Macaque Brain Research Articles

How does the macaque brain characterize face pareidolia?

How does the macaque brain characterize face pareidolia?

A population stereotaxic positron emission tomography brain template for the macaque and its application to ischemic model

PurposePositron emission tomography (PET) is a non-invasive imaging tool for the evaluation of brain function and neuronal activity in normal and diseased conditions with high sensitivity. The macaque monkey serves as a valuable model system in the field of translational medicine, for its phylogenetic proximity to man. To translation of non-human primate neuro-PET studies, an effective and objective data analysis platform for neuro-PET studies is needed. Materials and methodsA set of stereotaxic templates of macaque brain, namely the Institute of High Energy Physics & Jinan University Macaque Template (HJT), was constructed by iteratively registration and averaging, based on 30 healthy rhesus monkeys. A brain atlas image was created in HJT space by combining sub-anatomical regions and defining new 88 bilateral functional regions, in which a unique integer was assigned for each sub-anatomical region. ResultsThe HJT comprised a structural MRI T1 weighted image (T1WI) template image, a functional FDG-PET template image, intracranial tissue segmentations accompanied with a digital macaque brain atlas image. It is compatible with various commercially available software tools, such as SPM and PMOD. Data analysis was performed on a stroke model compared with a group of healthy controls to demonstrate the usage of HJT. ConclusionWe have constructed a stereotaxic template set of macaque brain named HJT, which standardizes macaque neuroimaging data analysis, supports novel radiotracer development and facilitates translational neuro-disorders research.

Statistical inference of body representation in the macaque brain

The sense of one's own body is a pillar of self-consciousness and could be investigated by inducing human illusions of artificial objects as part of the self. Here, we present a nonhuman primate version of a rubber-hand illusion that allowed us to determine its computational and neuronal mechanisms. We implemented a video-based system in a reaching task in monkeys and combined a casual inference model to establish an objective and quantitative signature for the monkey's body representation. Similar to humans, monkeys were more likely to perceive an external object as part of the self when the dynamics (spatial disparity) and the features (shape and structure) of visual (V) input was closer to proprioceptive (P) signals. Neural signals in the monkey's premotor cortex reflected the strength of illusion and the likelihood of misattributing the illusory hand to oneself, thus, revealing a cortical representation of body ownership.

Electromagnetic radiation modulates synchronization in cortical neurons of Macaque brain

We study dynamical synchronization in a model of a neural system representing 47 cortical regions of Macaque brain under the effect of an electromagnetic field. This system is constituted by local networks of densely interconnected excitatory and inhibitory neurons. Coupling between the local networks is introduced through sparsely distributed excitatory connectivity. Voltage- and ligand-gated ion channels determine the neural dynamics of the networks. The effect of electromagnetic field on the neural system is studied by modulating magnetic flux on the membrane potential using memristor coupling. With the application of electromagnetic field and the modulation of long-range synaptic coupling, the system easily makes transition to synchronization. It is found that the threshold for synchrony between coupled local networks is lowered by the applied electromagnetic field. Also, electromagnetic field causes the neural subsystems to make low amplitude oscillations with an approximate frequency of 130 Hz. This indicates that electromagnetic field gives rise to high-gamma activity in the cortical regions of the brain which increases selective attention. This may facilitate adaptive brain function by giving rise to a rich collection of dynamics and contribute to the origin of complex patterns observed in the EEG.

