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IntroductionVagus nerve stimulation (VNS) is a neuromodulation therapy that can reduce the seizure burden of children with medically intractable epilepsy. Despite the widespread use of VNS to treat epilepsy, there are currently no means to preoperatively identify patients who will benefit from treatment. The objective of the present study is to determine clinical and neural network-based correlates of treatment outcome to better identify candidates for VNS therapy.Methods and analysisIn this multi-institutional North American study, children undergoing VNS and their caregivers will be prospectively recruited. All patients will have documentation of clinical history, physical and neurological examination and video electroencephalography as part of the standard clinical workup for VNS. Neuroimaging data including resting-state functional MRI, diffusion-tensor imaging and magnetoencephalography will be collected before surgery. MR-based measures will also be repeated 12 months after implantation. Outcomes of VNS, including seizure control and health-related quality of life of both patient and primary caregiver, will be prospectively measured up to 2 years postoperatively. All data will be collected electronically using Research Electronic Data Capture.Ethics and disseminationThis study was approved by the Hospital for Sick Children Research Ethics Board (REB number 1000061744). All participants, or substitute decision-makers, will provide informed consent prior to be enrolled in the study. Institutional Research Ethics Board approval will be obtained from each additional participating site prior to inclusion. This study is funded through a Canadian Institutes of Health Research grant (PJT-159561) and an investigator-initiated funding grant from LivaNova USA (Houston, TX; FF01803B IIR).

The entorhinal cortex (EC) is a highly-interconnected hub for multisensory integration and memory processing1–3, containing diverse neuronal subtypes4,5 including subpopulations that are uniquely spatially-tuned6,7. Although many spatial and memory functions develop in infancy, it is considered that neurogenesis and neuronal migration to the EC occurs prenatally. Here we show that the postnatal human temporal lobe contains a prominent stream with large chains of young migrating neurons and many individual neurons breaking away directed into the EC. The EC stream forms between the second and third trimesters of prenatal development when the lateral ventricle walls in the temporal lobe collapse, displacing the subventricular zone (SVZ) and dividing radial glia. At birth, the EC stream follows a path of radial glial fibers in the site of the collapsed ventricle. Migratory chains persist up to 11 months postnatally; however, many individually migrating young neurons can still be detected in the EC at 2 years of age and a few isolated cells at 3 years of age. Within the EC at birth, immature neurons are a mixed population expressing markers of the medial ganglionic eminence (MGE) and caudal ganglionic eminence (CGE), but postnatally rapidly become primarily CGE-derived. Using single-nuclei RNAseq we identified these lineages and found that the MGE-derived neurons matured at earlier postnatal ages compared to those derived from the CGE. The CGE interneurons arriving and maturing the latest included subtypes expressing calretinin (CR), reelin (RELN), and vasoactive intestinal protein (VIP) many of which settle in layer II of the entorhinal cortex. This study reveals that the human EC is still being constructed during the first years of life revealing the largest known postnatal stream of migratory neurons in humans. The protracted postnatal arrival of a diverse population of interneurons could contribute to plasticity8,9 and proper excitation-inhibition balance10,11 within these highly connected brain circuits.

This case represents the unique occurrence of supratentorial dissemination of medulloblastoma in the absence of overt cerebellar disease. The authors present the case of a 64-year-old man who presented with headaches and intractable nausea with imaging abnormality seen only in the bilateral caudate. Follow-up imaging studies revealed a cerebellar lesion later confirmed by biopsy to be medulloblastoma. Subsequent biopsy of the originally evaluated caudate lesion demonstrated histologically identical medulloblastoma. Medulloblastoma should be considered in cases of supratentorial masses of unclear origin and should prompt careful inspection of the posterior fossa.