{"claims": [{"text": "Focal cortical dysplasia Type I causes severe drug-resistant epilepsy", "quote_or_locator": "Introduction: 'Focal cortical dysplasia (FCD) is a severe malformation of neocortical development, and is one of the leading causes of drug-resistant epilepsy.'"}, {"text": "Electron microscopy studies of FCD Type I show reduced excitatory synapse density on pyramidal neurons", "quote_or_locator": "Introduction: 'previous high-resolution electron microscopy (EM) studies of FCD Type I, a subtype lacking balloon cells, showed a reduction in excitatory synaptic density on pyramidal neurons'"}, {"text": "FCD Type I tissue contains enlarged excitatory synaptic contacts with extra-large spines, including spines with head diameters greater than 1 µm and spine volumes exceeding 1 µm³", "quote_or_locator": "Introduction: 'ultrastructural analyses also revealed a distinct population of enlarged excitatory synaptic contacts associated with extra-large spines. Relative to their counterparts in normal cortex, these synapses exhibited enlargement of both presynaptic and postsynaptic compartments, including a population of spines with head diameters greater than 1 µm and spine volumes exceeding 1 µm³.'"}, {"text": "The number of synaptic vesicles in presynaptic compartments in FCD Type I was 2.0-fold higher than in normal cortex", "quote_or_locator": "Introduction: 'The number of synaptic vesicles in presynaptic compartments was 2.0-fold higher than that observed in normal cortex'"}, {"text": "Control model spine density was 8 spines per 10 µm with head diameter 0.551 µm and neck diameter 0.148 µm", "quote_or_locator": "Methods 2.2: 'In the control model, each dendritic spine consisted of a spherical head and a cylindrical neck, with a total spine length of 1.823 µm. The spine head had a diameter of 0.551 µm and was connected to a cylindrical neck with a diameter of 0.148 µm and a length of 1.272 µm.'"}, {"text": "Epileptogenic model spine density was 3 spines per 10 µm with head diameter 0.718 µm and neck diameter 0.301 µm", "quote_or_locator": "Methods 2.2: 'In the epileptogenic model, dendritic spines were modeled as larger and thicker but shorter than control spines, based on the same volume electron microscopy dataset. Each epileptogenic spine had a head diameter of 0.718 µm, a neck diameter of 0.301 µm, a neck length of 0.978 µm, and a total spine length of 1.696 µm.'"}, {"text": "Somatic input resistance was 89.4 ± 0.93 MΩ in control model and 130.45 ± 1.33 MΩ in epileptogenic model", "quote_or_locator": "Results 3.1: 'Somatic input resistances in the control and epileptogenic models were 89.4 ± 0.93 and 130.45 ± 1.33 M (mean ± SEM), respectively.'"}, {"text": "Somatic input resistance was significantly higher in epileptogenic model than control (P < 0.0001)", "quote_or_locator": "Results 3.1: 'input resistance was significantly higher in the epileptogenic model (130.45 ± 1.33 M) than in the control model (89.4 ± 0.93 M; two-sided unpaired t-test, P < 0.0001).'"}, {"text": "EPSPs were significantly larger in epileptogenic model at spine head (5.58 vs. 6.25 mV), spine base (2.90 vs. 4.27 mV), and soma (0.125 vs. 0.204 mV)", "quote_or_locator": "Results 3.2: 'EPSPs evoked by the same synaptic activation were significantly larger in the epileptogenic model at the spine head (5.58 vs. 6.25 mV), spine base (2.90 vs. 4.27 mV), and soma (0.125 vs. 0.204 mV; all medians, control vs. epileptogenic; Mann-Whitney U-test, all P < 0.0001)'"}, {"text": "Spine neck diameter is the dominant structural determinant of head-shaft voltage compartmentalization", "quote_or_locator": "Results 3.3: 'Collectively, these results indicate that spine neck diameter is the dominant structural determinant of head–shaft voltage compartmentalization, because it strongly constrains spine neck axial resistance.'"