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Brain Stimulation & Neuromodulation September 2016 - BH Summit


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Brain Stimulation & Neuromodulation September 2016 - BH Summit

  1. 1. Brain Stimulation & Neuromodulation Jay A. Yeomans, MD, DFAPA Medical Director of Psychiatry Consult Liaison and Brain Stimulation Service Carolinas HealthCare System September 27th, 2016 First Annual CHS BH Summit
  2. 2. • No disclosures • Acknowledgements Dr. Mark George, et al. at MUSC • Objectives: • The participant will: • Be aware of the underlying premise of neuromodulation. • Be aware of the Neuropsychiatric indications for Brain Stimulation. • Be aware of the FDA approved classifications and non-FDA approved brain stimulation devices.
  3. 3. The Burden of Depression • Approximately 18.8 million adults aged 18 and older are stricken with depression in an given year (NIMH) • Suicides eclipse homicides in the US annually by one third (DHHS). The elderly are particularly at risk • Medications and psychotherapy may fail to alleviate severe depressions, particularly those complicated by psychosis or catatonia • Antidepressants may increase suicidality in some patients and may not be safely used during pregnancy.
  4. 4. Why Brain Stimulation for Depression? • limits of current treatment strategies NIMH STAR*D study: Sequenced treatment alternatives to relieve depression (screened > 4K pts) Focus on treatment of depressed patients when the 1st prescribed antidepressant proved inadequate & included remission as an outcome measure  4 levels (SSRI / antidepressant & CBT / Li or T3 & antidepressant / MAOI or combo antidepressant) • Level one: 1/3 remitted, then 1/3 with 2nd, 13% with 3rd and 13% with 4th  Data suggest that a patient with persistent depression can get well after trying several treatment strategies, but his or her odds of beating depression diminish as additional treatment strategies are needed 12 months later: 25% sustained remission w/level 1; 13% (L2), 4 % (L3) and 3% (L4)
  5. 5. Why Brain Stimulation for Depression? • Medication under treatment, e.g. ‘pseudoresistance’ – have not received sufficient guideline-concordant treatment • Side Effects from medication (non discriminate): e.g. weight gain, fatigue, etc. • Psychotherapy (patient resistance / limited INS coverage)
  6. 6. Important Points • Underlying premise of neuromodulation is that the brain is an electrochemical organ that can be modulated by pharmacotherapy or devise-based (ECT / TMS) approaches or their combination • There is an explosion of new techniques for electrically stimulating the brain, primarily focally • These new tools are changing neuroscience research and neuropsychiatric therapies • They validate and inform us about functional neuroanatomy
  7. 7. Figure 3.12. This is an example of the electro-chemical signaling from a dopamine neuron. If this were an inhibitory neuron, GABAor g lycine for example, the postsynaptic potential would be an IPSP and not an EPSP.The Brain is an Electrochemical Organ Electricity is the Currency of the Brain All of synaptic pharmacology simply serves to transmit electrical signals to the next neuron
  8. 8. Brain Stimulation Techniques (partial listing) • ECT - Electroconvulsive Therapy - Alternating current, directionless • Ultra brief pulse • (FEAST (Focal Electrically Administered Seizure Therapy) - Cycle it, turning it on and off rapidly and make sure all pulses are rectified, causing a direct current-like direction - Extremely fast tDCS. • TMS - Transcranial Magnetic Stimulation • VNS - Vagus Nerve Stimulation • DBS - Deep Brain Stimulation FDA Approved