Fine-Grained Parcellation of the Macaque Nucleus Accumbens by High-Resolution Diffusion Tensor Tractography

Limited in part by the spatial resolution of typical in vivo magnetic resonance imaging (MRI) data, recent neuroimaging studies have only identified a connectivity-based shell-core-like partitioning of the nucleus accumbens (Acb) in humans. This has hindered the process of making a more refined description of the Acb using non-invasive neuroimaging technologies and approaches. In this study, high-resolution ex vivo macaque brain diffusion MRI data were acquired to investigate the tractography-based parcellation of the Acb. Our results identified a shell-core-like partitioning in macaques that is similar to that in humans as well as an alternative solution that subdivided the Acb into four parcels, the medial shell, the lateral shell, the ventral core, and the dorsal core. Furthermore, we characterized the specific anatomical and functional connectivity profiles of these Acb subregions and generalized their specialized functions to establish a fine-grained macaque Acb brainnetome atlas. This atlas should be helpful in neuroimaging, stereotactic surgery, and comparative neuroimaging studies to reveal the neurophysiological substrates of various diseases and cognitive functions associated with the Acb.

Overexpression and activation of colony-stimulating factor 1 receptor in the SIV/macaque model of HIV infection and neuroHIV.

In the present study, we investigated whether colony-stimulating factor 1 receptor (CSF1R) is expressed on brain macrophages and microglia in the human and macaque brain and whether it is upregulated and activated after lentivirus infection in vivo and contributes to development of encephalitic lesions. We examined, using multi-label and semi-quantitative immunofluorescence microscopy, the protein expression level and cellular localization of CSF1R in brain tissues from uninfected controls and SIV-infected adult macaques with or without encephalitis and also from uninfected controls, HIV-infected encephalitic subjects and virally suppressed subjects. In the normal uninfected brain, CSF1R protein was detected only on microglia and brain macrophages but not on neurons, astrocytes or oligodendrocytes. Microglia constitutively expressed CSF1R at low levels, and its expression was largely unchanged in non-encephalitic and encephalitic animals. Brain macrophages, including perivascular macrophages (PVMs), expressed higher levels of CSF1R compared to microglia. Interestingly, we found significantly increased expression of CSF1R on the infected PVMs and lesional macrophages in the brains of encephalitic macaques. Moreover, the per cell expression of CSF1R determined by its mean pixel intensity (MPI) correlated positively with the MPI of SIV Gag p28 in SIV-infected PVMs. Using phosphorylated CSF1R at tyrosine residue 723 and phosphorylated signal transducer and activator of transcription 5 at tyrosine reside 694 as markers for CSF1R activation, we found selective activation of CSF1R signaling in infected brain macrophages in encephalitis. We also found colocalization of CSF1R and its ligand CSF1 in PVMs and lesional macrophages in the brains of encephalitic macaques and humans. Notably, elevated brain CSF1R expression was found in virally suppressed subjects. These findings point to opportunities for developing a specific approach targeting infected brain macrophages, with several brain-penetrant CSF1R inhibitors that are available now, in order to eliminate central nervous system macrophage reservoirs, while not affecting resting uninfected microglia and PVMs that show no CSF1R activation.

CHARTING DEVELOPMENT-BASED JOINT PARCELLATION MAPS OF HUMAN AND MACAQUE BRAINS DURING INFANCY.

Comparative characterization of early brain development between human and macaque using neuroimaging data is crucial to understand the mechanisms of brain development and evolution. To this end, joint cortical parcellation maps of human and macaque infant brains with corresponding regions are highly desirable, since they provide basic cortical parcels for both region-based and network-based studies of two closely-related species. To address this issue, we propose to leverage developmental patterns of cortical properties of both human and macaque infants for creating joint parcellation maps with inter-species comparability. The motivation is that the developmental patterns of cortical properties indicate underlying rapid changes of microstructures, which determine the molecular and functional principles of the cortex. Thus, developmental patterns are well suitable for defining distinct cortical regions in both structures and functions. To comprehensively capture the similarities of developmental patterns of vertices on cortical surfaces, for each species, we first construct two complementary similarity matrices: a low-order matrix and a high-order matrix. Then, we non-linearly fuse these four matrices together as a single matrix in a hierarchical manner, thus capturing the common and complementary information of both human and macaque infants. Finally, based on the fused similarity matrix, we apply the spectral clustering to derive the joint parcellation maps. By applying our method to 210 longitudinal human infant MRI scans and 140 longitudinal macaque infant MRI scans, we generate the first biologically-meaningful joint parcellation maps of human and macaque infants.

