Research Fellow Athinoula A. Martinos Center for Biomedical Imaging; Japan Society for the Promotion of Science, Massachusetts
Rationale: Patients with cortical reflex myoclonus manifest giant SEP/SEF with the subsequent C-reflex (jerk response) due to cortical hyperexcitability between primary sensory (S1) and motor cortices (M1). Some patients show bilateral C-reflexes (BCR) on both arms to unilateral stimulation with the contralateral arm about 10-ms delay from the ipsilateral one. BCR occurs within 50 ms. The significance and exact pathophysiology of this early abnormal response is yet to be established, mainly because the cross-talk from the giant component in the contralateral hemisphere (contra) hides the true response in the ipsilateral one (ipsi). We hypothesize that in BCR patients interhemispheric connectivity is enhanced, especially on S1/M1 cortices. Methods: Five patients with cortical reflex myoclonus (benign adult familial myoclonus epilepsy, BAFME, age 40-71 years, mean age 58.2 years) with BCR and fifteen healthy controls (HCs, age 24-50 years, mean 34.1) were recruited. The median nerve was electrically stimulated at the wrist unilaterally. MEG signals were recorded (Elekta, Neuromag). In BAFME patients (Figure 1A), SEF typically includes contra N20m (S1) and P25m (M1). BCR time delay was measured for the patients. Functional ROIs (fROI, Figure 1B) representing S1/M1 were defined using dSPM source estimates for contra N20m. The phase-locking factor (PLF) and the weighted phase-lag index (wPLI) were calculated. Especially, wPLI is a functional connectivity index that downweights zero-lag interactions. Desikan-Killiany Atlas parcellation defined 128 anatomical seed locations. PLF was evaluated in homologous fROIs to determine the optimal time-frequency window, while wPLI was evaluated (a) between contra fROI vs. all seeds in addition to ipsi fROI and (b) an all-to-all connectivity. Mann-Whitney U test was applied using correction for multiple comparisons based on the false discovery rate with a threshold of 0.05.
Results: Among five patients, seven arms showed BCR. They all showed giant SEFs. The average of onset-to-onset BCR time delay was 8.8 ms (SD= 0.9). The time-frequency plot of grand-averaged PLF in fROIs (Figure 1C) and wPLI between fROIs (Figure 1D) showed that in 30-50 ms and 30-100 Hz (white rectangle), PLF and wPLI were enhanced in BCR patients. This time window corresponded to the estimation that ipsi activity at around 35 ms was synchronized after P25m activity (at 25 ms) propagated with BCR time delay, 9 ms. The average wPLI for this time-frequency window between contra fROI vs. all seeds was significantly larger in BCR patients than in HCs for the homologous fROI, PreC, PostC, and other temporal seeds interhemispherically (p< 0.01, Figure 2A). The all-to-all connectivity analysis revealed significant connectivity in PreC-PreC, PostC-PreC, InfP-PreC and InfP-PostC interhemispherically and PreC-InfP, PostC-InfP intrahemispherically (p< 0.05, Figure 2B). These results indicated contra S1/M1 was strongly connected to ipsi M1 in BCR patients at 30-50 ms.
Conclusions: BCR time delay suggested the contra M1 activity was propagated to the ipsi M1 in 9 ms, which probably denies the possibility of direct input to ipsi M1 or thalamic projection. The early enhanced connectivity between contra S1/M1 and ipsi M1 occurs within 50 ms, too early to be consistent with top-down inputs from S2. Instead, it may be related to transcallosal propagation that is due to hyperexcitability in BAFME patients. (InfP, inferior parietal; PostC, postcentral; PreC, precentral; ROI, region of interest)
Funding: Please list any funding that was received in support of this abstract.: Nakatani Foundation for advancement of measuring technologies in biomedical engineering The Japan Epilepsy Research Foundation The Osaka Medical Research Foundation for Intractable Diseases Research Fellowships of Japan Society for the Promotion of Science for Young Scientists