Effects of sham-controlled double blind transcranial direct current stimulation in patients with disorders of consciousness
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1 Effects of sham-controlled double blind transcranial direct current stimulation in patients with disorders of consciousness THIBAUT Aurore PhD Student Physiotherapist Coma Science Group Cyclotron Research Centre & University & University Hospital of Liège Belgium
2 disorders of consciousness behavioural evaluation electrophysiology neuroimaging methods, ethics & quality of life perspectives AIM of the study Assessing the effect of transcranial direct current stimulation (tdcs) on cognition in patients with disorder of consciousness In a double blind sham controlled randomized study
3 Why direct current stimulation? Stimulation Population Effects Authors Prefrontal cortex Healthy subjects Memory Marshall et al, J Neurosci 2004 Alzheimer s patients Memory Ferrucci et al, Neurology 2008 Stroke patients Attention Jo et al, Am J Phys Med Rehabil 2009 Aphasic patients Language Baker et al, Stroke 2010 Non-invasive Easy to apply Cheap equipment
4 Methods Anode Cathode Direct current 2 ma 20 minutes Randomised double blind sham controlled
5 Methods CRS-R CRS-R CRS-R CRS-R tdcs tdcs h Responder : CRS-R post tdcs Statistics: Stata 10.0 ANOVA Wilcoxon signed-rank test Giacino, Arch Phys Med Rehabil 2004 Stata 10.0 (StataCorp Stata Statistical Software: Release 10. College Station, TX: StataCorp LP) > pre-tdcs > sham > pre-sham
6 Population 55 patients (16 women) 25 VS/UWS, 30 MCS aged 43 ± 18 y 25 traumatic / 30 non-traumatic 20 acute / 35 chronic (>3 months post insult)
7 Group data (n=55) CRS-R total scores N=55 17 responders 2 UWS; acute 15 MCS; 7acute/8chronic PRE POST PRE POST tdcs sham
8 Group data (n=55) CRS-R mean scores 17 responders 2 UWS; acute 15 MCS; 7acute/8chronic PRE POST PRE POST tdcs sham
9 UWS/UV vs MCS MCS (n=30) VS/UWS (n=25) CRS-R mean scores PRE POST PRE POST tdcs tdcs
10 Responders: audition subscale Consistent movment to command Reproducible movment to command Localisation of sounds Auditory sartle None PRE POST PRE POST tdcs sham
11 Responders: motor subscale Functional use of objects Automatic motor reaction Object manipulation Localization of noxious stimulation Flexion withdrawal Abnormal posturing None PRE POST PRE POST tdcs sham
12 Responders: communication Functional communication Intentionnal communication None PRE POST PRE POST tdcs sham
13 tdcs presumed mode of action Short term effects Modification of neuronal excitability (action potential) Long term effects Action on opening of ion channels (Na +, Ca 2+ ) Increase NMDA receptors excitability improve neuron excitability Nitsche et al., J Physiol 2000 Nitsche et al., Neuroscientist 2010
14 Neuroimagery Prefrontal stimulation Improvement of DMN connectivity (MRI) Increase of regional electrical activity in the PF and AC cortexes (EEG) ( ß and δ/θ) Motor stimulation rcbf increase in the left M1, right prefrontal cortex, right S1 (PET-scan) Functional connectivity increased within premotor, motor and sensorimotor areas (EEG) Keeser et al., J Neurosci, 2011 Keeser et al., Neuroimage, Lang et al., Eur J Neurosci, 2005 Polania, Nitsche and Paulus, HBM, 2010
15 disorders of consciousness behavioural evaluation electrophysiology neuroimaging methods, ethics & quality of life perspectives tdcs advantages DBS and Amantadine improve cognitive functions of patients with disorder of consciousess But invasive and pharmacological tdcs improve cognition of patients in minimally conscious state without risk of brain damage or seizure Schiff et al., Nature 2008 Giacino et al., New Eng J Med, 2012 Thibaut et al., in prep
16 tdcs critisisms Limitations: Short term effect Moderate clinical changes Superficial effect Improve electrode position
17 tdcs long term Effects last ± 90 minutes Short improvement Back to initial state Daily stimulations (5days) improvement and extension of benefits Hummel et al., Lancet 2006 Antal et al., J Pain Symptom Manage 2010
18 tdcs long term 1 week 1 week Prospective, randomized, controlled and double-blind study
19 tdcs - M1 Cognitive effects + Motor effects? Parameters: 2 ma 20 min Anode: M1 Cathode: supraorbicular controlateral cortex 1. Behavioral assessments: CRS-R & Ashworth 2. TMS: MEP & motor threshold Lang et al., 2004 Bohannon and Smith, 1987
20 tdcs M1
21 tdcs neurophysiology 1. Comparison of the results with: cortical lesions (MRI) cerebral metabolism (PET-scan) Stimulation of preserved or damaged cortex? 2. EEG brefore and after tdcs Better understanding of neurophysiological effect of tdcs
22 Conclusion tdcs improves cognition in minimally conscious state patients both acute and chronic; traumatic and non traumatic Future studies: 1. long term tdcs 2. tdcs on M1 3. neurophysiological effects
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