Source-level EEG and graph theory reveal widespread functional network alterations in focal epilepsy

Objective: The hypersynchronous neuronal activity associated with epilepsy causes widespread functional network disruptions extending beyond the epileptogenic zone. This altered network topology is considered a mediator for non-seizure symptoms, such as cognitive impairment. The aim of this study was to investigate functional network alterations in focal epilepsy patients with good seizure control and high quality of life. Methods: We compared twenty-two focal epilepsy patients and sixteen healthy controls on graph metrics derived from functional connectivity of source-level resting-state EEG. Graph metrics were calculated over a range of network densities in five frequency bands. Results: We observed a significantly increased small world index in patients relative to controls. On the local level, two left-hemisphere regions displayed a shift towards greater alpha band "hubness". The findings were not mediated by age, sex or education, nor by age of epilepsy onset, duration or focus lateralisation. Conclusions: Widespread functional network alterations are evident in focal epilepsy, even in a cohort characterised by successful anti-seizure medication therapy and high quality of life. These findings might support the position that functional network analysis could hold clinical relevance for epilepsy. Significance: Focal epilepsy is accompanied by global and local functional network aberrancies which might be implied in the sustenance of non-seizure symptoms. (c) 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe

Natural Allelic Variation Defines a Role for ATMYC1: Trichome Cell Fate Determination

The molecular nature of biological variation is not well understood. Indeed, many questions persist regarding the types of molecular changes and the classes of genes that underlie morphological variation within and among species. Here we have taken a candidate gene approach based on previous mapping results to identify the gene and ultimately a polymorphism that underlies a trichome density QTL in Arabidopsis thaliana. Our results show that natural allelic variation in the transcription factor ATMYC1 alters trichome density in A. thaliana; this is the first reported function for ATMYC1. Using site-directed mutagenesis and yeast two-hybrid experiments, we demonstrate that a single amino acid replacement in ATMYC1, discovered in four ecotypes, eliminates known protein–protein interactions in the trichome initiation pathway. Additionally, in a broad screen for molecular variation at ATMYC1, including 72 A. thaliana ecotypes, a high-frequency block of variation was detected that results in >10% amino acid replacement within one of the eight exons of the gene. This sequence variation harbors a strong signal of divergent selection but has no measurable effect on trichome density. Homologs of ATMYC1 are pleiotropic, however, so this block of variation may be the result of natural selection having acted on another trait, while maintaining the trichome density role of the gene. These results show that ATMYC1 is an important source of variation for epidermal traits in A. thaliana and indicate that the transcription factors that make up the TTG1 genetic pathway generally may be important sources of epidermal variation in plants

Source-level EEG and graph theory reveal widespread functional network alterations in focal epilepsy

Objective: The hypersynchronous neuronal activity associated with epilepsy causes widespread functional network disruptions extending beyond the epileptogenic zone. This altered network topology is considered a mediator for non-seizure symptoms, such as cognitive impairment. The aim of this study was to investigate functional network alterations in focal epilepsy patients with good seizure control and high quality of life. Methods: We compared twenty-two focal epilepsy patients and sixteen healthy controls on graph metrics derived from functional connectivity of source-level resting-state EEG. Graph metrics were calculated over a range of network densities in five frequency bands. Results: We observed a significantly increased small world index in patients relative to controls. On the local level, two left-hemisphere regions displayed a shift towards greater alpha band “hubness”. The findings were not mediated by age, sex or education, nor by age of epilepsy onset, duration or focus lateralisation. Conclusions: Widespread functional network alterations are evident in focal epilepsy, even in a cohort characterised by successful anti-seizure medication therapy and high quality of life. These findings might support the position that functional network analysis could hold clinical relevance for epilepsy. Significance: Focal epilepsy is accompanied by global and local functional network aberrancies which might be implied in the sustenance of non-seizure symptoms

The organization of functional neurocognitive networks in focal epilepsy correlates with domain-specific cognitive performance

Understanding and diagnosing cognitive impairment in epilepsy remains a prominent challenge. New etiological models suggest that cognitive difficulties might not be directly linked to seizure activity, but are rather a manifestation of a broader brain pathology. Consequently, treating seizures is not sufficient to alleviate cognitive symptoms, highlighting the need for novel diagnostic tools. Here, we investigated whether the organization of three intrinsic, resting-state functional connectivity networks was correlated with domain-specific cognitive test performance. Using individualized EEG source reconstruction and graph theory, we examined the association between network small worldness and cognitive test performance in 23 patients with focal epilepsy and 17 healthy controls, who underwent a series of standardized pencil-and-paper and digital cognitive tests. We observed that the specific networks robustly correlated with test performance in distinct cognitive domains. Specifically, correlations were evident between the default mode network and memory in patients, the central-executive network and executive functioning in controls, and the salience network and social cognition in both groups. Interestingly, the correlations were evident in both groups, but in different domains, suggesting an alteration in these functional neurocognitive networks in focal epilepsy. The present findings highlight the potential clinical relevance of functional brain network dysfunction in cognitive impairment