scholarly journals Targeted cortical reorganization using optogenetics in non-human primates

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Azadeh Yazdan-Shahmorad ◽  
Daniel B Silversmith ◽  
Viktor Kharazia ◽  
Philip N Sabes
Keyword(s):  
Large Scale ◽  
Network Connectivity ◽  
Cortical Reorganization ◽  
Strongly Correlated ◽  
Hebbian Plasticity ◽  
Two Measures ◽  
Evoked Activity ◽  
Large Scale Networks ◽  
Induced Changes ◽  
Stimulation Of

Brain stimulation modulates the excitability of neural circuits and drives neuroplasticity. While the local effects of stimulation have been an active area of investigation, the effects on large-scale networks remain largely unexplored. We studied stimulation-induced changes in network dynamics in two macaques. A large-scale optogenetic interface enabled simultaneous stimulation of excitatory neurons and electrocorticographic recording across primary somatosensory (S1) and motor (M1) cortex (Yazdan-Shahmorad et al., 2016). We tracked two measures of network connectivity, the network response to focal stimulation and the baseline coherence between pairs of electrodes; these were strongly correlated before stimulation. Within minutes, stimulation in S1 or M1 significantly strengthened the gross functional connectivity between these areas. At a finer scale, stimulation led to heterogeneous connectivity changes across the network. These changes reflected the correlations introduced by stimulation-evoked activity, consistent with Hebbian plasticity models. This work extends Hebbian plasticity models to large-scale circuits, with significant implications for stimulation-based neurorehabilitation.

scholarly journals Effects of dopamine agonist treatment on resting-state network connectivity in Parkinson’s disease

2020 ◽  
Author(s):  
David M. Cole ◽  
Bahram Mohammadi ◽  
Maria Milenkova ◽  
Katja Kollewe ◽  
Christoph Schrader ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Decision Making ◽  
Parkinson's Disease ◽  
Basal Ganglia ◽  
Dopamine Agonist ◽  
Resting State ◽  
Large Scale ◽  
Network Connectivity ◽  
Resting State Network ◽  
Large Scale Networks

ABSTRACTDopamine agonist (DA) medications commonly used to treat, or ‘normalise’, motor symptoms of Parkinson’s disease (PD) may lead to cognitive-neuropsychiatric side effects, such as increased impulsivity in decision-making. Subject-dependent variation in the neural response to dopamine modulation within cortico-basal ganglia circuitry is thought to play a key role in these latter, non-motor DA effects. This neuroimaging study combined resting-state functional magnetic resonance imaging (fMRI) with DA modification in patients with idiopathic PD, investigating whether brain ‘resting-state network’ (RSN) functional connectivity metrics identify disease-relevant effects of dopamine on systems-level neural processing. By comparing patients both ‘On’ and ‘Off’ their DA medications with age-matched, un-medicated healthy control subjects (HCs), we identified multiple non-normalising DA effects on frontal and basal ganglia RSN cortico-subcortical connectivity patterns in PD. Only a single isolated, potentially ‘normalising’, DA effect on RSN connectivity in sensori-motor systems was observed, within cerebro-cerebellar neurocircuitry. Impulsivity in reward-based decision-making was positively correlated with ventral striatal connectivity within basal ganglia circuitry in HCs, but not in PD patients. Overall, we provide brain systems-level evidence for anomalous DA effects in PD on large-scale networks supporting cognition and motivated behaviour. Moreover, findings suggest that dysfunctional striatal and basal ganglia signalling patterns in PD are compensated for by increased recruitment of other cortico-subcortical and cerebro-cerebellar systems.

scholarly journals Trips and Neurotransmitters: Discovering Principled Patterns across 6,850 Hallucinogenic Experiences

2021 ◽  
Author(s):  
Galen Ballentine ◽  
Sam Freesun Friedman ◽  
Danilo Bzdok
Keyword(s):  
Large Scale ◽  
Free Form ◽  
Association Cortex ◽  
Receptor Subtypes ◽  
Drug Induced ◽  
Psychological Phenomena ◽  
Input Pole ◽  
Large Scale Networks ◽  
Induced Changes ◽  
The Brain

