Key Points Question Is lateral hypothalamic deep brain stimulation (DBS) safe for the treatment of obesity in Prader-Willi syndrome? Findings In this case series of 4 patients with Prader-Willi syndrome treated with lateral hypothalamic DBS, 2 developed stimulation-induced manic symptoms and 2 developed infections, 1 of which was associated with skin picking. No major differences were found when postoperative anthropometric and calorimetric data were compared with baseline; hormonal levels, and results of blood workup, sleep studies, and neuropsychological evaluations also showed no change. Meaning Safety of lateral hypothalamic DBS was in the range of that demonstrated in patients with similar psychiatric conditions receiving DBS; however, in the small cohort of patients with Prader-Willi syndrome treated, DBS seemed largely ineffective for the treatment of obesity.

Relapse into drug use is a significant problem for people recovering from addiction. The ability that conditioned cues have to reinstate and reinvigorate drug-seeking is potentiated over time (incubation of seeking), posing an additional difficulty for maintaining abstinence. While the prefrontal cortex has been involved in the incubation phenomenon and the extracellular matrix, perineuronal nets (PNN) in particular, may play a vital role in brain plasticity associated to drug relapse, there are no comparative analyses between different drug classes and natural reinforcers. Here, we compare the effects of early (1 day) and protracted (30 days) withdrawal from to cocaine, heroin and sucrose self-administration on the PNN content of different territories of the prefrontal cortex of male Lewis rats. Our results show that cocaine selfadministration and protracted withdrawal decreased PNN content in the prelimbic cortex. Also, heroin self-administration increased PNN content in the infralimbic cortex, but this effect was lost after 30 days of withdrawal. Heroin self-administration also decreased PNNs in the insula, an effect that remained even after protracted withdrawal from the drug. Finally, the self-administration of sucrose-sweetened water decreased PNN content in the dorsomedial prefrontal cortex and increased PNNs in the insular cortex, which was still evident after protracted withdrawal. Our results show that three different rewards with specific pharmacological and physiological actions differentially modulate PNNs in specific areas of the rodent prefrontal cortex with potential implications for the incubation of seeking phenomenon.

Lateral hypothalamic area (LHA) local field potentials (LFPs) were recorded in a Prader–Willi patient undergoing deep brain stimulation (DBS) for obesity. During hunger, exposure to food‐related cues induced an increase in beta/low‐gamma activity. In contrast, recordings during satiety were marked by prominent alpha rhythms. Based on these findings, we have delivered alpha‐frequency DBS prior to and during food intake. Despite reporting an early sensation of fullness, the patient continued to crave food. This suggests that the pattern of activity in LHA may indicate hunger/satiety states in humans but attest to the complexity of conducting neuromodulation studies in obesity.

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The causality in the association between cannabis use and the risk of developing schizophrenia has been the subject of intense debate in the last years. The development of animal models recapitulating several aspects of the disease is crucial for shedding light on this issue. Maternal infections are a known risk for schizophrenia. Here, we used the maternal immune activation (MIA) model combined with THC exposure during adolescence to examine several behaviours in rats (working memory in the Y maze, sociability in the three-chamber test, sucrose preference as a measure, prepulse inhibition and formation of incidental associations) that are similar to the different symptom clusters of the disease. To this end, we administered LPS to pregnant dams and when the offspring reached adolescence, we exposed them to a mild dose of THC to examine their behaviour in adulthood. We also studied several parameters in the dams, including locomotor activity in the open field, elevated plus maze performance and their response to LPS, that could predict symptom severity of the offspring, but found no evidence of any predictive value of these variables. In the adult offspring, MIA was associated with impaired working memory and sensorimotor gating, but surprisingly, it increased sociability, social novelty and sucrose preference. THC, on its own, impaired sociability and social memory, but there were no interactions between MIA and THC exposure. These results suggest that, in this model, THC during adolescence does not trigger or aggravate symptoms related to schizophrenia in rats.