Unraveling How Transcutaneous Afferent Patterned Stimulation Provides Noninvasive Treatment of Refractory Essential Tremor Through Modulation of VIM Thalamus
Cuong Luu1, Youngwon Youn1, Jordan Ranum2, Jennifer Perrault2, Bryan Krause3, Matthew Banks3, Laura Buyan-Dent4, Kip Ludwig1, Wendell Lake1, Aaron Suminski1
1Neurological Surgery, 2Wisconsin Institute for Translational Neuroengineering, 3Neuroscience, 4Neurology, University of Wisconsin, School of Medicine and Public Health
Objective:
To investigate the neural mechanism of how transcutaneous afferent patterned stimulation (TAPS) improves upper limb essential tremor (ET).
Background:
ET likely originates from dysfunctional oscillatory activity in the cerebello-thalamo-cortical (CTC) network. Putatively, frequency-calibrated TAPSTM therapy propagates along afferent wrist nerves and reduces tremors by desynchronizing the ventral intermediate (VIM) thalamus, a hub in the CTC network. However, this is unconfirmed.
Design/Methods:
In eight prospectively enrolled ET patients (2 female; 65±7 years old), tremor was graded in both upper limbs using the Tremor Research Group Essential Tremor Rating Assessment Scale (TETRAS) before and after 40 minutes of TAPS in the dominant hand. Intraoperatively, local field potentials (LFP) superior to and within the VIM were measured with TAPS ON and OFF. LFP modulation index (MILFP) was quantified as the fractional difference of LFP power in the TAPS ON versus OFF conditions. Regression analysis assessed the relationship between MILFP and 1) the fractional difference in TETRAS score improvement between the treated and untreated limb; 2) distance from the ventrocaudal VIM.
Results:
TAPS therapy significantly improved TETRAS scores in the treated limb (0.61; p=0.008) and the untreated limb (0.35; p=0.008). The treated limb further demonstrated a significantly greater TETRAS score improvement than the untreated limb (p=0.047). Regression found that the MILFP of the alpha band (8-12 Hz) was preferentially enhanced in patients who had greater relative TETRAS improvement in their treated versus untreated limb (F(1,52)=15.313, p<0.001), and that alpha band MILFP was also most strongly enhanced closest to the ventrocaudal VIM in these patients (F(1,52)=8.371, p=0.006).
Conclusions:
This study suggests the underlying mechanism of TAPS involves modulation of alpha band LFP in the ventrocaudal VIM. Future investigation needs to explore the degree to which unilateral therapy leads to a bilateral tremor reduction and broader modulation of the CTC network.
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