Spreading Depolarizations and Seizures in Clinical Subdural Electrocorticographic Recordings

The brain is the organ most sensitive to energy depletion. In contrast to other tissues, the neural network and biophysical structures that support information processing under physiological conditions are prone to abrupt, near-complete breakdown of cellular homeostasis under certain pathological conditions. Known as spreading depolarization (SD), this breakdown moves slowly as a giant wave of sudden electrochemical discharge between neurons en masse and triggers toxic changes that shorten the time span of energy depletion which neurons can survive. Epileptiform activity is the other important pathological network event that occurs in the form of either the interictal-ictal continuum or ictal epileptiform events (IEEs). Based on electrochemical gradients across the neuronal membranes in different conditions, IEE and SD represent thermodynamically two different levels of free energy between the physiological state and dead tissue. Accordingly, IEE is closer to physiology, while SD is closer to dead tissue. Among the many variables reflecting this thermodynamic hierarchy, the negative direct current (DC) shift is the one most readily measurable in humans. Here, we performed a direct comparison between DC amplitudes of IEE and SD in the human brain and found that the negative DC shift of SD exceeds that of IEE by a factor of 14, consistent with the known electrochemical, electrophysiological, and thermodynamic differences between these pathological network events in lower species.