Biology subjects

Theys, T.

Publications and source records attributed to Theys, T..

12 recordsLinked to original sources

bioRxiv2026

Epicranial electrical stimulation improves non-navigational spatial memory in macaque monkeys

BackgroundThe hippocampus and medial temporal lobe are crucial for spatial memory, and their dysfunction is linked to Alzheimers disease (AD), with changes detectable even in preclinical stages. Recently, neuromodulation has gained interest as a potential treatment due to its beneficial effects on AD pathology and cognitive performance. However, outcomes vary significantly based on stimulation parameters and study conditions, and evidence from large animal models remains limited. ObjectiveTo assess whether epicranial current stimulation (ECS) at 40 Hz can improve non-navigational spatial memory and hippocampal activations. MethodsThree rhesus macaques were implanted with spiral platinum electrodes bilaterally on the skull and were trained in a non-navigational spatial memory task. ECS was applied at 40 Hz or at 10 Hz and performance across multiple sessions was evaluated. We further performed ECS during fMRI to examine the spread of activations caused by ECS across the brain in a block-design experiment. ResultsECS at 40 Hz improved performance in a non-navigational spatial memory task, while 10 Hz ECS had minimal or negative effects. Concurrent ECS-fMRI showed extensive brain activations at 40 Hz, including significant hippocampal activations, which was not observed at 10 Hz. ConclusionsOur results show that ECS could be a minimally-invasive and effective approach to improve memory performance and activate the hippocampus. ECS could represent a potential treatment for patients suffering from memory impairment.

neuroscience↗

bioRxiv2025

An intracortical brain-machine interface based on macaque ventral premotor activity

The majority of brain-machine interface (BMI) studies have focused on decoding intended movements based on neural activity of primary motor (M1) and dorsal premotor cortex (PMd). The ventral premotor cortex (PMv), and more specifically area F5c, has been implicated in object grasping and action observation, and may represent an alternative for motor BMI control due to its phasic modulation during action observation. Using chronically implanted Utah arrays in F5c, PMd, and M1 in two male macaques, we compared the efficacy of controlling a motor BMI based on neural activity of each area. PMv decoding reached similar or even higher success rates than M1 and PMd in a 2D cursor control task, especially when controlling for the number of motion selective channels that were used by the decoder. We found similar results during a 2D robot avatar control task in a simulated 3D environment. At both the multi-unit and the population level, neural responses were highly similar during the training phase (passive observation of cursor movements) and the online decoding phase, and only a small subset of neurons modulated its selectivity for the direction of motion. Thus, ventral premotor area F5c may represent an alternative for online motor BMI control. Significance statementWe present the first study on online cursor and robot avatar control using neural activity of ventral premotor cortical area F5c. Known for decades for the presence of mirror neurons, which are active during both action execution and action observation, area F5c can support online BMI control with performance comparable to that of dorsal premotor and primary motor cortex. The population dynamics in all three areas were highly similar between the training phase and the online decoding phase.

neuroscience↗

bioRxiv2024

Fine-grained neural coding of bodies and body parts in human visual cortex

The visual image of a human body provides a valuable source of socially relevant information. However, our understanding of the neuronal mechanisms underlying body perception in humans remains limited given the spatiotemporal constraints of functional imaging. Here we recorded multi-unit spiking activity in two neurosurgical patients in or near the extrastriate body area (EBA), a critical region for body perception. Our recordings revealed a strong preference for human bodies over a large range of control stimuli. Notably, this preference was driven by a distinct selectivity for body parts. Moreover, the observed body selectivity generalized to non-photographic depictions of bodies such as silhouettes and stick figures. Overall, our study provides an unprecedented access into the representation of bodies in the human visual cortex to bridge the gap between human neuroimaging and macaque electrophysiology studies, and form a solid basis for computational models of human body processing.

neuroscience↗

bioRxiv2023

Neuronal tuning and population representations of shape and category in human visual cortex.