}, {"text": "Spine head size variations had no significant effect on EPSP amplitude", "quote_or_locator": "Results 3.3: 'no significant differences in EPSP amplitude were observed at any measurement site after varying spine head size (head: P = 0.3745, base: P = 0.5361, soma: P = 0.2944)'"}, {"text": "Control model required 157 spines to elicit a spike; epileptogenic model required 41 spines", "quote_or_locator": "Results 3.4: 'The control model required activation of 157 spines to elicit a spike, whereas the epileptogenic model reached spike initiation with only 41 spines (Figure 4A), corresponding to a 3.82-fold reduction in the number of activated spines required for spike initiation.'"}, {"text": "Epileptogenic model showed 3.82-fold reduction in spike threshold", "quote_or_locator": "Results 3.4: 'corresponding to a 3.82-fold reduction in the number of activated spines required for spike initiation'"}, {"text": "Under sparse input (<3.4 Hz), epileptogenic model firing was up to 2.15-fold higher than control", "quote_or_locator": "Results 3.4: 'at higher input rates (≥3.4 Hz), firing rates differed only modestly (1.04-fold), whereas under sparse input (<3.4 Hz), firing in the epileptogenic model was markedly enhanced, reaching up to 2.15-fold higher than control in average.'"}, {"text": "Spine morphology alterations were modeled based on quantitative volume electron microscopy measurements from FCD tissue", "quote_or_locator": "Methods 2.1: 'Model cell morphology was based on previously described morphological features of human pyramidal neurons (Benavides-Piccione et al., 2024). This choice was motivated by the similarity of these features to neurons examined in electrophysiological (Cho et al., 2024) and volume electron microscopy studies (Kim et al., 2026) of FCD tissue.'"}, {"text": "Simulations were conducted using NEURON v8.2 with Python v3.10", "quote_or_locator": "Methods 2.6: 'All simulations in this paper were conducted in NEURON (v8.2) (Hines and Carnevale, 2001) with Python (v3.10)'"}], "prompt_version": "p1.0", "verdicts": [{"claim": "Focal cortical dysplasia Type I causes severe drug-resistant epilepsy", "verdict": "supported", "evidence": "Focal cortical dysplasia (FCD) is a severe malformation of neocortical development, and is one of the leading causes of drug-resistant epilepsy.", "note": null}, {"claim": "Electron microscopy studies of FCD Type I show reduced excitatory synapse density on pyramidal neurons", "verdict": "supported", "evidence": "previous high-resolution electron microscopy (EM) studies of FCD Type I, a subtype lacking balloon cells, showed a reduction in excitatory synaptic density on pyramidal neurons", "note": null}, {"claim": "FCD Type I tissue contains enlarged excitatory synaptic contacts with extra-large spines, including spines with head diameters greater than 1 µm and spine volumes exceeding 1 µm³", "verdict": "supported", "evidence": "ultrastructural analyses also revealed a distinct population of enlarged excitatory synaptic contacts associated with extra-large spines. Relative to their counterparts in normal cortex, these synapses exhibited enlargement of both presynaptic and postsynaptic compartments, including a population of spines with head diameters greater than 1 µm and spine volumes exceeding 1 µm³.", "note": null}, {"claim": "The number of synaptic vesicles in presynaptic compartments in FCD Type I was 2.0-fold higher than in normal cortex", "verdict": "supported", "evidence": "The number of synaptic vesicles in presynaptic compartments was 2.0-fold higher than that observed in normal cortex", "note": null}, {"claim": "Control model spine density was 8 spines per 10 µm with head diameter 0.551 µm and neck diameter 0.148 µm", "verdict": "supported", "evidence": "In the control model, each dendritic spine consisted of a spherical head and a cylindrical neck, with a total spine length of 1.823 µm. The spine head had a diameter of 0.551 µm and was connected to a cylindrical neck with a diameter of 0.148 µm and a length of 1.272 µm.", "note": null}, {"claim": "Epileptogenic model spine density was 3 spines per 10 µm with head diameter 0.718 µm and neck diameter 