The nucleus accumbens (NAc), ventromedial prefrontal cortex (vmPFC), and cingulate gyrus (Cg) are key regions in the control of mood-related behaviors. Electrical stimulation of these areas induces antidepressant-like effects in both patients and animal models. Another structure whose limbic connections are receiving more interest in the context of mood-related behaviors is the medial part of the subthalamic nucleus (STN). Here, we tested the hypothesis that the mood-related effects of NAc, vmPFC, and Cg are accompanied by changes in the neural activity of the STN. We performed high-frequency stimulation (HFS) of the NAc, vmPFC, and Cg. Animals were behaviorally tested for hedonia and forced swim immobility; and the cellular activities in the different parts of the STN were assessed by means of c-Fos immunoreactivity (c-Fos-ir). Our results showed that HFS of the NAc and vmPFC, but not Cg reduced anhedonic-like and forced swim immobility behaviors. Interestingly, there was a significant increase of c-Fos-ir in the medial STN with HFS of the vmPFC, but not the NAc and Cg as compared to the sham. Correlation analysis showed that the medial STN is associated with the antidepressant-like behaviors in vmPFC HFS animals. No behavioral correlation was found with respect to behavioral outcome and activity in the lateral STN. In conclusion, HFS of the vmPFC induced profound antidepressant-like effects with enhanced neural activity in the medial part of the STN.
BackgroundThe availability of deep brain stimulation (DBS), a highly efficacious treatment for several movement disorders, remains low in developing countries, with scarce data available on utilization and outcomes.ObjectiveWe characterized the DBS cohort and outcomes at a Malaysian quaternary medical center.MethodsA retrospective chart review was done on DBS-related surgery at the University of Malaya, including clinico-demographic, genetics, and outcomes data focusing on post-operative medication reduction and complications.Results149 Parkinson's disease (PD) patients underwent DBS targeting the subthalamic nucleus. Six had globus pallidus internus DBS (primarily for dystonia). Only 16.1% of patients were government-funded. Of the 133 PD patients operated in the past decade (2013-2022), 25 (18.8%) had disease duration <5 years. At 6-12 months post-DBS, median levodopa-equivalent daily dose (LEDD) reduction was 440.5 [418.9] mg/day, corresponding to a reduction of ≥50% and ≥30% in 42.2% and 69.8% of patients, respectively. LEDD reductions were larger in the early-onset and short-duration subgroups. Three patients (1.9% of 155) had symptomatic intracranial hemorrhage, resulting in stroke in two. Pathogenic monogenic or GBA1 variants were detected in 12/76 (16%) of patients tested, mostly comprising the "severe" GBA1 variant p.L483P (12%).ConclusionsThis is the largest report on DBS from Southeast Asia. The procedures were effective, and complication rates on par with international norms. Our study found a high frequency of GBA1-PD; and included a substantial number of patients with short-duration PD, who had good outcomes. It also highlights regional inequities in access to device-aided therapy.