The Netherlands Institute for Neuroscience (NIN) (Dutch: Nederlands Herseninstituut) is a research institute of the Royal Netherlands Academy of Arts and Sciences (KNAW) that carries out neuroscience research with special emphasis on the brain and visual system. Although the institute's focus is on understanding the fundamental mechanisms underlying brain function, its research spans the development, plasticity and aging of the brain and is often linked to clinical research questions. The research program is carried out in 17 research groups. In addition, the NIN includes the Netherlands Brain Bank and the Netherlands Sleep Registry..
Perivascular aggregations of leukocytes, referred to as perivascular cuffs, are a pathological phenomenon in progressive multiple sclerosis (MS). Perivascular cuffing is an exaggerated form of compartmentalized inflammation present in progressive disease. By studying traits of perivascular cuffs, this study aims to elucidate processes within the perivascular niche of the MS brain. We characterized n = 255 MS donors from the Netherlands Brain Bank for the presence of perivascular cuffs and investigated their association with clinical and pathological donor characteristics. Furthermore, we examined the proportional abundance of different cell types and functional markers in n = 457 perivascular cuffs present in different lesion stages within a cohort of n = 18 MS brain donors. MS donors with detected perivascular cuffs (25.5
To perceive and navigate complex sensory environments, animals combine sensory information from multiple modalities in specialized brain circuits. Known as multisensory integration, this process typically depends on the existence of co-aligned topographic connections from several sensory areas to downstream circuits exhibiting multimodal representations. How such topographically co-aligned connectivity necessary for multisensory integration gets set up in early stages of development is still unknown. Inspired by the role of spontaneous activity in refining topographic connectivity between early sensory circuits, here we investigated the potential of such spontaneous activity to also guide the co-alignment of multiple sensory modalities in RL, a higher-order associative cortical area rostro-lateral to V1. Analyzing spontaneous activity simultaneously recorded in primary visual and somatosensory cortex and area RL at different developmental ages before sensory experience, we identify candidate features of this activity to guide the emergence of co-aligned topographic multisensory projections with somatosensory leading the visual projection. We confirm this hypothesis using a computational model of activity-dependent circuit refinement, and show that the correlation of spontaneous activity between the visual and somatosensory primary cortex can establish an optimal fraction of multisensory neurons in RL for stimulus decoding. Our model provides an exciting new computational perspective of the role of spontaneous activity in the emergence of topographically co-aligned multimodal sensory representations in downstream circuits, specialized for the processing of rich sensory environments.
INTRODUCTION:Although it has become clear that alterations in lipid metabolism are associated with Alzheimer's disease (AD), it is unclear how they contribute to both cognitive decline and the pathophysiology of AD. METHODS:Lipidomics and activity-based protein profiling (ABPP) were performed in the frontal cortex of control, AD and resilient donors, that is, individuals with AD pathology without cognitive decline. RESULTS:The most pronounced alterations in lipids were in ω6-derived oxylipins, which were particularly increased in AD. Triacylglycerols (TAGs) and lipid droplets (LDs) were more abundant in the AD donors compared to the resilient donors. Multi-omics factor analysis (MOFA) showed that increased ω6-derived oxylipins and the loss of inhibitory neurons were associated with amyloid beta (Aβ) plaque load. DISCUSSION:Our multi-omics data show a molecular response associated with Aβ load shared among AD and resilient donors, but reduced LDs in resilient donors compared to AD. HIGHLIGHTS:Comprehensive lipidomics analysis of frontal cortex from controls, Alzheimer's disease (AD) patients and resilient individuals. ω6 Oxylipins, markers of neuroinflammation, are increased in both AD and resilience. Resilient donors have reduced triacylglycerols and lipid droplets compared to AD. Multi-omics integration shows a molecular response to amyloid beta plaques associated with ω6-derived oxylipins and loss of interneurons.
Brain stimulation is a powerful tool for understanding cortical function and holds the promise of therapeutic interventions to treat neuropsychiatric disorders such as impaired vision. Prototypical approaches to visual prosthetics apply patterns of electric microstimulation to the early visual cortex and can evoke percepts of simple symbols such as letters. However, these approaches are limited by the number of electrodes that can be implanted in early visual regions. Instead, higher-level visual regions are known to underlie the representations of complex visual objects such as faces and scenes and thus constitute a promising target for stimulating the cortex to elicit more complex visual experience. We developed a computational framework composed of two main components to address the challenge of stimulating cortex in high-dimensional object space spanned by higher-level visual cortex: 1. a causally predictive model that predicts primate behavior from image and stimulation input via topographic models and perturbation modules. 2. a mapping procedure that translates optimal model stimulation sites to monkey cortex. Testing our approach in two macaque monkeys that perform a visual recognition task, our results suggest that model-guided microstimulation is a promising approach to steer complex visual behavior. This proof-of-principle establishes a foundation for next-generation visual prosthetics that could restore complex visual experiences by stimulating higher-level visual cortex.
Reliably detecting consciousness in unresponsive patients remains an urgent ethical and clinical challenge, as no behavior-independent marker is currently accepted in clinical practice. We characterize consciousness as linked to a representation of the embodied subject of experience, mediated by multisensory integration within the peripersonal space (PPS) system. We test whether a neural marker of PPS representation could detect consciousness and predict clinical outcome in disorders of consciousness (DoC) patients. Using high-density electroencephalography (EEG) during a task-free audiotactile task, we derive a PPS index based on high-beta oscillations. In healthy participants, the PPS index is present during wakefulness and dreaming, but absent in dreamless sleep. In 72 DoC patients, the PPS index correlates with behavioral measures of consciousness and predicts recovery at discharge. The index is associated with forebrain mesocircuit integrity. These findings highlight a bedside-compatible electrophysiological marker with potential clinical utility for detecting covert consciousness and predicting outcomes in non-responsive patients.
