Magnetic and Electrical Stimulation in the Treatment of Aphasia Transcranial Magnetic Stimulation (TMS) Transcranial Direct Current Stimulation (tdcs) No financial conflicts Roy Hamilton, MD, MS, FAAN, FANA Associate Professor of Neurology & Physical Medicine & Rehabilitation University of Pennsylvania Uses Faraday principle Induces current in neurons Neurons fire (depolarize) Focally alters brain activity Direct current via electrodes Subthreshold stimulation Changes firing rates Numerous practical advantages How do intact cognitive systems work? Reorganized How do Systems injured systems differ from Using brain stimulation normal systems? to better understand AND treat neurologic Normal Systems disorders Cognitive Outcomes Can we facilitate reorganization of injured neural systems? Does it work? Hypothesis-guided Neuromodulation Poeppel D., Current Opinions in Neurobiology, 214 Turkeltaub et al. Neurology, 211 Language Network Dorsal: Sensorimotor/Articulatory Network (Composition & Control) Ventral: Lexicosemantic Network (Concepts & Word Meanings) 1
Intact (A) Left hemisphere perisylvian recruitment (B) Right hemisphere homolog recruitment (C) Interhemispheric inhibition (D) Inefficient compensatory right hemisphere (E) Torres et al., 213 Turkeltaub et al. Neurology, 211 Homologues, homotopes, and noncontributors High resolution Excites or inhibits Pulses and patterns TMS Low risk of seizure Potentially long-term effects Turkeltaub et al. Neurology, 211 Sham TMS 2 Month follow-up Baseline testing & MRI Sitefinding Crossover TMS 2 Month follow-up 6 Month follow-up 1 Hz = Inhibitory Stimulation Harvey et al., Cognitive & Behavioral Neurology, 217 2
% Change in Naming (Post-Pre rtms) Number of Items 25 2 2 16 15 12 1 8 5 4 Unique Nouns Total Nouns Total Verbs Unique Words Unique Verbs Narrative length (seconds) 4 75 32 6 24 45 Pre TMS 16 3 Post TMS 8 15 CCW CIU OCW Speech rate (wpm) Narrative Words Medina et al., Brain Stimulation, 213 Shah-Basak, Wurzman, et al., 216 5 4 3 2 1-1 M1 BA 44 Post. Inf. Post Sup Ant BA BA 45 BA 45 45 Sham rtms -2 Garcia et al., JoVE, 213 A noisy node? Is the RH s role monolithic? NO! tdcs Practical Advantages: Inexpensive Even safer Combines with concurrent therapies Turkeltaub et al. Cortex, 211 3
% Change WAB Aphasia Quotient Low resolution: bug or feature? F3/F4 Frontal Lobe Contralateral Mastoid (reference) Phase 2 Sham tdcs 1 sessions over 2 weeks 2-Week 2-month Screening Phase 1 Optimal Montage Finding Baseline Testing Sham Real Real tdcs 2.mA for 2 minutes 1 sessions over 2 weeks 2-Week 2-month Turkeltaub et al., Neurology, 211 Shah-Basak et. al., Frontiers Hum. Neurosci., 215 3 25 2 15 1 5 2 Weeks 2 Months Real tdcs (n=6) Sham tdcs (n=4) WAB Aphasia Quotient Scoring -25 = very severe 26-5 = severe 51-75 = moderate 76 and above = mild Baseline abilities influence tdcs effects Norise et al., 217-5 Real tdcs Sham tdcs -1 Shah-Basak et. al., Frontiers Hum. Neurosci., 215 Neurodegenerative aphasia syndromes Monti et al., JNNP, 213 Shah-Basak & Wurzman, et al., RNN, 216 Adapted from Wilson et al., 212 4
z score change from baseline tdcs to treat PPA 1 Global Performance Real Sham.8.6.4 Wilson, S. M. et al., 212.2 -.2 -.4 -.6 -.8-1 Low High N=4 lvppa; 2 nappa Left frontal anode; parietal cathode 1 days; 1.5 ma x 2 minutes; 25 cm 2 pads Gervits McConathey et al. Brain et al., & 217 Language, 216 tdcs + Semantic Feature Training N=3 svppa; N=1 lvppa; N=1 AD (anomia) 2 Weeks (1 days) of treatment Left parietal anode; forehead cathode 1.5 ma x 2 minutes; 25 cm 2 pads Hung et al., 217 Future Directions TMS for post-stroke aphasia Move toward larger, more definitive studies Pair with imaging & other tools to stratify/optimize treatment tdcs for post-stroke aphasia Consistency/organizing principles around parameter selection Enhance rigor, reproducibility, and reporting tdcs for PPA Move beyond pilot trials Determine PPA subtype-response relationships ALL Further consideration of the role of concurrent behavioral speech therapies Consider stimulation beyond traditional language regions Conclusions A bihemispheric post-stroke language network. Focal manipulation of a noisy node with TMS enhances language performance. Network control properties may inform which are the best nodes to manipulate. Diffuse DC stimulation may facilitate recovery in post-stoke aphasia and PPA. Faculty Roy Hamilton, MD, MS H. Branch Coslett, MD Sudha Kessler, MD John Magdaglia, PhD Students Perelman School Of Medicine Catherine Norise Undergraduates Hannah Juhel Melvin Reyes Shreya Parchure Postdoctoral Fellows Rachel Wurzman, PhD Denise Harvey, PhD Research Staff Olufunsho Faseyitan, MS Daniela Sacchetti, MS Eric McConathey Laura Deloretta Follow us on Twitter @PennMedLCNS LCNS email: braintms@mail.med.upenn.edu LCNS website: http://www.med.upenn.edu/lcns Collaborators Priyanka Shah-Basak, PhD (SickKids) Peter Turkeltaub, MD, PhD (Georgetown) Jared Medina, PhD (U. Delaware) Margaret Naeser, PhD (Boston University) Alvaro Pascual-Leone, MD, PhD (Harvard) 5
Membrane polarization effects de Berker et al., 213 6