Giulia Paparella

Effects of cerebellar theta-burst stimulation on arm and neck movement kinematics in patients with focal dystonia

OBJECTIVE To investigate the cerebellar inhibitory influence on the primary motor cortex in patients with focal dystonia using a cerebellar continuous theta-burst stimulation protocol (cTBS) and to evaluate any relationship with movement abnormalities. METHODS Thirteen patients with focal hand dystonia, 13 patients with cervical dystonia and 13 healthy subjects underwent two sessions: (i) cTBS over the cerebellar hemisphere (real cTBS) and (ii) cTBS over the neck muscles (sham cTBS). The effects of cerebellar cTBS were quantified as excitability changes in the contralateral primary motor cortex, as well as possible changes in arm and neck movements in patients. RESULTS Real cerebellar cTBS reduced the excitability in the contralateral primary motor cortex in healthy subjects and in patients with cervical dystonia, though not in patients with focal hand dystonia. There was no correlation between changes in primary motor cortex excitability and arm and neck movement kinematics in patients. There were no changes in clinical scores or in kinematic measures, after either real or sham cerebellar cTBS in patients. CONCLUSIONS The reduced cerebellar inhibitory modulation of primary motor cortex excitability in focal dystonia may be related to the body areas affected by dystonia as opposed to being a widespread pathophysiological abnormality. SIGNIFICANCE The present study yields information on the differential role played by the cerebellum in the pathophysiology of different focal dystonias.

Bradykinesia in early and advanced Parkinson's disease

BACKGROUND Motor impairment in Parkinsons disease (PD) includes slowness (bradykinesia), decreased amplitude (hypokinesia), impaired rhythm and a progressive reduction in speed and amplitude during movement repetition (sequence effect). In the present study we aimed to analyse bradykinesia features in newly-diagnosed and drug-näive patients with PD. Kinematic data were compared with PD patients in the advanced stages of the disease and with healthy controls. We also investigated the effect of selegiline on motor impairment in early PD. METHODS Fourteen newly-diagnosed and drug-näive PD patients in the early stage of the disease, 11 patients with advanced PD and 20 healthy controls performed a repetitive finger tapping task. Early PD patients were assessed in two separate sessions at baseline and four weeks after treatment with selegiline (10 mg taken daily). The repetitive finger movement was analysed using kinematic techniques. RESULTS The speed and amplitude of repetitive finger movement were lower in early PD patients than in healthy controls. Early PD patients also had a progressive decrement of movement amplitude (sequence effect). Patients with advanced PD had lower speed, amplitude and movement regularity during finger tapping in comparison to early PD and healthy controls but no sequence effect. In early PD, selegiline improved both the movement speed and amplitude though it did not influence the sequence effect. CONCLUSIONS The study yields an objective characterization of motor impairment in early and advanced PD. The kinematic assessment of the effects of selegiline on movement abnormalities in early PD provides a better understanding and interpretation of their pathophysiological mechanisms.

Altered Kinematics of Facial Emotion Expression and Emotion Recognition Deficits Are Unrelated in Parkinson’s Disease

Background Altered emotional processing, including reduced emotion facial expression and defective emotion recognition, has been reported in patients with Parkinson’s disease (PD). However, few studies have objectively investigated facial expression abnormalities in PD using neurophysiological techniques. It is not known whether altered facial expression and recognition in PD are related. Objective To investigate possible deficits in facial emotion expression and emotion recognition and their relationship, if any, in patients with PD. Methods Eighteen patients with PD and 16 healthy controls were enrolled in this study. Facial expressions of emotion were recorded using a 3D optoelectronic system and analyzed using the facial action coding system. Possible deficits in emotion recognition were assessed using the Ekman test. Participants were assessed in one experimental session. Possible relationship between the kinematic variables of facial emotion expression, the Ekman test scores, and clinical and demographic data in patients were evaluated using the Spearman’s test and multiple regression analysis. Results The facial expression of all six basic emotions had slower velocity and lower amplitude in patients in comparison to healthy controls (all Ps < 0.05). Patients also yielded worse Ekman global score and disgust, sadness, and fear sub-scores than healthy controls (all Ps < 0.001). Altered facial expression kinematics and emotion recognition deficits were unrelated in patients (all Ps > 0.05). Finally, no relationship emerged between kinematic variables of facial emotion expression, the Ekman test scores, and clinical and demographic data in patients (all Ps > 0.05). Conclusion The results in this study provide further evidence of altered emotional processing in PD. The lack of any correlation between altered facial emotion expression kinematics and emotion recognition deficits in patients suggests that these abnormalities are mediated by separate pathophysiological mechanisms.

Blinking in patients with clinically probable multiple system atrophy

Clinical studies in patients with MSA document facial motor abnormalities, but no studies have objectively assessed blinking abnormalities in this condition.