Regional Molecular Mapping of Primate Synapses during Normal Healthy Aging

SummaryNormal mammalian brain aging is characterized by the selective loss of discrete populations of dendritic spines and synapses, particularly affecting neuroanatomical regions such as the hippocampus. Although previous investigations have quantified this morphologically, the molecular pathways orchestrating preferential synaptic vulnerability remain to be elucidated. Using quantitative proteomics and healthy rhesus macaque and human patient brain regional tissues, we have comprehensively profiled the temporal expression of the synaptic proteome throughout the adult lifespan in differentially vulnerable brain regions. Comparative profiling of hippocampal (age vulnerable) and occipital cortex (age resistant) synapses revealed discrete and dynamic alterations in the synaptic proteome, which appear unequivocally conserved between species. The generation of these unique and important datasets will aid in delineating the molecular mechanisms underpinning primate brain aging, in addition to deciphering the regulatory biochemical cascades governing neurodegenerative disease pathogenesis.

Solid Phase Microextraction-Based Miniaturized Probe and Protocol for Extraction of Neurotransmitters from Brains in Vivo.

Despite the importance of monitoring and correlating neurotransmitter concentrations in the brain with observable behavior and brain areas in which they act, in vivo measurement of multiple neurochemicals in the brain remains a challenge. Here, we propose an alternative solid phase microextraction-based (SPME) chemical biopsy approach as a viable method for acquirement of quantitative information on multiple neurotransmitters by one device within a single sampling event, with multisite measurement capabilities and minimized invasiveness, as no tissue is removed. The miniaturized SPME probe developed for integrated in vivo sampling/sample preparation has been thoroughly optimized with respect to probe shape, desorption solvent, and extracting phase tailored for extraction of small hydrophilic molecules via synthesis and functionalization of the SPME coating. Experimental evaluations of sampling time and storage strategy led to achieving appropriate temporal resolution versus recovery balance as well as little or no analyte loss, respectively. Validation of the developed SPME-HPLC-MS/MS protocol in a surrogate brain matrix yielded satisfactory accuracies of 80-100%, precision below 17%, as well as linear dynamic range and limits of quantitation suitable for determining neurochemicals at physiologically relevant levels. Finally, we present a proof-of-concept in vivo application in macaque brain, where several target neurotransmitters were extracted simultaneously from three brain areas. The developed probe and protocol are herein presented as a potential powerful addition to the existing in vivo toolbox for measurements of local levels of neurochemicals in multiple brain systems implicated in the neuropathology of psychiatric disorders.

Making waves with ultrasound.

Targeted ultrasound stimulation can specifically modulate the functional connectivity profiles of targeted structures — including deep structures — in the macaque brain, with effects lasting for up to 2 hours following stimulation.

Disparity level identification using the voxel-wise Gabor model of fMRI data.

Perceiving disparities is the intuitive basis for our understanding of the physical world. Although many electrophysiology studies have revealed the disparity-tuning characteristics of the neurons in the visual areas of the macaque brain, neuron population responses to disparity processing have seldom been investigated. Many disparity studies using functional magnetic resonance imaging (fMRI) have revealed the disparity-selective visual areas in the human brain. However, it is unclear how to characterize neuron population disparity-tuning responses using fMRI technique. In the present study, we constructed three voxel-wise encoding Gabor models to predict the voxel responses to novel disparity levels and used a decoding method to identify the new disparity levels from population responses in the cortex. Among the three encoding models, the fine-coarse model (FCM) that used fine/coarse disparities to fit the voxel responses to disparities outperformed the single model and uncrossed-crossed model. Moreover, the FCM demonstrated high accuracy in predicting voxel responses in V3A complex and high accuracy in identifying novel disparities from responses in V3A complex. Our results suggest that the FCM can better characterize the voxel responses to disparities than the other two models and V3A complex is a critical visual area for representing disparity information.