Psychedelics are thought to alter states of consciousness by disrupting how the higher association cortex governs bottom-up sensory signals. Individual hallucinogenic drugs are usually studied in participants in controlled laboratory settings. Here, we have explored word usage in 6,850 free-form testimonials with 27 drugs through the prism of 40 neurotransmitter receptor subtypes, which were then mapped to 3D coordinates in the brain via their gene transcription levels from invasive tissue probes. Despite the variable subjective nature of hallucinogenic experiences, our pattern-learning approach delineated how drug-induced changes of conscious awareness (e.g., dissolving self-world boundaries or fractal distortion of visual perception) are linked to cortex-wide anatomical distributions of receptor density proxies. The dominant explanatory factor related ego-dissolution-like phenomena to a constellation of 5-HT2A, D2, KOR, and NMDA receptors, anchored especially in the brain's deep hierarchy (epitomized by the associative higher-order cortex) and shallow hierarchy (epitomized by the visual cortex). Additional factors captured psychological phenomena in which emotions (5-HT2A and Imidazoline1) were in tension with auditory (SERT, 5-HT1A) or visual (5-HT2A) sensations. Each discovered receptor-experience factor spanned between a higher-level association pole and a sensory input pole, which may relate to the previously reported collapse of hierarchical order among large-scale networks. Simultaneously considering many psychoactive molecules and thousands of natural language descriptions of drug experiences our framework finds the underlying semantic structure and maps it directly to the brain. These advances could assist in unlocking their wide-ranging potential for medical treatment.

scholarly journals Widespread attenuating changes in brain connectivity associated with the general factor of psychopathology in 9- and 10-year olds

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chandra Sripada ◽  
Mike Angstadt ◽  
Aman Taxali ◽  
Daniel Kessler ◽  
Tristan Greathouse ◽  
...  
Keyword(s):  
Large Scale ◽  
Brain Connectivity ◽  
Network Connectivity ◽  
Quadrant Analysis ◽  
Default Network ◽  
General Factor ◽  
Multiple Control ◽  
Control Networks ◽  
Large Scale Networks ◽  
P Factor

AbstractConvergent research identifies a general factor (“P factor”) that confers transdiagnostic risk for psychopathology. Large-scale networks are key organizational units of the human brain. However, studies of altered network connectivity patterns associated with the P factor are limited, especially in early adolescence when most mental disorders are first emerging. We studied 11,875 9- and 10-year olds from the Adolescent Brain and Cognitive Development (ABCD) study, of whom 6593 had high-quality resting-state scans. Network contingency analysis was used to identify altered interconnections associated with the P factor among 16 large-scale networks. These connectivity changes were then further characterized with quadrant analysis that quantified the directionality of P factor effects in relation to neurotypical patterns of positive versus negative connectivity across connections. The results showed that the P factor was associated with altered connectivity across 28 network cells (i.e., sets of connections linking pairs of networks); pPERMUTATION values < 0.05 FDR-corrected for multiple comparisons. Higher P factor scores were associated with hypoconnectivity within default network and hyperconnectivity between default network and multiple control networks. Among connections within these 28 significant cells, the P factor was predominantly associated with “attenuating” effects (67%; pPERMUTATION < 0.0002), i.e., reduced connectivity at neurotypically positive connections and increased connectivity at neurotypically negative connections. These results demonstrate that the general factor of psychopathology produces attenuating changes across multiple networks including default network, involved in spontaneous responses, and control networks involved in cognitive control. Moreover, they clarify mechanisms of transdiagnostic risk for psychopathology and invite further research into developmental causes of distributed attenuated connectivity.

scholarly journals Identifying and quantifying potential super-spreaders in social networks

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Dayong Zhang ◽  
Yang Wang ◽  
Zhaoxin Zhang
Keyword(s):  
Social Networks ◽  
Information Flow ◽  
Time Complexity ◽  
Large Scale ◽  
Network Connectivity ◽  
Sir Model ◽  
The Other ◽  
Nearest Neighbours ◽  
Large Scale Networks ◽  
Accuracy And Stability

Abstract Quantifying the nodal spreading abilities and identifying the potential influential spreaders has been one of the most engaging topics recently, which is essential and beneficial to facilitate information flow and ensure the stabilization operations of social networks. However, most of the existing algorithms just consider a fundamental quantification through combining a certain attribute of the nodes to measure the nodes’ importance. Moreover, reaching a balance between the accuracy and the simplicity of these algorithms is difficult. In order to accurately identify the potential super-spreaders, the CumulativeRank algorithm is proposed in the present study. This algorithm combines the local and global performances of nodes for measuring the nodal spreading abilities. In local performances, the proposed algorithm considers both the direct influence from the node’s neighbourhoods and the indirect influence from the nearest and the next nearest neighbours. On the other hand, in the global performances, the concept of the tenacity is introduced to assess the node’s prominent position in maintaining the network connectivity. Extensive experiments carried out with the Susceptible-Infected-Recovered (SIR) model on real-world social networks demonstrate the accuracy and stability of the proposed algorithm. Furthermore, the comparison of the proposed algorithm with the existing well-known algorithms shows that the proposed algorithm has lower time complexity and can be applicable to large-scale networks.

