IDEAL approach to the evaluation of machine learning technology in epilepsy surgery: protocol for the MAST trial

Epilepsy and epilepsy surgery lend themselves well to the application of machine learning (ML) and artificial intelligence (AI) technologies. This is evidenced by the plethora of tools developed for applications such as seizure detection and analysis of imaging and electrophysiological data. However, few of these tools have been directly used to guide patient management. In recent years, the Idea, Development, Exploration, Assessment, Long-Term Follow-Up (IDEAL) collaboration has formalised stages for the evaluation of surgical innovation and medical devices, and, in many ways, this pragmatic framework is also applicable to ML/AI technology, balancing innovation and safety. In this protocol paper, we outline the preclinical (IDEAL stage 0) evaluation and the protocol for a prospective (IDEAL stage 1/2a) study to evaluate the utility of an ML lesion detection algorithm designed to detect focal cortical dysplasia from structural MRI, as an adjunct in the planning of stereoelectroencephalography trajectories in children undergoing intracranial evaluation for drug-resistant epilepsy

Sleep homeostasis, seizures, and cognition in children with focal epilepsy

AIM: To investigate the link between sleep disruption and cognitive impairment in childhood epilepsy by studying the effect of epilepsy on sleep homeostasis, as reflected in slow-wave activity (SWA). METHOD: We examined SWA from overnight EEG-polysomnography in 19 children with focal epilepsy (mean [SD] age 11 years 6 months [3 years], range 6 years 6 months-15 years 6 months; 6 females, 13 males) and 18 age- and sex-matched typically developing controls, correlating this with contemporaneous memory consolidation task scores, full-scale IQ, seizures, and focal interictal discharges. RESULTS: Children with epilepsy did not differ significantly from controls in overnight SWA decline (p = 0.12) or gain in memory performance with sleep (p = 0.27). SWA was lower in patients compared to controls in the first hour of non-rapid eye movement sleep (p = 0.021), although not in those who remained seizure-free (p = 0.26). Full-scale IQ did not correlate with measures of SWA in patients or controls. There was no significant difference in SWA measures between focal and non-focal electrodes. INTERPRETATION: Overnight SWA decline is conserved in children with focal epilepsy and may underpin the preservation of sleep-related memory consolidation in this patient group. Reduced early-night SWA may reflect impaired or immature sleep homeostasis in those with a higher seizure burden

Corticobulbar Tract Injury, Oromotor Impairment and Language Plasticity in Adolescents Born Preterm

Children born preterm are at risk of impairments in oromotor control, with implications for early feeding and speech development. In this study, we aimed to identify (a) neuroanatomical markers of persistent oromotor deficits using diffusion-weighted imaging (DWI) tractography and (b) evidence of compensatory neuroplasticity using functional MRI (fMRI) during a language production task. In a cross-sectional study of 36 adolescents born very preterm (<33 weeks’ gestation) we identified persistent difficulties in oromotor control in 31% of cases, but no clinical diagnoses of speech-sound disorder (e.g., dysarthria, dyspraxia). We used DWI-tractography to examine the microstructure (fractional anisotropy, FA) of the corticospinal and corticobulbar tracts. Compared to the unimpaired group, the oromotor-impaired group showed (i) reduced FA within the dorsal portion of the left corticobulbar tract (containing fibres associated with movements of the lips, tongue, and larynx) and (ii) greater recruitment of right hemisphere language regions on fMRI. We conclude that, despite the development of apparently normal everyday speech, early injury to the corticobulbar tract leads to persistent subclinical problems with voluntary control of the face, lips, jaw, and tongue. Furthermore, we speculate that early speech problems may be ameliorated by cerebral plasticity – in particular, recruitment of right hemisphere language areas

NMDA-receptor antibodies alter cortical microcircuit dynamics

NMDA-receptor antibodies (NMDAR-Abs) cause an autoimmune encephalitis with a diverse range of EEG abnormalities. NMDAR-Abs are believed to disrupt receptor function, but how blocking this excitatory synaptic receptor can lead to paroxysmal EEG abnormalities-or even seizures-is poorly understood. Here we show that NMDAR-Abs change intrinsic cortical connections and neuronal population dynamics to alter the spectral composition of spontaneous EEG activity and predispose brain dynamics to paroxysmal abnormalities. Based on local field potential recordings in a mouse model, we first validate a dynamic causal model of NMDAR-Ab effects on cortical microcircuitry. Using this model, we then identify the key synaptic parameters that best explain EEG paroxysms in pediatric patients with NMDAR-Ab encephalitis. Finally, we use the mouse model to show that NMDAR-Ab-related changes render microcircuitry critically susceptible to overt EEG paroxysms when these key parameters are changed, even though the same parameter fluctuations are tolerated in the in silico model of the control condition. These findings offer mechanistic insights into circuit-level dysfunction induced by NMDAR-Ab

Sleep homeostasis, seizures, and cognition in children with focal epilepsy

AIM To investigate the link between sleep disruption and cognitive impairment in childhood epilepsy by studying the effect of epilepsy on sleep homeostasis, as reflected in slow-wave activity (SWA). METHOD We examined SWA from overnight EEG-polysomnography in 19 children with focal epilepsy (mean [SD] age 11 years 6 months [3 years], range 6 years 6 months-15 years 6 months; 6 females, 13 males) and 18 age- and sex-matched typically developing controls, correlating this with contemporaneous memory consolidation task scores, full-scale IQ, seizures, and focal interictal discharges. RESULTS Children with epilepsy did not differ significantly from controls in overnight SWA decline (p = 0.12) or gain in memory performance with sleep (p = 0.27). SWA was lower in patients compared to controls in the first hour of non-rapid eye movement sleep (p = 0.021), although not in those who remained seizure-free (p = 0.26). Full-scale IQ did not correlate with measures of SWA in patients or controls. There was no significant difference in SWA measures between focal and non-focal electrodes. INTERPRETATION Overnight SWA decline is conserved in children with focal epilepsy and may underpin the preservation of sleep-related memory consolidation in this patient group. Reduced early-night SWA may reflect impaired or immature sleep homeostasis in those with a higher seizure burden

