Phd in CLINICAL EXPERIMENTAL NEUROSCIENCE AND PSYCHIATRY

Thesis title: NEUROIMAGING CORRELATES OF BRADYKINESIA IN PATIENTS WITH ESSENTIAL TREMOR

Essential tremor (ET) is a movement disorder characterized primarily by postural and kinetic tremor of the upper limbs. The presence of etiological variability and additional symptoms of uncertain significance configures it as heterogeneous clinical syndrome. In ET, movement slowness without sequence effect has objectively been documented by kinematic analysis of repetitive movements of the upper limb and fingers. When movement slowness (bradykinesia) or other soft neurological signs are present, the new tremor classification suggests the term ET-plus. Bradykinesia is the cardinal symptom of Parkinson's disease (PD) and is typically related to basal ganglia (BG) dysfunction. Although the role of the cerebellum as a central tremor oscillator is well known in ET, the involvement of other brain areas, such as the BG, as determinants of bradykinesia is unclear. Recently, a dysfunction of brain networks was hypothesized as the substrate of bradykinesia in PD, and it is not excluded that the same occurs in ET. In the present thesis, we will first provide an updated overview of altered voluntary movement execution in ET and discuss major findings from clinical and experimental studies. In the experimental part of this thesis, we will show the results of two studies aimed at identifying voluntary movement abnormalities in ET patients using an optoelectronic kinematic system. Repetitive finger movements, the most useful task for bradykinesia assessment in PD clinical practice, were analysed. Various parameters were measured, including movement velocity, amplitude and velocity and amplitude reduction during movement repetition. Then, we will aim to demonstrate the possible neuroradiological substrates of bradykinesia in ET, correlating the kinematic parameters of finger movements to the results provided by dopamine transporter single-photon emission computed tomography (DAT-SPECT) in the first study and volumetric and functional magnetic resonance imaging (MRI) in the second. The data suggested a possible role of the BG and cerebellum in the genesis of impaired voluntary movement in ET, further confirming the heterogeneity of this neurological condition.