scholarly journals Distinct local and brain-wide networks are activated by layer-specific optogenetic stimulations of motor cortex

2020 ◽  
Author(s):  
Russell Chan ◽  
Mazen Asaad ◽  
Bradley Edelman ◽  
Hyun Joo Lee ◽  
Hillel Adesnik ◽  
...  
Keyword(s):  
Motor Cortex ◽  
System Architecture ◽  
Large Scale ◽  
Primary Motor Cortex ◽  
Cortical Circuits ◽  
Electrophysiological Recordings ◽  
Subcortical Regions ◽  
Large Scale Networks ◽  
Motor Thalamus ◽  
Stimulation Of

Abstract Primary motor cortex consists of a stack of interconnected but distinct layers, and plays a prominent role in motor control through large-scale networks. However, differential effects of M1 layer-specific functional pathways remain elusive, especially at the macroscopic and mesoscopic scales. Here, we combined layer-specific Cre-driver mouse lines, optogenetics, and fMRI with electrophysiological recordings to identify distinct M1 layer-specific networks. Neuronal activities initiated in L2/3 were mainly confined within M1, while stimulation of L4, L5, and L6 evoked distinct responses in M1 and motor-related subcortical regions, including the striatum and motor thalamus. Although motor cortex has long been considered agranular (without L4), our results structurally, functionally, and neurovascularly confirm the presence of L4. We also find that layer-specific fMRI responses closely couple with laminar electrophysiological recordings. Overall, our results elucidate distinct brain-wide neural archetypes of M1 layer-specific cortical circuits that provide important insights in uncovering the motor system architecture.

Thalamic and Cortical Contributions to Neural Plasticity After Limb Amputation

2000 ◽  
Vol 83 (5) ◽  
pp. 3154-3159 ◽  
Author(s):  
S. L. Florence ◽  
T. A. Hackett ◽  
F. Strata
Keyword(s):  
Neural Plasticity ◽  
Large Scale ◽  
Receptive Fields ◽  
Cortical Reorganization ◽  
Limb Amputation ◽  
The Face ◽  
The Relationship ◽  
Area 3B ◽  
Made In ◽  
Stimulation Of

Little is known about the substrates for the large-scale shifts in the cortical representation produced by limb amputation. Subcortical changes likely contribute to the cortical remodeling, yet there is little data regarding the extent and pattern of reorganization in thalamus after such a massive deafferentation. Moreover, the relationship between changes in thalamus and in cortex after injuries of this nature is virtually unexplored. Multiunit microelectrode maps were made in the somatosensory thalamus and cortex of two monkeys that had long-standing, accidental forelimb amputations. In the deprived portion of the ventroposterior nucleus of the thalamus (VP), where stimulation to the hand would normally activate neurons, new receptive fields had emerged. At some recording sites within the deprived zone of VP, neurons responded to stimulation of the remaining stump of the arm and at other sites neurons responded to stimulation of both the stump and the face. This same overall pattern of reorganization was present in the deprived hand representation of cortical area 3b. Thus thalamic changes produced by limb amputation appear to be an important substrate of cortical reorganization. However, a decrease in the frequency of abnormal stump/face fields in area 3b compared with VP and a reduction in the size of the fields suggests that cortical mechanisms of plasticity may refine the information relayed from thalamus.

scholarly journals COMICS: a community property-based triangle motif clustering scheme

2019 ◽  
Vol 5 ◽  
pp. e180 ◽  
Author(s):  
Yufan Feng ◽  
Shuo Yu ◽  
Kaiyuan Zhang ◽  
Xiangli Li ◽  
Zhaolong Ning
Keyword(s):  
Large Scale ◽  
Statistical Data ◽  
Network Connectivity ◽  
Network Structures ◽  
Human Beings ◽  
Network Partition ◽  
Community Property ◽  
High Efficient ◽  
Motif Clustering ◽  
Large Scale Networks

