What is it about?
Post-traumatic stress disorder (PTSD) causes intrusive symptoms and avoidance behaviors due to dysregulation in various brain regions, including the hippocampus. Deep brain stimulation (DBS) shows promise for refractory PTSD cases. In rodents, DBS improves fear extinction and reduces anxiety-like behaviors, but its effects on active-avoidance extinction remain unexplored. Medial forebrain bundle intracranial self-stimulation (MFB-ICSS) enhances two-way active avoidance (TWAA) conditioning by activating brain regions involved in reinforcement, learning, and memory, including the hippocampus. Methods: This study investigates whether reinforcing DBS in the MFB enhances the extinction of conditioned active avoidance responses and examines its effects on hippocampal mossy fiber sprouting using Timm staining. We administered MFB-ICSS treatment following two 50-trial extinction sessions and assessed short-term (24 hours) and long-term (28 days) extinction in a TWAA task in rats. Results: MFB-ICSS enhances short-term extinction and accelerates long-term reacquisition of extinction in a spontaneous recovery test. MFB-ICSS also promotes mossy fiber sprouting in the CA2 and CA3 regions of the hippocampus, with CA3 staining positively correlated with the level of extinction. Conclusions: These findings suggest that MFB stimulation may enhance extinction and promote neural plasticity mechanisms, including mossy fiber sprouting. However, it does not fully prevent spontaneous recovery, highlighting the need for further optimization of treatment parameters. These results are relevant for PTSD as they suggest a potential enhancement in therapy for extinguishing avoidance responses in patients.
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Why is it important?
This study is important because it explores a novel approach to treating refractory PTSD using deep brain stimulation (DBS) of the medial forebrain bundle (MFB). The research demonstrates that MFB stimulation enhances both short-term and long-term extinction of active avoidance behaviors, which are relevant to PTSD symptoms. Importantly, it links this behavioral improvement to increased mossy fiber sprouting in the hippocampus, particularly in the CA2 and CA3 regions, providing evidence of treatment-induced neural plasticity. This finding not only offers insights into the neural mechanisms underlying the treatment's effectiveness but also suggests a potential biomarker for treatment efficacy. While the treatment doesn't fully prevent spontaneous recovery, it opens avenues for optimizing DBS parameters in PTSD treatment. The study's translational potential is significant, as it suggests possible applications for enhancing extinction therapy in PTSD patients, potentially improving outcomes for those resistant to conventional therapies.
Perspectives
Deep brain stimulation (DBS) is emerging as a promising treatment for refractory post-traumatic stress disorder (PTSD), offering hope for severe cases unresponsive to conventional therapies. Research focuses on stimulating specific brain regions such as the amygdala, prefrontal cortex, hippocampus, and ventral striatum, with early clinical trials showing safety and potential efficacy. DBS appears to modulate neural circuits involved in fear and anxiety responses, potentially inducing neuroplasticity. The heterogeneity of PTSD necessitates personalized approaches, and researchers are exploring biomarkers to guide treatment. While DBS shows promise, more extensive clinical trials are needed to fully establish its efficacy, optimal targeting, and long-term safety for PTSD treatment. This evolving perspective highlights DBS as a potential breakthrough, bridging neuroscience, psychiatry, and neurosurgery, while emphasizing the need for further research to optimize its application in treating this complex disorder.
Carles Tapias Espinosa
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This page is a summary of: Deep brain stimulation of the medial forebrain bundle promotes the extinction of active avoidance and is associated with mossy fibber sprouting in the hippocampus, Behavioural Brain Research, March 2025, Elsevier,
DOI: 10.1016/j.bbr.2024.115411.
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