Evaluation of Submillimeter Diffusion Imaging of the Macaque Brain Using Readout-Segmented EPI at 7T.

The purpose of the present study was to achieve submillimeter-level diffusion tensor imaging (DTI) of the macaque brain by using diffusion weighted (DW) readout-segmented echo planar imaging (rsEPI) with an optimized protocol at 7T MRI. Three anesthetized macaques were included in this study. Under different scan settings, we compared the signal-to-noise ratio (SNR) and geometric distortion of DW images, implemented an optimized protocol for submillimeter-level DTI acquisition, and evaluated its performance. The parallel-imaging-enabled (in GRAPPA mode) monopolar or monopolar+ diffusion scheme has higher SNR versus bipolar scheme, whereas trivial differences in SNR and image geometric distortion occurred when using increased readout segments with monopolar and monopolar+ that did not reach statistical significance. Submillimeter-level (0.8 mm isotropic) DTI data provide a sharper delineation of white matter contour than the 1 mm level. The rsEPI technique with parallel imaging enabled, and with the shortest readout segments in conjunction with monopolar/monopolar+ diffusion encoding scheme, may be optimal for submillimeter-level diffusion imaging over macaque brains in vivo. rsEPI could effectively merit high-resolution DTI for in vivo macaque brain submillimeter structural architecture investigations at ultrahigh fields.

Optic Nerve Degeneration and Reduced Contrast Sensitivity Due to Folic Acid Deficiency: A Behavioral and Electrophysiological Study in Rhesus Monkeys.

The purpose of the research was to elucidate the role of folic acid (B9) deficiency in the development of nutritional optic neuritis and to characterize the neurophysiological consequences of optic nerve degeneration in the cortical visual system. A combined behavioral and electrophysiological approach was applied to study luminance contrast sensitivity in two macaque monkeys affected by nutritional optic neuritis and in two healthy monkeys for comparison. For one monkey, a follow-up approach was applied to compare visual performance before onset of optic neuropathy, during the disease, and after treatment. Optic nerve degeneration developed as a consequence of insufficient dietary intake of folic acid in two exemplars of macaque monkeys. The degeneration resulted in markedly reduced luminance contrast sensitivity as assessed behaviorally. In one monkey, we also measured visual activity in response to varying contrast at the level of single neurons in the cortical visual system and found a striking reduction in contrast sensitivity, as well as a marked increase in the latency of neuronal responses. Prolonged daily folate supplementation resulted in a significant recovery of function. Folic acid deficiency per se can lead to the development of optic nerve degeneration in otherwise healthy adult animals. The optic nerve degeneration strongly affects contrast sensitivity and leads to a distinct reduction in the strength and velocity of the incoming signal to cortical visual areas of the macaque brain, without directly affecting excitability and functional properties of cortical neurons.

Neurons in the Macaque Dorsal Premotor Cortex Respond to Execution and Observation of Actions.

We identified neurons in dorsal premotor cortex (PMd) of the macaque brain that respond during execution and observation of reaching-to-grasp actions, thus fulfilling the mirror neuron (MirN) criterion. During observation, the percentage of grip-selective MirNs in PMd and area F5 were comparable, and the selectivity indices in the two areas were similar. During execution, F5-MirNs were more selective than PMd-MirNs for grip, which was reflected in the higher selectivity indices in F5 than in PMd. PMd displayed grip-related information earlier than F5 during both conditions. In both areas, the number of neurons exhibiting congruent visual and motor selectivity did not differ from that expected by chance. However, both the PMd and F5 neuronal ensembles provided observation-execution matching, suggesting that the congruency may be achieved in a distributed fashion across the selective elements of the population. Furthermore, representational similarity analysis revealed that grip encoding in PMd and F5 is alike during both observation and execution. Our study provides direct evidence of mirror activity in PMd during observation of forelimb movements, and suggests that PMd is a node of the MirN circuit.

