scholarly journals Why not record from every electrode with a CMOS scanning probe?

2018 ◽  
Author(s):  
George Dimitriadis ◽  
Joana P. Neto ◽  
Arno Aarts ◽  
Andrei Alexandru ◽  
Marco Ballini ◽  
...  

AbstractIt is an uninformative truism to state that the brain operates at multiple spatial and temporal scales, each with each own set of emergent phenomena. More worthy of attention is the point that our current understanding of it cannot clearly indicate which of these phenomenological scales are the significant contributors to the brain’s function and primary output (i.e. behaviour). Apart from the sheer complexity of the problem, a major contributing factor to this state of affairs is the lack of instrumentation that can simultaneously address these multiple scales without causing function altering damages to the underlying tissue. One important facet of this problem is that standard neural recording devices normally require one output connection per electrode. This limits the number of electrodes that can fit along the thin shafts of implantable probes generating a limiting balance between density and spread. Sharing a single output connection between multiple electrodes relaxes this constraint and permits designs of ultra-high density probes.Here we report the design and in-vivo validation of such a device, a complementary metal-oxide-semiconductor (CMOS) scanning probe with 1344 electrodes; the outcome of the European research project NeuroSeeker. We show that this design targets both local and global spatial scales by allowing the simultaneous recording of more than 1000 neurons spanning 7 functional regions with a single shaft. The neurons show similar recording longevity and signal to noise ratio to passive probes of comparable size and no adverse effects in awake or anesthetized animals. Addressing the data management of this device we also present novel visualization and monitoring methods. Using the probe with freely moving animals we show how accessing a number of cortical and subcortical brain regions offers a novel perspective on how the brain operates around salient behavioural events. Finally, we compare this probe with lower density, non CMOS designs (which have to adhere to the one electrode per output line rule). We show that an increase in density results in capturing neural firing patterns, undetectable by lower density devices, which correlate to self-similar structures inherent in complex naturalistic behaviour.To help design electrode configurations for future, even higher density, CMOS probes, recordings from many different brain regions were obtained with an ultra-dense passive probe.


2013 ◽  
pp. 438-445
Author(s):  
Nobuyuki Okamura ◽  
Shozo Furumoto ◽  
Manabu Tashiro ◽  
Katsutoshi Furukawa ◽  
Hiroyuki Arai ◽  
...  

Alzheimer’s disease (AD) and many other neurodegenerative disorders belong to the family of protein misfolding diseases. These diseases are characterized by the deposition of insoluble protein aggregates containing an enriched ß-sheet structure. To evaluate PET amyloid-imaging tracer [11C]BF-227 as an agent for in vivo detection of various kinds of misfolded protein, a [11C]BF-227 PET study was performed in patients with various protein misfolding diseases, including AD, frontotemporal dementia (FTD), dementia with Lewy bodies (DLB), sporadic Creutzfeldt-Jakob disease (sCJD) and Gerstmann-Sträussler-Scheinker disease (GSS). BF-227 binds to ß-amyloid fibrils with high affinity. Most of the AD patients showed prominent retention of [11C]BF-227 in the neocortex. In addition, neocortical retention of BF-227 was observed in the subjects with mild cognitive impairment who converted to AD during follow-up. DLB patients had elevated [11C]BF-227 uptake in the neocortex. However, FTD and sCJD patients showed no cortical retention of [11C]BF-227. Patients with multiple system atrophy had elevated BF-227 binding in the putamen. Finally, GSS patients had elevated BF-227 uptake in the cerebellum and other brain regions. This chapter confirms that BF-227 can selectively bind to a-synuclein and prion protein deposits using postmortem brain samples. Based on these findings, [11C]BF-227 is not necessarily specific for ß-amyloid in AD patients. However, this tracer could be used to detect various types of protein aggregates in the brain.



Brain ◽  
2020 ◽  
Vol 143 (5) ◽  
pp. 1476-1497 ◽  
Author(s):  
Min Guo ◽  
Jian Wang ◽  
Yanxin Zhao ◽  
Yiwei Feng ◽  
Sida Han ◽  
...  

