Resting State Functional Connectivity Signature of Treatment Effects of Repetitive Transcranial Magnetic Stimulation in Mal de Debarquement Syndrome

Abstract

Repetitive transcranial magnetic stimulation (rTMS) has been used in experimental protocols to treat mal de debarquement syndrome (MdDS), a neurological condition that represents a maladaptive brain state resulting from entrainment to external oscillating motion. Medical treatments and biomarkers for MdDS remain limited but neuromodulation with rTMS has shown evidence for therapeutic effects. This study took a neuroimaging approach to examine the neuromodulatory effect of rTMS on MdDS. Twenty individuals with MdDS underwent five daily treatments of rTMS over bilateral dorsolateral prefrontal cortex (DLPFC). Participants received 1 Hz over right DLPFC (1200 pulses) followed by 10 Hz over left DLPFC (2000 pulses). Resting state functional magnetic resonance imaging was acquired before and after treatments to determine functional connectivity changes associated with a positive treatment effect. A single-subject-based analysis protocol was developed to capture the degree of resting state functional connectivity (RSFC) between the rTMS target and the entorhinal cortex (EC), an area previously shown to be hypermetabolic in MdDS. Our results showed that rocking motion perception in subjects was modulated by rTMS over the DLPFC. Improvements in symptoms correlated most strongly with a post-rTMS reduction in functional connectivity between the left EC and the precuneus, right inferior parietal lobule, and the contralateral EC, which are part of the posterior default mode network. Positive response to rTMS correlated with higher baseline RSFC between the DLPFC and the EC. Our findings suggest that baseline prefrontal-limbic functional connectivity may serve as a predictor of treatment response to prefrontal stimulation in MdDS and that RSFC may serve as a dynamic biomarker of symptom status.

Electrophysiological Signatures of Intrinsic Functional Connectivity Related to rTMS Treatment for Mal de Debarquement Syndrome

“…4 ), i.e., treatment responders were individuals with high baseline IFC values that reduced following rTMS. These data were consistent with high baseline resting state functional connectivity between DLPFC and entorhinal cortex correlating with treatment response to rTMS in MdDS (Yuan et al 2017 ). The DLPFC is also the main target for rTMS treatment of medically refractory depression, with a resultant large body of literature on the neuroimaging correlates of DLPFC stimulation for depression (Perera et al 2016 ; Fischer et al 2016 ).…”

“…Sensory entrainment to motion that does not revert back to the native state has neuroimaging signatures (Ding et al 2014 ; Yuan et al 2017 ; Cha et al 2012 ). Functional neuroimaging of the MdDS brain state has revealed increased metabolism in the left entorhinal cortex and amygdala, two brain areas that exhibit entrainment to periodic electrical stimulation (Cha et al 2012 ; Egorov et al 2002 , 2006 ; Fransén et al 2006 ).…”

“…Repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) is able to acutely reduce the perception of oscillating self-motion in MdDS (Cha et al 2013 ). Connectivity between the entorhinal cortex and the posterior default mode network decreases with symptom improvement after rTMS over DLPFC (Ding et al 2014 ; Yuan et al 2017 ; Cha et al 2012 ). Laterality plays a role in the optimal treatment paradigm in MdDS with right-handed subjects responding better to left DLPFC 10 Hz stimulation and left-handed subjects responding better to right DLPFC 10 Hz stimulation.…”

Visual Vertigo, Motion Sickness, and Disorientation in Vehicles

“…63 Transcranial magnetic stimulation is a potential treatment. 64 MdDS is discussed elsewhere in this issue.…”

Mal de Debarquement Syndrome

“…36 Markers of symptom improvement after DLPFC stimulation include a reduction in connectivity within the posterior default mode network, specifically a reduction in connectivity with the entorhinal cortex. [37][38][39] Moreover, symptom improvement was characterized by reduced longrange connectivity (frontoparietal) in the high α À band (11)(12)(13) and β-bands (14-30 Hz), and an increase in connectivity in the low α-band (8-10 Hz). 39…”