r TMS workshop RNCM 3

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  • Hello Everyone My name is JA MF, I am in charge of an hospitalisation unit in the university departement of psychiatry in Marseille And i work both in the rTMS unit and the neurophysiological unit in this university departement of psychiatry Today i d like to speak about rTMS treatment in psychiatry, and the aim today is to examine and to give key to respond to this question : is rTMS an Stimulation or an Interaction device?
  • r TMS workshop RNCM 3

    1. 1. Why rTMS is not effective for some patients with depression ? There are two classical We will focus on two less classical factor of variability factor of variability a c   Clinical Stimulation Neuro-anatomical Neuro-functional variability Parameters variability variability S variability T Age  E  P Motor threshold Treatmentrefractoriness Number of pulse Anatomical … 2 precision on the Step 3 Duration of Frequency EDM left DLPFC Interaction  MRI guided rTMSMicoulaud-Franchi et al., submittedMicoulaud-Franchi and Vion-Dury, 2011
    2. 2. The talk will propose an historical point of view Specifically for the case of Major Depressive Episode, the first major therapeutic goal set for TMS With 3 historical steps FromStep 1 18th Century: Historical Background Electrical Brain “Stimulation” in Psychiatry P L A NStep 2 End of the 20th Century : Validation of rTMS treatment as a focal brain stimulation ToStep 3 21-22th Century: Future Proposition Electrical Brain “Interaction” in Psychiatry
    3. 3. Why stimulate a focal brain region in depression ? Sadness Happiness More happyTMS may affect mood states Less sad ☐ DLPFC Right ☐ DLPFC Right Less happy More sadGeorge et al. 1996, Pascual Leone et al. 1996.  DLPFC Left  DLPFC Left S T E PLeft frontal lobe is involved in the L R L R 2pathogenis of depressionGeorge et al. 1994. Healthy Depressed Martinot et al. 1990
    4. 4. “Hypometabolic brain region is variable in depression!”Left frontal lobe is involved in the L R L Rpathogenesis of depressionBUTPET studies show divergent results.The hemispheric asymmetry in brain metabolismin the prefrontal cortex can favor right or the left Sside. Other studies have found a general T Healthy Depressed Ehypofrontality. PIidaka et al. 1997, Nikolaus et al. 2000. 3 These divergent findings might be due to the phenotypic and pathophysiological heterogeneity of depression  rTMS should probably target specific hypometabolic brain regions to interact with each different phenotypic depressed patients
    5. 5. Why rTMS is not effective for some patient with depression ? There are two classical We will focus on two less factor of variability classical possible variability ac   Clinical Stimulation Neuro-anotomical Neuro-functional variability Parameters variability variability S variability T Age ar i E  P Motor threshold Treatment Targetrefractoriness Number of pulse Anatomical 3 precision on the hypometabolism Duration of Frequency left DLPFC brain region EDM  r MRI guided rTMS PET fMRIMicoulaud-Franchi et al., submitted Guided rTMSMicoulaud-Franchi and Vion-Dury, 2011
    6. 6. Neuro-functional factor of variability  Target definition according to functional activity Brain hypometabolism• PET guided rTMS treatment (PET) R LThe DLPFC with lower metabolic activity wasselected.A neuronavigational system was used to placethe magnetic coil above each individuals’selected cortical region.Results did not support the hypothesis of Sincreased antidepressant effect T EHerwig et al. 2003 PPaillere Martinot et al. 2010 3• fMRI guided rTMS treatment Brain hyperactivityEncouraging results for the (BOLD)treatment of hallucinations.Jardri et al. 2008,Montagne Larmurier et al. 2009
    7. 7. Why stimulate a focal brain region in depression ? Sadness Happiness More happyTMS may affect mood states Less sad ☐ DLPFC Right ☐ DLPFC Right Less happy More sadGeorge et al. 1996, Pascual Leone et al. 1996.  DLPFC Left  DLPFC Left S T E PLeft frontal lobe is inolved in the L R L R 2pathogenis of depressionGeorge et al. 1994. Healthy Depressed Martinot et al. 1990