Abstract Accumulation of neuronal α-synuclein is a prominent feature in Parkinson’s disease. More recently, such abnormal protein aggregation has been reported to spread from cell to cell and exosomes are considered as important mediators. The focus of such research, however, has been primarily in neurons. Given the increasing recognition of the importance of non-cell autonomous-mediated neurotoxicity, it is critical to investigate the contribution of glia to α-synuclein aggregation and spread. Microglia are the primary phagocytes in the brain and have been well-documented as inducers of neuroinflammation. How and to what extent microglia and their exosomes impact α-synuclein pathology has not been well delineated. We report here that when treated with human α-synuclein preformed fibrils, exosomes containing α-synuclein released by microglia are fully capable of inducing protein aggregation in the recipient neurons. Additionally, when combined with microglial proinflammatory cytokines, these exosomes further increased protein aggregation in neurons. Inhibition of exosome synthesis in microglia reduced α-synuclein transmission. The in vivo significance of these exosomes was demonstrated by stereotaxic injection of exosomes isolated from α-synuclein preformed fibrils treated microglia into the mouse striatum. Phosphorylated α-synuclein was observed in multiple brain regions consistent with their neuronal connectivity. These animals also exhibited neurodegeneration in the nigrostriatal pathway in a time-dependent manner. Depleting microglia in vivo dramatically suppressed the transmission of α-synuclein after stereotaxic injection of preformed fibrils. Mechanistically, we report here that α-synuclein preformed fibrils impaired autophagy flux by upregulating PELI1, which in turn, resulted in degradation of LAMP2 in activated microglia. More importantly, by purifying microglia/macrophage derived exosomes in the CSF of Parkinson’s disease patients, we confirmed the presence of α-synuclein oligomer in CD11b+ exosomes, which were able to induce α-synuclein aggregation in neurons, further supporting the translational aspect of this study. Taken together, our study supports the view that microglial exosomes contribute to the progression of α-synuclein pathology and therefore, they may serve as a promising therapeutic target for Parkinson’s disease.



Molecules ◽  
2020 ◽  
Vol 25 (19) ◽  
pp. 4496 ◽  
Author(s):  
Inbar Schlachet ◽  
Hen Moshe Halamish ◽  
Alejandro Sosnik

Intranasal (i.n.) administration became an alternative strategy to bypass the blood–brain barrier and improve drug bioavailability in the brain. The main goal of this work was to preliminarily study the biodistribution of mixed amphiphilic mucoadhesive nanoparticles made of chitosan-g-poly(methyl methacrylate) and poly(vinyl alcohol)-g-poly(methyl methacrylate) and ionotropically crosslinked with sodium tripolyphosphate in the brain after intravenous (i.v.) and i.n. administration to Hsd:ICR mice. After i.v. administration, the highest nanoparticle accumulation was detected in the liver, among other peripheral organs. After i.n. administration of a 10-times smaller nanoparticle dose, the accumulation of the nanoparticles in off-target organs was much lower than after i.v. injection. In particular, the accumulation of the nanoparticles in the liver was 20 times lower than by i.v. When brains were analyzed separately, intravenously administered nanoparticles accumulated mainly in the “top” brain, reaching a maximum after 1 h. Conversely, in i.n. administration, nanoparticles were detected in the “bottom” brain and the head (maximum reached after 2 h) owing to their retention in the nasal mucosa and could serve as a reservoir from which the drug is released and transported to the brain over time. Overall, results indicate that i.n. nanoparticles reach similar brain bioavailability, though with a 10-fold smaller dose, and accumulate in off-target organs to a more limited extent and only after redistribution through the systemic circulation. At the same time, both administration routes seem to lead to differential accumulation in brain regions, and thus, they could be beneficial in the treatment of different medical conditions.



