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Where Neuromodulation and Neuropsychology Meet: Promoting Plasticity for Brain Health Sarah H

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Where Neuromodulation and Neuropsychology Meet: Promoting Plasticity for Brain Health Sarah H Where Neuromodulation and Neuropsychology Meet: Promoting Plasticity for Brain Health Sarah H. Lisanby, MD Director, NIMH Translational Research Division Chief, Noninvasive Neuromodulation Unit, NIMH Intramural Research Program Co-Lead, Team B, NIH BRAIN Initiative THE BRAIN INITIATIVE® All Rights Reserved, Duke Medicine 2007 Disclosures • Patent on TMS technology, licensed to university, no royalties • Unlabeled/unapproved uses of drugs or products in this presentation – Transcranial magnetic stimulation (TMS) – Transcranial direct current stimulation (tDCS) – Magnetic Seizure Therapy (MST) All Rights Reserved, Duke Medicine 2007 Take Home Points • Neuromodulation and Neuropsychology can interact by – Testing causal hypotheses about neural origins of cognitive/affective processes in health and disease – Discovering mechanisms of action of cognitive/ behavioral interventions – Developing paired interventions targeted to specific domains of function All Rights Reserved, Duke Medicine 2007 Neuromodulation TMS Plasticity Paired Intervention Outline • Neuromodulation in Brain Health • Transcranial Magnetic Stimulation (TMS) • Brain Plasticity – How to measure it – How to modulate it • Pairing Neuromodulation with Cognitive Interventions All Rights Reserved, Duke Medicine 2007 Neuromodulation Neuromodulation ECT Electroconvulsive Therapy All Rights Reserved, Duke Medicine 2007 Transcranial Magnetic Magnetic Seizure Stimulation Therapy TMS MST Magnetic Electrical TDCS/TACS ECT Transcranial Direct or Electroconvulsive Alternating Current Therapy Optical, RF and Watch This Space THz Stimulation – Low Level Other Light, Near LIFUS InfraRed, Low Intensity Focused Millimeter UltraSound waves, TeraHz Neuromodulation Neuromodulation Promoting Brain Health Correlation Causation TreatmentCure All Rights Reserved, Duke Medicine 2007 Neuromodulation Neuromodulation Promoting Brain Health • Complementary to Neuropharm and Psychosocial Interventions • 3rd pillar of modern mental health practice • Promise to turn knowledge of circuitry into therapeutic targets Pharmacology Pharmacology Psychosocial Int. Psychosocial Int. Neuromodulation All Rights Reserved, Duke Medicine 2007 Neuromodulation Neuromodulation Promoting Brain Health • Complementary to Neuropharm and Psychosocial Interventions • 3rd pillar of modern mental health practice • Promise to turn knowledge of circuitry into therapeutic targets TMS All Rights Reserved, Duke Medicine 2007 Neuromodulation TMS Plasticity Paired Intervention Outline • Neuromodulation in Brain Health • Transcranial Magnetic Stimulation (TMS) • Brain Plasticity – How to measure it – How to modulate it • Pairing Neuromodulation with Cognitive Interventions All Rights Reserved, Duke Medicine 2007 TMS Transcranial Magnetic Stimulation (TMS) • Noninvasive – Uses magnetic fields – No anesthesia or seizure • Neuromodulation – Stimulates circuits • Neuroscience tool – Test brain-behavior relationships • Treatment tool – FDA cleared for depression All Rights Reserved, Duke Medicine 2007 TMS From RomeECT to to Focal Sheffield Neuromodulation ECT circa 1938 TMS today All Rights Reserved, Duke Medicine 2007 TMS From Rome to Sheffield by way of Montreal • Direct electrical stimulation of the cortex under local anesthesia • Discovery of the mapping of cortical areas - homonculus • Advance in surgical treatment of epilepsy by localizing seizure focus • Breakthrough, but invasive Wilder Penfield 1891 - 1976 All Rights Reserved, Duke Medicine 2007 TMS From Rome to Sheffield by way of Edinburgh • Relationship between electricity and magnetism • Electro-magnetic induction Wilder Penfield 1891 - 1976 James Maxwell 1831-1879 All Rights Reserved, Duke Medicine 2007 TMS From Rome to Sheffield Wilder Penfield 1891 - 1976 James Maxwell Anthony Barker 1831-1879 Circa 1985 All Rights Reserved, Duke Medicine 2007 TMS From Sheffield to a TMS Clinic near you All Rights Reserved, Duke Medicine 2007 Neuromodulation TMS Plasticity Paired Intervention Outline • Neuromodulation in Brain Health • Transcranial Magnetic Stimulation (TMS) • Brain Plasticity – How to measure it – How to modulate it • Pairing Neuromodulation with Cognitive Interventions All Rights Reserved, Duke Medicine 2007 Plasticity TMS and Plasticity • Measuring plasticity – Pre/post intervention • To inform mechanisms of action – Differences between patient groups and healthy volunteers • To inform pathophysiology of disease • Modulating plasticity – Therapeutic potential as monotherapy, and – Paired with cognitive/beh intervention to achieve synergistic effects All Rights Reserved, Duke Medicine 2007 Plasticity All Rights Reserved, Duke Medicine 