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.

Keywords: EEG; Inter-independent component phase coherence; Intrinsic functional connectivity; Mal de debarquement syndrome; rTMS.

Fig. 1

Change in visual analogue scores (VAS) following rTMS

Fig. 2

Spatial and spectral patterns of 19 selected independent components arranged over the cortex according to the approximate locations of their neural substrates: A spatial patterns, B normalized grand averaged power spectra from 2 to 50 Hz

Fig. 3

Intrinsic functional connectivity changes correlated to VAS score change following rTMS. Red and blue lines indicate positive and negative correlations, respectively. Red: connectivity decreases with symptom improvement; blue: connectivity increases with symptom improvement. The weight of the lines represents levels of significance: heavy: p < 0.005, medium: p < 0.01, light: p < 0.05. White circles with numbering indicate the ICs noted in Fig. 2

Fig. 4

Intrinsic functional connectivity (IFC) with baseline values significantly correlated with VAS score changes following rTMS. Red: low baseline connectivity correlated with symptom improvement; blue: high baseline connectivity correlated with symptom improvement. Dashed lines indicate IFCs that were identified in both the symptom correlation analysis shown in Fig. 3 and in the baseline correlation analysis. The weight of the lines represents levels of significance: heavy: p < 0.005, medium: p < 0.01, light: p < 0.05. White circles with numbering indicate the ICs noted in Fig. 2

Fig. 5

Relationship between all simultaneously detected IFCs across all frequency bands (dashed lines in Fig. 4) and treatment effects for all subjects: blue, black and red dots represent positive, neutral and negative responders, respectively