  9. 9. Brain Stimulation Techniques (partial listing) • tACS – transcranial Alternating Current Stimulation Cranial Electrotherapy Stimulators (CES) • tDCS - transcranial Direct Current Stimulation • MST - Magnetic Seizure Therapy - Super TMS – limited to cortex for site of seizure • LFMS- Low field magnetic stimulation • TENS - transcutaneous Electrical Nerve Stimulation • Transcranial pulsed ultrasound • eTNS (external trigeminal nerve stimulation) FDA Classi- fication
  10. 10. When it First Started, Things Were Rough
  11. 11. History of ECT • 16th century, camphor by mouth to induce convulsions to ‘cure lunacy’ • 1934: Meduna, Hungarian Neuropsychiatrist, believed Schizophrenia and Epilepsy were antagonistic disorders - epileptics have many glial cells, Schizophrenia have too few - ergot, causing seizures might stop or cure schizophrenia (sic) • Injected patients w/Schizophrenia with camphor oil to cause a seizure, Patient had a 60 sec grand mal seizure, ‘woke up’.. Full recovery, left hospital … • Later replaced camphor with metrazol … spread throughout Europe. • 1937: AmJPsych: ‘therapeutic seizure’ (worldwide) (Drawing by Renato Sabattini, PhD)
  12. 12. What about ‘Electrical’ CT? • 1938 -Italian psychiatrists, working in Rome, Cerletti and Bini, worked on electrical parameters that could induce seizures. Dog model • treated Italian man, ? Psychotic depression - recovered after 11 treatments Nominated for the Nobel Prize ECT was born… • Kalinowsky started ECT at NY State Psychiatric Hospital/ Columbia Presbyterian Hospital in NY 1940’s – Widespread use throughout the world … RUL 1950’s – Modifications in ECT technique initially curare then (‘52 – Holmberg) used succinylcholine as a muscle relaxant with ECT Standard treatment for hospitalized depression
  13. 13. History of ECT • 1960’s – 1980s … Decline in use of ECT • Psychoanalyst marginalized ECT • Pharmaceutical industry marginalized ECT • 1960s counterculture hostility toward ECT • 1961: Erving Goffman’s Asylums • 1962: Ken Kesey’s anti-psychiatry novel / play (‘70) / movie (‘75): One Flew Over the Cuckoo’s Nest
  14. 14. 1980’s: Resurgence in the use of ECT 1985: JAMA “not a single controlled study has shown another form of treatment to be superior to ECT in the short-term management of severe depression” How does ECT (therapeutic seizures) modify mood? • A) Brain Structure … o hippocampal neurogenesis • B) Neurotransmitter Enhancement … o after Seizure - flood of Catecholamines: 5HT, NE DA, GABA & BDNF • C) Normalization of Neuro-Endocrine Abnormalities … o Surge of Hypothalamic & Pituitary peptide (prolactin & TRH) o Hypercortisolemia frequently found in Melancholia - Cortisol function normalizes; TSH & GH responses are abnormal during illness and normalize with remission
  15. 15. How does ECT (therapeutic seizures) modify mood? D) Electrophysiology … Anticonvulsant effects (kindling) Analogous to Cardioversion: heart in a dysrhythmic state is restored to normal rhythm by an electrical stimulus Cerebroversion: hyperactive hypothalamic-pituitary system (leads to a breakdown of the feedback mechanism in the stress response) is normalized after a therapeutic seizure. •
  16. 16. How does ECT (therapeutic seizures) modify mood? Ctrl-Alt-Delete ----------------------------- Downsides Headache Nausea Myalgia Retrograde / anterograde amnesia Mini Mental State Exam / Montgomery Depression Rating Scale
  17. 17. BITEMPORAL (BT), RIGHT UNILATERAL (RU), and BIFRONTAL (BF) POSITIONS Letemendia et al., 1993
  18. 18. Electroconvulsive Therapy ECT • Guideline recommendations – Acute Treatment of Depression, especially psychotic or suicidal – Acute Mania – Catatonia – Helpful in treatment refractory conditions (e.g. treatment for intractable seizures) – Need for rapid definitive intervention – Medically ill, risk of inanition – Elderly – Pregnancy (teratogenicity a function of exposure duration / succinylcholine: low ratio of placental transfer) • New findings / where the field is going? – Right unilateral, ultra brief pulse – Perhaps FEAST, MST
  19. 19. Acute & Maintenance ECT
