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Supplemental Table 1. Neuroimaging and Neurophysiology Findings and Clinical Impressions.

Suspected Epileptogenic Zone*

Subject MRI Findings Interictal SEEG Ictal SEEG Surgery Performed Outcome

Subj. 1 Right mesial temporal sclerosis, right thalamic and periventricular white matter loss, cystic change near right caudothalamic notch, severe thinning of corpus callosum, right cerebral peduncle smaller than the left, and punctate foci of hemosiderin in both hemispheres (likely perinatal stroke)

Frequent-to-abundant IEDs in right hippocampus and amygdala;

occasional IEDs seen in temporal neocortex

Onset in right hippocampus and amygdala

Right hippocampus and amygdala

R temporal lobectomy sz-free

Subj. 2 Subtle left temporal/hippocampal T2 hyperintensity

Frequent-to-abundant IEDs in the left hippocampus, amygdala, and anterior temporal neocortex;

occasional IEDs in the insula, temperoparietal junction, and lateral temporal neocortex

Initial seizures with onset isolated to left

hippocampus and early spread to amygdala; later seizures in a cluster included concurrent or initial onset in the insula

Left hippocampus and amygdala with possible secondary insular site

L hippocampus laser ablation

sz-persist

Subj. 3 Mild volume loss of right anterior

temporal lobe Frequent IEDs in right hippocampus;

occasional IEDs in the lateral temporal neocortex

Seizures arising from the right hippocampus

Right hippocampus R temporal lobectomy sz-free

Subj. 4 Postoperative changes showing partial left anterior medial temporal lobectomy, T2 hyperintensity in the remaining anterior left temporal lobe, and nodular subependymal gray matter heterotopia adjacent to the right frontal horn

IEDs were abundant in the anterior insula, posterior margin of the insula, temporal operculum, and superior temporal gyrus

Two seizure onset zones:

1) posterior margin of insula; 2) temporal operculum (6 seizures)

L insula, temporal operculum, and superior temporal gyrus

L temporal lobe, anterior/inferior L insula resection

sz-free

Subj. 5 Small right temporal pole with abnormal signal and blurring of the gray-white junction; malrotated right hippocampus with intrinsic signal abnormality and loss of internal architecture

IEDs abundant in anterior and posterior hippocampus and amygdala; occasional IEDs in anterior and posterior insula and posterior cingulate

Anterior hippocampus and amygdala

R hippocampus and amygdala

R temporal lobectomy sz-free

Subj. 6 Nonspecific punctate T2

hyperintensities in frontal lobe Frequent IEDs arising from L amygdala, anterior and posterior hippocampus, and anterior and posterior insula

Eight seizures arising from the left hippocampus and a single seizure arising from the anterior insula

Left hippocampus L Temporal lobectomy sz-persist

(2)

(semiologically similar to the others and amygdala electrode was non- functional during this event)

Subj. 7 Subtle volume loss of left temporal lobe; increased left hippocampus T2 signal without volume loss

Intrinsic epileptogenicity at the temporal operculum, abundant IEDs in the anterior and posterior insula, frequent IEDs in the hippocampus, and occasional IEDs in the amygdala

Temporal operculum onset with rapid spread to anterior insula

Temporal operculum and anterior insula

L STG and inferior anterior insula resection

sz-free

Subj. 8 Subtle cortical thickening and gray- white matter blurring in the anterior left frontal lobe

Abundant IEDs in superior frontal sulcus (aligned with MRI lesion)

Superior frontal sulcus seizure onset

Superior frontal sulcus lesion

L superior frontal gyrus and neighboring sulcal resection

sz-persist

Subj. 9 Originally had a left parietal vascular lesion resected prior to epilepsy;

pre-surgical MRI showed left parietal and posterior temporal resection cavity with T2 hyperintense margins, areas of cystic encephalomalacia along the mesial left parietal region

Abundant IEDs in primary sensory cortex; frequent IEDs in the supramarginal gyrus, precuneus, and inferior parietal lobule

Earliest onset in primary sensory cortex with rapid spread across anterior parietal lobe and supplementary sensorimotor cortex

Sensory cortex and surrounding tissue

L parietal lobe resection

sz-free

Subj. 10 Focal area of gliosis and atrophy in right posterior parasagittal parietal lobe

Frequent IEDs near parietal lesion and throughout the hippocampus;

occasional IEDs at the temporal- occipital junction, calcarine cortex, and inferior occipital gyrus

Majority of seizures arose from anterior

hippocampus with a single atypical seizure arising from the isthmus of the cingulate

R hippocampus R partial temporal lobectomy and amygdalohippocampe ctomy

sz-persist

Subj. 11 Subtle area of gray/white blurring along a gyrus at the mesial posterior left frontal lobe

Frequent-to-abundant IEDs from inferior frontal gyrus near the lesion, mid cingulate gyrus, and leg motor cortex

