PMC:6864578 / 7520-9777 JSONTXT

{"project":"TEST0","denotations":[{"id":"31409150-229-234-3813","span":{"begin":415,"end":416},"obj":"[\"23324316\"]"},{"id":"31409150-50-55-3814","span":{"begin":465,"end":466},"obj":"[\"18375756\"]"},{"id":"31409150-221-226-3815","span":{"begin":841,"end":842},"obj":"[\"17093119\"]"},{"id":"31409150-234-239-3816","span":{"begin":1621,"end":1622},"obj":"[\"22075227\"]"}],"text":"The relative paucity of networks capable of supporting seizures is evident from the extensive parameter search that the authors had to undertake to find networks with ictal transitions. This raises an interesting question of whether ictal transitions are restricted to a subset of networks implemented with the same average local and long-range connections, as observed in dentate network models of epileptogenesis.5 The presence of microcircuit connectivity motifs6 within global network structure may explain why only a subset of networks, even among those with similar average connectivity, support ictal transition. The requirement for sparse long-range connections is intriguing in the context of the dentate circuit changes in epilepsy, where long-range mossy cell connections are decreased and local-sprouted connections are enhanced.4 Since experimental data suggest that network dimensions may influence the “ictogenic” conditions, future studies should explore how the requirement for sparse long-range connectivity scales with network size and aberrant network reorganizations in disease. Although the model was developed based on experimental data, the limitations posed by the monolayer organotypic culture system and model simplifications need to be considered while interpreting the findings, as acknowledged by the authors. Specifically, since the network implementation does not adequately capture inhibitory circuits or include extracellular ionic mechanisms, the specific parameters defining the goldilocks zone may change when effects of inhibitory and ionic mediators on ictal onset are considered.7,8 An interesting conundrum in the findings is that while absence of long-range connections precludes ictal transitions, long-range connections do not appear to seed or drive ictal onset. Analyzing the velocities of ictal and interictal spread as a function of the density of long-range connections could shed light on whether sparse long-range connections aid development of partially depressed network spaces by hastening interictal propagation. If so, it would be interesting to explore whether specific combinations of network dimension and synaptic parameters could precipitate seizures in networks with different structural motifs."}

{"project":"0_colil","denotations":[{"id":"31409150-23324316-3813","span":{"begin":415,"end":416},"obj":"23324316"},{"id":"31409150-18375756-3814","span":{"begin":465,"end":466},"obj":"18375756"},{"id":"31409150-17093119-3815","span":{"begin":841,"end":842},"obj":"17093119"},{"id":"31409150-22075227-3816","span":{"begin":1621,"end":1622},"obj":"22075227"}],"text":"The relative paucity of networks capable of supporting seizures is evident from the extensive parameter search that the authors had to undertake to find networks with ictal transitions. This raises an interesting question of whether ictal transitions are restricted to a subset of networks implemented with the same average local and long-range connections, as observed in dentate network models of epileptogenesis.5 The presence of microcircuit connectivity motifs6 within global network structure may explain why only a subset of networks, even among those with similar average connectivity, support ictal transition. The requirement for sparse long-range connections is intriguing in the context of the dentate circuit changes in epilepsy, where long-range mossy cell connections are decreased and local-sprouted connections are enhanced.4 Since experimental data suggest that network dimensions may influence the “ictogenic” conditions, future studies should explore how the requirement for sparse long-range connectivity scales with network size and aberrant network reorganizations in disease. Although the model was developed based on experimental data, the limitations posed by the monolayer organotypic culture system and model simplifications need to be considered while interpreting the findings, as acknowledged by the authors. Specifically, since the network implementation does not adequately capture inhibitory circuits or include extracellular ionic mechanisms, the specific parameters defining the goldilocks zone may change when effects of inhibitory and ionic mediators on ictal onset are considered.7,8 An interesting conundrum in the findings is that while absence of long-range connections precludes ictal transitions, long-range connections do not appear to seed or drive ictal onset. Analyzing the velocities of ictal and interictal spread as a function of the density of long-range connections could shed light on whether sparse long-range connections aid development of partially depressed network spaces by hastening interictal propagation. If so, it would be interesting to explore whether specific combinations of network dimension and synaptic parameters could precipitate seizures in networks with different structural motifs."}

