Comparison of the electrically evoked leg withdrawal reflex in cerebellar patients and healthy controls.

The aim of this study was to analyze the contribution of the cerebellum in the performance of the lower limb withdrawal reflexes. This has been accomplished by comparing the electrically evoked responses in cerebellar patients (CBL) with those in sex- and age-matched healthy control subjects (CTRL). The stimulus was applied to the subjects' medial plantar nerve in four blocks of ten trials each with switching the stimulus from one leg to the other after each block. Responses of the main muscle groups (tibial muscle: TA; gastrocnemius muscle: GA; rectus femoris muscle: RF; biceps femoris muscle: BI) of both legs were recorded during each stimulus. The group of CBL patients consisted of both focally lesioned patients (CBLf) and patients presenting a diffuse degenerative pathology (CBLd). (1) For the withdrawal reflex in CTRL subjects, responses were observed in distal and proximal muscles of the ipsilateral side and corresponding concomitant responses on the side contralateral to the stimulation, whereas in CBL patients responses were restricted primarily to distal muscles, particularly the TA of the ipsilateral, i.e. the stimulated, side. (2) The sequence of activation of the different distal and proximal muscles ipsilateral to the stimulation, derived from latencies and times-to-peak, was for the CTRL group: TA-GA-BI-RF. This sequence was found also in the CBLf patients on their unaffected side. However, on their affected side CBLf patients showed very early GA activation, almost simultaneously with TA and RF activations and before BI activation. RF activation before BI activation was also found in CBLd. In the latter group, GA was activated after RF but before BI with all responses typically delayed. (3) The general pattern of the electrically evoked lower limb reflex consisted of an early, excitatory F1 component and a later, excitatory F2 component of larger amplitude observed in the CTRL subjects and the CBLd patients. In contrast to this pattern CBLf patients exhibited large F1 components followed by small F2 components. (4) The characteristic differences in the withdrawal reflex responses of cerebellar patients depended on the type of the lesion, providing evidence for an important involvement of the cerebellum in the control of the performance of withdrawal reflexes.

Classically conditioned postural reflex in cerebellar patients.

The aim of the current study was to compare postural responses to repetitive platform-evoked perturbations in cerebellar patients with those of healthy subjects using a classical conditioning paradigm. The perturbations consisted of tilting of the platform (unconditioned stimulus: US) at random time intervals, preceded by an auditory signal that represented the conditioning stimulus (CS). Physiological reactions were recorded biomechanically by measuring the vertical ground forces, yielding the center of vertical pressure (CVP), and electrophysiologically by EMG measurements of the main muscle groups of both legs. The recording session consisted of a control section with US-alone trials, a testing section with paired stimuli and a brief final section with US-alone trials. Healthy control subjects were divided into those establishing conditioned responses (CR) in all muscles tested (strategy I) and those with CR in the gastrocnemius muscles only (strategy II), suggesting an associative motor-related process is involved. Patients with a diffuse, non-localized disease were almost unable to establish CR. This was also true for a patient with a focal surgical lesion with no CR on the affected side but who, simultaneously, showed an essentially normal CR incidence on the intact side. During US-alone trials healthy controls exhibited a remarkable decay of the UR amplitude due to a non-associative motor-related process such as habituation. The decay was most prominent in the paired trials section. In contrast, patients showed no significant differences in the UR amplitude throughout the entire recording session. Analysis of the CVP supported the electrophysiological findings, showing CR in the controls only. The differences between the responses of control subjects and those of the cerebellar patients imply strongly that the cerebellum is involved critically in controlling associative and non-associative motor-related processes.

Classical conditioning of postural reflexes.

Unexpected external perturbations of body equilibrium elicit compensatory postural reflexes. The reflex patterns change only minimally, even after repetitive perturbations. This study addressed the question of whether classical conditioning can alter the reflex patterns. In the first session 27 healthy subjects were tested when standing on an unexpectedly tilting platform. Electromyographic (EMG) activity from different leg muscles and the vertical ground forces, from which the centre of vertical pressure (CVP) was computed, were recorded. In a subsequent session subjects were tested using the classical conditioning paradigm with the tilting platform as the unconditioned stimulus (US) and a prior auditory signal as the conditioning stimulus (CS). The decay of the unconditioned response (UR) observed in the first session was similar and small in all subjects. During conditioning, 22% of the subjects established conditioned responses (CR) in all muscles recorded (strategy 1). UR amplitudes of the anterior tibialis (TA) decayed more than in the first session. The resulting CVP excursions were similar to those observed in US-alone trials. The remaining subjects exhibited CR only in the gastrocnemius muscle but developed a substantial decay of UR, resulting in very small CVP excursions (strategy 2). Our data suggest that processing of US-preceding conditioning stimulus leads to different strategies in the control of postural adjustment with assumed underlying associative and non-associative plastic processes.

Changes in conditioned postural responses. Comparison between cerebellar patients and healthy subjects.

Postural responses elicited by external perturbation change characteristically during classical conditioning. This is assumed to be controlled by the cerebellum. In this study conditioning of postural responses in cerebellar patients was compared with that of healthy subjects. Subjects were tested when standing on a platform. Perturbations consisted of platform tilts (unconditioned stimulus, US), preceded by an auditory signal (conditioned stimulus, CS). The recording session consisted of US-alone and paired CS-US trials. In healthy subjects, unconditioned response (UR) amplitude decayed significantly with time in the recording session, especially strongly during paired trials. Amplitudes of cerebellar patients, however, decayed modestly and continuously, independently of the presence (paired trials) or otherwise of a CS. In addition, only healthy subjects established conditioned responses. Our data suggest that the prior auditory information is used to prepare postural responses. Deficits in cerebellar patients suggest a possible role of the cerebellum in controlling this plastic motor-related process.

A possible role of the human cerebellum in conditioning of the jaw-opening reflex.

The role of the human cerebellum in classical conditioning of the jaw-opening reflex was investigated using positron emission tomography (PET) in healthy subjects. The jaw-opening reflex was elicited by electrical stimulation of the right corner of the mouth (unconditioned stimulus, US). The conditioned stimulus was a tone preceding the US and coterminating with the US. Changes of regional cerebral blood flow (rCBF) were correlated with the rate of conditioning per PET scan. Conditioning effects were present in one third of all subjects. In these subjects, a significant increase of rCBF in the ipsilateral, intermediate cerebellum was shown during ongoing conditioning. Thus, the intermediate cerebellum appears to be involved in classical conditioning of the jaw-opening reflex in humans.