Seizures arose from mid- cingulate gyrus

Medial frontal lobe lesion near primary leg motor and cingulate

L medial frontal lesionectomy

sz-persist

Subj. 12 Foreshortened corpus callosum and

incompletely inverted hippocampi Frequent synchronous IEDs across medial and lateral temporal cortex with spread to TPOJ, supramarginal gyrus, and orbitofrontal cortex

Single atypical seizure with diffuse onset maximal in anterior temporal neocortex

R temporal lobe R temporal lobectomy sz-persist

Subj. 13 Small right hippocampus with obscured internal architecture; right frontal/anterior insula heterotopia and neighboring dysplasia

Abundant IEDs in pars triangularis and anterior insula; occasional-to- frequent discharges in orbitofrontal cortex, gyrus rectus, and middle temporal gyrus

Seizure onset in right anterior insula with broad perisylvian spread

R anterior insula R anterior insula resection

sz-persist

(3)

Subj. 14 Right frontal subcortical lesion, involving cortex, non-enhancing and stable over time

Frequent IEDs in the frontal pole, orbitofrontal cortex, anterior cingulate, and medial frontal lobe.

Heralding spikes in anterior cingulate followed by evolving fast activity in the medial frontal lobe lesion

R medial frontal lobe lesion

R motor-sparing frontal lobectomy

sz-free

Subj. 15 Remote infarct with posterior frontal and perirolandic cortical and white matter volume loss with gliosis;

encephalomalacia extends from the trigone of the left lateral ventricle to the posterior parietal cortex with mild cortical and white matter volume loss; a third small focus of

encephalomalacia in the deep white matter adjacent to the trigone of the right lateral ventricle is identified

Abundant IEDs arising from anterior parietal lobe around area of encephalomalacia; occasional-to- frequent IEDs seen in lateral parietal cortex, posterior insula, and middle and superior frontal gyri

Seizures arising from superior parietal lobe

Right parietal area of encephalomalacia and surrounding parietal cortex

R lateral parietal lobe partial resection

sz-persist

Subj. 16 Probable focal cortical dysplasia in

the anterior right temporal lobe IEDs continuous at temporal tip, frequent in hippocampus and posterior insula

Seizures arose from posterior insula

Suspected posterior insula seizure onset but resection planned to include suspected FCD in temporal lobe

R anterior temporal lobectomy,

amygdalohippocampe ctomy, mid insula resection

sz-persist

Subj. 17 Subtle focal blurring in orbitofrontal

region Frequent-to-abundant IEDs broadly

distributed across the frontal lobe including the inferior and middle frontal gyri, orbitofrontal cortex, and middle and anterior cingulate;

rare IEDs in the posterior insula, hippocampus, and superior temporal gyrus

Seizures arose

synchronously across the inferior and middle frontal gyri and orbitofrontal cortex

Broad onset through frontal lobe centered around orbitofrontal cortex

R frontal lobe disconnection

sz-free

Subj. 18 No abnormalities identified Frequent IEDs arising from the hippocampus and amygdala; rare IEDs arising from the inferior frontal gyrus

Seizures arising from anterior and posterior hippocampus and amygdala

Right medial temporal lobe

R temporal lobectomy sz-free

Subj. 19 R>L hippocampal T2 hyperintensity, obscured internal architecture;

similar in anterior temporal lobes R>L

Abundant IEDs in the hippocampus, frequent IEDs in the insula

150 seizures arose from the right temporal lobe; 2 seizures started in the anterior insula

Multifocal:

Hippocampus and anterior insula

R temporal lobectomy sz-free

Subj. 20 Embolized AVM in right temporal

lobe Occasional-to-frequent IEDs arising

from anterior hippocampus and amygdala

Onset in right anterior hippocampus and amygdala

Right medial temporal lobe

R temporal lobectomy sz-free

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Subj. 21 Left anterior and medial temporal cortical dysplasia, left hippocampal sclerosis

Abundant IEDs in the temporal tip, anterior superior temporal gyrus, amygdala, and hippocampus;

frequent IEDs in the orbitofrontal cortex and anterior insula

Two patterns with one seizure population arising from the amygdala and anterior hippocampus and the second arising from the temporal tip

Medial temporal lobe and anterior temporal neocortex

L temporal, hippocampal, basal frontal lobectomy

sz-persist

Subj. 22 No abnormalities identified. Abundant IEDs in the superior temporal gyrus, middle temporal gyrus, temporal tip, amygdala, and hippocampus; occasional IEDs in the precuneus, cuneus, hand motor, primary visual cortex, middle temporal gyrus, and basal temporal cortex

Seizures arising from anterior temporal neocortex

Anterior temporal lobe L temporal neocortex resection

sz-persist

*This is the suspected epileptogenic zone based on a combination of the pre-implantation imaging and neurophysiology as well as the results of the SEEG findings. Abbreviations: IED, interictal epileptiform discharge; R, right; L, left; FCD, focal cortical dysplasia; AVM: arteriovenous malformation.

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