The involvement of the human cerebellum in eyeblink conditioning

Abstract

Besides its known importance for motor coordination, the cerebellum plays a major role in associative learning. The form of cerebellum-dependent associative learning, which has been examined in greatest detail, is classical conditioning of eyeblink responses. The much advanced knowledge of anatomical correlates, as well as cellular and molecular mechanisms involved in eyeblink conditioning in animal models are of particular importance because there is general acceptance that findings in humans parallel the animal data. The aim of the present review is to give an update of findings in humans. Emphasis is put on human lesion studies, which take advantage of the advances of high-resolution structural magnetic resonance imaging (MRI). In addition, findings of functional brain imaging in healthy human subjects are reviewed. The former helped to localize areas involved in eyeblink conditioning within the cerebellum, the latter was in particular helpful in delineating extracerebellar neural substrates, which may contribute to eyeblink conditioning. Human lesion studies support the importance of cortical areas of the ipsilateral superior cerebellum both in the acquisition and timing of conditioned eyeblink responses (CR). Furthermore, the ipsilateral cerebellar cortex seems to be also important in extinction of CRs. Cortical areas, which are important for CR acquisition, overlap with areas related to the control of the unconditioned eyeblink response. Likewise, cortical lesions are followed by increased amplitudes of unconditioned eyeblinks. These findings are in good accordance with the animal literature. Knowledge about contributions of the cerebellar nuclei in humans, however, is sparse. Due to methodological limitations both of human lesion and functional MRI studies, at present no clear conclusions can be drawn on the relative contributions of the cerebellar cortex and nuclei.

Dynamic Associations in the Cerebellar–Motoneuron Network during Motor Learning

“…In particular, the information collected has led to a better understanding of the physiological mechanisms underlying the role of cerebellar centers in neural control of movement (Eccles et al, 1967;Thach et al, 1992;Welsh and Llinás, 1997;Lang et al, 2006;Gerwig et al, 2007;Cheron et al, 2008). At the same time, recent analytical procedures have enabled the determination of how deep brain stimulation suppresses synchronized firing activities to improve its therapeutic efficiency in certain motor disorders (Llinás et al, 1999;Titcombe et al, 2001) by using different timedelayed feedback strategies (Rusemblum and Pikovski, 2004) and phase-resetting techniques (Tass, 2003).…”

Hippocampal theta-band activity and trace eyeblink conditioning in rabbits.

“…The memory trace of the conditioned response (CR) acquired during classical eyeblink conditioning (Gormezano, Schneiderman, Deaux , & Fuentes, 1962) is thought to reside in the cerebellum (in humans see , Cheng Disterhoft, Power, Ellis, & Desmond, 2008;Gerwig, Kolb, & Timmann, 2007;in animals, Christian & Thompson, 2005;McCormick, Lavond, Clark, Kettner, Rising, & Thompson, 1981; for a review see Thompson, 2005). The hippocampus is not required for learning when the most simple (delay) form of eyeblink conditioning is applied (Schmaltz & Theios, 1972), but becomes increasingly important if the relations between the conditioning stimuli are more complex, like in trace conditioning (Berger & Orr, 1983;Moyer, Deyo, Disterhoft, 1990;Solomon, Vander Schaaf, Thompson, & Weisz, 1986) or when an unusually long inter-stimulus interval is used in delay conditioning (Beylin, Gandhi, Wood, Talk, Matzel, & Shors, 2001).…”

The Pre-Supplementary and Primary Motor Areas Generate Rhythm for Voluntary Eye Opening and Closing Movements

“…When we try to move our lid by selfpaced, we should produce rhythm by ourselves. Previous studies have reported that the M1, primary somatosensory cortex, SMA, premotor cortex, and cerebellar hemisphere are related to the self generation of rhythmic movements (Gerwig et al 2007;Thaut et al 2008). Moreover, Spencer et al (2007) suggested that subregions of the cerebellum are selectively engaged during tasks involving event timing.…”

“…Spontaneous blinks seem to arise from a central "blink generator" that can be influenced by several factors, such as visual and cognitive task requirements, and emotion. Neurobiological studies have identified the cerebellum and its brainstem connections as essential components of the eyeblink conditioning circuit (Gerwig et al 2007). Other forebrain areas, including basal ganglia, neocortex, and septal nuclei, have been less extensively studied but may also play a role in eyeblink conditioning.…”