Biology subjects

Pejin, A.

Publications and source records attributed to Pejin, A..

3 recordsLinked to original sources

bioRxiv2025

Non-vectorial Integration of Intersectional Short-Pulse Stimulation Enables Enhanced Deep Brain Modulation and Effective Seizure Control

Transcranial electrical stimulation (TES) holds promise to treat neurological disorders, but its efficacy is limited by poor spatial focality and depth of penetration. Here, we examined the potential utility of Intersectional Short-Pulse (ISP) stimulation of deeper brain penetration. Using computational modeling and in vivo patch-clamp recordings in rats, we demonstrate that neurons integrate ISP-induced electric fields in a non-vectorial manner. This mechanism allows ISP to overcome some limits of conventional TES, achieving spatially limited stimulation across cortical and subcortical structures. In a rat model of temporal lobe epilepsy, closed-loop ISP stimulation significantly outperformed conventional TES in reducing seizure duration and severity. ISP reduced hippocampal seizure duration by 49% and 41% compared to sham stimulation and conventional TES and significantly reduced motor seizure severity. Our findings demonstrate that ISP stimulation can rapidly terminate hippocampal seizures, offering a potential new approach for non-invasive neuromodulation with applications across diverse neurologic and psychiatric disorders.

neuroscience↗

bioRxiv2024

Hippocampal sharp wave ripples mediate generalization and subsequent fear attenuation via closed-loop brain stimulation in rats

The balance between stimulus generalization and discrimination is essential in modulating behavioral responses across different contexts. Excessive fear generalization is linked to neuropsychiatric disorders such as generalized anxiety disorder (GAD) and PTSD. While hippocampal sharp wave-ripples (SWRs) and concurrent neocortical oscillations are central to the consolidation of contextual memories, their involvement in non-hippocampal dependent memories remains poorly understood. Here we show that closed-loop disruption of SWRs, after the consolidation of a cued fear conditioning, leads to atypical memory discrimination that would normally be generalized. Furthermore, SWR-triggered closed-loop stimulation of the basolateral amygdala (BLA) during memory reconsolidation inhibits fear generalization and enhances subsequent extinction. Comparable effects were observed when stimulating the infralimbic cortex either post-training or after a brief memory reactivation. A consistent increase in gamma incidence within the amygdala was identified in animals subjected to closed-loop BLA or infralimbic cortex neuromodulation. Our findings highlight the functional role of hippocampal SWRs in modulating the qualitative aspects of amygdala-dependent memories. Targeting the amygdala activity via prefrontal cortex with closed-loop SWR triggered stimulation presents a potential foundation of a non-invasive therapy for GAD and PTSD.

neuroscience↗

bioRxiv2022

Closed-loop brain stimulation to reduce pathologic fear

Maladaptive processing of trauma related memory engrams leads to dysregulated fear reactions. In post-traumatic stress disorder (PTSD), dysfunctional extinction learning prevents discretization of trauma-related memory engrams and leads to generalized fear responses. PTSD is postulated as a mnemonic-based disorder, but we lack markers or treatments targeting pathological fear memory processing. Hippocampal sharp wave-ripples (SWRs) and concurrent neocortical oscillations are scaffolds to consolidate contextual memory, but their role during fear processing remains poorly understood. We demonstrate that closed-loop SWRs triggered neuromodulation of the medial forebrain bundle (MFB) can enhance the consolidation of fear extinction. It modified fear memories that became resistant to induced recall (i.e., renewal and reinstatement) and did not reemerge spontaneously as a PTSD-like phenotype. The effects are mediated by D2 receptor signaling induced synaptic remodeling in the basolateral amygdala. These results suggest that SWRs help consolidating fear extinction memories. Furthermore, enhancing the consolidation of extinction engrams by SWR-triggered induction of reward signals can alleviate pathologic fear reactions in a rodent model of PSTD. No adverse effects were seen, suggesting this potential therapy for PTSD and anxiety disorders.

neuroscience↗