We are happy to present Dr Neil Todd who will talk about non-invasive electrophysiological recording of the human cerebellum during motor learning and timing.

14.12.2021 | Hella Kastbjerg

Dato	tor 16 dec
Tid	09:15 — 10:45
Sted	Zoom

SPEAKER
Dr Neil Todd. Senior Research Fellow, Prince of Wales Hospital Clinical School, UNSW, NSW, Australia, and Honorary Senior Lecturer, Department of Psychology, University of Exeter, UK.

TITLE
Non-invasive electrophysiological recording of the human cerebellum during motor learning and timing.

ZOOM
https://aarhusuniversity.zoom.us/j/63057113763

ABSTRACT
The cerebellum has long fascinated neuroscientists for its remarkable anatomical structure, its unique physiological properties and the critical role that it plays in motor control.  Since the pioneering work of Dow (1938, 1939, 1958) in elucidating the high-frequency characteristics of the cerebellar cortex and associated potentials, of Eccles and co-workers (Eccles et al., 1967) in a description of its functional architecture and of theorists in providing an account of its role as a Hebbian learning mechanism (Marr, 1969; Albus, 1971; Ito, 2001), a substantial literature has accumulated in the last half century on human cerebellar neuroanatomy and physiology. This has made use of a wide range of in vitro and in vivo methods. However, despite the development more recently of non-invasive imaging techniques, such as MRI, reliable methods for high temporal resolution, non-invasive measurement of the human cerebellum have not been brought forward, thus retarding greater understanding of its function.

Over the last decade or so, we have investigated central vestibular projections by means of evoked potentials using the same acoustic and inertial activations of the vestibular end-organs that produce vestibular evoked myogenic potentials (VEMPs) which are manifestations of the vestibular reflex pathways. Using high-density EEG recordings and applying brain electrical source analysis methods we have been able to estimate the origins of these potentials as including cerebellar sources (Todd et al 2008, 2014, 2016).

More recently using the above methods we provided evidence that short latency potentials of likely cerebellar origin co-occur with the VEMPs (Todd et al 2017), and further that these are likely associated with cerebellar control of the vestibular reflexes, hence we use the term vestibular cerebellar evoked potentials (or VsCEPs) (Todd et al 2018b). The likely climbing-fibre (CF) origin of the VsCEPs is supported by their polarity (surface positive-negative), magnitude (as high as 200 μV in some individuals), latency (around 10 ms) and laterality (earlier contra-lateral to the side of an impulsive stimulus) (Govender et al 2020), all consistent with the known properties of the olivo-cerebellar projections (Eccles et al., 1967). No other neural elements are likely to generate evoked responses with such amplitudes.

In the course of this work, we also discovered that it is possible to record non-invasively the spontaneous activity of the cerebellum, known as the electrocerebellogram (or ECeG) (Todd et al 2018a, 2019), which has a much higher frequency power spectral profile than is typical of EEG.  Further evidence to support the climbing-fibre (CF) interpretation of the VsCEPs is their invariable association with post-CF response (CFR) pausing and bursting in the high-frequency ECeG (Govender et al 2020; Todd et al 2021). Consistent with the inhibitory action of Purkinje cells, the post-CFR pausing can be linked to facilitation of target motor neurones in spinal and ocular reflex pathways (Eccles et al., 1967; Todd et al 2021a; Todd et al 2021b). For this reason, the CFRs, post-CFR pausing in the ECeG and their correlated spinal/ocular reflex outputs can be interpreted according to the Marr/Albus/Ito learning theoretic perspective as the signalling pathway linking unconditional stimuli (US) and unconditioned responses (UR) in classical conditioning, thus providing a vehicle for the non-invasive physiological investigation of the human cerebellum during learning.

In order to explore this possibility, we have been conducting a series of experiments to study the role of the human cerebellum during motor learning and timing, including in classical conditioning. In this form of motor learning the pairing of a conditional stimulus (CS), such an auditory tone, with a US, such a vestibular head-tap, which produces a blink UR (Halmagyi and Gresty 1983), after learning can lead to a conditioned response (CR) whereby the auditory CS alone will produce a blink reflex (Todd et al 2021b). Of particular interest is the idea that the CR is mediated by learned pausing in the ECeG (Jirenhed and Hesslow 2016).  In conjunction with a high-resolution cerebellar extension to the 10-10 system we can investigate the cortical and sub-cortical voluntary and involuntary neural pathways underlying timed sensory-motor associations. This can also be extended to sensory-motor timing of rhythmic sequences (Todd et al 2019c, submitted, ab).

