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

Abstract

To determine intrinsic functional connectivity (IFC) related to symptom changes induced by rTMS in mal de debarquement syndrome (MdDS), a motion perceptual disorder induced by entrainment to oscillating motion. Twenty right-handed women (mean age: 52.9 ± 12.6 years; mean duration illness: 35.2 ± 24.2 months) with MdDS received five sessions of rTMS (1 Hz right DLPFC, 10 Hz left DLPFC) over consecutive days. High-density (128-channel) resting-state EEG were recorded prior to and following treatment sessions and analyzed using a group-level independent component (IC) analysis. IFC between 19 ICs was quantified by inter-IC phase coherence (ICPC) in six frequency bands (delta, theta, low alpha, high alpha, beta, gamma). Correlational analyses between IFCs and symptoms were performed. Symptom improvement after rTMS was significantly correlated with (1) an increase in low alpha band (8–10 Hz) IFC but a decrease of IFC in all other bands, and (2) high baseline IFC in the high alpha (11–13 Hz) and beta bands (14–30 Hz). Most treatment related IFC changes occurred between frontal and parietal regions with a linear association between the degree of symptom improvement and the number of coherent IFC changes. Frequency band and region specific IFC changes correlate with and can predict symptom changes induced by rTMS over DLPFC in MdDS. MdDS symptom response correlates with high baseline IFC in most frequency bands. Treatment induced increase in long-range low alpha IFC and decreases in IFC in other bands as well as the proportion of coherent IFC changes correlate with symptom reduction.

Neuroimaging Markers of Mal de Débarquement Syndrome

“…Simultaneously acquired fMRI-EEG data on individuals with MdDS have provided cross-modal validation of biomarkers found separately, showing that brain network-level changes associated with clinical effects are consistent across modalities of different temporal resolutions (49,69,70,(72)(73)(74). Our data showed that after rTMS at DLPFC, EEG synchronization changes in medial frontal gyrus were associated with fMRI-measured connectivity changes involving deeper cortical structures, particularly in a network that includes the entorhinal cortex and right IPL, indicating that the modulatory effect of rTMS is at least partially related to reducing the connectivity within the DMN (49,73).…”

“…Measurement of this connectivity was reflected through independent component phase coherence (ICPC), a calculation of synchronicity at individual frequency bands (delta, theta, low alpha, high alpha, beta, and gamma) on an independent component level rather than an individual channel level ( 69 ). ICPC calculations on 128-channel EEG data collected pre and post rTMS have shown distinct differences in synchronizations across independent component regions and frequencies ( 69 , 70 ). In general, reduction in ICPC in the delta, high alpha, beta, and gamma bands were noted with symptom improvement, whereas increase in ICPC was noted in the low alpha band ( Figure 6A ).…”

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…”

“…[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…”

Weak rTMS-induced electric fields produce neural entrainment in humans

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