Y P O Transcranial Alternating Current Stimulation - tACS C T O N O Emiliano Santarnecchi D - Berenson-Allen Center for Non-invasive Brain Stimulation, Department of Cognitive Neurology | Beth E Israel Deaconess Medical Center | Harvard Medical School | Boston, MA, USA S - Center for Complex System study, Engineering and Mathematics Department, University of Siena, Italy A E esantarn@bidmc.harvard.edu L P
Y A rapidly growing field P O “tACS allows to modulate brain oscillations in a C frequency specific manner” T O TMS: Transcranial Magnetic N Stimulation O tDCS: transcranial Direct D Current Stimulation E tACS: transcranial Alternate S Current Stimulation A tRNS: transcranial Random E Noise Stimulation L P Santarnecchi et al. 2015 Curr Opin Behav Sci * PubMed Search : “Transcranial magnetic Stimulation”, “Transcranial Direct Current Stimulation”, Transcranial Alternating Current Stimulation”
Y Outline P O C • Oscillatory pattern and synchronicity in the brain T tACS - Mechanism of action O tACS evidence • N Perception (Hands-On session tomorrow) O Cortico-spinal excitability and effects on the motor system D Cognition E Phase-Related activity S A State and Trait – dependency E Therapeutic potential L P
Y P O C Questions? Comments? Ideas? Feedback? T O N O D E S • Kirsten Building - KS-450 A E • esantarn@bidmc.harvard.edu L P
Y Disclosure P O C Emiliano Santarnecchi serves as consultant for EBNeuro , a joint stock company developing biomedical devices for neurostimulation, neuromodulation and T O electroencephalography. N He has no actual or potential conflict of interest in relation to this presentation, O none of the tools presented in the following slides are property of EBNeuro. D E S A E L P
Y P O C • Experience with EEG/Brain Oscillations? T O N O D • Experience with tACS? E S A E L P
Y tCS techniques P O C T O N O D E S A E L P Santarnecchi et al. 2015 Curr Opin Behav Sci
Y Mechanism of action P O DC Stimulation AC Stimulation C Constant Oscillating T Fields Fields O Synchrony Effect N E O Membrane Network D Polarization Synchrony E Amplify S the Output Spike Rate Spike Phase A Synchronize Change Change E the I nput L P
Y tACS effect P O C T O N O D E S A E L P Santarnecchi and Rossi (2017)
Y P O C T O N Why tACS? O D E S A E L P
Y Brain Oscillatory Activity P O C T O N O Hans Berger (1921) D E S A E L P
Y EEG Oscillations and BEHAVIOURAL CORRELATES P O Sleep, learning, C motivational processing T O Memory, emotional N regulation, creativity O Active inhibition of task- D irrelevant areas E S Mainly Motor activity A E L Abstract mental activity, P cognitive control, perceptual binding
Y “Natural Frequencies” P Beta: movement O Alpha : automatic movements C Gamma : selective attention T O N O Ѳ : working /long-term memory D E S Alpha: visual perception A E L P Θ : spatial orienting
Y EEG Oscillations and PATHOLOGY P O • Reduced synchrony in Schizophrenia C • Reduced amplitude in Alzheimer • Increased Amplitude in Bipolar dis. T O • Reduced synchrony in Schizophrenia N • Reduced synchrony in Alzheimer O • Reduced coherence in Alzheimer D • Increased phase-locking at Frontal and Central electrodes in Schizophrenia E • Reduced Coherence in Alzheimer and S Schizophrenia A • Increased amplitude in Parkinson • Increased Coherence in Bipolar dis. E L • Decreased/increased amplitude in Schizophrenia (?) P • Increased Phase-locked response in ADHD
Y Inducing “Entrainment” P O • Are these oscillatory patterns immutable? C T O N O D E Entrainment of endogenous oscillatory pattern Changes in behaviour S • Oscillatory cycle establishes a recurrent temporal reference frame that allows for the coding of temporal relations between groups of neural elements A E • This reference frame is not fixed but is subject to dynamic changes (phase resetting), especially in pathological states . L tACS induces entrainment of brain oscillations following the same principle P (theta, alpha, beta, gamma, ..) Tuth et al. 2012, Current Biology
Y tACS: Parameters P O Phase ? Cyclic patterns in behaviour C T O N Sleep–wake cycles are evident even if external O light conditions are held constant (grey shade) D Phase, angles, degrees….. Intrinsic oscillators (circadian clocks) which cause Oscillators are in opposite E periodicity in bodily function phase (anti-phase) S A Frequency? E Number of cycles x second L (1 cycle * second=1Hz) P 2Hz 10Hz
