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State-Dependent Entrainment of Prefrontal Cortex Local Field Potential Activity Following Patterned Stimulation of the Cerebellar Vermis.

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.

SUBMITTER: Tremblay SA

PROVIDER: S-EPMC6828963 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Cue-induced craving is a significant barrier to obtaining abstinence from cocaine. Neuroimaging research has shown that cocaine cue exposure evokes elevated activity in a network of frontal-striatal brain regions involved in drug craving and drug seeking. Prior research from our laboratory has demonstrated that when targeted at the medial prefrontal cortex (mPFC), continuous theta burst stimulation (cTBS), an inhibitory form of non-invasive brain stimulation, can decrease drug cue-related activity in the striatum in cocaine users and alcohol users. However, it is known that there are individual differences in response to repetitive transcranial magnetic stimulation (rTMS), with some individuals being responders and others non-responders. There is some evidence that state-dependent effects influence response to rTMS, with baseline neural state predicting rTMS treatment outcomes. In this single-blind, active sham-controlled crossover study, we assess the striatum as a biomarker of treatment response by determining if baseline drug cue reactivity in the striatum influences striatal response to mPFC cTBS. The brain response to cocaine cues was measured in 19 cocaine-dependent individuals immediately before and after real and sham cTBS (110% resting motor threshold, 3600 total pulses). Group independent component analysis (ICA) revealed a prominent striatum network comprised of bilateral caudate, putamen, and nucleus accumbens, which was modulated by the cocaine cue reactivity task. Baseline drug cue reactivity in this striatal network was inversely related to change in striatum reactivity after real (vs. sham) cTBS treatment (ρ = -.79; p < .001; R 2 Adj = .58). Specifically, individuals with a high striatal response to cocaine cues at baseline had significantly attenuated striatal activity after real but not sham cTBS (t 9 = -3.76; p ≤ .005). These data demonstrate that the effects of mPFC cTBS on the neural circuitry of craving are not uniform and may depend on an individual's baseline frontal-striatal reactivity to cues. This underscores the importance of assessing individual variability as we develop brain stimulation treatments for addiction.

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State-Dependent Entrainment of Prefrontal Cortex Local Field Potential Activity Following Patterned Stimulation of the Cerebellar Vermis.

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