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TMS-evoked EEG responses in symptomatic and recovered patients with mild traumatic brain injury Jussi Tallus 1, Pantelis Lioumis2, Heikki Hämäläinen3, Seppo Kähkönen2, Olli Tenovuo*1 1Department of Neurology, University of Turku, Finland, 2Biomag Laboratory, Finland, 3Department of Psychology, University of Turku, Finland *presenting author Background • Most patients recover from mild traumatic brain injury (mTBI) within 3 months • About 15% develop persistent symptoms • Diffuse neuronal damage and anterior brain tract dysfunction are probably involved in at least some mTBI cases with chronic sequels (according to diffusion tensor imaging and fMRI studies) TMS-EEG • Transcranial magnetic stimulation (TMS): A rapidly changing magnetic field induces a brief, focal electric field in the brain • TMS with EEG enables real-time measurement of brain responses to standardized stimulation • Excitation occurs on cortical gray matter, but cortico-cortical and thalamo-cortical connections modify the activity of the stimulated circuits Participants • 19 mTBI (GCS 13-15) patients, 11 with persistent symptoms and 8 fully recovered • 9 healthy controls • No signs of injury in MRI in visual inspection • No CNS affecting medications Experimental procedure • Single pulse TMS on left dorsolateral prefrontal cortex (DLPFC) and left primary motor cortex (M1) in trains of 100 pulses (at 0.3Hz) • Motor thresholds (MTs) measured using EMG, stimulus trains applied with intensities 90%, 100%, and 110% MT in randomized order Data analysis • Responses averaged for every stimulation condition • Pools of 4-6 electrodes created for 8 regions of interest: left and right hemisphere prefrontal cortex (LPFC & RPFC), motor cortex (LMC & RMC), temporal cortex (LTC & RTC), and parietal cortex (LPC & RPC) Results • In all groups, the same peaks were identified in the TMS–evoked EEG responses. • Statistically significant differences between the groups in peak amplitudes and latencies were observed in all time ranges, especially P30 and N100 deflections, and later in P200, P300, and the 370-440 ms time range mean amplitude. Controls vs patients, 90% MT Results • Differences in the earlier deflections were mostly seen in the frontal areas. Recovered vs symptomatic P30-N100 Results • Differences in the late (P300, 370-440 ms mean amplitude) time range were most pronounced in the temporal and parietal electrodes. Controls vs patients 300-500 ms Results • Patients in the symptomatic group were found to miss one or more of the normally appearing peaks more often than controls (p = 0.024). Control Symptomatic mTBI Symptomatic mTBI Recovered vs symptomatic, 90% MT N100-P200 deflection Recovered vs symptomatic 1 symptomatic Function 2 2 recovered 3 control 3 2 Group centroid 1 Function 1 Stepwise linear discriminant analysis of all three groups: 85.7% correctly grouped. Variables included: DLPFC 90% MT right parietal and right prefrontal P30 amplitudes, M1 90% MT left temporal P300 amplitude, and DLPFC 110% MT right prefrontal N100 amplitude. Conclusions Based on current knowledge, interpretation of the observed changes seen is uncertain: – P30: may be related to an early spreading of activation to functionally connected areas (longer latencies in the symptomatic subjects) – N100: thought to reflect a cortical inhibitory process triggered by TMS (more negative in the symptomatic group on prefrontal areas) – P300 and later: current knowledge very limited, higher cognitive processes? (consistently lowest in the symptomatic subjects) Conclusions • A validated combination of TMS-evoked EEG responses could be valuable in separating mTBI subjects from controls and recovered mTBI subjects from those with chronic sequels (LDA of the two patient groups with three best variables grouped correctly 100% of cases)