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Kopchick, J.

Publications and source records attributed to Kopchick, J..

3 recordsLinked to original sources

A novel mathematical construction for identifying attractors from task-driven fMRI data

Functional brain imaging data can provide a window into the task-driven network states that shape brain function (or dysfunction). Conventionally, these network states can be represented as bivariate correlation matrices (which are formed from fMRI time series from multiple brain regions/nodes within any task window). Here, we treat these conventional connectivity matrices as connectivity terrains in order to recover local structure. In principle, any such terrain can be traversed node by node, where from any node, one can move towards its nearest functional neighbor (i.e., its maximally correlated node). In terrains with meaningful structure, such traversals across multiple nodes should converge to attractor nodes; here, the nodes that flow into a shared attractor form an attractor basin, which effectively is a sub-network within the system. Extant methods (e.g., degree distribution and characteristic path length) can summarize global network properties but cannot identify attractor nodes and basins. Here, we construct a new relation, called transitive maximal correlation (TMC) that can recover attractors and attractor basins in connectivity terrains. Node A is said to be transitively maximally correlated to node B if and only if B is an attractor into which A flows. We first develop the mathematical basis for deriving a TMC matrix TMC(M) from a bivariate correlation matrix M (before explaining this with hypothetical data). We next apply the TMC relation to connectivity terrains derived from real fMRI time series data, where these data were acquired in two distinct task-domains (that varied in their extent of cross-cerebral demand): i) associative learning and ii) visually guided motor control. We show that TMC is remarkably sensitive to inter-hemispheric structure in the connectivity terrain; here, attractor pairs that were inter-hemispheric homologues were more likely to be observed for the cross-cerebral learning task, than the more circumscribed motor-control data. We confirm the condition-specific sensitivity of TMC showing that observed attractor basins differed significantly across conditions of the learning task. Finally, we demonstrate that TMC complements graph theoretic constructions like path length and betweenness centrality. We suggest that TMC is a mathematically sound and novel method for capturing functional properties of brain networks.

neuroscience↗

Learning evoked centrality dynamics in the schizophrenia brain: Entropy, heterogeneity and inflexibility of brain networks

BackgroundBrain network dynamics are responsive to task induced fluctuations, but such responsivity may not hold in schizophrenia (SCZ). We introduce and implement Centrality Dynamics (CD), a method developed specifically to capture task-driven dynamic changes in graph theoretic measures of centrality. We applied CD to fMRI data in SCZ and Healthy Controls (HC) acquired during a learning paradigm. MethodsfMRI (3T Siemens Verio) was acquired in 88 participants (49 SCZ). Time series were extracted from 246 functionally defined cerebral nodes. We applied a dynamic widowing technique to estimate 280 partially overlapping connectomes (30,135 region-pairs in each connectome). In each connectome we calculated every nodes Betweenness Centrality (BC) before building 246 unique time series (representing a nodes CD) from a nodes BC in successive connectomes. Next, in each group nodes were clustered based on similarities in CD. ResultsClustering gave rise to fewer sub-networks in SCZ, and these were formed by nodes with greater functional heterogeneity. These sub-networks also showed greater ApEn (indicating greater stochasticity) but lower amplitude variability (suggesting less adaptability to task-induced dynamics). Higher ApEn was associated with worse clinical symptoms. LimitationsCentrality Dynamics is a new method for network discovery in health and schizophrenia but will need further extension to other tasks and psychiatric conditions, before we achieve a fuller understanding of its promise. ConclusionThe brains functional connectome is not static under task-driven conditions, and characterizing the dynamics of the connectome will provide new insight on the dysconnection syndrome that is schizophrenia. Centrality Dynamics provides novel characterization of task-induced changes in the brains connectome and shows that in the schizophrenia brain, learning-evoked sub-network dynamics were less responsive to learning evoked changes and showed greater stochasticity.

neuroscience↗

Hepatic fructose metabolism is antagonized by growth hormone/insulin-like growth factor signaling via regulation of ketohexokinase expression

Overconsumption of added sugars such as fructose has been associated with a remarkable decline in metabolic health. Fructose is primarily metabolized by the small intestines and the liver, via phosphorylation mediated by ketohexokinase (KHK). KHK activity is traditionally viewed as lacking negative feedback mechanisms, such as those present to limit glucose metabolism, leading to excessive fat accumulation characteristic of metabolic dysfunction-associated liver disease (MASLD). In this study, we observe KHK downregulation in hepatocytes of diet-induced and genetic models of MASLD. Reduced KHK coincides with decreased flux of fructose-derived carbons into glycolytic and amino acid metabolic pathways, suggesting the presence of mechanisms that limit KHK-mediated fructolysis in the liver. We subsequently focused on the growth hormone (GH)/insulin-like growth factor (IGF) signaling pathway as a potential mechanism antagonizing KHK expression. In transgenic mice with enhanced GH signaling, KHK levels are reduced, whereas reduced GH activity leads to increased KHK expression. Additionally, administration of GH and IGF-1 in liver cell cultures induces time-dependent degradation of KHK, facilitated by direct interactions between KHK and the IGF-1 receptor (IGF-1R). Single-nuclei RNA sequencing revealed elevated IGF-1R expression in hepatocytes from diet-induced MASLD mice, supported by human MASLD patient samples, which also show reduced KHK expression. Taken together, these findings describe a novel pathway by which GH/IGF-1 signaling regulates KHK, offering new insights into how the liver adapts to metabolic stress to limit fructose-driven liver dysfunction.

molecular biology↗