Berenson-Allen Center for Noninvasive Brain Stimulation Berenson-Allen Center for Noninvasive Brain Stimulation Beth Israel Deaconess Medical Center Beth Israel Deaconess Medical Center Harvard Medical School Harvard Medical School Y P Non-Invasive Brain Stimulation and Behavioral Therapy O Dylan J. Edwards PhD Director, Moss Rehabilitation Research Institute, Philadelphia C Professor of Neuroscience, ECU Australia !"#$#%&"'()'#*'+',-./ T !"#$%&'()*+,-%.*/0%),012*'!13%/0,!1456 O N Berenson-Allen Center for Noninvasive Brain Stimulation Beth Israel Deaconess Medical Center Harvard Medical School Adaptive Limitations and advantages of restorative methods ! .? O Brain D Plasticity Pharmacology Stimulation E Maladaptive Behavioral S Intervention A E L Smaller Coil P How does repetitive behavior affect motor cortex? Focality / Specificity Network activation
Y P Motor map changes with skilled practice O C Simple repetitive finger movements increase excitability T O N 012"&3*3$2'34'!56 Magstim Magstim Magstim Magstim 789:!'5. Stimulating coil Stimulating coil O How does NIBS affect motor cortex? ) ( ) ( D ! ! !"##$%%&'())) 5;"<*(' 6=&>#*'%(<3%?&>$" E *"+,-'.'/"0"#' S EMG EMG EMG EMG Instrument Instrument Instrument Instrument Di Lazzaro et al. (1998) A E SICF Berenson-Allen Center for Noninvasive Brain Stimulation L Beth Israel Deaconess Medical Center Harvard Medical School “An excited neuron tends to decrease its P discharge to inactive neurons, and increase this discharge to any active neuron, and therefore to form a route to it, whether there are intervening TMS 1.5 msec. neurons between the two or not. With repetition, Amplitude (% control) this tendency is prepotent in the formation of 300 neural routes”. 250 (Hebb, 1932, p.13). 200 150 I-waves williamcalvin.com Donald Hebb 100 Periodicity ~ 1.5ms 50 1 1.5 2 2.5 3 3.5 4 4.5 5 Inter-stimulus Interval (ms) Ziemann et al, 1998 The Organisation of Behaviour: A Neuropsychological Theory. D.O. HEBB (1949) D Edwards
Rate-dependent TMS protocols Long-term potentiation Y High-frequency Excitatory ~10Hz Pre-synaptic Glu P REPETITIVE Na+ Ca++ Low-frequency Inhibitory ~1Hz Na+ Mg++ O NMDA AMPA Post-synaptic 50Hz EPSP Dendritic spine Intermittent Excitatory C 5Hz AMPA THETA BURST 2 sec 8 sec Inhibitory Continuous T Thickbroom (2007) Ex Brain Res. O N LTP/ LTD Long-term potentiation Long-term depression O Pre-synaptic Glu Glu Na+ D Ca++ Ca++ Na+ Mg++ Mg++ NMDA NMDA AMPA AMPA C Post-synaptic CaMKII ! EPSP Dendritic spine Ca++ Ca++ CaM CaMKII CaM E PP2B N AMPA S Thickbroom (2007) Ex Brain Res. Thickbroom (2007) Ex Brain Res. A E Berenson-Allen Center for Noninvasive Brain Stimulation L Beth Israel Deaconess Medical Center Harvard Medical School P 7%>+62;'-*+&*%,-*.//?* !"#$%&'(%)*+&*%,-*.//0* @"AA'"*+&*%,-*.//4* 1%,2"3*+&*%,-*.//4* 5633+,*+&*%,-*.//4* B(+A)'*+&*%,8-*.//:* 7%,+,,'*+&*%,8-*.//4****9'3* B(+A)'*+&*%,8-*.//= +&*%,8-*.//:*5633+,*+&* 1%)C6(*+&*%,8-*.//=* %,-*.//:*9;+<(*+&*%,8-* 7%>+62;'*+&*%,8-*.//=* .//=*5633+,*+&*%,-* @"AA'"-*+&*%,8-*.//:** .//=** D+(;%;)-*+&*%,8-*.//E* Webster et al (2006) Webster et al (2006) IMPROVED CORTICOMOTOR OUTPUT FROM IPSI-LESIONAL M1 & IMPROVED MOTOR BEHAVIOUR Clinical application - rTMS, Stroke Motor Recovery