0.301 µm", "verdict": "supported", "evidence": "In the epileptogenic model, dendritic spines were modeled as larger and thicker but shorter than control spines, based on the same volume electron microscopy dataset. Each epileptogenic spine had a head diameter of 0.718 µm, a neck diameter of 0.301 µm, a neck length of 0.978 µm, and a total spine length of 1.696 µm.", "note": null}, {"claim": "Somatic input resistance was 89.4 ± 0.93 MΩ in control model and 130.45 ± 1.33 MΩ in epileptogenic model", "verdict": "supported", "evidence": "Somatic input resistances in the control and epileptogenic models were 89.4 ± 0.93 and 130.45 ± 1.33 M (mean ± SEM), respectively.", "note": null}, {"claim": "Somatic input resistance was significantly higher in epileptogenic model than control (P < 0.0001)", "verdict": "supported", "evidence": "input resistance was significantly higher in the epileptogenic model (130.45 ± 1.33 M) than in the control model (89.4 ± 0.93 M; two-sided unpaired t-test, P < 0.0001).", "note": null}, {"claim": "EPSPs were significantly larger in epileptogenic model at spine head (5.58 vs. 6.25 mV), spine base (2.90 vs. 4.27 mV), and soma (0.125 vs. 0.204 mV)", "verdict": "supported", "evidence": "EPSPs evoked by the same synaptic activation were significantly larger in the epileptogenic model at the spine head (5.58 vs. 6.25 mV), spine base (2.90 vs. 4.27 mV), and soma (0.125 vs. 0.204 mV; all medians, control vs. epileptogenic; Mann-Whitney U-test, all P < 0.0001)", "note": null}, {"claim": "Spine neck diameter is the dominant structural determinant of head-shaft voltage compartmentalization", "verdict": "supported", "evidence": "Collectively, these results indicate that spine neck diameter is the dominant structural determinant of head–shaft voltage compartmentalization, because it strongly constrains spine neck axial resistance.", "note": null}, {"claim": "Spine head size variations had no significant effect on EPSP amplitude", "verdict": "supported", "evidence": "no significant differences in EPSP amplitude were observed at any measurement site after varying spine head size (head: P = 0.3745, base: P = 0.5361, soma: P = 0.2944)", "note": null}, {"claim": "Control model required 157 spines to elicit a spike; epileptogenic model required 41 spines", "verdict": "supported", "evidence": "The control model required activation of 157 spines to elicit a spike, whereas the epileptogenic model reached spike initiation with only 41 spines (Figure 4A), corresponding to a 3.82-fold reduction in the number of activated spines required for spike initiation.", "note": null}, {"claim": "Epileptogenic model showed 3.82-fold reduction in spike threshold", "verdict": "supported", "evidence": "corresponding to a 3.82-fold reduction in the number of activated spines required for spike initiation", "note": null}, {"claim": "Under sparse input (<3.4 Hz), epileptogenic model firing was up to 2.15-fold higher than control", "verdict": "supported", "evidence": "at higher input rates (≥3.4 Hz), firing rates differed only modestly (1.04-fold), whereas under sparse input (<3.4 Hz), firing in the epileptogenic model was markedly enhanced, reaching up to 2.15-fold higher than control in average.", "note": null}, {"claim": "Spine morphology alterations were modeled based on quantitative volume electron microscopy measurements from FCD tissue", "verdict": "supported", "evidence": "Model cell morphology was based on previously described morphological features of human pyramidal neurons (Benavides-Piccione et al., 2024). This choice was motivated by the similarity of these features to neurons examined in electrophysiological (Cho et al., 2024) and volume electron microscopy studies (Kim et al., 2026) of FCD tissue.", "note": null}, {"claim": "Simulations were conducted using NEURON v8.2 with Python v3.10", "verdict": "supported", "evidence": "All simulations in this paper were conducted in NEURON (v8.2) (Hines and Carnevale, 2001) with Python (v3.10)", "note": null}]}