Functional magnetic resonance imaging in clinical practice: state of the art and science

BACKGROUND: Functional magnetic resonance imaging (fMRI) has become a mainstream neuroimaging modality in the assessment of patients being evaluated for brain tumour and epilepsy surgeries. Thus, it is important for doctors in primary care settings to be well acquainted with the present and potential future applications, as well as limitations, of this modality.OBJECTIVE: The objective of this article is to introduce the theoretical principles and state-of-the-art clinical applications of fMRI in brain tumour and epilepsy surgery, with a focus on the implications for clinical primary care.DISCUSSION: fMRI enables non-invasive functional mapping of specific cortical tasks (eg motor, language, memory-based, visual), revealing information about functional localisation, anatomical variation in cortical function, and disease effects and adaptations, including the fascinating phenomenon of brain plasticity. fMRI is currently ordered by specialist neurologists and neurosurgeons for the purposes of pre-surgical assessment, and within the context of an experienced multidisciplinary team to prepare, conduct and interpret the scan. With an increasing number of patients undergoing fMRI, general practitioners can expect questions about the current and emerging role of fMRI in clinical care from these patients and their families

Novel surface features for automated detection of focal cortical dysplasias in paediatric epilepsy.

Focal cortical dysplasia is a congenital abnormality of cortical development and the leading cause of surgically remediable drug-resistant epilepsy in children. Post-surgical outcome is improved by presurgical lesion detection on structural MRI. Automated computational techniques have improved detection of focal cortical dysplasias in adults but have not yet been effective when applied to developing brains. There is therefore a need to develop reliable and sensitive methods to address the particular challenges of a paediatric cohort. We developed a classifier using surface-based features to identify focal abnormalities of cortical development in a paediatric cohort. In addition to established measures, such as cortical thickness, grey-white matter blurring, FLAIR signal intensity, sulcal depth and curvature, our novel features included complementary metrics of surface morphology such as local cortical deformation as well as post-processing methods such as the "doughnut" method - which quantifies local variability in cortical morphometry/MRI signal intensity, and per-vertex interhemispheric asymmetry. A neural network classifier was trained using data from 22 patients with focal epilepsy (mean age = 12.1 ± 3.9, 9 females), after intra- and inter-subject normalisation using a population of 28 healthy controls (mean age = 14.6 ± 3.1, 11 females). Leave-one-out cross-validation was used to quantify classifier sensitivity using established features and the combination of established and novel features. Focal cortical dysplasias in our paediatric cohort were correctly identified with a higher sensitivity (73%) when novel features, based on our approach for detecting local cortical changes, were included, when compared to the sensitivity using only established features (59%). These methods may be applicable to aiding identification of subtle lesions in medication-resistant paediatric epilepsy as well as to the structural analysis of both healthy and abnormal cortical development.This research was supported by the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London. SA received funding from the Rosetrees Trust (A711). KW received funding from the James Baird Fund and the Wellcome Trust (WT095692MA). TB from Great Ormond Street Hospital Children's Charity (V1213 and V2416). LR and PCF are funded by the Wellcome Trust and the Bernard Wolfe Health Neuroscience Fund

Motor Abilities in Adolescents Born Preterm Are Associated With Microstructure of the Corpus Callosum

Background: Preterm birth is associated with increased risk of neuromotor impairment. Rates of major neuromotor impairment (cerebral palsy) have decreased; however, in a large proportion of those who do not develop cerebral palsy impaired neuromotor function is observed and this often has implications for everyday life. The aim of this study was to investigate motor performance in preterm born adolescents without cerebral palsy, and to examine associations with alterations of motor system pathway structure. Design/Methods: Thirty-two adolescents (12 males) without cerebral palsy, born before 33 weeks of gestation (mean 27.4 weeks, SD 2.4; birth weight mean 1,084.5 g; SD 387.2), treated at a single tertiary unit, were assessed (median age 16 years; min 14, max 18). Timed performance and quality of movements were assessed with the Zürich Neuromotor Assessment. Neuroimaging included Diffusion Magnetic Resonance Imaging for tractography of the major motor tracts and measurement of fractional anisotropy as a measure of microstructure of the tracts along the major motor pathways. Separate analyses were conducted for areas with predominantly single and predominantly crossing fiber regions. Results: Motor performance in both tasks assessing timed performance and quality of movements, was poorer than expected in the preterm group in relation to norm population. The strongest significant correlations were seen between performance in tasks assessing movement quality and fractional anisotropy in corpus callosum fibers connecting primary motor, primary somatosensory and premotor areas. In addition, timed motor performance was significantly related to fractional anisotropy in the cortico-spinal and thalamo-cortical to premotor area fibers, and the corpus callosum. Conclusions: Impairments in motor abilities are present in preterm born adolescents without major neuromotor impairment and in the absence of focal brain injury. Altered microstructure of the corpus callosum microstructure appears a crucial factor, in particular for movement quality