Fabiana Santana Kragelund holds a Master’s and Ph.D. in Biological Sciences with a specialization in Neuroscience from the Federal University of Rio Grande do Sul, Brazil. During her Master’s studies, she was awarded a scholarship to conduct research at the University of Buenos Aires, where she focused on electrophysiology and the endocannabinoid system. As part of her Ph.D., she received a scholarship for a research exchange at the University of Amsterdam, where she worked on deep brain stimulation (DBS) in an obsessive-compulsive disorder model. Following her doctoral studies, she completed a postdoctoral fellowship at the University of Modena, Italy. Currently, she is a researcher at the University of Rostock, Germany, where her work focuses on elucidating the mechanisms underlying DBS for dystonia.

Title: Deep Brain Stimulation into Globus Pallidus Internus Modulates Cerebellar Activity in a Dystonic Animal Model

Abstract

Background: Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is an established therapy for drug-resistant dystonia. However, its mechanisms of action remain only partially understood. This study examines how pallidal DBS influences neuronal activity and network connectivity in the cerebellar cortex using a dystonic animal model, the dtsz hamster.

Methods: Female dystonic dtsz hamsters and non-dystonic controls were housed under standard conditions. Dystonia severity was assessed using the triple stimulation technique. At 31–48 days old, dtsz hamsters underwent DBS surgery, with bipolar electrodes implanted in the entopeduncular nucleus (EPN, the rodent homolog of the human GPi). Stimulation was applied for 11 days (130 Hz, 50 μA, 60 μs). Control groups included untreated dtsz hamsters, non-dystonic controls, and sham-DBS-treated dtsz hamsters. Following DBS treatment, cerebellar slices (200 μm) were prepared and recorded using a high-density microelectrode array (HD-MEA) to assess neuronal activity across the molecular, Purkinje, and granular layers. Key electrophysiological parameters, including mean firing rate (MFR), interspike interval (ISI), and spike amplitude, were analyzed. Connectivity networks were evaluated using graph theory and Pearson correlation to assess spatiotemporal neuronal interactions. Statistical comparisons were conducted using ANOVA and post-hoc tests, with significance set at p < 0.05.

Results: HD-MEA analysis revealed significantly reduced MFR and spike amplitudes in dystonic hamsters compared to healthy controls. Pallidal DBS restored these parameters to levels comparable to the healthy group, suggesting a normalization of cerebellar cortical activity. Connectivity analysis demonstrated altered neuronal interactions in dystonic hamsters, which were partially restored by DBS. Neural activity patterns in treated animals formed organized communities similar to those observed in healthy controls.

Conclusions: These findings suggest that pallidal DBS exerts therapeutic effects in dystonia by modulating cerebellar cortical activity and restoring network connectivity. The observed reductions in MFR and spike amplitudes in dystonic hamsters may reflect impaired neuronal communication and synaptic plasticity. DBS counteracted these abnormalities, highlighting its role in normalizing cerebellar function and reinforcing the concept of dystonia as a network disorder.