Evoked responses to single pulse electrical stimulation reveal impaired striatal excitability in a rat model of Parkinson's disease.

BACKGROUND: Sensorimotor beta oscillations are increased in Parkinson's disease (PD) due to the alteration of dopaminergic transmission. This electrophysiological read-out is reported both in patients and in animal models such as the 6-OHDA rat model obtained with unilateral nigral injection of 6-hydroxydopamine (6-OHDA). Current treatments, based on dopaminergic replacement, transiently normalize this pathological beta activity and improve patients' quality of life. OBJECTIVES: We wanted to assess in vivo whether the abnormal beta oscillations can be correlated with impaired striatal or cortical excitability of the sensorimotor system and modulated by the pharmacological manipulation of the dopaminergic system. METHODS: In the unilateral 6-OHDA rat model and control animals, we used intra-striatal and intra-cortical single-pulse electrical stimulation (SPES) and concurrent local field potentials (LFP) recordings. In the two groups, we quantified basal cortico-striatal excitability from time-resolved spectral analyses of LFP evoked responses induced remotely by intracerebral stimulations. The temporal dependance of cortico-striatal excitability to dopaminergic transmission was further tested using electrophysiological recordings combined with levodopa injection. RESULTS: LFP evoked responses after striatal stimulation showed a transient reduction of power in a large time-frequency domain in the 6-OHDA group compared to the sham group. This result was specific to the striatum, as no significant difference was observed in cortical LFP evoked responses between the two groups. This impaired striatal excitability in the 6-OHDA group was observed in the striatum at least during the first 3 months after the initial lesion. In addition, the striatum responses to SPES during a levodopa challenge showed a transient potentiation of the decrease of responsiveness in frequencies below 40 Hz. CONCLUSION: The spectral properties of striatal responses to SPES show high sensitivity to dopaminergic transmission in the unilateral 6-OHDA rat model. We thus propose that this approach could be used in preclinical models as a time-resolved biomarker of impaired dopaminergic transmission capable of monitoring progressive neurodegeneration and/or challenges to drug intake.

Single-pulse electrical stimulation methodology in freely moving rat.

BACKGROUND: Cortico-cortical evoked potentials (CCEP) are becoming popular to infer brain connectivity and cortical excitability in implanted refractory epilepsy patients. Our goal was to transfer this methodology to the freely moving rodent. NEW METHOD: CCEP were recorded on freely moving Sprague-Dawley rats, from cortical and subcortical areas using depth electrodes. Electrical stimulation was applied using 1 ms biphasic current pulse, cathodic first, at a frequency of 0.5 Hz, with intensities ranging from 0.2 to 0.8 mA. Data were then processed in a similar fashion to human clinical studies, which included epoch selection, artefact correction and smart averaging. RESULTS: For a large range of tested intensities, we recorded CCEPs with very good signal to noise ratio and reproducibility between animals, without any behavioral modification. The CCEP were composed of different components according to recorded and stimulated sites, similarly to human recordings. COMPARISON WITH EXISTING METHODS: We minimally adapted a clinically-motivated methodology to a freely moving rodent model to achieve high translational relevance of future preclinical studies. CONCLUSIONS: Our results indicate that the CCEP methodology can be applied to freely moving rodents and transferred to preclinical research. This will be of interest to address various neuroscientific questions, in physiological and pathological conditions.

Electroencephalographic correlates of low-frequency vagus nerve stimulation therapy for Crohn's disease.

OBJECTIVES: In the context of the first clinical trial of vagus nerve stimulation (VNS) in Crohn's disease (CD), our main objective was to quantify the acute and chronic effects of VNS on brain activity in CD patients. METHODS: We measured the electroencephalogram (EEG) in 9CD patients under VNS at 10 Hz just before VNS initiation, after 6 weeks and after 12 months of chronic VNS. RESULTS: Acute VNS induced increased spectral power in delta and theta bands on frontal, temporal and occipital electrodes. The main significant modulation was the 12 months' chronic effect of VNS which consisted mainly in a decreased power in the alpha frequency band which was correlated with the normalization of bowel mucosal inflammation, anxiety state and vagal tone. CONCLUSIONS: In addition to the activation of vagal efferent fibers that regulate the autonomic nervous system, our data suggest that chronic VNS has a regulatory action via afferent vagal fibers on anxio-depressive symptomatology associated to CD, which could be directly highlighted by the modulation of EEG alpha power known to be associated to depressed states. SIGNIFICANCE: This is the first report of the central effects of VNS in CD patients.