Object recognition and categorization are essential cognitive processes which engage considerable neural resources in the human ventral visual stream. However, the tuning properties of human ventral stream neurons for object shape and category are virtually unknown. We performed the first large-scale recordings of spiking activity in human Lateral Occipital Complex in response to stimuli in which the shape dimension was dissociated from the category dimension. Consistent with studies in nonhuman primates, the neuronal representations were primarily shape-based, although we also observed category-like encoding for images of animals. Surprisingly, linear decoders could reliably classify stimulus category even in data sets that were entirely shape-based. In addition, many tuning curves showed an interaction between shape and category tuning. These results represent the first detailed study on shape and category coding at the neuronal level in the human ventral visual stream, furnishing essential evidence that reconciles human imaging and macaque single-cell studies.

neuroscience↗

bioRxiv2022

LRRC37B is a species-specific regulator of voltage-gated channels and excitability in human cortical neurons

The enhanced cognitive abilities characterizing the human species result from specialized features of neurons and circuits, but the underlying molecular mechanisms remain largely unknown. Here we report that the hominid-specific gene LRRC37B encodes a novel receptor expressed in a subset of human cortical pyramidal neurons (CPNs). LRRC37B protein localizes at the axon initial segment (AIS), the specialized domain triggering action potentials. LRRC37B ectopic expression in mouse CPNs in vivo leads to reduced intrinsic excitability, a distinctive feature of some classes of human CPNs. At the molecular level, LRRC37B acts as a receptor for the secreted ligand FGF13A and interacts with the voltage gated sodium channel (VGSC) beta subunit SCN1B, thereby inhibiting the channel function of VGSC, specifically at the AIS. Electrophysiological recordings in adult human cortical slices reveals that endogenous expression of LRRC37B in human CPNs reduces neuronal excitability. LRRC37B thus acts as a species-specific modifier of human cortical neuron function, with important implications for human brain evolution and diseases.

neuroscience↗

bioRxiv2022

Deep proteomic analysis of human microglia and model systems reveal fundamental biological differences of in vitro and ex vivo cells

Using high resolution quantitative mass spectrometry, we have generated the most comprehensive human and mouse microglia proteomic datasets to date, consisting of over 11,000 proteins across all six microglia groups. Microglia from different sources share a core protein signature of over 5600 proteins, yet fundamental differences are observed between species and culture conditions, indicating limitations for human disease modelling in mouse or in in vitro cultures of microglia. Mouse ex vivo microglia show important differences at the proteome level such as differential expression of inflammation and Alzheimers Disease associated proteins. We identify a tenfold difference in the protein content of ex vivo and in vitro cells and significant proteome differences associated with protein synthesis, metabolism, microglia marker expression and environmental sensors. Culturing microglia induces rapidly increased growth, protein content and inflammatory protein expression. These changes can be restored by engrafting in vitro cells into the brain, with xenografted hESC-derived microglia closely resembling microglia from human brain. This data provides an important resource for the field and highlights important considerations needed when using model systems to study human physiology and pathology of microglia.

neuroscience↗

bioRxiv2021

An atlas of white matter anatomy, its variability, and reproducibility based on Constrained Spherical Deconvolution of diffusion MRI

