Cerebello-thalamo-cortical network is intrinsically altered in essential tremor: evidence from a resting state functional MRI study.

Cerebello-thalamo-cortical network is suggested to be involved in the pathophysiology of Essential Tremor (ET). 23 patients with ET and 23 matched HC underwent a 3T-MRI with acquisition of a resting state sequence. Connectivity was investigated using a seed-based regression analyses approach. In ET patients were observed: Reduced connectivity between left primary motor cortex (M1) seed and right premotor cortex and cerebellum and bilateral premotor, parietal areas, supplementary motor area (SMA); Increased connectivity between left somatosensory cortex (S1) seed and parietal areas, M1, premotor cortex, SMA; reduced connectivity of this seed with cerebellum. Increased connectivity of SMA seed with premotor cortex and decreased with parietal and precentral areas; Increased connectivity between left thalamus seed and cerebellum; Reduced connectivity between right cerebellum seeds and other cerebellar areas, precentral and premotor areas. ET showed altered connectivity within the cortical sensory-motor network and between cerebral cortex and cerebellum. The increased connectivity between cerebellum and thalamus is consistent with their crucial role in tremor generation. These findings support the dynamical entrainment of multiple central oscillators throughout the cerebello-thalamo-cortical network in ET. This evidence is strengthened by the finding that this network is altered also when the core symptom is absent.

Morphometric and functional MRI changes in essential tremor with and without resting tremor.

The etiopathogenesis of essential tremor (ET) is still debated, since the predominant role of circuit dysfunction or brain degenerative changes has not been clearly established. The relationship with Parkinson's Disease (PD) is also controversial and resting tremor occurs in up to 20 % of ET. We investigated the morphological and functional changes associated with ET and we assessed potential differences related to the presence (ET+R) or absence (ET-R) of resting tremor. 32 ET patients (18 ET+R; 14 ET-R) and 12 healthy controls (HC) underwent 3T-MRI protocol including Spoiled Gradient T1-weighted sequence for Voxel-Based Morphometry (VBM) analysis and functional MRI during continuous writing of "8" with right dominant hand. VBM analysis revealed no gray and white matter atrophy comparing ET patients to HC and ET+R to ET-R patients. HC showed a higher BOLD response with respect to ET patients in cerebellum and other brain areas pertaining to cerebello-thalamo-cortical circuit. Between-group activation maps showed higher activation in precentral gyrus bilaterally, right superior and inferior frontal gyri, left postcentral gyrus, superior and inferior parietal gyri, mid temporal and supramarginal gyri, cerebellum and internal globus pallidus in ET-R compared to ET+R patients. Our findings support that the dysfunction of cerebello-thalamo-cortical network is associated with ET in absence of any morphometric changes. The dysfunction of GPi in ET+R patients, consistently with data reported in PD resting tremor, might suggest a potential role of this structure in this type of tremor.