2020 ◽  
Vol 117 (33) ◽  
pp. 20244-20253 ◽  
Author(s):  
Muhua Zheng ◽  
Antoine Allard ◽  
Patric Hagmann ◽  
Yasser Alemán-Gómez ◽  
M. Ángeles Serrano

Structural connectivity in the brain is typically studied by reducing its observation to a single spatial resolution. However, the brain possesses a rich architecture organized over multiple scales linked to one another. We explored the multiscale organization of human connectomes using datasets of healthy subjects reconstructed at five different resolutions. We found that the structure of the human brain remains self-similar when the resolution of observation is progressively decreased by hierarchical coarse-graining of the anatomical regions. Strikingly, a geometric network model, where distances are not Euclidean, predicts the multiscale properties of connectomes, including self-similarity. The model relies on the application of a geometric renormalization protocol which decreases the resolution by coarse-graining and averaging over short similarity distances. Our results suggest that simple organizing principles underlie the multiscale architecture of human structural brain networks, where the same connectivity law dictates short- and long-range connections between different brain regions over many resolutions. The implications are varied and can be substantial for fundamental debates, such as whether the brain is working near a critical point, as well as for applications including advanced tools to simplify the digital reconstruction and simulation of the brain.



2006 ◽  
Vol 86 (3) ◽  
pp. 451-463 ◽  
Author(s):  
A J VandenBygaart

The distribution of soil organic carbon (SOC) in the landscape is governed by multiple factors and processes occurring at multiple scales. Thus, an understanding of landscape processes and pedology should aid in designing approaches to study SOC stock changes. Numerous factors affect distribution of SOC in the landscape at varying spatial and temporal scales. Each of these is summarized to set the stage for outlining a proposed approach to monitoring SOC in the agricultural landscape. Many tools are used to assess the variability of soil properties at varying spatial scales. Pedological knowledge and interpretation of landscape processes can be used to understand the spatial distribution of SOC in the landscape. I show that semi-variograms and the minimum detectable difference may be of limited value in deriving a universal approach to assess SOC change. Issues to be considered or resolved before initiating a monitoring system include depth of sampling and influence of management, compositing and sub-sampling, changes in bulk density, landscape effects and SOC dynamics. After considering these issues, I propose an approach to monitor SOC stock change in agroecosystems, acknowledging that any methodology likely cannot be strictly and universally applicable. The approach considers issues such as location, plot layout, and experimental and statistical design. Such an approach, derived from a landscape and pedology perspective, may make the measurement and verification of SOC at varying scales a less daunting task. Key words: Soil organic carbon change, landscape, pedology, experimental design



Author(s):  
Nobuyuki Okamura ◽  
Shozo Furumoto ◽  
Manabu Tashiro ◽  
Katsutoshi Furukawa ◽  
Hiroyuki Arai ◽  
...  

Alzheimer’s disease (AD) and many other neurodegenerative disorders belong to the family of protein misfolding diseases. These diseases are characterized by the deposition of insoluble protein aggregates containing an enriched ß-sheet structure. To evaluate PET amyloid-imaging tracer [11C]BF-227 as an agent for in vivo detection of various kinds of misfolded protein, a [11C]BF-227 PET study was performed in patients with various protein misfolding diseases, including AD, frontotemporal dementia (FTD), dementia with Lewy bodies (DLB), sporadic Creutzfeldt-Jakob disease (sCJD) and Gerstmann-Sträussler-Scheinker disease (GSS). BF-227 binds to ß-amyloid fibrils with high affinity. Most of the AD patients showed prominent retention of [11C]BF-227 in the neocortex. In addition, neocortical retention of BF-227 was observed in the subjects with mild cognitive impairment who converted to AD during follow-up. DLB patients had elevated [11C]BF-227 uptake in the neocortex. However, FTD and sCJD patients showed no cortical retention of [11C]BF-227. Patients with multiple system atrophy had elevated BF-227 binding in the putamen. Finally, GSS patients had elevated BF-227 uptake in the cerebellum and other brain regions. This chapter confirms that BF-227 can selectively bind to a-synuclein and prion protein deposits using postmortem brain samples. Based on these findings, [11C]BF-227 is not necessarily specific for ß-amyloid in AD patients. However, this tracer could be used to detect various types of protein aggregates in the brain.



