Epileptiform Discharges

Epileptiform discharge is the electrical sign of seizure susceptibility. In experimental models, applying penicillin to the cortex causes asynchronous paroxysmal depolarization bursts in neurons, leading to EEG-recorded spikes. These bursts are followed by long-lasting afterhyperpolarization, triggering inhibitory activity in the surrounding cortex, contralateral cortex, and thalamus. This results in a slow-wave following each spike, forming the spike-and-wave complex often seen in epilepsy. The surrounding inhibition also contributes to the intermittent slow-wave activity associated with an active spike focus.

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Generation of Paroxysmal Depolarization Bursts

Hippocampal pyramidal cells, particularly in the CA2 and CA3 regions, have an intrinsic ability to generate prolonged depolarization responses with action potentials. Single sodium-mediated action potentials activate a calcium current, leading to a depolarizing afterpotential. These afterpotentials can summate, resulting in a sustained depolarizing envelope. During bursts, slow calcium-dependent action potentials may occur, which are terminated by calcium-dependent potassium currents, causing hyperpolarization lasting up to 1 second. Burst generation can happen in both dendrites and the soma.

 

Neuronal Synchronization

Horseradish peroxidase injections in CA3 neurons reveal extensive axonal branching. Dual intracellular recordings show two types of inhibitory neurons: one generates bursts with fast IPSPs blocked by convulsant drugs, while the other produces slower IPSPs unaffected by these drugs. Neuronal synchronization can occur despite inhibition if excitatory transmission is strong enough. Chronic experimental foci show a decrease in GABAergic axon terminals, and repetitive seizures lead to a loss of somatostatin-containing interneurons and reduced recurrent inhibition. Synchronized events, rare in neocortical slices, can be induced with drugs like penicillin. Interictal spikes often occur during light sleep when TCR discharge is synchronized.

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Generalized Epilepsy

Generalized seizures result from heightened cortical excitability. Cortical spiking precedes deep epileptiform discharges, with thalamocortical connections essential for triggering spike-and-wave bursts. Experiments show intense oscillation within the thalamocortical loop during spike-and-wave paroxysms. In generalized epilepsy, these discharges are often linked to sleep or arousal. The brainstem reticular formation modulates cortical excitability, influencing spike-and-wave activity. The substantia nigra, particularly its GABAergic mechanisms, plays a key role in controlling generalized convulsions. The main effect of 3-Hz spike-and-wave activity is a temporary impairment of cognitive functions, which normalizes once the discharge stops.

 

Delta Waves

The cerebral cortex is the origin of all cortical activity, with brain tumors, abscesses, and infarcted areas being electrically silent. Bilaterally synchronous paroxysmal activity, such as epileptiform discharges and rhythmic delta waves, are linked to disorders of gray matter at cortical and subcortical levels. In contrast, lesions in white matter, like in demyelinating diseases, show polymorphic delta activity. Diseases affecting cortical gray matter, like Alzheimer's, cause widespread irregular slow waves. Thalamic lesions lead to ipsilateral delta waves, sometimes mixed with spindle-like rhythms. Intermittent rhythmic delta waves likely arise from abnormal thalamocortical interactions. The caudate nucleus may inhibit cortical activity, and conditions like hypoglycemia and hypercapnia alter neuronal firing and EEG amplitude.