•During visual naming, high-gamma modulation occurs in a posteroanterior sequential pattern with overlapping temporal profiles.•Cortical activations during visual naming represent cognitive ...sub-components with different relative contributions from the left and right cerebral hemispheres.•Post-surgical neuropsychological deficits correlated with the location of resected parcels within the visual naming network.
Cerebral spatiotemporal dynamics of visual naming were investigated in epilepsy patients undergoing stereo-electroencephalography (SEEG) monitoring.
Brain networks were defined by Parcel-Activation-Resection-Symptom matching (PARS) approach by matching high-gamma (50–150 Hz) modulations (HGM) in neuroanatomic parcels during visual naming, with neuropsychological outcomes after resection/ablation of those parcels. Brain parcels with >50% electrode contacts simultaneously showing significant HGM were aligned, to delineate spatiotemporal course of naming-related HGM.
In 41 epilepsy patients, neuroanatomic parcels showed sequential yet temporally overlapping HGM course during visual naming. From bilateral occipital lobes, HGM became increasingly left lateralized, coursing through limbic system. Bilateral superior temporal HGM was noted around response time, and right frontal HGM thereafter. Correlations between resected/ablated parcels, and post-surgical neuropsychological outcomes showed specific regional groupings.
Convergence of data from spatiotemporal course of HGM during visual naming, and functional role of specific parcels inferred from neuropsychological deficits after resection/ablation of those parcels, support a model with six cognitive subcomponents of visual naming having overlapping temporal profiles.
Cerebral substrates supporting visual naming are bilaterally distributed with relative hemispheric contribution dependent on cognitive demands at a specific time. PARS approach can be extended to study other cognitive and functional brain networks.
Improvement in visual naming abilities throughout the childhood and adolescence supports development of higher-order linguistic skills. We investigated neuronal circuits underlying improvement in the ...speed of visual naming with age, and age-related dynamics of these circuits.
Response times were electronically measured during an overt visual naming task in epilepsy patients undergoing stereo-EEG monitoring. Coherence modulations among pairs of neuroanatomic parcels were computed and analyzed for relationship with response time and age.
During the overt visual naming task, mean response time (latency) significantly decreased from 4 to 23 years of age. Coherence modulations during visual naming showed that increased connectivity between certain brain regions, particularly that between left fusiform gyrus/left parahippocampal gyrus and left frontal operculum, is associated with improvement in naming speed. Also, decreased connectivity in other brain regions, particularly between left angular and supramarginal gyri, is associated with decreased mean response time. Further, coherence modulations between left frontal operculum and both left fusiform and left posterior cingulate gyri significantly increase, while that between left angular and supramarginal gyri significantly decrease, with age.
Naming speed continues to improve from pre-school years into young adulthood. This age-related improvement in efficiency of naming environmental objects occurs likely because of strengthened direct connectivity between semantic and phonological nodes, and elimination of intermediate higher-order cognitive steps.
Summary
Objective
The understanding of childhood absence epilepsy (CAE) has been revolutionized over the past decade, but the biological mechanisms responsible for variable treatment outcomes are ...unknown. Our purpose in this prospective observational study was to determine how pretreatment ictal network pathways, defined using a combined electroencephalography (EEG)–functional magnetic resonance imaging (EEG‐fMRI) and magnetoencephalography (MEG) effective connectivity analysis, were related to treatment response.
Methods
Sixteen children with newly diagnosed and drug‐naive CAE had 31 typical absence seizures during EEG‐fMRI and 74 during MEG. The spatial extent of the pretreatment ictal network was defined using fMRI hemodynamic response with an event‐related independent component analysis (eICA). This spatially defined pretreatment ictal network supplied prior information for MEG‐effective connectivity analysis calculated using phase slope index (PSI). Treatment outcome was assessed 2 years following diagnosis and dichotomized to ethosuximide (ETX)–treatment responders (N = 11) or nonresponders (N = 5). Effective connectivity of the pretreatment ictal network was compared to the treatment response.