  20. 20. ECT Summary • ECT is a safe & very effective treatment for depressive disorders either first-line treatment or after medications fail.* • Between 80% and 90% of patients will respond to ECT. It is the most efficient and fast-acting treatment for urgent-care, severely depressed patients for which medications take 4-6 weeks to work.* • Treatment of choice for Catatonia, Failure-to thrive, Psychotic & Suicidal depression. *APA Taskforce book, The Practice of Electroconvulsive Therapy, 2001
  21. 21. Functional neuroimaging studies suggest a role of cortical governance over limbic activity Transcranial Magnetic Stimulation for Depression Holy Grail Focal Noninvasive Nonconvulsive stimulate the prefrontal cortex to lance depression
  22. 22. Brain Connectivity This area is involved in depression TMS • Takes advantage of the natural brain circuitry • Dorsolateral prefrontal cortex: DLPFC – (lateral aspect of the middle frontal gyrus) • Interconnected with limbic structures that play a role in mood modulation & depression • Effect neural activity at the site of stimulation as well as distal regions that are interconnected with the DLPFC – implicated in mood, motivation and arousal
  23. 23. TMS HISTORY • 1831 - *Michael Faraday - principle of electromagnetic induction • 1896 - D’Arsonval - first TMS • 1903 - patent: Pollacsek and Beer • 1910 - Sylvanius P. Thompson: 3 papers on TMS and phosphenes • 1959 - Kolin demonstrated magnetic fields stimulate frog muscle • 1985 - Barker, modern TMS • 1993 - First therapeutic cases reported in depression
  24. 24. Early TMS Sylvanius P.Thompson with one of the first transcranial magnetic stimulators (1910) Thompson SP. A physiological effect of an alternating magnetic field. Proc R Soc Lond B Biol Sci. 1910;82:396- 398.
  25. 25. Applications of TMS • Investigative Tool – (sTMS) Mapping the cortex of the brain – Probing neural networks by stimulation or inhibition at different places and times – Measuring cortical excitability in health and disease, and response to drugs – Modulating brain function to study the pathophysiology of a variety of neuropsychiatric conditions • Treatment Tool – Neuropsychiatric conditions; depression, pain, substance craving, anxiety (OCD), Tourette’s Disorder, etc. – Alter physiologic states like reversing sleep deprivation
  26. 26. Faraday’s law A time-varying current (di/dt) in a wire loop will induce a magnetic field Electricity and magnetic energy are interchangeable current flowing through a coil produces a magnetic field proportional to the current (& perpendicular to the current)
  27. 27. 35 How TMS works • Electrical current flowing through a coil induces a magnetic field • Pass a current through a hand held coil, whose shape determines the properties and the size of the field • The coil is driven by a machine - switches the large current necessary in a very precise / controlled way • The coil is held on the scalp and the magnetic field (2 Tesla) passes through the skull (unimpeded) and into the brain • Alternating (pulsating) magnetic fields induce electrical current in underlying brain tissue • Small induced currents influence the brain areas below
  28. 28. How TMS Works George MS. Sci Am. 2003;289:66-73.
  29. 29. Output: Motor Evoked Potential Single Pulse TMS is an Investigational Tool
  30. 30. homunculus
  31. 31. TMS Intensity Motor Threshold (MT) • Stimulate the motor cortex (gyrus) which is oriented 45 degrees backwards – axon lies on the gyrus • Evoked muscle twitch threshold in response to motor cortex stimulation. • Defined as lowest intensity capable of inducing at least 5 out of 10 MEPs (of ≥ 50 v in thumb muscle). • Or, approximately, lowest intensity capable of making thumb muscle visibly twitch 5 0f 10 times • Best available index of how sensitive an individual's cortex is to having a seizure with rTMS.