Virtual dissection of white matter (WM) using diffusion MRI tractography is confounded by its poor reproducibility. Despite the increased adoption of advanced reconstruction models, early region-of-interest driven protocols based on diffusion tensor imaging (DTI) remain the dominant reference for virtual dissection protocols. Here we bridge this gap by providing a comprehensive description of typical WM anatomy reconstructed using a reproducible automated subject-specific parcellation-based approach based on probabilistic constrained-spherical deconvolution (CSD) tractography. We complement this with a WM template in MNI space comprising 68 bundles, including all associated anatomical tract selection labels and associated automated workflows. Additionally, we demonstrate bundle inter- and intra-subject variability using 40 (20 test-retest) datasets from the human connectome project (HCP) and 5 sessions with varying b-values and number of b-shells from the single-subject Multiple Acquisitions for Standardization of Structural Imaging Validation and Evaluation (MASSIVE) dataset. The most reliably reconstructed bundles were the whole pyramidal tracts, primary corticospinal tracts, whole superior longitudinal fasciculi, frontal, parietal and occipital segments of the corpus callosum and middle cerebellar peduncles. More variability was found in less dense bundles, e.g., the first segment of the superior longitudinal fasciculus, fornix, dentato-rubro-thalamic tract (DRTT), and premotor pyramidal tract. Using the DRTT as an example, we show that this variability can be reduced by using a higher number of seeding attempts. Overall inter-session similarity was high for HCP test-retest data (median weighted-dice = 0.963, stdev = 0.201 and IQR = 0.099). Compared to the HCP-template bundles there was a high level of agreement for the HCP test-retest data (median weighted-dice = 0.747, stdev = 0.220 and IQR = 0.277) and for the MASSIVE data (median weighted-dice = 0.767, stdev = 0.255 and IQR = 0.338). In summary, this WM atlas provides an overview of the capabilities and limitations of automated subject-specific probabilistic CSD tractography for mapping white matter fasciculi in healthy adults. It will be most useful in applications requiring a highly reproducible parcellation-based dissection protocol, as well as being an educational resource for applied neuroimaging and clinical professionals. O_FIG O_LINKSMALLFIG WIDTH=182 HEIGHT=200 SRC="FIGDIR/small/464139v2_ufig1.gif" ALT="Figure 1"> View larger version (52K): org.highwire.dtl.DTLVardef@18e7c79org.highwire.dtl.DTLVardef@18e2213org.highwire.dtl.DTLVardef@5f124borg.highwire.dtl.DTLVardef@1aa242c_HPS_FORMAT_FIGEXP M_FIG Graphical abstract(Top) shows the FWT pipeline for both CSTs, AF, and motor CC bundles. (Left to right) show the required input structural parcellation maps and a priori atlases for FWT and the resulting virtual dissection include/exclude VOIs. FWT provides two approaches to virtual dissection: (1) is a bundle-specific approach where streamlines are only seeded for the bundle of interest, (2) is a whole brain tractography followed by streamlines segmentation, (top right) shows output tractograms. (Middle) Group-averaged T1 and fODF images are generated from the HCP test-retest data, and FWT is applied to generate the HCP-atlas using the bundle-specific approach (1*). FWTs whole brain tracking and segmentation approach (2*) was applied to the HCP and MASSIVE dataset (right and left) and conducted model-based, and pair-wise similarity analyses and generated voxel-wise cumulative maps per bundle. FWT= Fun With Tracts, FS= FreeSurfer, MSBP= MultiScaleBrainParcellator, PD25= NIST Parkinsons histological, JHU= Johns Hopkins university, Juelich= Juelich university histological atlas, AC/PC= anterior commissure/posterior commissure) UKBB= UK Biobank, SUIT (spatially unbiased cerebellar atlas template), dMRI= diffusion magnetic resonance imaging, CSD= constrained spherical deconvolution, fODF= fiber orientation distribution function, CST= corticospinal tract, AF= arcuate fasciculus, CC= corpus callosum, HCP= human connectome project, MASSIVE= Multiple acquisitions for standardization of structural imaging validation and evaluation. C_FIG

neuroscience↗

bioRxiv2020

Face neurons in human visual cortex

The exquisite capacity of primates to detect and recognize faces is crucial for social interactions. Although disentangling the neural basis of human face recognition remains a key goal in neuroscience, direct evidence at the single-neuron level is virtually nonexistent. We recorded from face-selective neurons in human visual cortex, in a region characterized by functional magnetic resonance imaging (fMRI) activations for faces compared to objects (i.e. the occipital face area, OFA). The majority of visually responsive neurons in this fMRI activation showed strong selectivity at short latencies for faces compared to objects. Feature scrambled faces and face-like objects could also drive these neurons, suggesting that the OFA is not tightly-tuned to the visual attributes that typically define whole human faces. These single-cell recordings within the human face processing system provide vital experimental evidence linking previous imaging studies in humans and invasive studies in animal models.