Results
Patterns of pretreatment connectivity demonstrated strongest connections in the thalamus and posterior brain regions (parietal, posterior cingulate, angular gyrus, precuneus, and occipital) at delta frequencies and the frontal cortices at gamma frequencies (P < .05). ETX treatment nonresponders had pretreatment connectivity, which was decreased in the precuneus region and increased in the frontal cortex compared to ETX responders (P < .05).
Significance
Pretreatment ictal connectivity differences in children with CAE were associated with response to antiepileptic treatment. This is a possible mechanism for the variable treatment response seen in patients sharing the same epilepsy syndrome.
Summary
Objectives
Metabolic imaging studies, such as positron emission tomography (PET), allow for an assessment of physiologic functioning of the brain, and 18Ffluoro‐2‐deoxyglucose (FDG)–PET is ...now a commonly used technique in presurgical epilepsy evaluations. Focal interictal decreases in glucose consumption are often but inconsistently concordant with the ictal onset area, and the underlying mechanisms are poorly understood. The current study tests the hypothesis that areas of glucose hypometabolism, determined by FDG‐PET, are associated with mitochondrial dysfunction in patients with medically intractable epilepsy associated with isolated focal cortical dysplasia (FCD).
Methods
Measures of electron transport chain (ETC) functioning and mitochondrial abnormalities (ETC complex biochemistry, protein kinase B subtype 1 (Akt1), glial fibrillary acidic protein (GFAP)) were assessed in surgical resection specimens that had hypometabolic abnormalities and those that were normal on FDG‐PET. Determination of FDG‐PET abnormalities was based on coregistration of statistical parametric mapping (SPM) results with postsurgical images.
Results
Twenty‐two patients (11 male, 11 female; mean age at the time of surgery 10.5 ± 4.4 years), with pathologically confirmed FCD, were included in this retrospective review. Complex IV function was found to be significantly reduced in areas of hypometabolism (p = 0.014), whereas there was a trend toward a significant reduction in complex II and III function in areas of hypometabolism (p = 0.08, p = 0.059, respectively). These decreases were independent of cortical dysplasia severity (p = 0.321) and other clinical epilepsy measures.
Significance
This study suggests an association between glucose hypometabolism and reduced mitochondrial complex IV functioning, which is independent of the degree of cortical dysplasia. This supports the role of cellular energy failure as a potential mechanism for intractable epilepsy.
•Stimulation within auditory cortex produced facial expressions and perioral motor responses in approximately one-third of patients.•Cortical sites with motor and language responses within transverse ...temporal gyrus and adjacent cortex (TGG+) showed different yet overlapping neurophysiologic characteristics.•TTG+ likely participates in non-verbal responses to low-level auditory and/or emotional cues during a communicative discourse.
We investigated the role of transverse temporal gyrus and adjacent cortex (TTG+) in facial expressions and perioral movements.
In 31 patients undergoing stereo-electroencephalography monitoring, we describe behavioral responses elicited by electrical stimulation within the TTG+. Task-induced high-gamma modulation (HGM), auditory evoked responses, and resting-state connectivity were used to investigate the cortical sites having different types of responses on electrical stimulation.
Changes in facial expressions and perioral movements were elicited on electrical stimulation within TTG+ in 9 (29%) and 10 (32%) patients, respectively, in addition to the more common language responses (naming interruptions, auditory hallucinations, paraphasic errors). All functional sites showed auditory task induced HGM and evoked responses validating their location within the auditory cortex, however, motor sites showed lower peak amplitudes and longer peak latencies compared to language sites. Significant first-degree connections for motor sites included precentral, anterior cingulate, parahippocampal, and anterior insular gyri, whereas those for language sites included posterior superior temporal, posterior middle temporal, inferior frontal, supramarginal, and angular gyri.
Multimodal data suggests that TTG+ may participate in auditory-motor integration.
TTG+ likely participates in facial expressions in response to emotional cues during an auditory discourse.
•Stereo-EEG sensorimotor mapping was prospectively compared with reference neuroanatomy.•Electrical stimulation mapping localized anatomic sensorimotor parcels with high accuracy.•Sensorimotor ...thresholds below after-discharge thresholds suggest safety of stereo-EEG ESM.
