Morphological correlates of pyramidal cell axonal myelination in mouse and human neocortex.

The axons of neocortical pyramidal neurons are frequently myelinated. Heterogeneity in the topography of axonal myelination in the cerebral cortex has been attributed to a combination of electrophysiological activity, axonal morphology, and neuronal-glial interactions. Previously, we showed that axonal segment length and caliber are critical local determinants of fast-spiking interneuron myelination. However, the factors that determine the myelination of individual axonal segments along neocortical pyramidal neurons remain largely unexplored. Here, we used structured illumination microscopy to examine the extent to which axonal morphology is predictive of the topography of myelination along neocortical pyramidal neurons. We identified critical thresholds for axonal caliber and interbranch distance that are necessary, but not sufficient, for myelination of pyramidal cell axons in mouse primary somatosensory cortex (S1). Specifically, we found that pyramidal neuron axonal segments with a caliber < 0.24 µm or interbranch distance < 18.10 µm are rarely myelinated. Moreover, we further confirmed that these findings in mice are similar for human neocortical pyramidal cell myelination (caliber < 0.25 µm, interbranch distance < 19.00 µm), suggesting that this mechanism is evolutionarily conserved. Taken together, our findings suggest that axonal morphology is a critical correlate of the topography and cell-type specificity of neocortical myelination.

Local axonal morphology guides the topography of interneuron myelination in mouse and human neocortex.

GABAergic fast-spiking parvalbumin-positive (PV) interneurons are frequently myelinated in the cerebral cortex. However, the factors governing the topography of cortical interneuron myelination remain incompletely understood. Here, we report that segmental myelination along neocortical interneuron axons is strongly predicted by the joint combination of interbranch distance and local axon caliber. Enlargement of PV+ interneurons increased axonal myelination, while reduced cell size led to decreased myelination. Next, we considered regular-spiking SOM+ cells, which normally have relatively shorter interbranch distances and thinner axon diameters than PV+ cells, and are rarely myelinated. Consistent with the importance of axonal morphology for guiding interneuron myelination, enlargement of SOM+ cell size dramatically increased the frequency of myelinated axonal segments. Lastly, we confirm that these findings also extend to human neocortex by quantifying interneuron axonal myelination from ex vivo surgical tissue. Together, these findings establish a predictive model of neocortical GABAergic interneuron myelination determined by local axonal morphology.

Extracranial Trigger Site Surgery for Migraine: A Systematic Review With Meta-Analysis on Elimination of Headache Symptoms.

Introduction: The headache phase of migraine could in selected cases potentially be treated by surgical decompression of one or more "trigger sites," located at frontal, temporal, nasal, and occipital sites. This systematic review with subsequent meta-analysis aims at critically evaluating the currently available evidence for the surgical treatment of migraine headache and to determine the effect size of this treatment in a specific patient population. Methods: This study was conducted following the PRISMA guidelines. An online database search was performed. Inclusion was based on studies published between 2000 and March 2018, containing a diagnosis of migraine in compliance with the classification of the International Headache Society. The treatment must consist of one or more surgical procedures involving the extracranial nerves and/or arteries with outcome data available at minimum 6 months. Results: Eight hundred and forty-seven records were identified after duplicates were removed, 44 full text articles were assessed and 14 records were selected for inclusion. A total number of 627 patients were included in the analysis. A proportion of 0.38 of patients (random effects model, 95% CI [0.30-0.46]) experienced elimination of migraine headaches at 6-12 months follow-up. Using data from three randomized controlled trials, the calculated odds ratio for 90-100% elimination of migraine headaches is 21.46 (random effects model, 95% CI [5.64-81.58]) for patients receiving migraine surgery compared to sham or no surgery. Conclusions: Migraine surgery leads to elimination of migraine headaches in 38% of the migraine patients included in this review. However, more elaborate randomized trials are needed with transparent reporting of patient selection, medication use, and surgical procedures and implementing detailed and longer follow-up times.

The Impacts of Tumor and Tumor Associated Epilepsy on Subcortical Brain Structures and Long Distance Connectivity in Patients With Low Grade Glioma.

Low grade gliomas in cerebral cortex often cause symptoms related to higher cerebral functions such as attention, memory and executive function before treatment is initiated. Interestingly, focal tumors residing in one cortical region can lead to a diverse range of symptoms, indicating that the impact of a tumor is extended to multiple brain regions. We hypothesize that the presence of focal glioma in the cerebral cortex leads to alterations of distant subcortical areas and essential white matter tracts. In this study, we analyzed diffusion tensor imaging scans in glioma patients to study the effect of glioma on subcortical gray matter nuclei and long-distance connectivity. We found that the caudate nucleus, putamen and thalamus were affected by cortical glioma, displaying both volumetric and diffusion alterations. The cerebellar cortex contralateral to the tumor side also showed significant volume decrease. Additionally, tractography of the cortico-striatal and cortico-thalamic projections shows similar diffusion alterations. Tumor associated epilepsy might be an important contributing factor to the found alterations. Our findings indeed confirm concurrent structural and connectivity abrasions of brain areas distant from brain tumor, and provide insights into the pathogenesis of diverse neurological symptoms in glioma patients.