Objective: To evaluate Dentate Nucleus (DN) functional connectivity (FC) changes and their relationship with motor and non-motor symptoms in essential tremor (ET).

Background: Previous functional MRI studies evaluated the importance of functional alterations in the cerebellum and other brain areas pertaining to the cerebello-thalamo-cortical circuit in ET patients. In particular, the DN is the main output pathway of the cerebellum and to date no studies have assessed the FC changes of this nucleus as a seed. Our hypothesis is that functional abnormalities in the DN can have a role in the pathophysiology of motor and non-motor disturbance in ET.

Method: We studied 26 ET patients and 26 healthy subjects (HS). Tremor severity was assessed by using Fahn-Tolosa-Marin Tremor Rating Scale (FTM-TRS). Cognitive profile was assessed by using the Montreal Cognitive Assessment (MoCA) and the Frontal Assessment Battery (FAB). Depression and anxiety were respectively evaluated by means of the Beck depression inventory (BDI) and the Beck anxiety inventory (BAI). All the subjects underwent to a 3T MRI protocol and a kinematic evaluation of tremor. Left and right DN coordinates were identified in MNI standard space to study FC of the DN by means of a seed based analysis using FSL tools.

Results: There was a significant decreased DN-FC with several cortical, sub-cortical and cerebellar areas in ET patients compared with HS. In particular, in ET patients, the DN-FC with SMA, pre- and post- central gyri and prefrontal cortex negatively correlated with the TRS and disease duration, whereas DN-FC with associative prefrontal and parietal cortex, basal ganglia and thalamus, positively correlated with the MOCA scores. In addition DN-FC changes in the thalamus and caudate significantly correlated with the peak frequency. No significant correlations were found between the DN-FC and mood disorders, as assessed by BDI and BAI scales.

Conclusion: Our study demonstrated an abnormal DN-FC in ET patients. In particular we found that FC alterations of the DN with sensori-motor areas significantly correlated with tremor severity and disease duration whereas DN-FC abnormalities with associative prefrontal and parietal cortical areas, as well as with thalamus and basal ganglia significantly correlated with the patients’ cognitive status.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/dentate-nucleus-functional-connectivity-changes-and-their-relationship-with-motor-and-non-motor-symptoms-in-patients-with-essential-tremor/