No detection of CD4-independent human immunodeficiency virus 1 envelope glycoproteins in brain tissue of patients with or without neurological complications

Macrophage (mac)-tropic human immnunodeficiency virus type 1 (HIV-1) and simian immnunodeficiency virus (SIV) in brain are associated with neurological disease. Mac-tropic HIV-1 evolves enhanced CD4 interactions that enable macrophage infection via CD4, which is in low abundance. In contrast, mac-tropic SIV is associated with CD4-independent infection via direct CCR5 binding. Recently, mac-tropic simian-human immunodeficiency virus (SHIV) from macaque brain was also reported to infect cells via CCR5 without CD4. Since SHIV envelope proteins (Envs) are derived from HIV-1, we tested more than 100 HIV-1 clade B Envs for infection of CD4-negative, CCR5+ Cf2Th/CCR5 cells. However, no infection was detected. Our data suggest that there are differences in the evolution of mac-tropism in SIV and SHIV compared to HIV-1 clade B due to enhanced interactions with CCR5 and CD4, respectively.

Visual and Vestibular Selectivity for Self-Motion in Macaque Posterior Parietal Area 7a.

We examined the responses of neurons in posterior parietal area 7a to passive rotational and translational self-motion stimuli, while systematically varying the speed of visually simulated (optic flow cues) or actual (vestibular cues) self-motion. Contrary to a general belief that responses in area 7a are predominantly visual, we found evidence for a vestibular dominance in self-motion processing. Only a small fraction of neurons showed multisensory convergence of visual/vestibular and linear/angular self-motion cues. These findings suggest possibly independent neuronal population codes for visual versus vestibular and linear versus angular self-motion. Neural responses scaled with self-motion magnitude (i.e., speed) but temporal dynamics were diverse across the population. Analyses of laminar recordings showed a strong distance-dependent decrease for correlations in stimulus-induced (signal correlation) and stimulus-independent (noise correlation) components of spike-count variability, supporting the notion that neurons are spatially clustered with respect to their sensory representation of motion. Single-unit and multiunit response patterns were also correlated, but no other systematic dependencies on cortical layers or columns were observed. These findings describe a likely independent multimodal neural code for linear and angular self-motion in a posterior parietal area of the macaque brain that is connected to the hippocampal formation.

Post mortem high resolution diffusion MRI for large specimen imaging at 11.7 T with 3D segmented echo-planar imaging

Background: Diffusion weighted imaging (DWI) is the only in vivo technique allowing for the mapping of tissue fiber architecture. Post mortem DWI is an increasingly popular method, since longer acquisition times (compared to in vivo) allow higher spatial and angular resolutions to be achieved. However, DWI protocols must be adapted to post mortem tissue (e.g., tuning acquisition parameters to account for changes in T1/T2).New method: In this work, we developed a framework to obtain high quality diffusion weighted images on post mortem large samples by using a combination of fast imaging with 3D diffusion-weighted segmented EPI (3D-DW seg-EPI), Gadolinium soaking and data denoising. Analyses including tractography were used to check the quality of the acquired data, including a comparison with 3D-DW SE acquisitions.Comparison with existing method: Effects on diffusion data of each of the components of the framework were tested: 3D-DW seg-EPI versus 3D-DW SE EPI; with and without data denoising; with and without Gd-soaking.Conclusions: Our study demonstrated the feasibility of analysing anatomical connectivity using diffusion imaging of a post mortem macaque brain with a 3D-DW seg-EPI sequence acquired at ultra-high field. The combination of high angular and spatial resolution DWI with Gd-soaking and denoising provided data allowing us to perform diffusion tractography with results very similar to those obtained with a 3D-DW SE acquisition (with shorter acquisition times: 222 h versus 37 h for 3D-DW seg-EPI).

Rhesus Macaque Brain Atlas Regions Aligned to an MRI Template.