    8. 8. “Surprising lateralized mood effect in healthy subject!”TMS may affect mood states Sadness Happiness More happy Less sadBUT ☐ DLPFC Right ☐ DLPFC RightThe lateralized effect in healthy subject isopposed to depressed patients…Stimulation to the left side induce Less happy More sad“depression” in healthy subjects! S  DLPFC Left  DLPFC LeftAnd an improvement of depression in T Edepressed patients… PGeorge et al. 1996, Pascual Leone et al. 1996. 3 These TMS studies raise the possibility that stimulation may impact differently healthy subject as compared to depressed patients  The reasons could be specific interactions of rTMS with mood state and specific brain activity
    9. 9. rTMS has a brain network effect Coil position rTMS stimulates a focal region But has an effect on many regions These “network effects” could dependon the connected brain activity context Activation of S of each stimulus connected T E brain areas P This context is determining by : 3 1 - Brain electrophysiological activity 2 – Neuro-Cognitive activity of the subject during stimulation And could influence the therapeutic efficacy of rTMS
    10. 10. Why rTMS is not effiacy for some patient with depression ? There are two classical We will focus on two less factor of variability classical possible variability ac   Clinical Stimulation Neuro-anotomical Neuro-functional variability Parameters variability variability S variability T Age ar i E  P Motor threshold Treatment Target Controlledrefractoriness Number of pulse Anatomical 3 precision on the hypometabolism network Duration of Frequency left DLPFC brain region effect of rTMS EDM  r f PET IRMf Cognitive EEG MRI guided rTMS priming contingent Guided rTMS rTMSMicoulaud-Franchi et al., submitted rTMSMicoulaud-Franchi and Vion-Dury, 2011
    11. 11. Controlling the network effect of rTMS with electrophysiological measurement It is possible to combine EEG recording with rTMSEach pulse of rTMS can be applied in response to a selected pattern of background EEG activity analyzed in real time Price named this rTMS: Najib et al. 2011 EEG contingent rTMS S T or Interactive rTMS E P 3The intention is to stimulate an activated network in the hope that will reinforce the activation It is feasible in an rTMS clinical trial A trend toward a greater clinical effect than the standard rTMS was found Price et al. 2010
    12. 12. Controlling the network effect of rTMS with neurocognitive activity MEP during rTMS amplitude Experimental studies found that specificneurocognitive activity can modify the effect of a TMS pulse on motor cortex  What is the effect of positive and negative guided mood activity (by cognitive emotional procedure) during rTMS Bonnard Let go Resist S stimulation in depression ? et al. T E 2003 P Depression intenstity Isserles et al. found that negative guided Negative 3mood activity in depressed patients during rTMS treatment disrupts the therapeutic Positive Neutre effect Neural networks mediating negative emotions may disrupt the therapeutic Isserles et al. network effect of rTMS 2011
    13. 13. Finger et al. Electrical Brain More Third step : Focal Stimulation in Electrical Brain Interaction psychiatry Electrical Brain Focal Stimulation in psychiatry Electrical Brain Focal/Global Interaction in psychiatry S T E P The stimulation has to be focalized BUT the effect of 3 stimulation interact with the global activity of the brain. Electrical Brain Global Camphor Stimulation in Metrazole psychiatry
    14. 14. The talk has proposed an historical point of view FromStep 1 18th Century: Historical Background Electrical Brain “Stimulation” in Psychiatry ToStep 3 21-22th Century: Future Proposition C O Electrical Brain “Interaction” in Psychiatry N C L Future Electrical Brain Interaction Treatment in Psychiatry will necessitate collaboration between Neuro-computational, Experimental, and Clinical approaches And … an active patient
    15. 15. Brain stimulation:Neuro-computational, Experimental, and Clinical approaches May 31st – June 1st 2012 Thank you for your attention Special thank you to: Dr Agnes Trebuchon Dr Aileen McGonigal Dr Raphaëlle Richieri Pr Christophe Lançon Dr Jean Vion-Dury
    16. 16. 4th Annual Computational Neurosciences Workshop Marseille Brain stimulation:Neuro-computational, Experimental, and Clinical approaches May 31st – June 1st 2012 rTMS Treatment in Psychiatry: Stimulation or Interaction? Jean-Arthur MICOULAUD-FRANCHI M.D. Chef de Clinique - Assistant Ph.D. Student in Neuroscience

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