Voxel-based morphometry and task functional magnetic resonance imaging in essential tremor: evidence for a disrupted brain network

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.

Imaging the Pathophysiology of Essential Tremor—A Systematic Review

“…In contrast, the authors observed increased activity in the ION in only two out of 12 patients, supporting a pivotal role of the cerebellum in tremor genesis and refuting the single oscillator ION hypothesis ( 16 ). Subsequently, numerous task-based fMRI studies have confirmed that altered cerebellar and cerebello-thalamico-cortical activity is correlated to clinical tremor manifestation and task performance ( 36 , 40 , 62 – 64 , 66 , 67 ). One study did not report a significant difference in functional connectivity during an emotion processing and finger tapping task in ET patients compared with HC.…”

“…Cerebellar atrophy is commonly reported in ET patients ( 15 , 22 , 26 , 28 – 32 , 36 , 37 , 43 , 46 , 48 ). However, an equivocal number of studies found no morphological cerebellar changes ( 18 , 21 , 25 , 33 – 35 , 38 – 42 , 49 ), and even increased cerebellar gray matter volume in young ET subjects has been reported ( 27 , 45 ).…”

“…There is no consistent pattern of atrophy. Moreover, alongside volume loss, gray matter volume gain has been observed in various cortical regions, and some studies did not identify any cortical differences between ET patients and HC ( 15 , 22 , 23 , 26 , 33 – 36 , 38 , 41 , 44 , 45 , 47 ). Of note, the clinical phenotype of ET is associated with distinct morphological brain changes.…”

The Role of the Cerebellum in Tremor – Evidence from Neuroimaging

“…Indeed, task-specific fMRI studies have provided evidence that ET is associated with cerebellar deactivations when performing a motor task [ 18 19 20 ]. One of these studies showed that task-related dentate nucleus activation correlated positively with tremor severity, whereas a decrease in BOLD activity was found in widespread cerebellar as well as cortical regions during finger tapping [ 19 ].…”

A Critical Review of Alien Limb-Related Phenomena and Implications for Functional Magnetic Resonance Imaging Studies

“…Findings on ET suggested that tremor is generated by the same neural network that is activated upon voluntary movement (63,64). Another fMRI study investigated ET patients and healthy controls maintaining a posture as well as controls simulating tremor (65). Tremor in ET patients was associated with decreased cerebellar, TABLE 2 | Activated areas during voluntary movements revealed by fMRI studies performed on healthy volunteers.…”