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Neurophysiological effects and behavioral outcomes after tDCS and tPCS in patients with disorders of consciousness: a case study

Sepehr Mortaheb1*, Alice Barra1, Manon Carrière1, Mariachiara L. Binda Fossati1, Geraldine Martens1, 2, Yelena Bodien2, Jorge L. Morales-Quezada3, Felipe Fregni3, Joseph Giacino2, Steven Laureys1 and Aurore Thibaut1, 3*
  • 1 Coma Science Group, GIGA Consciousness-GIGA Research, University of Liege, Belgium
  • 2 Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital and Harvard Medical School, United States
  • 3 Neuromodulation Center, Spaulding Rehabilitation Hospital, Harvard Medical School, United States

Introduction: Research on severely brain-damaged patients with disorders of consciousness (DOC) recently revealed a wide range of therapeutic possibilities through non-invasive brain stimulation (NIBS)[1-4]. Transcranial direct current stimulation (tDCS) and transcranial pulsed current stimulation (tPCS) are safe and inexpensive NIBS techniques that could be easily implemented in rehabilitative programs. The mechanisms of these NIBS techniques are based on delivering a low-intensity current to the brain via scalp electrodes, modifying neuronal features in different ways according to the type of current applied[5]. TDCS over left dorsolateral prefrontal cortex (DLPFC) has shown to improve cognitive functions in DOC patients as measured by the Coma Recovery Scale-Revised (CRS-R) in about 50% of patients in minimally conscious state (MCS) [6,7]. TPCS has been used to modulate cortical and subcortical neural connectivity within a frequency range comprises of 6-10Hz[8]. It was successfully employed as a tool for enhancing motor skills and cognitive functions in healthy volunteers [9] and has shown promising results on brain activity and connectivity, as measured with quantitative electroencephalogram (qEEG), being theoretically able to reach deeper brain structures than tDCS [10,11] due to specific localization of current delivery. These two NIBS techniques have been shown to induce different neural changes in healthy volunteers and in patients with chronic visceral pain[12]. This experimental protocol aims to compare the effects of tPCS and tDCS on neurophysiological outcomes in one patient with DOC using qEEG. Furthermore, we will also evaluate the effects of tPCS and tDCS on behavioral outcomes (i.e., CRS-R). Methods: This is a double-blind sham-controlled case-report on one MCS+ patient who suffered a subarachnoid haemorrhage 15 months prior. The subject received 3 sessions in a randomized way, with a minimum interval of 5 days between each treatment condition: (i) active tPCS with sham tDCS, (ii) sham tPCS with active tDCS, and (iii) sham tPCS with sham tDCS (see Fig.1). Furthermore, before and after each session we performed CRS-R and recorded 10 minutes of resting EEG using 25 electrodes montage based on 10-20 standard. The stimulation target for tDCS was the left DLPFC with an intensity of 2mA for 20 minutes, while the target for tPCS was on the bimastoid line with an intensity of 2mA peak to peak and a random frequency of 6-10Hz for 20 minutes. EEG data were filtered from 1Hz to 40Hz and were further divided into 2 seconds epochs. Visual inspection and independent component analysis (ICA) were used to remove eyeblinks and muscle artefacts. Bad channels were interpolated using spherical interpolation and data were re-referenced to the overall average of electrodes. A z-score normalization was, then, performed on each channel. Power of EEG signal was calculated for each standard frequency bands: Delta (0-4 Hz), Theta (4-8 Hz), Alpha (8-12 Hz) and Beta (12-25 Hz), and multitapers method was used to compute power spectral density [13]. Non-parametric corrected cluster permutation test [14] was performed to compare the significant difference of the power topographic maps before and after each session. Electrode clusters with p-value below 0.01 were considered as significant power changes. Results and Discussion: Considering EEG analysis, after anodal tDCS, the two tailed cluster permutation test showed significant increase in the power of Alpha and Beta bands in all electrodes and decrease in the power of Delta and Theta bands in frontal electrode clusters. Electrode clusters with significant power change (p<0.01) are shown in Fig.2 for each stimulation modality. After active tPCS, a significant power increase was observed only in Theta power. This was consistent with the frequency of pulses used for tPCS (i.e., 6-10Hz) as well as the peak frequency in the power spectral density of EEG signals of the patient (i.e., 6-10Hz) (Fig.3). TDCS, but not tPCS, resulted in a significant improvement in CRS-R total score. Indeed, after anodal tDCS, the patient’s CRS-R total score increased from 10 to 15 (defining the patient as a tDCS responder[6]). The patient’s diagnosis remained the same after tDCS (MCS+) but she showed systematic response to commands and objects’ localisation that were not observed before. On the other hand, before and after active tPCS, the CRS-R score remained at 14. In the sham condition, the CRS-R score decreased from 15 to 13 after the session. Increase of Alpha and Beta power and decrease of Theta and Delta power after anodal tDCS is consistent with the increase of consciousness level [15,16] and therefore, could underlie the behavioral outcome increase observed in CRS-R scores. However, increase of Theta power after active tPCS did not result in any improvement in the behavioural outcome of the patient. This could be related to the number of tPCS sessions or the frequency of stimulation. However, it could be relevant to mention that even if not behavioral changes were obsevred with the CRS-R, the patient’s caregivers and relatives noticed that she stayed awake for longer period of time during the day and had difficulties to sleep at night for two days after the tPCS session. Therefore, it may be hypothesized that the CRS-R was not sensitive enough, in her case, to capture behavioural changes following tPCS. Conclusion: In this first experimental clinical trial, the effect of active tDCS and tPCS on neurophysiological and behavioral outcomes were tested in one patient in MCS. The results showed that the anodal tDCS significantly increased alpha and beta EEG frequency bands and decreased delta and theta frequency bands which was paralleled by a clinical improvement observed with the CRS-R score. On the other hand, active tPCS had no significant behavioral effect on the CRS-R score but induced a significant increase in theta power as expected by the selected stimulation frequency range (i.e., 6-10Hz). It may be possible that several sessions are needed to induce clinical changes with tPCS, or, that this patient has underlying neurophysiological patterns that respond to tDCS and not tPCS. In conclusion, we here show that the effects of tDCS and tPCS induced distinct neurophysiological and clinical effects. Based on this experiment, anodal tDCS is confirmed as a promising tool to improve behavioural responsiveness of patients with DOC. On the other hand, active tPCS should be studied more to explore its effect on these patients and their level of consciousness. EEG and behavioural markers of responsiveness should be explored in large sample clinical trials.