Functional Improvements TMS correlates Y sRT/cRT Resting MT Pinch force acceleration Transcallosal Inhibition P How does combined intervention affect fingers/thumb AROM MEP Amplitude motor cortex? Movement accuracy O Purdue Pegboard JTT C Webster et al (2006) Webster et al (2006) IMPROVED CORTICOMOTOR OUTPUT FROM IPSI-LESIONAL M1 & IMPROVED MOTOR BEHAVIOUR T O Altering cortical excitability before repetitive synaptic activity N Berenson-Allen Center for Noninvasive Brain Stimulation Beth Israel Deaconess Medical Center Harvard Medical School O D E • 1mA 10mins tDCS • rTMS at 5Hz 100stim train at AMT – decreases SICI, but not lasting change in excitability as tested by single pulse TMS • Result= after effects of tDCS can generate opposite effects of rTMS or S conversely can alter the after effects of tDCS Lang et al (2004) Buch et al 2011, J Neurosci A E Motor systems example If ! L Motor Training = improvement in function ‘X’ P and ! Is coupling NIBS with therapy good? NIBS = improvement in function ‘X’ does ! Motor Training = improvement in function + 2X, X 2 , or 0?? NIBS
SICF Berenson-Allen Center for Noninvasive Brain Stimulation Berenson-Allen Center for Noninvasive Brain Stimulation Beth Israel Deaconess Medical Center Beth Israel Deaconess Medical Center Harvard Medical School Harvard Medical School Y Anodal tDCS combined with robotic motor training P O 1mV C Pre-tDCS Post-tDCS Post-Robot T %1/2 Edwards et al (2009) O N Anodal tDCS combined with robotic motor training Robotics for assessment of performance kinematics O Pre – training Post - training D Group SICI Index Conditioned / uncond MEP amplitude * p < 0.05 E 1 * 0.5 S 0 Pre Post Post tDCS tDCS Robot Edwards et al (2009) A E 9==(%'*&@A'%3A3)&<"'#)'B;%C(DE3%>(**+'F(G'H3%C L Edwards PI: R01 HD069776 P Robotics with brain stimulation in patients with motor dysfunction
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relim data for Nexstim NICHE Trial N'-&.&/0!1% T >M(&L/0!1%% O N Repetitive Transcranial Magnetic Stimulation (rTMS) O Aiming tool: centering, rotation, tilting D Nexstim NICHE Trial 2014-16 Electrical field display /#3-34"#%53"#6789: 'I'FE!-,-JKL/L Parameters: 0MN'O&<1#%?'P#%Q(2'OME E • 900 pulses • 1 Hz rTMS (inhibitory) to M1 of non-lesioned hemisphere • 110% of motor threshold for S Extensor Digitorum Communis Patient set up (m.EDC) A E Nexstim NICHE Trial 2014-16 Task Oriented Rehabilitation L Improvement ! 5 UEFM points 6 mths post (Primary) Patient Goals: P • Cut food with knife & fork Experimental group: • Cook 67% (95% CI, 58%–75%) n=117 • Reach for items above shoulder height P =0.76 Control Group: • Fasten clothing (buttons, 65% (95% CI, 52%–76%) n=52 zippers, laces) • Hold grandchild • Hold tools in affected hand • Driving Mean change UEFM • Golf points 6 mths Experimental: 8.2 ±7pts Person Control: 8.5 ±8pts Environment Occupation Occupation P =0.87 Collaborative process between therapist and patient Harvey et al, 2018 Stroke
How does unaffected M1 excitability Y relate to hemiparesis? !"#$%&"'()& *+,-&.'()& P O C T O N n=103 VLSM in 3-12month Post-Stroke (hemiparesis) O = J D E F M S Hot colour = maximum overlap for unaffected hemisphere hyper-excitability !"#$%&'()'*+,-.&'/+0+'12%'-+3&40'5"06'72%37+.89$:72%37+.'90%2;&'<=>'+?"+.'@A'BCD'5"06'.&E'72%37+.89$:72%37+.' 90%2;&'+4/'<F>'90%2;&'.&9"24',+9;'&,-.2G&/'12%'H$+430+3I&'+4+.G9"9'21'"41+%7324'I2.$,&''<J>'@2-2#%+-6"7' ,+-9'21'@B*',202%'&I2;&/'-20&43+.9'12%'=KF'+4/82%'LMJ'6+4/',$97.&9'21'$4+N&70&/'6&,"9-6&%&'<%"#60>' Courtesy A .Boes MD March 2017 +4/'<M>'+N&70&/'6&,"9-6&%&'<.&E>)'C&9-249&'+,-."0$/&9'+%&'42%,+."O&/'1%2,',"4",$,'<%&/>'02',+?",$,' <56"0&>)''P%+G'"9'42'%&9-249&)'' A E Berenson-Allen Center for Noninvasive Brain Stimulation L Beth Israel Deaconess Medical Center Harvard Medical School P 03")D")%3C('#=1#"&#R Other cortical areas? P3G'&"')1('>()G3%C'?&"%;=)(?R M"'FMB6';"(4;*R Webster et al (2006) Webster et al (2006) E#>'&)'A('(44(<)&Q(*2'<3@A&>(?'G&)1'6:')1(%#=2R
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