2015 ◽  
Vol 370 (1668) ◽  
pp. 20140165 ◽  
Author(s):  
Leonardo L. Gollo ◽  
Andrew Zalesky ◽  
R. Matthew Hutchison ◽  
Martijn van den Heuvel ◽  
Michael Breakspear

For more than a century, cerebral cartography has been driven by investigations of structural and morphological properties of the brain across spatial scales and the temporal/functional phenomena that emerge from these underlying features. The next era of brain mapping will be driven by studies that consider both of these components of brain organization simultaneously—elucidating their interactions and dependencies. Using this guiding principle, we explored the origin of slowly fluctuating patterns of synchronization within the topological core of brain regions known as the rich club, implicated in the regulation of mood and introspection. We find that a constellation of densely interconnected regions that constitute the rich club (including the anterior insula, amygdala and precuneus) play a central role in promoting a stable, dynamical core of spontaneous activity in the primate cortex. The slow timescales are well matched to the regulation of internal visceral states, corresponding to the somatic correlates of mood and anxiety. In contrast, the topology of the surrounding ‘feeder’ cortical regions shows unstable, rapidly fluctuating dynamics likely to be crucial for fast perceptual processes. We discuss these findings in relation to psychiatric disorders and the future of connectomics.



2017 ◽  
Author(s):  
Giri P. Krishnan ◽  
Oscar C. González ◽  
Maxim Bazhenov

AbstractResting or baseline state low frequency (0.01-0.2 Hz) brain activity has been observed in fMRI, EEG and LFP recordings. These fluctuations were found to be correlated across brain regions, and are thought to reflect neuronal activity fluctuations between functionally connected areas of the brain. However, the origin of these infra-slow fluctuations remains unknown. Here, using a detailed computational model of the brain network, we show that spontaneous infra-slow (< 0.05 Hz) fluctuations could originate due to the ion concentration dynamics. The computational model implemented dynamics for intra and extracellular K+ and Na+ and intracellular Cl- ions, Na+/K+ exchange pump, and KCC2 co-transporter. In the network model representing resting awake-like brain state, we observed slow fluctuations in the extracellular K+ concentration, Na+/K+ pump activation, firing rate of neurons and local field potentials. Holding K+ concentration constant prevented generation of these fluctuations. The amplitude and peak frequency of this activity were modulated by Na+/K+ pump, AMPA/GABA synaptic currents and glial properties. Further, in a large-scale network with long-range connections based on CoCoMac connectivity data, the infra-slow fluctuations became synchronized among remote clusters similar to the resting-state networks observed in vivo. Overall, our study proposes that ion concentration dynamics mediated by neuronal and glial activity may contribute to the generation of very slow spontaneous fluctuations of brain activity that are observed as the resting-state fluctuations in fMRI and EEG recordings.



2018 ◽  
Author(s):  
Célian Bimbard ◽  
Charlie Demené ◽  
Constantin Girard ◽  
Susanne Radtke-Schuller ◽  
Shihab Shamma ◽  
...  

A major challenge in neuroscience is to longitudinally monitor whole brain activity across multiple spatial scales in the same animal. Functional UltraSound (fUS) is an emerging technology that offers images of cerebral blood volume over large brain portions. Here we show for the first time its capability to resolve the functional organization of sensory systems at multiple scales in awake animals, both within structures by precisely mapping sensory responses, and between structures by elucidating the connectivity scheme of top-down projections. We demonstrate that fUS provides stable (over days), yet rapid, highly-resolved 3D tonotopic maps in the auditory pathway of awake ferrets, with unprecedented sharp functional resolution (100μm). This was performed in four different brain regions, including small (1-2mm3 size), subcortical (8mm deep) and previously undescribed structures in the ferret. Furthermore, we used fUS to map longdistance projections from frontal cortex, a key source of sensory response modulation, to auditory cortex.



2020 ◽  
Vol 10 (3) ◽  
pp. 5552-5555

An Oxylite/LDF system (Oxford Optronix, UK) driven by a sensor made of optical fibres for the tissue oxygen tension (pO2) and for the Laser Doppler Blood Flow (BF) was implemented. This has allowed pO2 and BF real time measurements in discrete brain areas of anaesthetised rats that were then challenged with exogenous oxygen (O2) and carbon dioxide (CO2). The results gathered were compared with data obtained following treatment with drugs that have excitatory influence upon the brain activity such as amphetamine or with a central nervous system (CNS) depressant such as CI-966. Altogether these experiments support the methodology for in vivo investigation of pharmacological effects on cerebral oxygen metabolism and could provide new understandings on the effects of psychostimulants and anticonvulsants on selected brain regions.



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