important for the visual control of grasping and manipulation and for object recognition. Although there has been some progress in our understanding of how 3D shape is extracted from motion and other monocular cues, little is known of how the human brain extracts 3D shape from disparity, commonly regarded as the strongest depth cue. Previous fMRI studies in the awake monkey have established that the interaction between stereo (present or absent) and the order of disparity (zero or second order) constitutes the MR signature of regions housing second-order disparity-selective neurons (Janssen et al., 2000; Srivastava et al., 2006; Durand et al., 2007; Joly et al., 2007). Testing the interaction between stereo and order of disparity in a large cohort of human subjects, revealed the involvement of five IPS regions (VIPS/V7*, POIPS, DIPSM, DIPSA, and phAIP), as well as V3 and the V3A complex in occipital cortex, the posterior inferior temporal gyrus (ITG), and ventral premotor cortex (vPrCS) in the extraction and processing of 3D shape from stereo. Control experiments ruled out attention and convergence eye movements as confounding factors. Many of these regions, DIPSM, DIPSA, phAIP, and probably posterior ITG and ventral premotor cortex, correspond to monkey regions with similar functionality, whereas the evolutionarily new or modified regions are located in occipital (the V3A complex) and occipitoparietal cortex (VIPS/V7* and POIPS). Interestingly, activity in these occipital regions correlates with the depth amplitude perceived by the subjects in the 3D surfaces used as stimuli in these fMRI experiments.

Visual field map clusters in macaque extrastriate visual cortex.

The macaque visual cortex contains >30 different functional visual areas, yet surprisingly little is known about the underlying organizational principles that structure its components into a complete "visual" unit. A recent model of visual cortical organization in humans suggests that visual field maps are organized as clusters. Clusters minimize axonal connections between individual field maps that represent common visual percepts, with different clusters thought to carry out different functions. Experimental support for this hypothesis, however, is lacking in macaques, leaving open the question of whether it is unique to humans or a more general model for primate vision. Here we show, using high-resolution blood oxygen level-dependent functional magnetic resonance imaging data in the awake monkey at 7 T, that the middle temporal area (area MT/V5) and its neighbors are organized as a cluster with a common foveal representation and a circular eccentricity map. This novel view on the functional topography of area MT/V5 and satellites indicates that field map clusters are evolutionarily preserved and may be a fundamental organizational principle of the Old World primate visual cortex.

In vivo and ex vivo 19-fluorine magnetic resonance imaging and spectroscopy of beta-cells and pancreatic islets using GLUT-2 specific contrast agents.

The assessment of the ß-cell mass in experimental models of diabetes and ultimately in patients is a hallmark to understand the relationship between reduced ß-cell mass/function and the onset of diabetes. It has been shown before that the GLUT-2 transporter is highly expressed in both ß-cells and hepatocytes and that D-mannoheptulose (DMH) has high uptake specificity for the GLUT-2 transporter. As 19-fluorine MRI has emerged as a new alternative method for MRI cell tracking because it provides potential non-invasive localization and quantification of labeled cells, the purpose of this project is to validate ß-cell and pancreatic islet imaging by using fluorinated, GLUT-2 targeting mannoheptulose derivatives (19 FMH) both in vivo and ex vivo. In this study, we confirmed that, similar to DMH, 19 FMHs inhibit insulin secretion and increase the blood glucose level in mice temporarily (approximately two hours). We were able to assess the distribution of 19 FMHs in vivo with a temporal resolution of about 20 minutes, which showed a quick removal of 19 FMH from the circulation (within two hours). Ex vivo MR spectroscopy confirmed a preferential uptake of 19 FMH in tissue with high expression of the GLUT-2 transporter, such as liver, endocrine pancreas and kidney. No indication of further metabolism was found. In summary, 19 FMHs are potentially suitable for visualizing and tracking of GLUT-2 expressed cells. However, current bottlenecks of this technique related to the quick clearance of the compound and relative low sensitivity of 19 F MRI need to be overcome. Copyright © 2016 John Wiley & Sons, Ltd.