Comparison of the Classically Conditioned Withdrawal Reflex in Cerebellar Patients and Healthy Control Subjects During Stance: I. Electrophysiological Characteristics

Abstract

The aim of this study was to demonstrate the involvement of the human cerebellum in the classically conditioned lower limb withdrawal reflex in standing subjects. Electromyographic activity was recorded from the main muscle groups of both legs of eight patients with cerebellar disease (CBL) and eight control subjects (CTRL). The unconditioned stimulus (US) consisted of electrical stimulation of the tibial nerve at the medial malleolus. The conditioning stimulus (CS) was an auditory signal given via headphones. Experiments started with 70 paired conditioning stimulus-unconditioned stimulus(CSUS) trials followed by 50 US-alone trials. The general reaction consisted of lifting and flexing the stimulated (stepping) leg with accompanying activation of the contralateral (supporting) leg. In CTRL, the ipsilateral (side of stimulation) flexor and contralateral extensor muscles were activated characteristically. In CBL, the magnitudes of ipsilateral flexor and contralateral extensor muscle activation were reduced comparably. In CTRL, the conditioning process increased the incidence of conditioned responses (CR), following a typical learning curve, while CBL showed a clearly lower CR incidence with a marginal increase, albeit, at a shorter latency. Conditioning processes also modified temporal parameters by shortening unconditioned response (UR) onset latencies and UR times to peak and, more importantly in CBL, also the sequence of activation of muscles, which became similar to that of CTRL. The expression of this reflex in standing subjects showed characteristic differences in the groups tested with the underlying associative processes not being restricted exclusively to the CR but also modifying parameters of the innate UR.

The Implementation of Predictions During Sequencing

“…Moreover, several studies investigated the biomechanical characteristics of patients with degenerative cerebellar atrophy (spinocerebellar ataxia, or SCA), finding these to consist of decreases in step length, gait speed, and ankle torque; increased step width; impaired interjoint coordination; and marked variability of all global segmental gait parameter values (Palliyath et al, 1998; Mitoma et al, 2000; Earhart and Bastian, 2001; Morton and Bastian, 2003; Serrao et al, 2012; Wuehr et al, 2013). Moreover, previous findings (Konczak and Timmann, 2007; Bastian, 2011; Goodworth and Peterka, 2012; Timmann et al, 2013) suggest that lesions of the cerebellum may induce abnormalities in the spatial and temporal pattern of muscle activation resulting in specification gait impairments. In this regard, Martino et al, 2014 (J Neurophysiol 2014) found that SCA patients showed a widening of muscle activation profiles as a consequence of improper motor planning (feedforward control) and processing of proprioceptive information (Bastian, 2011), leading to inaccurate movements.…”

Contribution of the Cerebellum in Cue-Dependent Force Changes During an Isometric Precision Grip Task

“…The only exception was the lower limb withdrawal reflex in standing subjects. In this special case [ 11 , 12 , 14 , 38 ], CBL were able to increase significantly the CR incidence (Table 2 CBL 1st block vs. 5th block). Comparing the mean CFC incidence of CTRL (1/3) with the CFC incidence of young subjects 2/3, see [ 15 ], suggests that the capability to produce CFC depends primarily on the cerebellum, but an age-dependency has also to be taken into account.…”

“…The involvement of the cerebellum as a putative structure for associative learning of motor actions and sensory stimuli has been studied extensively in humans using the method of classical conditioning, for review see [ 1 ]. Simple avoiding reflexes have been most frequently tested as for instance the eye-blink reflex [ 2 – 5 ] or the lower limb withdrawal reflex in both reclining subjects [ 6 – 9 ] and standing subjects [ 10 – 12 ]. Avoiding reactions involving larger and more complex behaviour like a postural reaction to prevent a fall have also been studied, e.g.…”