Abstract
The pathophysiology of essential tremor (ET) is controversial and might be further elucidated by advanced neuroimaging. Focusing on homogenous ET patients diagnosed according to the 2018 consensus criteria, this study aimed to: (1) investigate whether task functional MRI (fMRI) can identify networks of activated and deactivated brain areas, (2) characterize morphometric and functional modulations, relative to healthy controls (HC). Ten ET patients and ten HC underwent fMRI while performing two motor tasks with their upper limb: (1) maintaining a posture (both groups); (2) simulating tremor (HC only). Activations/deactivations were obtained from General Linear Model and compared across groups/tasks. Voxel-based morphometry and linear regressions between clinical and fMRI data were also performed. Few cerebellar clusters of gray matter loss were found in ET. Conversely, widespread fMRI alterations were shown. Tremor in ET (task 1) was associated with extensive deactivations mainly involving the cerebellum, sensory-motor cortex, and basal ganglia compared to both tasks in HC, and was negatively correlated with clinical tremor scales. Homogeneous ET patients demonstrated deactivation patterns during tasks triggering tremor, encompassing a network of cortical and subcortical regions. Our results point towards a marked cerebellar involvement in ET pathophysiology and the presence of an impaired cerebello-thalamo-cortical tremor network.
Highlights
The pathophysiology of essential tremor (ET) is controversial and might be further elucidated by advanced neuroimaging
This study explored in-vivo morphological and functional brain modulations associated with ET in a homogeneous cohort of patients diagnosed according to the 2018 consensus c riteria[1] by using voxel-based morphometry (VBM) and task functional magnetic resonance imaging (MRI) (fMRI)
ET patients displayed statistically different activation and deactivation mapping when tremor triggered by maintaining a posture with their right arm was compared with both the same task and the simulation of tremor in healthy controls (HC)
Summary
The pathophysiology of essential tremor (ET) is controversial and might be further elucidated by advanced neuroimaging. Essential tremor (ET) has recently been redefined as an isolated tremor syndrome characterized by bibrachial postural and/or kinetic tremor which has been present for at least 3 years and may affect other body parts (e.g. head, voice, lower limbs) but is not associated with other neurological signs (e.g., parkinsonism, dystonia, ataxia)[1]. ET might be secondary to abnormal oscillatory activity within a tremor-generating network including the inferior olive, cerebellum, red nucleus, thalamus, and sensory-motor c ortex[4,8]. In this context, advanced magnetic resonance imaging (MRI) may provide novel insights to shed light on the pathophysiology of E T5,7,9
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