Treatment-Specific Network Modulation of MRI-Guided Focused Ultrasound Thalamotomy in Essential Tremor

Abstract

MRI-guided focused ultrasound (MRgFUS) thalamotomy is a novel, effective, and non-invasive treatment for essential tremor (ET). However, the network mediating MRgFUS in treating ET is not precisely known. This study aimed to identify the disease-specific network associated with the therapeutic effects of MRgFUS thalamotomy on ET and investigate its regional characteristics and genetic signatures to gain insights into the neurobiological mechanism of ET and MRgFUS thalamotomy. Twenty-four ET patients treated with MRgFUS thalamotomy underwent resting-state functional MRI at baseline and postoperative 6 months to measure the fractional amplitude of low-frequency fluctuation (fALFF). Ordinal trends canonical variates analysis (OrT/CVA) was performed on the within-subject fALFF data to identify the ET-related network. Genetic functional enrichment analysis was conducted to study the genetic signatures of this ET-related network using brain-wide gene expression data. OrT/CVA analysis revealed a significant ET-related network for which subject expression showed consistent increases after surgery. The treatment-induced increases in subject expression were significantly correlated with concurrent tremor improvement. This network was characterized by increased activity in the sensorimotor cortex and decreased activity in the posterior cingulate cortex. It was correlated with an expression map of a weighted combination genes enriched for mitochondria relevant ontology terms. This study demonstrates that the therapeutic effects of MRgFUS thalamotomy on ET are associated with modulating a distinct ET-related network which may be driven by mitochondria relevant neurobiological mechanism. Quantification of treatment-induced modulation on the ET-related network can provide an objective marker for evaluating the efficacy of MRgFUS thalamotomy.

Alteration of White Matter Connectivity for MR‐Guided Focused Ultrasound in the Treatment of Essential Tremor

“…27 However, few studies have used this approach to explore the changes in the WM network in patients treated to MRgFUS. 6,8 This study found a great improvement in the strength of rich-club connection after MRgFUS thalamotomy compared to pre-operation, while the connections between hub nodes and peripheral nodes vs. peripheral nodes and peripheral nodes were not statistically significant. It has been speculated that whether these changes in WM network induced by MRgFUS are driven by the strength of rich-club connections in ET patients, which is worth further exploration.…”

“…38 A recent study has proposed that the therapeutic effects of MRgFUS thalamotomy on ET are associated with modulating a distinct ET-related network, including the sensorimotor and posterior cingulate cortex, which may be driven by mitochondria-relevant neurobiological mechanisms. 8 Another structural network study also supported this point that there was a U-shaped subnetwork sensitive to MRgFUS thalamotomy in patients with tremor-dominant PD. 6 Additionally, from the point of the network level, no significant changes within the ablated lesion was detected via modular analysis; however, a significant difference in left thalamus was reported via voxel-based analysis, also accompanied by changes in the motor area.…”

“…Crossley et al also reported that these characteristics could make rich‐club nodes particularly vulnerable to pathogenic factors 27 . However, few studies have used this approach to explore the changes in the WM network in patients treated to MRgFUS 6,8 . This study found a great improvement in the strength of rich‐club connection after MRgFUS thalamotomy compared to pre‐operation, while the connections between hub nodes and peripheral nodes vs. peripheral nodes and peripheral nodes were not statistically significant.…”

“…However, there are few studies on brain network analysis for ET patients treated with MRgFUS. 6,8 Based on the experience of tremor-dominant Parkinson's disease (PD), MRgFUS thalamotomy-related network has been detected by using diffusion tensor imaging (DTI) data, which is found to be critical for clinical tremor recovery, lesion progression, and operation-related parameters. 6 Rich-club organization is characterized by a highcapacity central core and its connections play a key role in the global integration of neural information among regions of the brain.…”

“…Therefore, brain network analysis might be suitable for exploring the pathogenesis and symptom remission mechanism of ET. However, there are few studies on brain network analysis for ET patients treated with MRgFUS 6,8 . Based on the experience of tremor‐dominant Parkinson's disease (PD), MRgFUS thalamotomy‐related network has been detected by using diffusion tensor imaging (DTI) data, which is found to be critical for clinical tremor recovery, lesion progression, and operation‐related parameters 6 …”