Y P O C T O N tACS: experimental evidence O D E S A E L P
Y Early evidence: tACS and Phosphenes.. P O Kanai et al., 2008 Rationale C alpha T O beta gamma N Eye Open/Closed Alpha (Adrian, 1934) O What is frequency sensitivity of tACS-evoked Visual Sensation? D tACS Frequency Phosphene Threshold E S Design A Electrodes Inion (+ 4cm) - Vertex E Current 0-40Hz, 0-1mA, 5s each L P Subjects 8 Healthy
Y tACS and Phosphene: frequency specific effects P O Kanai et al., 2008 Results C T O N O D E S A Occipital tACS can evoke phosphene perception ( via the retina ….probably) • E • Greater stimulation at alpha band (dark) and beta band (light) L P
Y tACS effect on brain oscillations: in vitro evidence P O C T O tACS might shift intrinsic dominant oscillations and N “tune the system” O D E Higher stimulation S frequency A E L P
Y First animal evidence P O Ozen et al., 2010 • tACS at 1.5Hz (delta) induce AC Fields in the Brain C Rat T (in-vivo) O N O D 0.8-1.7Hz • Effect of Stimulation Amplitude • AC fields can phase-locked spiking activity E Homogenous Phase Larger Amplitude S More Neurons A E L P
Y Endogenous Resonance Principle P O Ozen et al., 2010 C tACS induced Synaptic mediated Oscillations Oscillations Push & pull T O Coherent I ncoherent N cooperate or compete Exploring O S =sleep Sleep D R =rest tACS ~ 1.5Hz E =exploration E S A Phase-locked (25-50% ) E L No Phase-locked P
Y P O C T O N tACS in humans: effects on O cortico-spinal Excitability D E S A E L P
Y tACS and Corticospinal Excitability Mot ot or or Mod odalit y P O Feurra et al., 2011 Journal of Neuroscience Question C • Are beta (20Hz) oscillations in motor cortex functional or epiphenomenon? T Amplitude of TMS induced MEP* tACS over M1 O N Design O 10xTMS 10xTMS 10xTMS 10xTMS 10xTMS 10xTMS 10xTMS D tACS E S Electrodes C4 (TMS hot-spot) + P4 (control) – Pz A Current 5, 10, 20, 40Hz, 0.5mA* , 90s E Subjects 15 Healthy L * Kept below phosphene or skin sensation threshold. P * MEP- Motor Evoked Potential ,indicating the strength of the corticospinal response
Y tDCS effects on the motor cortex P O TMS evoked potential (TEP) C T O N O D E S A E L P
Y tDCS effects on the motor cortex P O Santarnecchi et al., 2014 C T O N O D E S A E L P
Y tDCS effects on the motor cortex P O Santarnecchi et al., 2014 C PRE ONLINE POST (30’) (15’) (15’) T O N Anodal and Cathodal O tDCS modulate (increase/decrease D excitability) right after the stimulation E respect to Sham. S A E L P
Y tACS and Corticospinal Excitability P O Feurra et al., 2011 Journal of Neuroscience Results C T MEP Amplitude (µV) O N O D E S A E • Parietal tACS @ 20HZ specifically increases MEP amplitude L P
Y P O C T O N tACS and Motor Performance O D E S A E L P
Y tACS and Motor performance P O Santarnecchi et al. 2017, Brain Res.Bull. Question C • Are Gamma oscillations in motor cortex functional or epiphenomenon? T O Muthukumaraswamy 2010 N • Tracking task using MEG O • Observed an Increase in D Gamma activity (~90HZ) in the motor cortex during E movement. S • What does Gamma A oscillations in the motor E cortex represent..? L P
Y tACS and Motor performance - II P O Santarnecchi et al. 2017, Brain Res.Bull. Question C • Are Gamma oscillations in motor cortex functional or epiphenomenon? T O Visuomotor task + 10, 20, 60, 80Hz and Sham tACS on the motor cortex. N Effects on several components of the motor O program: Acceleration, Pursuit, Loops, Turns, etc.. (o) D High spatial and temporal resolution analyses. E S A E L P
Y tACS and Motor performance - III P O C 60Hz 80Hz • Significant enhancement T of performance during TURNS during Gamma O tACS (80Hz) , with a trending result for 60Hz N tACS. O • Effect is present in a D specific time window (200-700ms after each E TURN) , coherently with MEG studies showing S increase in EEG power at A 90HZ during a similar task. E • No effects during Loop, L Acceleration, Pursuit P
Y P O C T O N tACS and Cognition O D E S A E L P
Y Memory Consolidation P O Rationale Sleep Architecture C T O N O D E S A * (neocortex) (Pons-LGN) (hyppocampus) (hyppocampus) (thalamus) E L 0.8Hz 8-14Hz 100-300Hz 4-8Hz P Non- Declarative memory Declarative memory for further reading see Diekelmann, 2010 * PGO: ponto-geniculooccipital
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