With the development of science and technology, network scales of various fields have experienced an amazing growth. Networks in the fields of biology, economics and society contain rich hidden information of human beings in the form of connectivity structures. Network analysis is generally modeled as network partition and community detection problems. In this paper, we construct a community property-based triangle motif clustering scheme (COMICS) containing a series of high efficient graph partition procedures and triangle motif-based clustering techniques. In COMICS, four network cuttingconditionsare considered based on the network connectivity. We first divide the large-scale networks into many dense subgraphs under the cuttingconditionsbefore leveraging triangle motifs to refine and specify the partition results. To demonstrate the superiority of our method, we implement the experiments on three large-scale networks, including two co-authorship networks (the American Physical Society (APS) and the Microsoft Academic Graph (MAG)), and two social networks (Facebook and gemsec-Deezer networks). We then use two clustering metrics, compactness and separation, to illustrate the accuracy and runtime of clustering results. A case study is further carried out on APS and MAG data sets, in which we construct a connection between network structures and statistical data with triangle motifs. Results show that our method outperforms others in both runtime and accuracy, and the triangle motif structures can bridge network structures and statistical data in the academic collaboration area.

Secretagogue-induced changes in subcellular Ca2+ distribution in isolated pancreatic acini

1981 ◽  
Vol 240 (2) ◽  
pp. G130-G140
Author(s):  
R. L. Dormer ◽  
J. A. Williams
Keyword(s):  
Atomic Absorption Spectrometry ◽  
High Speed ◽  
Microsomal Fraction ◽  
Absorption Spectrometry ◽  
Subcellular Fractionation ◽  
Differential Centrifugation ◽  
Zymogen Granules ◽  
Pancreatic Acini ◽  
Induced Changes ◽  
Stimulation Of

In a prior study, we demonstrated that pancreatic secretagogues increased both the uptake into and washout of 45Ca2+ from isolated mouse pancreatic acini. The net result of these processes was an initial fall in total acinar cell Ca2+ content. In the present study, we have employed subcellular fractionation of acini under conditions that minimized posthomogenization redistribution of Ca2+ in order to localize those organelles involved in intracellular Ca2+ fluxes. Homogenization and differential centrifugation of acini, preloaded with 45Ca2+ and subjected to a period of washout, showed that carbachol induced an increased loss of 45Ca2+ from all fractions isolated. The high-speed microsomal fraction lost 45Ca2+ to a greater extent than did whole acini; measurement of total Ca2+ by atomic absorption spectrometry showed a net loss of Ca2+ from this fraction. Purification of the lower-speed fractions indicated that carbachol increased 45Ca2+ exchange with both zymogen granules and mitochondria, but net Ca2+ levels in these organelles were unchanged. It was concluded that stimulation of pancreatic acini by carbachol results in the release of calcium from a microsomal compartment leading to a rise in cytoplasmic Ca2+, increased exchange with granule and mitochondrial Ca2+, and increased efflux of Ca2+ from the cell.

scholarly journals Contribution of Ionotropic Glutamatergic Receptors to Excitability and Attentional Signals in Macaque Frontal Eye Field

2021 ◽  
Author(s):  
Miguel Dasilva ◽  
Christian Brandt ◽  
Marc Alwin Gieselmann ◽  
Claudia Distler ◽  
Alexander Thiele
Keyword(s):  
Attentional Control ◽  
Large Scale ◽  
Neuronal Excitability ◽  
Cell Types ◽  
Receptor Activation ◽  
Frontal Eye Field ◽  
Control Signals ◽  
Cognitive Operations ◽  
Eye Field ◽  
Large Scale Networks

Abstract Top-down attention, controlled by frontal cortical areas, is a key component of cognitive operations. How different neurotransmitters and neuromodulators flexibly change the cellular and network interactions with attention demands remains poorly understood. While acetylcholine and dopamine are critically involved, glutamatergic receptors have been proposed to play important roles. To understand their contribution to attentional signals, we investigated how ionotropic glutamatergic receptors in the frontal eye field (FEF) of male macaques contribute to neuronal excitability and attentional control signals in different cell types. Broad-spiking and narrow-spiking cells both required N-methyl-D-aspartic acid and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor activation for normal excitability, thereby affecting ongoing or stimulus-driven activity. However, attentional control signals were not dependent on either glutamatergic receptor type in broad- or narrow-spiking cells. A further subdivision of cell types into different functional types using cluster-analysis based on spike waveforms and spiking characteristics did not change the conclusions. This can be explained by a model where local blockade of specific ionotropic receptors is compensated by cell embedding in large-scale networks. It sets the glutamatergic system apart from the cholinergic system in FEF and demonstrates that a reduction in excitability is not sufficient to induce a reduction in attentional control signals.

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