  32. 32. Prefrontal Positioning F3 and other rules for positioning Borckardt, in blue Anderson, in red MUSC Locate F3? EEG Beam F3 Brain net
  33. 33. Factors that influence the effects of TMS: Length/Distance Frequency Shape of the coil Intensity (Cognitive) Engagement • Depth of penetration ~2 cm, at junction between grey and white matter • Cannot stimulate medial or sub- cortical areas
  35. 35. Frequency High vs. Low Frequency rTMS • Low frequency rTMS = stimulation rates  1 Hz • High frequency rTMS = stimulation rates  1 Hz •In the motor cortex high frequency rTMS (5-20 Hz) may temporarily increase excitability while low frequency rTMS may temporarily decrease excitability. *(TBS) Theta burst suppression 3 burst of pulses given at 50Hz & repeated every 200ms Depression Treatment in 6 minutes
  36. 36. Stimulate 1.5 cm Stimulate 3 cm Non focal
  37. 37. Transcranial Magnetic Stimulation Neuronetics (2008): 10 Hz for 37.5 min Brainsway (2013): 18 Hz for 20 min (deep / helmet / H coil) MagVenture (2015): 35-37 min (theta burst: 5 Hz for 6 min) Magstim (2015) 4 devices FDA Approved
  38. 38. Transcranial Magnetic Stimulation (TMS)
  39. 39. Overview of TMS 1) Electrical energy in insulated coil on the scalp induces 2) Pulsed magnetic field of about 1.5 Tesla in strength 3) Passes unimpeded through the cranium for 2-3 cm 4) In turn induces a focal electrical current in the brain 5) Get desired local and distal effects on the target neural circuitry 6) Delivered as single pulses or repeated trains (rTMS)
  40. 40. Migraine w/aura sTMS – occipital Other TMS Applications? (April 2016) Pain acute/chronic: standard LPFC daily several weeks or motor cortex Fibromyalgia very positive results (Short, et al 2014) Stroke recovery usually subacute (after 2-3 mo): either high frequency ipsilateral or low frequency contralateral, combined w/rehab Addictions ability to decrease cue-induced craving in the lab / open label potential clinical reduction in 1-2/52 (Brainsway) OCD RDLPFC / R orbitofrontal low frequency *acute ?sustained (Brainsway) P
  41. 41. Other TMS Applications (April 2016) Schizophrenia inhibitory stimulus over auditory cortex : decreased auditory hallucinations / negative sxs Development Disorders / Autism Epilepsy patient w/cortical focus / inhibitory TMS can reduce szs Tinnitus TMS over auditory cortex or prefrontal cortex (VNS) Depression (LDLPFC) pregnancy / BPD with mood component Dementia Aging/Cognitive Enhancement Epilepsy (Treatment Assessment Vulnerability?)
  42. 42. tACS Transcranial Alternating Current Stimulation Cranial Electrotherapy Stimulation (CES) ‘Electroceuticals’ • April 2016- FDA reclassified tACS (CES) into a split classification • Tx of insomnia / anxiety: Class II • Tx of depression: Class III • Fisher Wallace Stimulator: alternate current of 2mA of neurostimulation for 20’ per day • AlphaStim Device
  43. 43. tDCS Transcranial Direct Current Stimulation • ¼ potency of TMS • 1-2 milliampere current (ECT: 200 milliamperes) • floats ‘up & down excitability’ vs TMS which causes depolarization (change resting membrane potential - activated circuit is a better target) • Build up a tolerance (vs. TMS)? • tDCS will lower the seizure threshold • Shows promise during rehab for aphasia / Hopkins U. study on cognition in patients with Schizophrenia. • DOD & Video gamers
  44. 44. tDCS Transcranial Direct Current Stimulation • Consumer tDCS devices Thync – neurosignaling product – ‘vibing’ energy vibe or calm vibe - 5-35 min (intensity/duration) : edream (lucid dreams at 40Hz stim) • Anode (-) (front of head) –cathode (+) (back of head) like neutroceuticals; St. John’s Wort, Prevagen Caveat emptor
  45. 45. PsychotherapyPsychotropicmedicationsBrainStimulationPsy chotherapyPsychotropicmedicationsBrainStimulationPsych otherapyPsychotropicmedicationsBrainStimulationPsychoth erapyPsychotropicmedicationsBrainStimulationPsychothera pyPsychotropicmedicationsBrainStimulationStimulationPsy chotherapyPsychotropicmedicationsBrainStim
  46. 46. questions??? Stay tuned