Spikes and Seizures: Step Relatives or Siblings? Fourth International Seizure Prediction Workshop

1. Spikes and Seizures: Step Relatives or Siblings? Fourth International Seizure Prediction Workshop Kansas City, June 2009

2. Spikes & Seziures: Step-relatives Siblings? • Epilepsia. 2001 Do interictal discharges promote or control seizures? Experimental evidence from an in vitro model of epileptiform discharge. Avoli M. • Prog Neurobiol. 2001 63:541-67. Interictal spikes in focal epileptogenesis. de Curtis M, Avanzini G • Ann Neurol. 2003;53:382-9. Epileptiform ictal discharges are prevented by periodic interictal spiking in the olfactory cortex. Librizzi L, de Curtis M. • Ann Neurol. 1988;24:591-8.The relationship between interictal and ictal paroxysms in an in vitro. Rev Neurol (Paris)1999;155:468-71. • Interictal-ictal interactions and limbic seizure generation. Avoli M, Barbarosie Model of focal hippocampal epilepsy. Jensen MS, Yaari Y.

3. Spikes & Seizures: Step-relatives Siblings? • Focus theory • System is linear • System is deterministic • In-vitro models capture the all key features of intact spontaneously epileptic brain • Human recordings have important limitations

4. Spikes and Seizures: Step relatives or Sibling? Hume's Causality: • Precedence: X precedes Y in time • Contiguity: X and Y are contiguous in space and time • Constant Conjunction: X and Y always co-occur (or not occur). - Mixing is a property of systems with sensitive dependence on initial conditions which dictates that one phenomenon may depend sensitively on another phenomenon, yet be statistically independent of it (D. Ruelle). • Probabilistic Causality • Changes in conceptualization and the equivalent of DNA test is needed to understand both phenomena • We don’t have a good grasp of seizure and epilepsy “dynamics” yet make absolute distinctions -

6. The roots of the spike-seizure dichotomy are shallow yet have spread like “weeds” and are drought and fire resistant . Its logical and evidence-based underpinnings are feeble”

7. ECoG 2 min after bolus of alfentanil: activation of amygdala/hippocampal spikes and suppression of temporal neocortical spikes ECoG 10 min later: return to pre-activation baseline of amygdala/hippocampal spikes and reappearance of independent temporal neocortical spikes

8. Abnormal brain activity & discernible behavioral correlates =Ictal, otherwise = interictal

9. The spike-seizure dichotomy is the hybridized construct of the “ictiocentric” (“focus”) theory and the notion that neural networks processes are linear on a deterministic background.

10. Spikes & Seizures: Step-relatives or Siblings? • The dichotomy (spikes and seizures are “unrelated”) is an inevitable and regrettable collorary of the “ictiocentric” (“focus”) theory (a phrenology remnant) and of the stubborn adherence to the belief that “linear” laws govern the behavior pathologic neuronal networks • The dichotomy (spikes an seizures are unrelated is the inbred love child of the ictiocentric (“focus”) theory and of the belief that “linear” laws govern the behavior of normal or pathologic neuronal networks borne out of the mating between nu