{"project":"2_test","denotations":[{"id":"31409150-23324316-28640751","span":{"begin":415,"end":416},"obj":"23324316"},{"id":"31409150-18375756-28640752","span":{"begin":465,"end":466},"obj":"18375756"},{"id":"31409150-17093119-28640753","span":{"begin":841,"end":842},"obj":"17093119"},{"id":"31409150-22075227-28640754","span":{"begin":1621,"end":1622},"obj":"22075227"}],"text":"The relative paucity of networks capable of supporting seizures is evident from the extensive parameter search that the authors had to undertake to find networks with ictal transitions. This raises an interesting question of whether ictal transitions are restricted to a subset of networks implemented with the same average local and long-range connections, as observed in dentate network models of epileptogenesis.5 The presence of microcircuit connectivity motifs6 within global network structure may explain why only a subset of networks, even among those with similar average connectivity, support ictal transition. The requirement for sparse long-range connections is intriguing in the context of the dentate circuit changes in epilepsy, where long-range mossy cell connections are decreased and local-sprouted connections are enhanced.4 Since experimental data suggest that network dimensions may influence the “ictogenic” conditions, future studies should explore how the requirement for sparse long-range connectivity scales with network size and aberrant network reorganizations in disease. Although the model was developed based on experimental data, the limitations posed by the monolayer organotypic culture system and model simplifications need to be considered while interpreting the findings, as acknowledged by the authors. Specifically, since the network implementation does not adequately capture inhibitory circuits or include extracellular ionic mechanisms, the specific parameters defining the goldilocks zone may change when effects of inhibitory and ionic mediators on ictal onset are considered.7,8 An interesting conundrum in the findings is that while absence of long-range connections precludes ictal transitions, long-range connections do not appear to seed or drive ictal onset. Analyzing the velocities of ictal and interictal spread as a function of the density of long-range connections could shed light on whether sparse long-range connections aid development of partially depressed network spaces by hastening interictal propagation. If so, it would be interesting to explore whether specific combinations of network dimension and synaptic parameters could precipitate seizures in networks with different structural motifs."}

{"project":"MyTest","denotations":[{"id":"31409150-23324316-28640751","span":{"begin":415,"end":417},"obj":"23324316"},{"id":"31409150-18375756-28640752","span":{"begin":465,"end":467},"obj":"18375756"},{"id":"31409150-17093119-28640753","span":{"begin":841,"end":843},"obj":"17093119"},{"id":"31409150-22075227-28640754","span":{"begin":1621,"end":1623},"obj":"22075227"}],"namespaces":[{"prefix":"_base","uri":"https://www.uniprot.org/uniprot/testbase"},{"prefix":"UniProtKB","uri":"https://www.uniprot.org/uniprot/"},{"prefix":"uniprot","uri":"https://www.uniprot.org/uniprotkb/"}],"text":"The relative paucity of networks capable of supporting seizures is evident from the extensive parameter search that the authors had to undertake to find networks with ictal transitions. This raises an interesting question of whether ictal transitions are restricted to a subset of networks implemented with the same average local and long-range connections, as observed in dentate network models of epileptogenesis.5 The presence of microcircuit connectivity motifs6 within global network structure may explain why only a subset of networks, even among those with similar average connectivity, support ictal transition. The requirement for sparse long-range connections is intriguing in the context of the dentate circuit changes in epilepsy, where long-range mossy cell connections are decreased and local-sprouted connections are enhanced.4 Since experimental data suggest that network dimensions may influence the “ictogenic” conditions, future studies should explore how the requirement for sparse long-range connectivity scales with network size and aberrant network reorganizations in disease. Although the model was developed based on experimental data, the limitations posed by the monolayer organotypic culture system and model simplifications need to be considered while interpreting the findings, as acknowledged by the authors. Specifically, since the network implementation does not adequately capture inhibitory circuits or include extracellular ionic mechanisms, the specific parameters defining the goldilocks zone may change when effects of inhibitory and ionic mediators on ictal onset are considered.7,8 An interesting conundrum in the findings is that while absence of long-range connections precludes ictal transitions, long-range connections do not appear to seed or drive ictal onset. Analyzing the velocities of ictal and interictal spread as a function of the density of long-range connections could shed light on whether sparse long-range connections aid development of partially depressed network spaces by hastening interictal propagation. If so, it would be interesting to explore whether specific combinations of network dimension and synaptic parameters could precipitate seizures in networks with different structural motifs."}