REFERENCES

Albus JS. (1971). A theory of cerebellar function. Mathematical Biosciences 10, 25-61.

Dow RS. (1938). The electrical activity of the cerebellum and its functional significance. J. Physiol. 94, 67-86.

Dow RS. (1939). Cerebellar action potentials in response to stimulation of various afferent connections. J Neurophysiol. 2, 543-55.

Dow RS, Moruzzi G. (1958). Physiology and Pathology of Cerebellum. The University of Minnesota Press, Minneapolis.

Eccles JC, Ito M, Szentagothai J. (1967). The Cerebellum as a Neuronal Machine. Springer, Berlin.

Govender S, Todd NPM, Colebatch JG. (2020). Mapping the vestibular cerebellar evoked potential (VsCEP) following air- and bone-conducted vestibular stimulation. Exp. Brain Res. 238, 601-620.

Halmagyi GM, Gresty MA. (1983). Eye blink reflexes to sudden free falls: a clinical test of otolith function. J Neurol. Neurosurg. Psych. 46, 844-847.

Ito M. (2001). Cerebellar long-term depression: characterization, signal transduction, and functional roles. Physio.l Rev. 81, 1143-95.

Jirenhed DA, Hesslow G. (2016). Are Purkinje cell pauses drivers of classically conditioned blink responses? Cerebellum 15, 526-534.

Marr D. (1969). A theory of cerebellar cortex. J Physiol. 202, 437–470.

Todd NPM, Rosengren SM, Colebatch JG. (2008). A source analysis of vestibular evoked potentials produced by air- and bone-conducted sound. Clin Neurophysiol. 119, 1881-1894.

Todd NPM, Paillard AC, Kluk K, Whittle E, Colebatch JG. (2014).   Source analysis of short and long latency vestibular-evoked potentials (VsEPs) produced by left versus right ear air-conducted 500 Hz tone pips. Hear Res. 312, 91-102.

Todd NPM, Govender S, Colebatch JG. (2016). Vestibular-dependent inter-stimulus interval effects on sound evoked potentials of central origin. Hear. Res. 341, 190-201.

Todd NPM, Govender S, Colebatch JG. (2017). The inion response revisited: Evidence for a possible cerebellar contribution to vestibular-evoked potentials produced by air-conducted sound stimulation. J Neurophysiol. 117, 1000-1013.

Todd NPM, Govender S, Colebatch JG. (2018a). The human electrocerebellogram (ECeG) recorded non-invasively using scalp electrodes. Neurosci Letts. 682, 124-131.

Todd NPM, Govender S, Colebatch JG. (2018b). Vestibular cerebellar evoked potentials (VsCEPs) in humans and their modulation during optokinetic stimulation. J Neurophysiol. 120, 3099-3109.

Todd NPM, Govender S, Colebatch JG. (2019). Modulation of the human electro-cerebellogram (ECeG) during vestibular and optokinetic stimulation. Neurosci Letts. 712, 134497.

Todd NPM, Govender S, Lemieux L, Colebatch JG. (2021a). Source analyses of axial and vestibular evoked potentials associated with brainstem-spinal reflexes show cerebellar and cortical contributions. Neurosci Letts. 757, 135960.

Todd NPM, Govender S, Colebatch JG. (2021b). Non-invasive recording from the human cerebellum during a classical conditioning paradigm using the otolith-blink reflex. Neurosci Letts. 765, 136270.

Todd NPM, Keller PE, Govender S, Colebatch JG. (2021c). Effects of stimulus intensity and frequency on the force and timing of sensorimotor synchronisation. Timing and Time Perception 1, 1-23.

Todd NPM, Keller PE, Govender S, Colebatch JG. (submitted a). Evidence for the vestibular syncopation hypothesis I: Evoked potentials and source currents. Music Perception

Todd NPM, Keller PE, Govender S, Colebatch JG. (submitted b). Evidence for the vestibular syncopation hypothesis II: Spectral power and cerebello-frontal coherence. Music Perception