The Distinctive Sleep Pattern of the Human Calcarine Cortex: A Stereo-EEG Study

Study Objectives The aim of the study was to describe the spontaneous electroencephalographic (EEG) features of sleep in the human calcarine cortex, comparing them with the well-established pattern of the parietal cortex. Methods We analysed pre-surgical intracerebral EEG activity in calcarine and parietal cortices during NREM and REM sleep in 7 patients with drug-resistant focal epilepsy. The time course of the EEG spectral power and NREM vs. REM differences were assessed. Sleep spindles were automatically detected. To assess homeostatic dynamics, we considered the 1 st vs. 2 nd half of the night ratio in the delta frequency range (0.5-4 Hz) and the rise rate of delta activity during the 1 st sleep cycle. Results While the parietal area showed the classically described NREM and REM sleep hallmarks, the calcarine cortex exhibited a distinctive pattern characterized by: a) the absence of sleep spindles; b) a large similarity between EEG power spectra of NREM and REM; c) reduced signs of homeostatic dynamics, with a decreased delta ratio between the 1 st and the 2 nd half of the night, a reduced rise rate of delta activity during the 1 st NREM sleep cycle, and lack of correlation between these measures. Conclusions Besides describing for the first time the peculiar sleep EEG pattern in the human calcarine cortex, our findings provide evidence that different cortical areas may exhibit specific sleep EEG pattern, supporting the view of sleep as a local process and promoting the idea that the functional role of sleep EEG features should be considered at a regional level.

CCL2 is associated with microglia and macrophage recruitment in chronic traumatic encephalopathy

Background Neuroinflammation has been implicated in the pathogenesis of chronic traumatic encephalopathy (CTE), a progressive neurodegenerative disease association with exposure to repetitive head impacts (RHI) received though playing contact sports such as American football. Past work has implicated early and sustained activation of microglia as a potential driver of tau pathology within the frontal cortex in CTE. However, the RHI induced signals required to recruit microglia to areas of damage and pathology are unknown. Methods Postmortem brain tissue was obtained from 261 individuals across multiple brain banks. Comparisons were made using cases with CTE, cases with Alzheimer’s disease (AD), and cases with no neurodegenerative disease and lacked exposure to RHI (controls). Recruitment of Iba1+ cells around the CTE perivascular lesion was compared to non-lesion vessels. TMEM119 staining was used to characterize microglia or macrophage involvement. The potent chemoattractant CCL2 was analyzed using frozen tissue from the dorsolateral frontal cortex (DLFC) and the calcarine cortex. Finally, the amounts of hyperphosphorylated tau (pTau) and Aβ42 were compared to CCL2 levels to examine possible mechanistic pathways. Results An increase in Iba1+ cells was found around blood vessels with perivascular tau pathology compared to non-affected vessels in individuals with RHI. TMEM119 staining revealed the majority of the Iba1+ cells were microglia. CCL2 protein levels in the DLFC were found to correlate with greater years of playing American football, the density of Iba1+ cells, the density of CD68+ cells, and increased CTE severity. When comparing across multiple brain regions, CCL2 increases were more pronounced in the DLFC than the calcarine cortex in cases with RHI but not in AD. When examining the individual contribution of pathogenic proteins to CCL2 changes, pTau correlated with CCL2, independent of age at death and Aβ42 in AD and CTE. Although levels of Aβ42 were not correlated with CCL2 in cases with CTE, in males in the AD group, Aβ42 trended toward an inverse relationship with CCL2 suggesting possible gender associations. Conclusion Overall, CCL2 is implicated in the pathways recruiting microglia and the development of pTau pathology after exposure to RHI, and may represent a future therapeutic target in CTE.