{"project":"testtesttest","denotations":[{"id":"T27","span":{"begin":766,"end":770},"obj":"Body_part"},{"id":"T28","span":{"begin":1026,"end":1032},"obj":"Body_part"},{"id":"T30","span":{"begin":1220,"end":1226},"obj":"Body_part"},{"id":"T31","span":{"begin":1446,"end":1459},"obj":"Body_part"},{"id":"T32","span":{"begin":2024,"end":2030},"obj":"Body_part"}],"attributes":[{"id":"A27","pred":"uberon_id","subj":"T27","obj":"http://purl.obolibrary.org/obo/CL_0000000"},{"id":"A28","pred":"uberon_id","subj":"T28","obj":"http://purl.obolibrary.org/obo/UBERON_0002542"},{"id":"A29","pred":"uberon_id","subj":"T28","obj":"http://purl.obolibrary.org/obo/UBERON_0007380"},{"id":"A30","pred":"uberon_id","subj":"T30","obj":"http://purl.obolibrary.org/obo/UBERON_0000467"},{"id":"A31","pred":"uberon_id","subj":"T31","obj":"http://purl.obolibrary.org/obo/GO_0005576"},{"id":"A32","pred":"uberon_id","subj":"T32","obj":"http://purl.obolibrary.org/obo/UBERON_0000464"}],"text":"The relative paucity of networks capable of supporting seizures is evident from the extensive parameter search that the authors had to undertake to find networks with ictal transitions. This raises an interesting question of whether ictal transitions are restricted to a subset of networks implemented with the same average local and long-range connections, as observed in dentate network models of epileptogenesis.5 The presence of microcircuit connectivity motifs6 within global network structure may explain why only a subset of networks, even among those with similar average connectivity, support ictal transition. The requirement for sparse long-range connections is intriguing in the context of the dentate circuit changes in epilepsy, where long-range mossy cell connections are decreased and local-sprouted connections are enhanced.4 Since experimental data suggest that network dimensions may influence the “ictogenic” conditions, future studies should explore how the requirement for sparse long-range connectivity scales with network size and aberrant network reorganizations in disease. Although the model was developed based on experimental data, the limitations posed by the monolayer organotypic culture system and model simplifications need to be considered while interpreting the findings, as acknowledged by the authors. Specifically, since the network implementation does not adequately capture inhibitory circuits or include extracellular ionic mechanisms, the specific parameters defining the goldilocks zone may change when effects of inhibitory and ionic mediators on ictal onset are considered.7,8 An interesting conundrum in the findings is that while absence of long-range connections precludes ictal transitions, long-range connections do not appear to seed or drive ictal onset. Analyzing the velocities of ictal and interictal spread as a function of the density of long-range connections could shed light on whether sparse long-range connections aid development of partially depressed network spaces by hastening interictal propagation. If so, it would be interesting to explore whether specific combinations of network dimension and synaptic parameters could precipitate seizures in networks with different structural motifs."}