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Emerging trends in brain stimulation
- 1. Dr. Sujit KumarKar Assistant Professor in Psychiatry King George’s Medical University Lucknow
- 2. Evolution of treatmentof psychiatric disorders Psychotherapy Neuromodulation (ECT) Pharmacotherapy 5/13/2018 2
- 4. 5/13/2018 4 Nature ofstimuli • Direct electrical • Magnetic • Optogenetic • Thermal • Acoustic/Mechanical • Chemical Luan et al., 2014
- 5. 5/13/2018 5 Electrical • Controlledstimuli – Voltage / Current/ Charge • VCS, CCS – can be invasive as well non-invasive • QCS exclusively invasive • Voltage controlled: DBS, Pacemakers • Current controlled: tDCS, Cochlear implant • Charge controlled: Not in clinical use Luan et al., 2014
- 6. Transcranial Alternating CurrentStimulation (tACS) • Sine wave electric field regulating occillatory activity in stimulated brain regions • Similar to tDCS. • Works by depolarizing & hyperpolarizing neurons • Preliminary findings: – Frequency specific stimulation has the potential to improve cognitive performances (eg: theta frequency stimulation of DLPFC improves performance in N- back task) – Usefulness in Auditory Verbal Hallucination 5/13/2018 6 Moseley et al., 2016
- 7. Transcranial Random NoiseStimulation (tRNS) • A variant of tACS, uses constantly changing current • Stimulates at randomly changing frequencies (usually between 0.1 – 640 Hz) • tRNS at higher frequency (>100 Hz) produce more excitability than tDCS • Application on – Motor cortex: Implicit motor learning – Primary visual cortex: Perceptual learning • Higher rate of repetitive tRNS – Temporal summation effect (possibly larger effect than tDCS) 5/13/2018 7 Moseley et al., 2016
- 8. 5/13/2018 8 Magnetic (TMS,μ TMS) • μTMS (Micro TMS) – reduces spatial resolution by an order of magnitude • Limited to research use (in animal studies) • Invasive Luan et al., 2014
- 9. Magnetic Seizure Therapy •100% amplitude • HF (100Hz) • Use in resistant depressive disorder (U / B), Schizophrenia • Depression: RCT (MST Vs R UL ECT); n=37; MST equally efficacious and less cognitive side effects (Fitzgerald et al., 2018) – Remission rate- 30 - 40% (Cretaz et al., 2015) • Systematic review of 8 studies on unipolar & bipolar depression • Schizophrenia: Open-label pilot study (n=8) – Feasible, efficacious with negligible cognitive side effects (Tang et al., 2018) 5/13/2018 9
- 10. 5/13/2018 10 Optogenetic • Neuromodulationmediated through light sensitive proteins (opsins) • Opsins • Channelrhodopsins – Neural stimulation • Halorhodopsins - Neural inhibition • Invasive : Transcutaneous illumination or lasers • Genetic manipulation of the neuronal cell • Safety and ethical concerns Luan et al., 2014
- 11. 5/13/2018 11 Thermal • Neuromodulationmediated through temperature induced trans-membrane capacitance • Process of rapid localized heating alters membrane conductance • Limitation: Thermal damage to the tissue • Optically induced thermal modulation : Use of near infra red laser light • Microwave / RF heating of nanoparticles: RF radiation is absorbed by the magnetic nanoparticles which bind to specific protein targets of neurons Luan et al., 2014
- 12. 5/13/2018 12 Trigeminal NerveStimulation (TNS) • Next to Vagus Nerve Stimulation (VNS) • Bottom up stimulation of - monoaminergic brainstem nuclei, such as the locus ceruleus • Efficacy: TNS = VNS • Superior to VNS @ Minimal autonomic side effects • Use: Depression, Anxiety disorder, Epilepsy, Migraine • Recent evidences: Neuroplasticity @ Hippocampus (acute effect by increasing cellular proliferation; Chronic effect by reducing apoptosis of neurons) Transcutaneous Vagus Nerve Stimulation (tVNS) • Non-invasive bottom –up stimulation through Vagus Nerve • Target: Cutaneous representation of vagus in the external ear • Better than conventional VNS • FDA approval for cluster headache (2017) Mercante et al., 2018 Luan et al., 2014
- 13. 5/13/2018 13 Acoustic (Auricular)stimulation • Next to Vagal / Trigeminal stimulation Mercante et al., 2018 Luan et al., 2014
- 14. 5/13/2018 14 Acoustic (Auricular)stimulation • Stimulation produces effect similar to VNS & TNS • At the MID BRAIN level: Periaqueductal grey matter, the dorsal raphe nucleus, the substantia nigra and the red nucleus were the regions significantly activated by cymba concha stimulation • At the FOREBRAIN level: Primary somatosensory area, the amygdala, the fornix, the thalamus and the insula were consistently activated • Hippocampus & Hypothalamus Mercante et al., 2018 Luan et al., 2014
- 15. 5/13/2018 15 Chemical • Useof microfluids to control the chemical environment around neurons • Methods • Neurotransmitter modulation • Ionic concentration Luan et al., 2014
- 16. Ultrasound-mediated non-invasive brainstimulation • Focussed sonic stimulation of brain • Stimulation parameters: Pulse frequency, Pulse duration, Burst duration • Pulsed application of focussed ultrasound – Selectively stimulates specific brain areas at the acoustic intensity hat is compatible with regulatory safety limits on biological tissue* • Mech. Of Action: ??? Mechanical / Thermal / • Activation of ION CHANNELS** • Low intensity pulsed ultrasound (LIPUS) – Enhances protein levels of neurotrophic factors *** • LIPUS – Neuroprotective role 5/13/2018 16Kim H et al., 2014*; Kubanek et al., 2018**; Yang et al., 2015***
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- 18. Newer Neuromodulation methodsEvidences (studies) Magnetic Seizure Therapy (MTS) Human Transcranial Alternating Current Stimulation (tACS) Human Transcranial Random Noise Stimulation (tRNS) Human Optogenetics Animal Thermal Animal Auricular stimulation Human Trigeminal Nerve Stimulation Human Transcranial Ultrasound Animal Chemical Animal
- 19. Newer Neuromodulation methods Clinical use MagneticSeizure Therapy (MTS) Depression (U & B), Schizophrenia Transcranial Alternating Current Stimulation (tACS) Schizophrenia (AVH) Transcranial Random Noise Stimulation (tRNS) Cognitive enhancement , Pain Optogenetics Cognitive enhancement, Pain Thermal Epilepsy, brain tumor Auricular stimulation Depression, Anxiety disorder, Cognitive disorders, Epilepsy Trigeminal Nerve Stimulation Depression, Anxiety disorder, Migraine, Epilepsy Transcranial Ultrasound Neurodegenerative disorder, Cognitive enhancement Chemical Pain
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