Cell type-specific gene expression dynamics during human brain maturation.

The human brain undergoes protracted post-natal maturation, guided by dynamic changes in gene expression. To date, studies exploring these processes have used bulk tissue analyses, which mask cell type-specific gene expression dynamics. Here, using single nucleus (sn)RNA-Sseq on temporal lobe tissue, including samples of African ancestry, we build a joint paediatric and adult atlas of 54 cell subtypes, which we verify with spatial transcriptomics. We explore the differences in cell states between paediatric and adult cell types, revealing the genes and pathways that change during brain maturation. Our results highlight excitatory neuron subtypes, including the LTK and FREM subtypes, that show elevated expression of genes associated with cognition and synaptic plasticity in paediatric tissue. The new resources we present here improve our understanding of the brain during a critical period of its development and contribute to global efforts to build an inclusive cell map of the brain.

Deep brain stimulation in Parkinson's disease: analysis of the variation in final stimulating lead placement based on multi-tract electrode recordings

Background: Deep brain stimulation (DBS) of the subthalamic nucleus (SNT) is a treatment modality for Parkinson's Disease (PD). Either single central trajectory tract or multiple selected trajectory tracts based on microelectrode recordings (MER) are used for the placement of the final stimulating electrodes. This study aims to explore how many times trajectory tracts, other than the central tract are used for final lead placement.Methods: Retrospective analysis of a randomly selected convenience sample of 24 subjects from patients who had DBS by a single neurosurgeon. After MRI and CT assessment, planning using a stereotactic frame for variable trajectory placement of temporary electrodes and MER that was the basis for site and tract selection for the final electrode placements used for DBS. Results: Twenty four patients had 47 DBS electrodes placed: 1 unilateral and 23 bilateral. The central tract was used in 45 (95.75%) of these cases. The central trajectory tract accounted for 30 (63.83%), the anterior trajectory tract for 7 (14.89%), the medial tract for 5 (10.64%), the posterior for 4 (8.51%) and the lateral for 1 (2.13%) of final lead placements. Conclusion: The results of this study based on the predicted best stimulating sites following MER show that alternates to the central trajectory tract are required in 37% of site placements. A comparative study exploring clinical benefit is required to assess if variable electrode trajectory placement based on accurate physiological measurements is superior to single central trajectory placement

Stereotactic proton beam therapy for intracranial arteriovenous malformations.

PURPOSE: To investigate hypofractionated stereotactic proton therapy of predominantly large intracranial arteriovenous malformations (AVMs) by analyzing retrospectively the results from a cohort of patients. METHODS AND MATERIALS: Since 1993, a total of 85 patients with vascular lesions have been treated. Of those, 64 patients fulfilled the criteria of having an arteriovenous malformation and sufficient follow-up. The AVMs were grouped by volume: <14 cc (26 patients) and > or =14 cc (38 patients). Treatment was delivered with a fixed horizontal 200 MeV proton beam under stereotactic conditions, using a stereophotogrammetric positioning system. The majority of patients were hypofractionated (2 or 3 fractions), and the proton doses are presented as single-fraction equivalent cobalt Gray equivalent doses (SFEcGyE). The overall mean minimum target volume dose was 17.37 SFEcGyE, ranging from 10.38-22.05 SFEcGyE. RESULTS: Analysis by volume group showed obliteration in 67% for volumes <14 cc and 43% for volumes > or =14 cc. Grade IV acute complications were observed in 3% of patients. Transient delayed effects were seen in 15 patients (23%), becoming permanent in 3 patients. One patient also developed a cyst 8 years after therapy. CONCLUSIONS: Stereotactic proton beam therapy applied in a hypofractionated schedule allows for the safe treatment of large AVMs, with acceptable results. It is an alternative to other treatment strategies for large AVMs. AVMs are likely not static entities, but probably undergo vascular remodeling. Factors influencing angiogenesis could play a new role in a form of adjuvant therapy to improve on the radiosurgical results.

A quick and universal method for stereotactic visualization of the subthalamic nucleus before and after implantation of deep brain stimulation electrodes.

For deep brain stimulation (DBS) of the subthalamic nucleus (STN), it would be an advantage if the STN could be visualized with fast acquisition of MR images, allowing direct and individual targeting. We present a protocol for T2-weighted, nonvolumetric fast-acquisition MRI, implemented at 8 centers in 6 countries. Acquisition time varied between 3 min 5 s and 7 min 48 s according to the center, and imaging often provided visualization of the STN on axial and coronal scans. Postoperatively, the same imaging protocol permitted visualization of the target area and DBS electrodes with minimum artifacts. This imaging technique may contribute to a decrease in the number of electrode passes at surgery.