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Unilateral nigrostriatal 6-OHDA lesioning leads to widespread GMV changes, which extend beyond the nigrostriatal system and resemble advanced Parkinsonism. This study highlights the potential of structural MRI, and VBM in particular, for the system-level phenotyping of rodent models of Parkinsonism and provides a methodological framework for future studies in novel rodent models as they become available to the research community.

Our working hypothesis is that constant inter-pulse interval (IPI) electrical stimulation (ES) would resonate with endogenous epileptogenic reverberating circuits, favoring seizure, while random inter-interval ES protocol would promote desynchronization of such neural networks, interfering with the abnormal recruitment of neural structures. Male Wistar rats were stereotaxically implanted with a monopolar ES carbon-fiber electrode (minimizing fMRI artifact) in the amygdala. A 7T fMRI scanner was used to evaluate brain activity during ES, fixed four pulses per second ratio, using either a periodic IPI (ES-P) or random IPI (non-periodic ES-NP) stimulation paradigm. Appropriate imaging protocols were used to compare baseline BOLD (blood oxygen level dependent) MRI with scans during ES. A second series of experiments, both without stimuli and under the same ES paradigms, were evaluated during continuous infusion of pentylenetetrazole (PTZ, 4 mg/ml/min) through an i.v. catheter. Our results show that temporal lobe activation during ES-P or ES-NP did not present any statistical differences during ES. However, during PTZ infusion, PTZ-P facilitated recruitment of the temporal lobe ipsilateral to ES while PTZ-NP showed significantly less activation ipsilateral to ES and, in turn, less inter-hemispheric differences. Altogether, our results support the hypothesis of reverberating circuits being synchronized by ES-P and desynchronized by ES-NP. Time-coded low frequency stimulation may be an interesting alternative treatment for patients with refractory epilepsy.

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