We evaluated stereo-EEG electrical stimulation mapping (ESM) for localization of anatomic sensorimotor parcels in pediatric patients with drug-resistant epilepsy. We also analyzed sensorimotor and after-discharge thresholds, and the somatotopy of sensorimotor responses.
ESM was performed with 50 Hz, biphasic, 2–3 s trains, using 1–9 mA current. Pre- and post-implant neuroimaging was co-registered and intersected with Neurosynth reference, to classify each electrode contact as lying within/outside an anatomic sensorimotor parcel. Indices of diagnostic performance were computed. Sensorimotor and after-discharge thresholds were analyzed using multivariable linear mixed models.
In 15 patients (6 females), aged 5.5–21.2 years, ESM showed high accuracy (0.80), high specificity (0.86), and diagnostic odds ratio (11.4, p < 0.0001) for localization of sensorimotor parcels. Mean sensorimotor threshold (3.4 mA) was below mean after-discharge threshold (4.2 mA, p = 0.0004). Sensorimotor and after-discharge thresholds showed a significant decrease with increasing intelligence quotient. Somatotopy of sensorimotor responses was mapped to standardized brain parcels.
We provide evidence for diagnostic validity and safety of stereo-EEG sensorimotor ESM.
The somatotopy of sensorimotor responses elicited with electrical stimulation provide new insights into mechanisms of motor control and sensory perception.
•An approach for analysis of task-related high-gamma modulation in stereo-EEG using distribution of power differential clusters is described.•Stereo-EEG high-gamma language mapping effectively ...localized reference neuroanatomy (Neurosynth).•Stereo-EEG high-gamma language mapping also adequately classified electrical stimulation mapping speech/language sites.
A novel analytic approach for task-related high-gamma modulation (HGM) in stereo-electroencephalography (SEEG) was developed and evaluated for language mapping.
SEEG signals, acquired from drug-resistant epilepsy patients during a visual naming task, were analyzed to find clusters of 50–150 Hz power modulations in time–frequency domain. Classifier models to identify electrode contacts within the reference neuroanatomy and electrical stimulation mapping (ESM) speech/language sites were developed and validated.
In 21 patients (9 females), aged 4.8–21.2 years, SEEG HGM model predicted electrode locations within Neurosynth language parcels with high diagnostic odds ratio (DOR 10.9, p < 0.0001), high specificity (0.85), and fair sensitivity (0.66). Another SEEG HGM model classified ESM speech/language sites with significant DOR (5.0, p < 0.0001), high specificity (0.74), but insufficient sensitivity. Time to largest power change reliably localized electrodes within Neurosynth language parcels, while, time to center-of-mass power change identified ESM sites.
SEEG HGM mapping can accurately localize neuroanatomic and ESM language sites.
Predictive modelling incorporating time, frequency, and magnitude of power change is a useful methodology for task-related HGM, which offers insights into discrepancies between HGM language maps and neuroanatomy or ESM.
The understanding of Childhood Absence Epilepsy (CAE) has been revolutionized over the past decade but the biological mechanisms responsible for variable treatment outcomes are unknown. Our purpose ...was to determine how pre-treatment ictal network pathways, defined using a combined EEG-functional magnetic resonance imaging (EEG-fMRI) and magnetoencephalography (MEG) effective connectivity analysis, were related to treatment response.
Sixteen children with newly diagnosed and drug naïve CAE had 31 typical absence seizures during EEG-fMRI and 74 during MEG. The spatial extent of the pre-treatment ictal network was defined using fMRI hemodynamic response with an event related independent component analysis (eICA). This spatially defined pre-treatment ictal network supplied prior information for MEG effective connectivity analysis calculated using phase slope index (PSI). Treatment outcome was assessed 2 years following diagnosis and dichotomized to ethosuximide (ETX) treatment responders (N = 11) or non-responders (N = 5). Effective connectivity of the pre-treatment ictal network was compared to the treatment response.
Patterns of pre-treatment connectivity demonstrated strongest connections in the thalamus and posterior brain regions (parietal, posterior cingulate, angular gyrus, precuneus, and occipital) at delta frequencies and the frontal cortices at gamma frequencies (p < 0.05). ETX treatment non-responders had pre-treatment connectivity which was decreased in the precuneus region and increased in the frontal cortex compared to ETX responders (p < 0.05).