Neurophysiological correlates of bradykinesia in Parkinson’s disease

Many neurophysiological abnormalities have been described in the primary motor cortex of patients with Parkinsons disease. However, it is unclear whether there is any relationship between them and bradykinesia, one of the cardinal motor features of the condition. In the present study we aimed to investigate whether objective measures of bradykinesia in Parkinsons disease have any relationship with neurophysiological measures in primary motor cortex as assessed by means of transcranial magnetic stimulation techniques. Twenty-two patients with Parkinsons disease and 18 healthy subjects were enrolled. Objective measurements of repetitive finger tapping (amplitude, speed and decrement) were obtained using a motion analysis system. The excitability of primary motor cortex was assessed by recording the input/output curve of the motor-evoked potentials and using a conditioning-test paradigm for the assessment of short-interval intracortical inhibition and facilitation. Plasticity-like mechanisms in primary motor cortex were indexed according to the amplitude changes in motor-evoked potentials after the paired associative stimulation protocol. Patients were assessed in two sessions, i.e. OFF and ON medication. A canonical correlation analysis was used to test for relationships between the kinematic and neurophysiological variables. Patients with Parkinsons disease tapped more slowly and with smaller amplitude than normal, and displayed decrement as tapping progressed. They also had steeper input/output curves, reduced short-interval intracortical inhibition and a reduced response to the paired associative stimulation protocol. Within the patient group, bradykinesia features correlated with the slope of the input/output curve and the after-effects of the paired associative stimulation protocol. Although dopaminergic therapy improved movement kinematics as well as neurophysiological measures, there was no relationship between them. In conclusion, neurophysiological changes in primary motor cortex relate to bradykinesia in patients with Parkinsons disease, although other mechanisms sensitive to dopamine levels must also play a role.

Reversal of long term potentiation-like plasticity in primary motor cortex in patients with progressive supranuclear palsy

OBJECTIVE Abnormal primary motor cortex plasticity might be involved in the pathophysiology of progressive supranuclear palsy. In the present study we aimed to investigate possible abnormalities of depotentiation, a mechanism involved in plasticity regulation, in this condition. METHODS Primary motor cortex excitability, investigated with single and paired-pulse transcranial magnetic stimulation, as well as long-term potentiation-like plasticity and its reversibility, were studied using theta burst stimulation in 15 patients with progressive supranuclear palsy and 11 healthy controls. Participants underwent two sessions using (1) the intermittent theta-burst stimulation (potentiation protocol) and (2) intermittent theta-burst stimulation combined with a depotentiation protocol (a short continuous theta-burst stimulation). RESULTS Patients with PSP had higher corticospinal excitability and lower intracortical inhibition than healthy controls. Intermittent theta-burst stimulation elicited an abnormally increased long term potentiation-like effect in patients in comparison to healthy subjects. However, the depotentiation protocol was able to reverse the effects intermittent theta-burst stimulation on motor cortex excitability both in patients and in healthy controls. CONCLUSIONS Altered primary motor cortex plasticity in patients with PSP does not reflect an abnormality of depotentiation. SIGNIFICANCE This study provides information for a deeper understanding of the possible pathophysiological mechanisms underlying the altered M1 plasticity in PSP.

Effects of Transcranial Alternating Current Stimulation on Repetitive Finger Movements in Healthy Humans

Transcranial alternating current stimulation (tACS) is a noninvasive neurophysiological technique that can entrain brain oscillations. Only few studies have investigated the effects of tACS on voluntary movements. We aimed to verify whether tACS, delivered over M1 at beta and gamma frequencies, has any effect on repetitive finger tapping as assessed by means of kinematic analysis. Eighteen healthy subjects were enrolled. Objective measurements of repetitive finger tapping were obtained by using a motion analysis system. M1 excitability was assessed by using single-pulse TMS and measuring the amplitude of motor-evoked potentials (MEPs). Movement kinematic measures and MEPs were collected during beta, gamma, and sham tACS and when the stimulation was off. Beta tACS led to an amplitude decrement (i.e., progressive reduction in amplitude) across the first ten movements of the motor sequence while gamma tACS had the opposite effect. The results did not reveal any significant effect of tACS on other movement parameters, nor any changes in MEPs. These findings demonstrate that tACS modulates finger tapping in a frequency-dependent manner with no concurrent changes in corticospinal excitability. The results suggest that cortical beta and gamma oscillations are involved in the motor control of repetitive finger movements.

Differential effects of propranolol on head and upper limb tremor in patients with essential tremor and dystonia

Propranolol is used as the first-line treatment in essential tremor and it has also been proposed as a treatment for tremor in dystonia. However, several issues remain uncertain. For example, it is still not clear whether propranolol exerts a beneficial effect on head tremor. Moreover, no studies have investigated whether the effect of propranolol on head and upper limb tremor in essential tremor differs from that in dystonia. We aimed to assess the effects of propranolol on tremor in different body parts in essential tremor and in patients with tremor and dystonia. Twenty-nine patients with head and upper limb tremor were enrolled in the study, 14 with essential tremor, and 15 with dystonia. Participants underwent a clinical and kinematic analysis of tremor in two sessions, i.e., without (baseline) and ‘on therapy’ with propranolol. We found that head tremor was more severe in patients with dystonia, while upper limb tremor was more evident in patients with essential tremor (P < 0.05). Propranolol had no effect on head tremor in either group (all Ps > 0.05), but it did reduce upper limb tremor in patients with essential tremor. The present study demonstrates differential effects of propranolol on head and upper limb tremor in patients with essential tremor. The lack of effect on head and upper limb tremor in patients with dystonia suggests that the pathophysiological mechanisms underlying tremor in these two conditions and in different body parts may be distinct.