The neurophysiology of P 300--an integrated review

Event-related potentials (ERPs) are very small voltages recorded from the scalp which originate in the brain structures in response to specific events or stimuli. They appear as a series of peaks and troughs interspersed in the Electroencephalogram (EEG) waves. The exact neural origins and neuropsychological meaning of the P300 are imprecisely known, even though appreciable progress has been made in the last 25 years. In this review, we will focus on the possible neural generators of this potential. Given the attention and memory operations associated with P300 generation, the first human studies on the neural origins of this ERP focused on the hippocampal formation using depth electrodes implanted to assess sources of epileptic foci in patients. Other lesion studies have found that the integrity of the temporal-parietal lobe junction is involved with either generation or transmission processes subsequent to hippocampal activity and contributes to ERP measures. These findings imply that hippocampal absence does not eliminate the P300, but that the temporal-parietal junction does affect its production. As mentioned till now, the neuroelectric events that underlie P300 generation stem from the interaction between frontal lobe and hippocampal/temporal-parietal function. ERP and fMRI studies using oddball tasks have obtained patterns consistent with this frontal-to-temporal and parietal lobe activation pattern. Further support comes from magnetic resonance imaging (MRI) of gray matter volumes that suggest individual variation in P3a amplitude from distracter stimuli is correlated with frontal lobe area size, whereas P3b amplitude from target stimuli is correlated with parietal area size. Given distinct neuropsychological correlates for P3a and P3b, different neurotransmitters may be engaged for each constituent subcomponent under specific stimulus/task processing requirements. Available data suggest that dopaminergic/frontal processes for P3a and locus-coeruleus-norepinephrine/ parietal activity for P3b are reasonable to propose. This dual-transmitter P300 hypothesis is speculative but appears to account for a variety of findings and provides a useful framework for evaluating drug effects.