neuroscience↗

bioRxiv2020

Temporal dynamics of neural activity in macaque frontal cortex assessed with large-scale recordings

We make eye movements to objects before grasping these objects, and the gaze direction generally indicates where the object will be grasped. Hence, the brain has to coordinate eye-, arm- and hand movements. We performed large-scale recordings (more than 2000 responsive sites) in frontal cortex of monkeys during a saccade-reach-grasp task. When an object appeared in peripheral vision, the first burst of activity emerged in prearcuate areas (the FEF and area 45B), followed by dorsal and ventral premotor cortex, and a buildup of activity in primary motor cortex. After the saccade, prearcuate activity remained elevated while primary motor and premotor activity rose in anticipation of the upcoming arm and hand movement. Some premotor and prearcuate sites were equally active when the object appeared in peripheral vision and at the fovea, suggesting a role in eye-hand coordination. Thus, a large part of lateral frontal cortex is active during a saccade-reach-grasp task.

neuroscience↗

bioRxiv2020

Single nucleus sequencing fails to detect microglial activation

Single nucleus RNA-Seq (snRNA-Seq) methods are used as an alternative to single cell RNA-Seq methods, as they allow transcriptomic profiling of frozen tissue. However, it is unclear whether snRNA-Seq is able to detect cellular state in human tissue. Indeed, snRNA-Seq analyses of human brain samples have failed to detect a consistent microglial activation signature in Alzheimers Disease. A comparison of microglia from single cells and single nuclei of four human subjects reveals that ~1% of genes is depleted in nuclei compared to whole cells. This small population contains 18% of genes previously implicated in microglial activation, including APOE, CST3, FTL, SPP1, and CD74. We confirm our findings across multiple previous single nucleus and single cell studies. Given the low sensitivity of snRNA-Seq to this population of activation genes, we conclude that snRNA-Seq is not suited to detecting cellular activation in microglia in human disease.

neuroscience↗

bioRxiv2019

Single-cell selectivity and functional architecture of human lateral occipital complex.

The human lateral occipital complex (LOC) is more strongly activated by images of objects compared to scrambled controls, but detailed information at the neuronal level is currently lacking. We recorded with microelectrode arrays in the LOC of two patients, and obtained highly selective single-unit, multi-unit and high-gamma responses to images of objects. Contrary to predictions derived from functional imaging studies, all neuronal properties indicated that the subsector of LOC we recorded from occupies an unexpectedly high position in the hierarchy of visual areas. Notably, the response latencies of LOC neurons were long, the shape selectivity was spatially clustered, LOC receptive fields were large and bilateral, and a number of LOC neurons exhibited 3D-structure selectivity (a preference for convex or concave stimuli), which are all properties typical of end-stage ventral stream areas. Thus, our results challenge prevailing ideas about the position of the LOC in the hierarchy of visual areas.

neuroscience↗

bioRxiv2019

Stem cell derived human microglia transplanted in mouse brain to study genetic risk of Alzheimer's Disease

Summary paragraphGenetics highlight the central role of microglia in Alzheimers disease but at least 36% of AD-risk genes lack good mouse orthologues. Here, we show that embryonic stem cell (ESC)-derived human microglia successfully engraft the mouse brain and recapitulate transcriptionally primary human microglia derived from human surgical samples. Upon exposure to oligomeric A{beta} a wide range of AD-risk genes are expressed that are not readily studied in current mouse models for AD. This work provides a unique humanized animal model that will allow elucidating the role of genetic risk in the pathogenesis of AD.

neuroscience↗