Differences in Olivo-Cerebellar Circuit and Cerebellar Network Connectivity in Essential Tremor: a Resting State fMRI Study

Abstract

The olivo-cerebellar circuit is thought to play a crucial role in the pathophysiology of essential tremor (ET). Whether olivo-cerebellar circuit dysfunction is also present at rest, in the absence of clinical tremor and linked voluntary movement, remains unclear. Assessing this network in detail with fMRI is challenging, considering the brainstem is close to major arteries and pulsatile cerebrospinal fluid–filled spaces obscuring signals of interest. Here, we used methods tailored to the analysis of infratentorial structures. We hypothesize that the olivo-cerebellar circuit shows altered intra-network connectivity at rest and decreased functional coupling with other parts of the motor network in ET. In 17 ET patients and 19 healthy controls, we investigated using resting state fMRI intracerebellar functional and effective connectivity on a dedicated cerebellar atlas. With independent component analysis, we investigated data-driven cerebellar motor network activations during rest. Finally, whole-brain connectivity of cerebellar motor structures was investigated using identified components. In ET, olivo-cerebellar pathways show decreased functional connectivity compared with healthy controls. Effective connectivity analysis showed an increased inhibitory influence of the dentate nucleus towards the inferior olive. Cerebellar independent component analyses showed motor resting state networks are less strongly connected to the cerebral cortex compared to controls. Our results indicate the olivo-cerebellar circuit to be affected at rest. Also, the cerebellum is “disconnected” from the rest of the motor network. Aberrant activity, generated within the olivo-cerebellar circuit could, during action, spread towards other parts of the motor circuit and potentially underlie the characteristic tremor of this patient group.

Mapping Essential Tremor to a Common Brain Network Using Functional Connectivity Analysis

“…More specifically, this study showed the network hub and the sensorimotor cortices were anticorrelated in patients with ET, whereas these regions were positively correlated in healthy controls; these results support the hypothesis that the cerebellum may be "disconnected" from the motor network in ET. 43 As such, the decoupling of the cerebellum with other regions of this network has been suggested to impede communication between the cerebellum and motor cortex during action, which may give rise to tremor. 43 The cerebellum has a complex functional neuroanatomy which subserves a myriad of motor and nonmotor processes, 30 yet because of challenges of resolution and segmentation, cerebellar lobules have rarely been investigated separately in the ET literature.…”

“…43 As such, the decoupling of the cerebellum with other regions of this network has been suggested to impede communication between the cerebellum and motor cortex during action, which may give rise to tremor. 43 The cerebellum has a complex functional neuroanatomy which subserves a myriad of motor and nonmotor processes, 30 yet because of challenges of resolution and segmentation, cerebellar lobules have rarely been investigated separately in the ET literature. 44,45 Recent studies 30,31 have established that the organization of the cerebellum involves 2 motor representations (lobules I-VI and VIII; Figure 6), each of which has different contributions to motor processing.…”

“…More specifically, this study showed the network hub and the sensorimotor cortices were anticorrelated in patients with ET, whereas these regions were positively correlated in healthy controls; these results support the hypothesis that the cerebellum may be “disconnected” from the motor network in ET. 43 As such, the decoupling of the cerebellum with other regions of this network has been suggested to impede communication between the cerebellum and motor cortex during action, which may give rise to tremor. 43…”

“…43 As such, the decoupling of the cerebellum with other regions of this network has been suggested to impede communication between the cerebellum and motor cortex during action, which may give rise to tremor. 43…”

Large-scale networks changes in Wilson's disease associated with neuropsychiatric impairments: a resting-state functional magnetic resonance imaging study

“…The ICA, a data-driven and multivariate approach that makes no prior assumptions, has been shown to be a useful tool for detecting and isolating different brain function networks [18][19][20] . With the ICA approach used to analyse fMRI data, the spatial independent components (ICs) and the corresponding mixing matrix could be obtained, and the latter could be used to calculate functional connectivity between RSNs [20] .…”