Y Intensive Course in TMS P October 2016 O C T Translational value of TMS studies O in healthy subjects N into clinical populations O D E Shirley Fecteau S A Canada Research Chair in Cognitive Neuroplasticity E Associate Professor, Medical School, Université Laval sfecteau@bidmc.harvard.edu L P
Y Transcranial Magnetic Stimulation (TMS) and P transcranial Electric Current Stimulation (tES) over O the dorsolateral prefrontal cortex (DLPFC) can modulate behaviors in healthy subjects. C T O N O Impair Improve D ( virtual lesion ) ( neuroenhancement ) E S A E Can this be relevant Can this be a concern L P for my patients? for my patients?
Y Plan P O 1. Noninvasive brain stimulation (NIBS) can modulate human C behaviours (e.g., decision-making) in healthy subjects. T O N 2. Translational clinical relevance of this: proof-of-concept O evidence supporting that NIBS might be a valuable adjunct in D the treatment of substance use disorders. E S A 3. NIBS can modulate other human behaviours (e.g., motor E learning, language): potential translational clinical relevance? L P
Y TMS and tES over the DLPFC can modulate a vast variety of behaviours in healthy subjects: P O C - Risk-taking - Attention Mevorach et al. 2010 J Neurosci Knoch et al. 2006 J Neurosci, Science T Fecteau et al. 2007a J Neurosci O - Impulsivity - Self-control N Beeli et al. 2008a, b Behav Brain Funct Knoch et al. 2009 PNAS Cho et al., 2010 Brain Stimul Figner et al. 2010 Nat Neurosci O Hsu et al. 2011 Neuroimage D - Emotional processing - Planning D � Alfonso et al. 2000 Neurosci Lett Dockery et al. 2009 J Cogn Neurosci E Harmer et al. 2001 Nat Neurosci van Honk et al. 2002 Biol Psychiatry S van Rijn et al. 2005 Eur J Neurosci - Reward seeking A Fecteau et al. 2007b J Neurosci E L They are all involved in decision-making skills. P
Decision-making appears to rely upon a distributed bi-hemispheric network Y including the DLPFC, the orbitofrontal cortex, the anterior cingulated cortex, P and the insula. O C Patients with PFC lesion Neuroimaging studies in healthy subjects T O N O D E One role of the DLPFC is to integrate cognitive and emotionally relevant S information during decision-making. A E Cognitive, Reflective, Emotional, Reflexive, L Deliberative System Automatic System P inhibitory control / executive functions reward processing / motivation Damasio et al. 1996; Bechara 2005; Ernst & Paulus 2005; Sanfey et al. 2003 ; Evans 2008
Y P Examples of how TMS or tES when applied over the DLPFC can O modulate decision-making processes in healthy subjects. C T O N O D E S A E L P
1 Hz rTMS over the right (R) DLPFC can increase risk taking at the Risk Task Y in healthy subjects. P O C T O N O The Risk Task � D E S A E L P Knoch, Gianotti, Pascual-Leone, Treyer, Regard, Hohmann, Brugger (2006) Journal of Neuroscience
Can we decrease risk taking at the Risk Task in healthy subjects? Y P O C T O N The Risk Task O D 1Hz rTMS over anodal tDCS over the the R DLPFC R DLPFC E S A E L increased risk-taking decrease risk-taking ? P
tDCS (anodal over the R DLPFC coupled with cathodal over the left (L) Y DLPFC) can decrease risk taking and reward seeking at the Risk Task in P healthy subjects. O C T O N O The Risk Task � D E S A E L P Fecteau, Knoch, Fregni, Sultani, Boggio, Pascual-Leone (2007a) Journal of Neuroscience
tDCS over the DLFPC can decrease risk taking at the BART task in healthy Y subjects. P O C T O N O D E bilateral R DLPFC S bilateral L DLPFC unilateral L DLPFC unilateral R DLPFC A sham E L P Fecteau, Pascual-Leone, Zald, Liguori, Theoret, Boggio, Fregni (2007b) Journal of Neuroscience
cTBS over the R DLPFC can suppress impulsivity at the Delayed Discounting Y Task in healthy subjects. P O Would you prefer to receive: C $20 now $26 tomorrow T O N O D E S A E L P Cho, Pellecchia, Ko, Ray, Obeso, Houle, Strafella (2012) Brain Stimulation
tACS targeting prefrontal theta activity can suppress impulsivity at the Delayed Y Discounting Task and augment theta oscillatory activity in healthy subjects. P Would you prefer to receive: O $20 now $26 tomorrow C T O N O D Mean theta power for electrode locations DDT E P4 P3 S A E L P Dickler, Wensing, Joyal, Thiffault, Timofeev, Fecteau ( SOBP meeting , 2015; submitted article)