To aid in the analysis of rhesus macaque brain images, we aligned digitized anatomical regions from the widely used atlas of Paxinos et al. to a published magnetic resonance imaging (MRI) template based on a large number of subjects. Digitally labelled atlas images were aligned to the template in 2D and then in 3D. The resulting grey matter regions appear qualitatively to be well registered to the template. To quantitatively validate the procedure, MR brain images of 20 rhesus macaques were aligned to the template along with regions drawn by hand in striatal and cortical areas in each subject's MRI. There was good geometric overlap between the hand drawn regions and the template regions. Positron emission tomography (PET) images of the same subjects showing uptake of a dopamine D2 receptor ligand were aligned to the template space, and good agreement was found between tracer binding measures calculated using the hand drawn and template regions. In conclusion, an anatomically defined set of rhesus macaque brain regions has been aligned to an MRI template and has been validated for analysis of PET imaging in a subset of striatal and cortical areas. The entire set of over 200 regions is publicly available at https://www.nitrc.org/ . Graphical Abstract ᅟ.

Deep Learning Models Unveiled Functional Difference Between Cortical Gyri and Sulci.

It is largely unknown whether there is functional role difference between cortical gyral and sulcal regions. Recent advancements in neuroimaging studies demonstrate clear difference of structural connection profiles in gyral and sulcal areas, suggesting possible functional role difference in these convex and concave cortical regions. To explore and confirm such possible functional difference, we design and apply a powerful deep learning model of convolutional neural networks (CNN) that has been proven to be superior in learning discriminative and meaningful patterns on fMRI. By using the CNN model, gyral and sulcal fMRI signals are learned and predicted, and the prediction performance is adopted to demonstrate the functional difference between gyri and sulci. By using the Human Connectome Project (HCP) fMRI data and macaque brain fMRI data, an average of 83% and 90% classification accuracy has been achieved to separate gyral/sulcal HCP task fMRI signals at the population and individual subject level, respectively; 81% and 86% classification accuracy for resting state fMRI signals at the group and individual subject level, respectively. In addition, 78% classification accuracy has been achieved to separate gyral/sulcal resting state fMRI signals in macaque brains. Importantly, further analysis reveals that the discriminative features that are learned by CNNs to differentiate gyral/sulcal fMRI signals can be meaningfully interpreted, thus unveiling the fundamental functional difference between cortical gyri and sulci. That is, gyri are more global functional integration centers with simpler lower frequency signal components, while sulci are more local processing units with more complex higher frequency signal components.

Differences in cytoarchitecture of Broca's region between human, ape and macaque brains

Areas 44 and 45 have been identified in non-human primates as homologs of the human Broca region. Distribution of large and smaller pyramids and the ventro-lateral localization in the posterior frontal lobe enable their identification in non-human primates. Since only humans hold the ability of language, it has been hypothesized that differences in microstructure may, together with other anatomical factors, e.g., white matter tract connectivity, volumes of cortical areas and their molecular differentiation, be responsible for the lack (non-human primates) or ability (humans) of language. We sought to identify microstructural differences, by quantitatively studying the cytoarchitecture of areas 44 and 45 using layer-specific grey level indices (volume proportion of neuropil and cell bodies) in serially sectioned and cell body stained human, bonobo, chimpanzee, gorilla, orangutan and Macaca fascicularis brains. The main results are the interspecies differences in neuropil volume relative to cell bodies in all layers of both areas which allows a grouping of the different species into three major groups: Homo sapiens has the largest, great apes a markedly lower, and macaque the lowest neuropil volume. This indicates considerably more space for local and interregional connectivity in human brains, which matches recent studies of fiber tracts and spacing of cortical minicolumns because increasing connectivity also requires more space for axons and dendrites in the neuropil. The evolutionary enlargement of neuropil is, therefore, a major structural difference between humans and non-human primates which may correspond to the underlying functional differences.