Cerebellar theta burst stimulation dissociates memory components in eyeblink classical conditioning

Abstract

The cerebellum plays a critical role in forming precisely timed sensory-motor associations. This process is thought to proceed through two learning phases: one leading to memory acquisition; and the other leading more slowly to memory consolidation and saving. It has been proposed that fast acquisition occurs in the cerebellar cortex, while consolidation is dislocated into the deep cerebellar nuclei. However, it was not clear how these two components could be identified in eyeblink classical conditioning (EBCC) in humans, a paradigm commonly used to investigate associative learning. In 22 subjects, we show that EBCC proceeded through a fast acquisition phase, returned toward basal levels during extinction and then was consolidated, as it became evident from the saving effect observed when re-testing the subjects after 1 week of initial training. The results were fitted using a two-state multi-rate learning model extended to account for memory consolidation. Transcranial magnetic stimulation was used to apply continuous theta-burst stimulation (cTBS) to the lateral cerebellum just after the first training session. Half of the subjects received real cTBS and half sham cTBS. After cTBS, but not sham cTBS, consolidation was unaltered but the extinction process was significantly impaired. These data suggest that cTBS can dissociate EBCC extinction (related to the fast learning process) from consolidation (related to the slow learning process), probably by acting through a selective alteration of cerebellar plasticity.

Pronounced reduction of acquisition of conditioned eyeblink responses in young adults with focal cerebellar lesions impedes conclusions on the role of the cerebellum in extinction and savings

“…Because the Purkinje cells appear to be primarily affected in FRAXA, it has been argued that savings depend on areas outside the cerebellar cortex, possibly in the deep cerebellar nuclei (Koekkoek, et al, 2005). A recent study using cerebellar theta burst stimulation (cTBS) of the cerebellar hemisphere came to a similar conclusion (Monaco, Casellato, Koch, & D'Angelo, 2014). cTBS was applied in healthy subjects following acquisition and extinction on the first day of testing.…”

A Multiple-Plasticity Spiking Neural Network Embedded in a Closed-Loop Control System to Model Cerebellar Pathologies

“…These results were in line with the hypothesis that the cerebellar cortex plays a critical role in fast acquisition of plasticity that is later transferred to DCNs. 48,57,58 In the absence of an effective cerebellar cortex, learning of sensory-motor associations can just proceed at a slow rate and is incomplete. In addition to this common set of changes, adaptation to circuit damage showed characteristic differences among cases: PC loss caused a strong CR delay, MF impairment caused diffused plasticity alterations, LTD decrease caused only minor abnormalities in CR delay and synaptic plasticity.…”

“…18 Tuning of learning rule parameters and initial weights of the plastic connections was obtained through a Genetic Algorithm 45,46 , which was based on the evaluation of EBCC simulations in order to achieve physiological behavior. 47,48 Specifically, the protocol included two learning sessions so as to evaluate the proper physiological action of the different plasticity sites on multiple time scales. 18 Referring to one of the pathological protocols 23 , each session consisted of 100 acquisition and 30 extinction trials 49 , with ISI = 440 ms. After running the simulations for each one of the 12 individuals in a generation, they were assigned a fitness value based on the %CR in a moving window of 10 trials.…”

Repetitive TMS on Left Cerebellum Affects Impulsivity in Borderline Personality Disorder: A Pilot Study

“…Theta-burst cerebellar rTMS has been successfully used to modulate motor timing (Del Olmo et al, 2007) and procedural learning (Torriero et al, 2011) with a reflexion on finger movement (Del Olmo et al, 2007), saccadic eye movements (Colnaghi et al, 2011), eye-blink classical conditioning (Monaco et al, 2014). These effects are likely to involve metaplasticty of cerebello-cortical connectivity, with relevant effects in progressive supranuclear palsy (Brusa et al, 2014) in dystonia (Koch et al, 2014), ataxia (Bonnì et al, 2014).…”