Assessment of Event-Related EEG Power After Single-Pulse TMS in Unresponsive Wakefulness Syndrome and Minimally Conscious State Patients

Abstract

In patients without a behavioral response, non-invasive techniques and new methods of data analysis can complement existing diagnostic tools by providing a method for detecting covert signs of residual cognitive function and awareness. The aim of this study was to investigate the brain oscillatory activities synchronized by single-pulse transcranial magnetic stimulation (TMS) delivered over the primary motor area in the time-frequency domain in patients with the unresponsive wakefulness syndrome or in a minimally conscious state as compared to healthy controls. A time-frequency analysis based on the wavelet transform was used to characterize rapid modifications of oscillatory EEG rhythms induced by TMS in patients as compared to healthy controls. The pattern of EEG changes in the patients differed from that of healthy controls. In the controls there was an early synchronization of slow waves immediately followed by a desynchronization of alpha and beta frequency bands over the frontal and centro-parietal electrodes, whereas an opposite early synchronization, particularly over motor areas for alpha and beta and over the frontal and parietal electrodes for beta power, was seen in the patients. In addition, no relevant modification in slow rhythms (delta and theta) after TMS was noted in patients. The clinical impact of these findings could be relevant in neurorehabilitation settings for increasing the awareness of these patients and defining new treatment procedures.

Comparison of cortical EEG responses to realistic sham versus real TMS of human motor cortex

“…Also, the present cluster-based statistics approach is appropriate for exploratory analyses, as it minimizes false-positives involved in testing multiple time-points [34]. Four ANOVAs were performed, one for each of the 4 frequency bands of interest: alpha (8-12 Hz), beta-1 (13-19 Hz), beta-2 (20-29 Hz), and gamma (30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45). Time-frequency points that presented clusters with p<0.05 in the ANOVA were proceeded to the pairwise post hoc comparison with cluster-based t-tests.…”

“…Another possibility is that alpha/beta ERD over sensorimotor cortices elicited by TMS may simply reflect overall cortical activation, which would include cortico-cortical and cortico-subcortical circuits directly activated by TMS and, to a lesser extent, the re-afferent feedback from the MEPs [18]. Accordingly, one study demonstrated that patients with severe disorders of consciousness, unlike healthy controls, failed to present TMS induced alpha and beta desynchronization [44], likely representing a consequence of the breakdown of cortico-cortical neuronal processing in this condition [45,46]. Induced oscillations in the 110%RMT condition presented a significantly larger power increase in the beta band (event related synchronization/ERS) in a late time window (650 -800 ms) compared to 90%RMT, suggesting that this phenomenon might correspond specifically to the motor re-afference.…”

Characterizing the Cortical Oscillatory Response to TMS Pulse

“…Consequently, when applying several TMS pulses, a complex additive interaction between the exogenous event and endogenous neuronal cortical excitability is triggered (Kawasaki et al, 2014 ). Therefore, it is important to understand whether and how single TMS pulse per se affects the neuronal oscillations, and additionally in which terms: “phase-reset” of ongoing oscillations or “added-energy.” Then if TMS adds energy to the system, it should be evaluated if this energy is expressed in terms of oscillatory power increase of a specific frequency or is a temporal modulation of cortical oscillations in others frequency bands (Formaggio et al, 2016 ). In other words, it is critical to establish whether a TMS protocol applied to probe the brain state is actually changing the brain response by itself.…”

Cortical oscillations to measure anti-epileptic drug activity in clinical trials

“…The authors proposed that the thalamotomy served to reduce the abnormally high TMS-induced beta oscillations 34 . Another study demonstrated that patients with severe disorders of consciousness failed to show TMS induced alpha and beta desynchronization 35 . This pattern may reflect a consequence of the breakdown of cortico-cortical neuronal connectivity.…”