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Acknowledgements

The study was further supported by: The University Hospital of Liege, the Belgian National Funds for Scientific Research (FRS-FNRS), the Human Brain Project (EU-H2020-fetflagshiphbpsga1-ga720270),the Luminous project (EU-H2020-fetopenga686764),the Center-TBI project (FP7-HEALTH- 602150),the Public Utility Foundation ‘Université Européenne du Travail’,“Fondazione Europea di Ricerca Biomedica”, the Bial Foundation, the European Space Agency, the Mind Science Foundation and the European Commission.

References

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Keywords: Transcranial Direct Current Simulation, Transcranial pulsed current stimulation, disorders of consciousness, Minimally Conscious State, power spectral density

Conference: Belgian Brain Congress 2018 — Belgian Brain Council, LIEGE, Belgium, 19 Oct - 19 Oct, 2018.

Presentation Type: e-posters

Topic: NOVEL STRATEGIES FOR NEUROLOGICAL AND MENTAL DISORDERS: SCIENTIFIC BASIS AND VALUE FOR PATIENT-CENTERED CARE

Citation: Mortaheb S, Barra A, Carrière M, Binda Fossati ML, Martens G, Bodien Y, Morales-Quezada JL, Fregni F, Giacino J, Laureys S and Thibaut A (2019). Neurophysiological effects and behavioral outcomes after tDCS and tPCS in patients with disorders of consciousness: a case study. Front. Neurosci. Conference Abstract: Belgian Brain Congress 2018 — Belgian Brain Council. doi: 10.3389/conf.fnins.2018.95.00059

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Received: 22 Aug 2018; Published Online: 17 Jan 2019.

* Correspondence:
Mr. Sepehr Mortaheb, Coma Science Group, GIGA Consciousness-GIGA Research, University of Liege, Liege, Belgium, s.mortaheb@uliege.be
Dr. Aurore Thibaut, Coma Science Group, GIGA Consciousness-GIGA Research, University of Liege, Liege, Belgium, athibaut@ulg.ac.be