Effects of prefrontal theta burst stimulation on neuronal activity and subsequent eating behavior: an interleaved rTMS and fNIRS study.

The dorsolateral prefrontal cortex (dlPFC) and dorsomedial prefrontal cortex (dmPFC) are both important nodes for self-control and decision-making but through separable processes (cognitive control vs evaluative processing). This study aimed to examine the effects of excitatory brain stimulation [intermittent theta burst stimulation (iTBS)] targeting the dlPFC and dmPFC on eating behavior. iTBS was hypothesized to decrease consumption of appetitive snack foods, via enhanced interference control for dlPFC stimulation and reduced delay discounting (DD) for dmPFC stimulation. Using a single-blinded, between-subjects design, participants (N = 43) were randomly assigned to one of three conditions: (i) iTBS targeting the left dlPFC, (ii) iTBS targeting bilateral dmPFC or (iii) sham. Participants then completed two cognitive tasks (DD and Flanker), followed by a bogus taste test. Functional near-infrared spectroscopy imaging revealed that increases in the medial prefrontal cortex activity were evident in the dmPFC stimulation group during the DD task; likewise, a neural efficiency effect was observed in the dlPFC stimulation group during the Flanker. Gender significantly moderated during the taste test, with females in the dmPFC showing paradoxical increases in food consumption compared to sham. Findings suggest that amplification of evaluative processing may facilitate eating indulgence when preponderant social cues are permissive and food is appetitive.

Transcriptional control of brain tumor stem cells by a carbohydrate binding protein.

Brain tumor stem cells (BTSCs) and intratumoral heterogeneity represent major challenges in glioblastoma therapy. Here, we report that the LGALS1 gene, encoding the carbohydrate binding protein, galectin1, is a key regulator of BTSCs and glioblastoma resistance to therapy. Genetic deletion of LGALS1 alters BTSC gene expression profiles and results in downregulation of gene sets associated with the mesenchymal subtype of glioblastoma. Using a combination of pharmacological and genetic approaches, we establish that inhibition of LGALS1 signaling in BTSCs impairs self-renewal, suppresses tumorigenesis, prolongs lifespan, and improves glioblastoma response to ionizing radiation in preclinical animal models. Mechanistically, we show that LGALS1 is a direct transcriptional target of STAT3 with its expression robustly regulated by the ligand OSM. Importantly, we establish that galectin1 forms a complex with the transcription factor HOXA5 to reprogram the BTSC transcriptional landscape. Our data unravel an oncogenic signaling pathway by which the galectin1/HOXA5 complex maintains BTSCs and promotes glioblastoma.