2007 Motor Training AllPlasticity Rights Reserved, Duke Medicine 2007 TMS Measures Plasticity induced by Plasticity Motor Skill Learning “Play it again, Sam” Pascual-Leone 1995 Casablanca • Expansion of motor map following manual practice – evidence of neuroplasticity All Rights Reserved, Duke Medicine 2007 Hand-Arm Bimanual Intensive Therapy: HABIT AllPlasticity Rights Reserved, Duke Medicine 2007 TMS Measures Motor Map Expansion with Plasticity Hand-Arm Bimanual Intensive Therapy in CP Friel et al. Neurorehabil Neural Repair 2016 All Rights Reserved, Duke Medicine 2007 Paired Associative Stimulation (PAS) EMG: Motor Evoked EMG: Motor Evoked Potential (MEP) Potential (MEP) Synaptic coincidence: Hebbian plasticity S1 M S2 AllPlasticity Rights Reserved, Duke Medicine 2007 Stefan et al. 2000; Ridding et al. 2001 TMS Measures Plasticity Deficit in Plasticity Schizophrenia & Depression • Deficient PAS enhancement Schizophrenia Depression Frantseva et al Cerebral Cortex 2008 Player et al. Neuropsychopharm 2013 All Rights Reserved, Duke Medicine 2007 5 Hz rTMS to motor cortex EMG: Motor Evoked EMG: Motor Evoked Potential (MEP) Potential (MEP) EEG: TMS-Evoked EEG: TMS-Evoked Potentials (TMS-EP) Potentials (TMS-EP) Homo-synaptic plasticity Plasticity Plasticity Repetitive TMS (rTMS) Induces Plasticity Esser et al., Brain Res Bul 2006;69:86-94 All Rights Reserved, Duke Medicine 2007 Plasticity Therapeutic Value of rTMS-Induced Plasticity Neuronetics Brainsway Magstim Magventure Neurosoft 2008 2013 2015 2015 2016 • FDA Cleared for Depression • Evidence in off-label conditions – Level A evidence (Definite effect) for neuropathic pain – Level B evidence (Probable effect) for negative symptoms schizophrenia – Level C evidence (Possible effect) PTSD, auditory hallucinations, cigarette craving and consumption Lefaucheur et al. Clinical Neurophysiology 2014 George, Lisanby, Avery, McDonald et al. Arch Gen Psychiatry. 2010 All Rights Reserved, Duke Medicine 2007 Neuromodulation TMS Plasticity Paired Intervention Outline • Neuromodulation in Brain Health • Transcranial Magnetic Stimulation (TMS) • Brain Plasticity – How to measure it – How to modulate it • Pairing Neuromodulation with Cognitive Interventions All Rights Reserved, Duke Medicine 2007 Paired Intervention Rationale for Paired Intervention • TMS effects are state dependent – Muscle tone Resting Facilitated All Rights Reserved, Duke Medicine 2007 Paired Intervention Rationale for Paired Intervention • TMS effects are state dependent – Muscle tone – Eyes open/closed Eyes Open Eyes Closed Chen and Huang. NeuroReport 2018 All Rights Reserved, Duke Medicine 2007 Paired Intervention Rationale for Paired Intervention • TMS effects are state dependent – Muscle tone – Eyes open/closed – Sleep/wake TMS-Evoked Potential Massimini et al. Cogn Neurosci 2011 All Rights Reserved, Duke Medicine 2007 Paired Intervention Rationale for Paired Intervention • TMS effects are state dependent – Muscle tone – Eyes open/closed – Sleep/wake Massimini et al. Cogn Neurosci 2011 All Rights Reserved, Duke Medicine 2007 Paired Intervention Rationale for Paired Intervention • TMS effects are state dependent – Muscle tone – Eyes open/closed – Sleep/wake – Attention All Rights Reserved, Duke Medicine 2007 Paired Intervention Rationale for Paired Intervention • TMS effects are state dependent Motor Imagery (MI) • Brain state can be controlled by Instruction: – Instruction “stop contracting your thumb and just imagine the feel and sensation of the contraction” Chong & Stinear J Neurophysiol 2017 All Rights Reserved, Duke Medicine 2007 Paired Intervention Rationale for Paired Intervention • TMS effects are state dependent • Brain state can be controlled by – Instruction – Stimulation • Paired Pulse (ppTMS) Intracortical facilitation (ICF) Intracortical inhibition (ICI) All Rights Reserved, Duke Medicine 2007 Paired Intervention Rationale for Paired Intervention • TMS effects are state dependent • Brain state can be controlled by – Instruction – Stimulation • Paired Pulse (ppTMS) Inter-hemispheric inhibition All Rights Reserved, Duke Medicine 2007 Paired Intervention Rationale for Paired Intervention • TMS effects are state dependent • Brain state can be controlled by – Instruction – Stimulation • Paired Pulse (ppTMS) • Paired Associative Stimulation (PAS) Synaptic coincidence: Hebbian plasticity S1 M S2 All Rights Reserved, Duke Medicine 2007 Paired Intervention Rationale for Paired Intervention • TMS effects are state dependent • Brain state can be controlled by – Instruction – Stimulation • Paired Pulse (ppTMS) • Paired Associative Stimulation (PAS) • 2-Coil Paired Associative Stimulation (PAS) Fronto-Parietal Parieto-Frontal AllCasula Rights Reserved, Dukeet Medicine al. 2007NeuroImage 2016;143:204 Spike-Time Dependent Plasticity in Paired Intervention Prefrontal Cortex Pre Fronto-Parietal Dif Parieto-Frontal Post Global
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