Previous studies have revealed that greater neural pattern similarity across repetitions is associated with better subsequent memory. In this study, we used an artificial language training paradigm and representational similarity analysis to examine whether neural pattern similarity across repetitions before training was associated with post-training behavioral performance. Twenty-four native Chinese speakers were trained to learn a logographic artificial language for 12 days and behavioral performance was recorded using the word naming and picture naming tasks. Participants were scanned while performing a passive viewing task before training, after 4-day training and after 12-day training. Results showed that pattern similarity in the left pars opercularis (PO) and fusiform gyrus (FG) before training was negatively associated with reaction time (RT) in both word naming and picture naming tasks after training. These results suggest that neural pattern similarity is an effective neurofunctional predictor of novel word learning in addition to word memory.

Proliferative vitreoretinopathy (PVR) is a blinding eye disease and there is no effective pharmacological measure to prevent PVR development. The difficulty comes from lack of potent antiproliferative agent and lack of sustained delivery to cover high-risk time window for PVR to develop. Lipid prodrug of PMEG, hexadecyloxypropyl 9-[(2-phosphonomethoxy)ethyl]guanine (HDP-PMEG), was prepared and was evaluated as a pharmacological adjuvant to surgical management of PVR. A dose-escalation study determined that the highest nontoxic dose for intravitreal use in pigmented rabbits was 3 µg per eye. The genotoxicity of HDP-PMEG was harnessed as a perioperative preventative measure against PVR in a rabbit eye model while the sustained intravitreal pharmacological effect was evaluated on a laser-induced fibrovascular model in rat eye. After intravitreal 3 µg, HDP-PMEG particles in the rabbit vitreous was visible for at least 6 weeks. A single 50-min intravitreal infusion of HDP-PMEG demonstrated significant inhibition of PVR formation when compared with the eyes infused with only BSS (BSS vs. HDP-PMEG: estimate = 1.14, OR = 3.1, p = .027). A single intravitreal 104 ng (equivalent to 3 µg for rabbit eye) of HDP-PMEG significantly inhibit laser-induced fibrovascular proliferation in rat eye by 55% (least square mean pixel, BSS = 4763569.5 vs. HDP-PMEG = 2148129.7, p < .0001, generalized estimating equation [GEE]). Retinal fluorescein angiography showed the odds for BSS intervened eyes to have higher-rated FA leaking grades were 38.5 times compared with HDP-PMEG treated eyes (p < .0001, GEE). Our study results indicate that single intravitreal HDP-PMEG may be a promising ocular drug delivery as a perioperative intervention to prevent PVR reoccurrence following primary surgical management.

Background

Repetitive transcranial magnetic stimulation (rTMS) has been increasingly used as a treatment modality for chronic insomnia disorder (CID). However, our understanding of the mechanisms underlying the efficacy of rTMS is limited.

Objective

This study aimed to investigate rTMS-induced alterations in resting-state functional connectivity and to find potential connectivity biomarkers for predicting and tracking clinical outcomes after rTMS.

Methods

Thirty-seven patients with CID received a 10-session low frequency rTMS treatment applied to the right dorsolateral prefrontal cortex. Before and after treatment, the patients underwent resting-state electroencephalography recordings and a sleep quality assessment using the Pittsburgh Sleep Quality Index (PSQI).

Results

After treatment, rTMS significantly increased the connectivity of 34 connectomes in the lower alpha frequency band (8-10 Hz). Additionally, alterations in functional connectivity between the left insula and the left inferior eye junction, as well as between the left insula and medial prefrontal cortex, were associated with a decrease in PSQI score. Further, the correlation between the functional connectivity and PSQI persisted 1 month after the completion of rTMS as evidenced by subsequent electroencephalography (EEG) recordings and the PSQI assessment.

Conclusion

Based on these results, we established a link between alterations in functional connectivity and clinical outcomes of rTMS, which suggested that EEG-derived functional connectivity changes were associated with clinical improvement of rTMS in treating CID. These findings provide preliminary evidence that rTMS may improve insomnia symptoms by modifying functional connectivity, which can be used to inform prospective clinical trials and potentially for treatment optimization.

Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input-output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization^1-5. First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.