Pre-treatment ictal connectivity differences in children with CAE were associated with response to anti-epileptic treatment. This is a possible mechanism for the variable treatment response seen in patients sharing the same epilepsy syndrome.
We prospectively validated stereo-electroencephalography (EEG) electrical stimulation mapping (ESM) of language against a reference standard of meta-analytic functional magnetic resonance imaging ...(fMRI) framework (Neurosynth).
Language ESM was performed using 50 Hz, biphasic, bipolar, stimulation at 1–8 mA, with a picture naming task. Electrode contacts (ECs) were scored as ESM+ if ESM interfered with speech/language function. For each patient, presurgical MRI was transformed to a standard space and coregistered with computed tomographic (CT) scan to obtain EC locations. After whole-brain parcellation, this fused image data were intersected with three-dimensional language fMRI (Neurosynth), and each EC was classified as lying within/outside the fMRI language parcel. Diagnostic odds ratio (DOR) and other indices were estimated. Current thresholds for language inhibition and after-discharges (ADs) were analyzed using multivariable linear mixed models.
In 10 patients (5 females), aged 5.4–21.2 years, speech/language inhibition was noted with ESM on 87/304 (29%) ECs. Stereo-EEG language ESM was a valid classifier of fMRI (Neurosynth) language sites (DOR: 9.02, p < 0.0001), with high specificity (0.87) but poor sensitivity (0.57). Similar diagnostic indices were seen for ECs in frontal or posterior regions, and gray or white matter.
Language threshold (3.1 ± 1.5 mA) was lower than AD threshold (4.0 ± 2.0 mA, p = 0.0001). Language and AD thresholds decreased with age and intelligence quotient. Electrical stimulation mapping triggered seizures/auras represented patients' habitual semiology with 1 Hz stimulation.
Stereo-EEG ESM can reliably identify cerebral parcels with/without language function but may under detect all language sites. We suggest a 50-Hz stimulation protocol for language ESM with stereo-EEG.
•We validated electrical stimulation mapping with stereo-EEG for localization of language functional neuroanatomy•Stereo-EEG electrical stimulation classified language sites (diagnostic odds ratio 9.0) with high specificity (0.87)•We suggest 50 Hz stimulation for language localization and 1 Hz stimulation for attempt to reproduce habitual seizures
Objective
Electrical stimulation mapping (ESM) is the clinical standard for functional localization with subdural electrodes (SDE). As stereoelectroencephalography (SEEG) has emerged as an ...alternative option, we compared functional responses, afterdischarges (ADs), and unwanted ESM‐induced seizures (EISs) between the two electrode types.
Methods
Incidence and current thresholds for functional responses (sensory, motor, speech/language), ADs, and EISs were compared between SDE and SEEG using mixed models incorporating relevant covariates.
Results
We identified 67 SEEG ESM and 106 SDE ESM patients (7207 and 4980 stimulated contacts, respectively). We found similar incidence of language and motor responses between electrode types; however, more SEEG patients reported sensory responses. ADs and EISs occurred less commonly with SEEG than SDE. Current thresholds for language, face motor, and upper extremity (UE) motor responses and EIS significantly decreased with age. However, they were not affected by electrode type, premedication, or dominant hemispheric stimulation. AD thresholds were higher with SEEG than with SDE. For SEEG ESM, language thresholds remained below AD thresholds up to 26 years of age, whereas this relationship was inverse for SDE. Also, face and UE motor thresholds fell below AD thresholds at earlier ages for SEEG than SDE. AD and EIS thresholds were not affected by premedication.
Significance
SEEG and SDE have clinically relevant differences for functional brain mapping with electrical stimulation. Although evaluation of language and motor regions is comparable between SEEG and SDE, SEEG offers a higher likelihood of identifying sensory areas. A lower incidence of ADs and EISs, and a favorable relationship between functional and AD thresholds suggest superior safety and neurophysiologic validity for SEEG ESM than SDE ESM.
