Abstract
The cerebellum is involved in sensorimotor, cognitive, and emotional functions through cerebello-cerebral connectivity. Cerebellar neurostimulation thus likely affects cortical circuits, as has been shown in studies using cerebellar stimulation to treat neurological disorders through modulation of frontal EEG oscillations. Here we studied the effects of different frequencies of cerebellar stimulation on oscillations and coherence in the cerebellum and prefrontal cortex in the urethane-anesthetized rat. Local field potentials were recorded in the right lateral cerebellum (Crus I/II) and bilaterally in the prefrontal cortex (frontal association area, FrA) in adult male Sprague-Dawley rats. Stimulation was delivered to the cerebellar vermis (lobule VII) using single pulses (0.2 Hz for 60 s), or repeated pulses at 1 Hz (30 s), 5 Hz (10 s), 25 Hz (2 s), and 50 Hz (1 s). Effects of stimulation were influenced by the initial state of EEG activity which varies over time during urethane-anesthesia; 1 Hz stimulation was more effective when delivered during the slow-wave state (Stage 1), while stimulation with single-pulse, 25, and 50 Hz showed stronger effects during the activated state (Stage 2). Single-pulses resulted in increases in oscillatory power in the delta and theta bands for the cerebellum, and in frequencies up to 80 Hz in cortical sites. 1 Hz stimulation induced a decrease in 0–30 Hz activity and increased activity in the 30–200 Hz range, in the right FrA. 5 Hz stimulation reduced power in high frequencies in Stage 1 and induced mixed effects during Stage 2.25 Hz stimulation increased cortical power at low frequencies during Stage 2, and increased power in higher frequency bands during Stage 1. Stimulation at 50 Hz increased delta-band power in all recording sites, with the strongest and most rapid effects in the cerebellum. 25 and 50 Hz stimulation also induced state-dependent effects on cerebello-cortical and cortico-cortical coherence at high frequencies. Cerebellar stimulation can therefore entrain field potential activity in the FrA and drive synchronization of cerebello-cortical and cortico-cortical networks in a frequency-dependent manner. These effects highlight the role of the cerebellar vermis in modulating large-scale synchronization of neural networks in non-motor frontal cortex.
Highlights
There has been growing evidence supporting cerebellar involvement in cognitive and affective functions (Hoppenbrouwers et al, 2008; Strick et al, 2009; Bostan et al, 2013)
We investigated the effects of various frequencies of cerebellar vermis stimulation on the power and coherence of local field potential (LFP) oscillations in Crus I/II of the right lateral cerebellum (RCb) and bilateral dorsolateral prefrontal cortex (PFC) in the urethane-anesthetized rat
Both slow and fast oscillatory rhythms are thought to coordinate interactions between the cerebellum and cortical sites (O’Connor et al, 2002; Courtemanche and Lamarre, 2005; Ros et al, 2009; Courtemanche et al, 2013; Popa et al, 2013; Chen et al, 2016), and rhythmic cerebellar stimulation has been used as a therapeutic intervention in some disorders (Schutter et al, 2003; Schutter and van Honk, 2006, 2009; Demirtas-Tatlidede et al, 2010)
Summary
There has been growing evidence supporting cerebellar involvement in cognitive and affective functions (Hoppenbrouwers et al, 2008; Strick et al, 2009; Bostan et al, 2013). Stimulation of the vermis, the most medial region of the cerebellum, results in positive effects on cognition and mood associated with modulation of frontal oscillations (Schutter et al, 2003; Schutter and van Honk, 2006, 2009; Demirtas-Tatlidede et al, 2010). Low frequency FN stimulation (1 Hz) was shown to inhibit epileptogenic activity in the rat (Wang et al, 2008), while stimulating lateral cerebellar projections at 2 Hz has been shown to rescue medial frontal cortex delta activity in a rat model of schizophrenia (Parker et al, 2017)
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