Biology subjects

Spencer, D. D.

Publications and source records attributed to Spencer, D. D..

4 recordsLinked to original sources

bioRxiv2024

Widespread brain activity increases in frontal lobe seizures with impaired consciousness

Impaired consciousness is a serious clinical manifestation of epilepsy with negative consequences on quality of life. Little work has investigated impaired consciousness in frontal lobe seizures, a common form of focal epilepsy. In temporal lobe seizures, previous studies showed widespread cortical slow waves associated with depressed subcortical arousal and impaired consciousness. However, in frontal lobe epilepsy, it is not known whether cortical slow waves are present, or whether a very different cortical activity pattern may be related to impaired consciousness. We used intracranial EEG recordings of 65 frontal lobe seizures in 30 patients for quantitative analysis of ictal cortical activity and its relationship to impaired consciousness. Behavioral changes based on blinded review of seizure videos were used to classify focal aware, focal impaired awareness, and focal to bilateral tonic-clonic seizures. Changes in intracranial EEG power from preictal baseline were analyzed in different cortical regions and across frequency ranges in these three categories. We found that frontal lobe focal aware seizures showed approximately 40% increases in intracranial EEG power localized to the frontal lobe of seizure onset across frequency ranges, with relatively smaller changes in other cortical regions. Frontal lobe focal impaired awareness seizures showed approximately 50% increases in intracranial EEG power, not significantly different from focal aware seizures in the frontal lobe of seizure onset (P = 1.038), but significantly greater than focal aware seizures in other broad cortical regions (P < 0.001). Importantly, the widespread cortical increases in EEG power observed in focal impaired awareness versus focal aware seizures were seen not just in the frequency range of slow waves, but were also observed across other frequencies including fast activity. However, the widespread cortical increases in focal impaired awareness seizures differed from focal to bilateral tonic-clonic seizures where intracranial EEG power increased to a much higher level by approximately 600%. The large power increases in focal to bilateral tonic-clonic were significantly greater than in focal impaired awareness seizures both in the frontal lobe of seizure onset and in other cortical regions (P < 0.001). Our findings contrast with focal temporal lobe epilepsy, where impaired consciousness is associated with cortical slow waves. We can speculate that different focal seizure types produce impaired consciousness by impacting widespread cortical regions but through different physiological mechanisms. Insights gained by studying mechanisms of impaired consciousness may be the first step towards developing novel treatments to prevent this important negative consequence of epilepsy.

neuroscience↗

bioRxiv2019

The Connectivity Index: An Effective Metric for Grading Epileptogenicity

ObjectiveTo investigate the performance of a metric of functional connectivity to classify and grade the excitability of brain regions based on evoked potentials to single pulse electrical stimulation (SPES).\n\nMethodsPatients who received 1-Hz frequency stimulation between 2003 and 2014 at Yale at prospectively selected contacts were included. The stimulated contacts were classified as seizure onset zone (SOZ), highly irritative zone (IZp) or control. Response contacts were classified as seizure onset zone (SOZ), active interictal (IZp), quiet or other. The normalized number of responses was defined as the number of contacts with any evoked responses divided by the total number of recorded contacts, and the normalized distance is the ratio of the average distance between the site of stimulation and sites of evoked responses to the average distances between the site of stimulation and all other recording contacts. A new metric we labeled the connectivity index (CI) is defined as the product of the two values.\n\nResults57 stimulation-sessions in 22-patients were analyzed. The connectivity index (CI) of the SOZ was higher than control (median CI of 0.74 vs. 0.16, p = 0.0002). The evoked responses after stimulation of SOZ were seen at further distance compared to control (median normalized distance 0.96 vs. 0.62, p = 0.0005). It was 1.8 times more likely to record a response at SOZ than in non-epileptic contacts after stimulation of a control site. Habitual seizures were triggered in 27% of patients and 35 % of SOZ contacts (median stimulation intensity 4 mA) but in none of the control or IZp contacts. Non-SOZ contacts in multifocal or poor surgical outcome cases had a higher CI than non-SOZ contacts in those with localizable onsets (medians CI of 0.5 vs. 0.12, p = 0.04). There was a correlation between the stimulation current intensity and the normalized number of evoked responses (r = + 0.49, p 0.01) but not with distance (r = + 0.1, p 0.64)\n\nConclusionsWe found enhanced connectivity when stimulating the SOZ compared to stimulating control contacts; responses were more distant as well. Habitual auras and seizures provoked by SPES were highly predictive of brain sites involved in seizure generation.

neuroscience↗

bioRxiv2018

Presurgical language fMRI: Current technical practices in epilepsy surgical planning

Little is known about how language functional MRI (fMRI) is executed in clinical practice in spite of its widespread use. Here we comprehensively documented its execution in surgical planning in epilepsy. A questionnaire focusing on cognitive design, imaging acquisition, analysis and interpretation and practical considerations was developed. Individuals responsible for collecting, analyzing, and interpreting clinical language fMRI data at 63 epilepsy surgical programs responded. The central finding was of marked heterogeneity in all aspects of fMRI. Most programs use multiple tasks, with a fifth routinely using 2, 3, 4 or 5 tasks with a modal run duration of five minutes. Variants of over fifteen protocols are in routine use with forms of noun-verb generation, verbal fluency, and semantic decision-making used most often. Nearly all aspects of data acquisition and analysis vary markedly. Neither of the two best-validated protocols were used by more than 10% of respondents. Preprocessing steps are broadly consistent across sites, language-related blood flow is most often identified using general linear modeling (76% of respondents), and statistical thresholding typically varies by patient (79%). The software SPM is most often used. fMRI programs inconsistently include input from experts with all required skills (imaging, cognitive assessment, MR physics, statistical analysis, brain-behavior relationships). These data highlight marked gaps between the evidence supporting fMRI and its clinical application. Teams performing language fMRI may benefit from evaluating practice with reference to the best-validated protocols to date and ensuring individuals trained in all aspects of fMRI are involved to optimize patient care.

neuroscience↗

bioRxiv2017

Presurgical language fMRI: Current practices and patient outcomes in epilepsy surgical planning

The goal of this study was to document current clinical practice and report patient outcomes in presurgical language functional MRI (fMRI) for epilepsy surgery. Epilepsy surgical programs worldwide were surveyed as to the utility, implementation, and efficacy of language fMRI in the clinic; 82 programs responded between July 2015 and January 2016. Respondents were predominantly from the US (61%), were academic programs (85%), and predominantly evaluated adults (44%), both adults and children (40%), or children only (16%). Nearly all (96%) respondents reported using language fMRI. fMRI is used for language lateralization (100%) and for localizing (44%) language cortex to guide surgical margins. While typically considered useful, programs often reported at least one instance of disagreement with other measures (56%). When used to localize language cortex, direct brain stimulation typically confirmed fMRI findings (74%) but instances of unpredicted decline were reported by 17% of programs and unexpected preservation of function were reported by 54%. Programs reporting unexpected decline did not clearly differ from those which did not. Clinicians using fMRI to guide surgical margins typically map Brocas and Wernickes areas but not other known language areas. Language fMRI is widely used for lateralizing language cortex in patients with medically intractable epilepsy. It is also frequently used to localize language cortex though it is not yet well validated for this purpose. Many centers report cases of unexpected language preservation when fMRI activation is resected, and cases of language decline when it is not. Care will almost certainly be improved by standardizing protocols and accurately detailing the relationship between fMRI-positive areas and post-surgical language decline.

neuroscience↗