1 Hz rTMS over the R DLPFC can modulate self-interest at the Ultimatum Y Game in healthy subjects. P The Ultimatum Game O The proposer has $10 and offers you $2 C If you accept : If you reject : The proposer gets $0 and you get $0 The proposer gets $8 and you get $2 T O 1Hz rTMS over the R DLPFC N Elicited activity in both DLPFCs when contrasting Accepted more often unfair offers O unfair > fair offers D E S A E L P Knoch et al. (2006) Science Baumgartner et al. (2011) Nature Neuroscience
Y P Why is this relevant for patients? O C T O N O D E S A E L P
Rational of using NIBS in substance use disorders to reduce craving and Y consumption. P O - Risky decision-making: a characteristic Integration of relevant information C behavioural phenotype of substance use disorders. T O Reflective System N inhibitory control - Craving: powerful driving force balancing Reflexive System decisions toward maladaptive choices. reward processing O D E - Craving levels positively correlate with activations in the DLPFC. S A E L P Goldstein & Volkow (2002) American Journal of Psychiatry Epstein, Bang, Botvin (2007) Addictive Behaviors Wilson, Sayette, Fiez (2004) Nature Neuroscience
Patients with substance use disorders take greater risk at the Risk Task. Y P O C T O N O D E S A E L P Rogers, Everitt, Baldacchino, Blackshaw, Swainson, Wynne, Baker, Hunter, Carthy, Booker, London, Deakin, Sahakian, Robbins (1999) Neuropsychopharmacology
Patients with tobacco use disorders take greater risk at the BART. Y P O C T O N O D E S A E L P Lejuez, Aklin, Jones, Richards, Strong, Kahler, Read (2003) Experimental and Clinical Psychopharmacology
Patients with tobacco use disorders are more impulsive at the Delayed Y Discounting Task. P O Would you prefer to receive: C $20 now $26 tomorrow T O Smokers choose more often the smaller, immediate offer of money. N O D E S A E L P Mitchell & Wilson (2012) Psychopharmacology
Patients with tobacco use disorders display greater self-interest at the Y Ultimatum Game when the reward is relevant . P O C The proposer has $10 and offers you $2 T Ultimatum Game If you accept : If you reject : O The proposer gets $8 and you get $2 The proposer gets $0 and you get $0 N Smokers (and nonsmokers) reject most of the time unfair offers of money. O D E S The proposer has 10 cigarettes and offers you 2 cigarettes A Ultimatum Game If you reject : If you accept : E The proposer gets 0 and you get 0 cigarette The proposer gets 8 and you get 2 cigarettes L P Smokers accept most of the time unfair offers of cigarette. Takahashi (2007) NeuroEndocrinology Letters
Y P O NIBS over the DLPFC of healthy subjects can modulate decision-making behaviours. C T O N Impaired decision making processes seem to be linked to increased vulnerability for substance use disorders (behavioural phenotype). O D E S What happens when we apply NIBS over the DLPFC of individuals with A E substance use disorders? L P
Proof-of concept data supporting that tDCS can reduce craving for: Y - Nicotine P O - Alcohol C - Food T - Marijuana O - Psychostimulant N O D E S A E L P Jansen, Daams, Koeter, Veltman, van den Brink, Goudriaan (2013) Neuroscience and Biobehavioral Reviews
NIBS in patients with tobacco use disorders. Craving Use Y P 1 x 20Hz L DLPFC (Johann et al. 2003) O 1 x 20Hz L DLPFC (Eichhammer et al. 2003) C 10 x 10Hz L DLPFC (Amiaz et al. 2009) T 1 x 1Hz L SFG (Rose et al. 2011) rTMS O 1 x 10Hz SFG (Rose et al. 2011) N 1 x 10Hz L DLPFC (Li et al. 2013) 1 x 10Hz L DLPFC (Pripfl et al. 2013) O = 4 x 1Hz L DLPFC (Hayashi et al. 2013) D 13 x HF lateral PFC (Dinur-Klein et al. 2014) E = 10 x 1Hz R DLPFC (Trojak et al. 2015) S 1 x 2mA R/L DLPFC (Fregni et al. 2008) A E 5 x 2mA R/L DLPFC (Boggio et al. 2009) tDCS L 5 x 2mA R/L DLPFC (Fecteau et al. 2014) P = 1 x 2mA L DLPFC/ R supraorbital area (Xu et al. 2013) 1 x 1mA occipital / FPT (Meng et al. 2014) 1 x 1mA L DLPFC/ R supraorbital area (Faclone et al. 2015)
tDCS over the DLPFC suppressed craving in nicotine smokers. Y P This was a 3-arm, crossover, sham controlled, blind at 3 levels (subjects, tDCS provider, outcome assessors) study with smokers who do not wish to quit smoking receiving 3 single tDCS sessions. O C 7 Sham L DLPFC T Smoking craving (VAS) * � R DLPFC O 6 * � N 5 O D 4 E S post-tDCS pre-tDCS pre-tDCS post-tDCS pre-cue exposure post-cue exposure pre-cue exposure post-cue exposure A E L P Visual analog scale (VAS) VAS VAS VAS Fregni, Liguori, Fecteau, Nitsche, Pascual-Leone, Boggio (2008) J Clin Psychiatry
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