Microscale spatiotemporal dynamics during neocortical propagation of human focal seizures.
Some of the most clinically consequential aspects of focal epilepsy, e.g. loss of consciousness, arise from the generalization or propagation of seizures through local and large-scale neocortical networks. Yet, the dynamics of such neocortical propagation remain poorly understood. Here, we studied the microdynamics of focal seizure propagation in neocortical patches (4×4 mm) recorded via high-density microelectrode arrays (MEAs) implanted in people with pharmacologically resistant epilepsy. Our main findings are threefold: (1) a newly developed stage segmentation method, applied to local field potentials (LFPs) and multiunit activity (MUA), revealed a succession of discrete seizure stages, each lasting several seconds. These different stages showed characteristic evolutions in overall activity and spatial patterns, which were relatively consistent across seizures within each of the 5 patients studied. Interestingly, segmented seizure stages based on LFPs or MUA showed a dissociation of their spatiotemporal dynamics, likely reflecting different contributions of non-local synaptic inputs and local network activity. (2) As previously reported, some of the seizures showed a peak in MUA that happened several seconds after local seizure onset and slowly propagated across the MEA. However, other seizures had a more complex structure characterized by, for example, several MUA peaks, more consistent with the succession of discrete stages than the slow propagation of a simple wavefront of increased MUA. In both cases, nevertheless, seizures characterized by spike-wave discharges (SWDs, ~2-3 Hz) eventually evolved into patterns of phase-locked MUA and LFPs. (3) Individual SWDs or gamma oscillation cycles (25-60 Hz), characteristic of two different types of recorded seizures, tended to propagate with varying degrees of directionality, directions of propagation and speeds, depending on the identified seizure stage. However, no clear relationship was observed between the MUA peak onset time (in seizures where such peak onset occurred) and changes in MUA or LFP propagation patterns. Overall, our findings indicate that the recruitment of neocortical territories into ictal activity undergoes complex spatiotemporal dynamics evolving in slow discrete states, which are consistent across seizures within each patient. Furthermore, ictal states at finer spatiotemporal scales (individual SWDs or gamma oscillations) are organized by slower time scale network dynamics evolving through these discrete stages.
Department of Neuroscience, Brown University, Providence, RI, 02912, United States. Electronic address: fabien.wagner@epfl.ch.
Fabien B
FB
Wagner
Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, United States; Nayef Al-Rodhan Laboratories for Cellular Neurosurgery and Neurosurgical Technology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, United States.
Emad N
EN
Eskandar
Department of Neurosurgery, Alpert Medical School, Brown University, Providence, RI, 02912, United States; Norman Prince Neurosciences Institute, Brown University, Providence, RI, 02912, United States.
G Rees
GR
Cosgrove
Department of Neurosurgery, Children's Hospital and Harvard Medical School, Boston, MA, 02114, United States; Department of Neurosurgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02114, United States.
Joseph R
JR
Madsen
Department of Neurology, Alpert Medical School, Brown University, Providence, RI, 02912, United States.
Andrew S
AS
Blum
Department of Neurology, Alpert Medical School, Brown University, Providence, RI, 02912, United States.
N Stevenson
NS
Potter
School of Engineering, Brown University, Providence, RI, 02912, United States; Institute for Brain Science, Brown University, Providence, RI, 02912, United States; Center for Neurorestoration and Neurotechnology, U.S. Department of Veterans Affairs, Providence, RI, United States; Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, United States; Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02114, United States.
Leigh R
LR
Hochberg
Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, United States.
Sydney S
SS
Cash
Department of Neuroscience, Brown University, Providence, RI, 02912, United States; Institute for Brain Science, Brown University, Providence, RI, 02912, United States; Center for Neurorestoration and Neurotechnology, U.S. Department of Veterans Affairs, Providence, RI, United States. Electronic address: wilson_truccolo@brown.edu.
Wilson
W
Truccolo
D000328:Adult; D058256:Brain Waves; D000069279:Drug Resistant Epilepsy / Q000503:physiopathology*; D065818:Gamma Rhythm; D006801:Humans; D008297:Male; D008839:Microelectrodes; D008875:Middle Aged; D019579:Neocortex / Q000503:physiopathology*; D009474:Neurons / Q000502:physiology; D012640:Seizures / Q000503:physiopathology*; D012815:Signal Processing, Computer-Assisted; D055815:Young Adult
Collective dynamics; Cortical waves; Epilepsy; Neural state segmentation; Secondary generalization