Updating P300: An integrative theory of P3a and P3b

Abstract

The empirical and theoretical development of the P300 event-related brain potential (ERP) is reviewed by considering factors that contribute to its amplitude, latency, and general characteristics. The neuropsychological origins of the P3a and P3b subcomponents are detailed, and how target/ standard discrimination difficulty modulates scalp topography is discussed. The neural loci of P3a and P3b generation are outlined, and a cognitive model is proffered: P3a originates from stimulusdriven frontal attention mechanisms during task processing, whereas P3b originates from temporalparietal activity associated with attention and appears related to subsequent memory processing. Neurotransmitter actions associating P3a to frontal/dopaminergic and P3b to parietal/norepinephrine pathways are highlighted. Neuroinhibition is suggested as an overarching theoretical mechanism for P300, which is elicited when stimulus detection engages memory operations.

The P3 Event-Related Potential is a Biomarker for the Efficacy of Vagus Nerve Stimulation in Patients with Epilepsy

“…The hypothesis that the LC-NE system contributes to P3 generation during a target detection task is consistent with the allocation of attentional resources and arousal effects in humans [13,[17][18][19]. Monkey studies with the oddball paradigm have shown that the conditions for generating the P3 are highly similar to those for the LC phasic response: both are preferentially elicited by attended, task-relevant, arousing, and salient stimuli that are important for goal-directed behavior [15,20].…”

“…Monkey studies with the oddball paradigm have shown that the conditions for generating the P3 are highly similar to those for the LC phasic response: both are preferentially elicited by attended, task-relevant, arousing, and salient stimuli that are important for goal-directed behavior [15,20]. Furthermore, the timing and topographic distribution of intracranial and scalp-recorded P3 activity are consistent with the anatomical and physiological activation of temporoparietal areas by the LC-NE system [13,15]. Finally, lesions of the LC cell bodies reduce the auditory P3 amplitude in monkeys, indicating that the LC nucleus and its ascending fibers are important in the generation and modulation of the P3 [21].…”

“…However, it is possible that the threshold for "functional" activation of the LC-NE system (reflected by the behavioral improvement) is much lower than the threshold for the antiepileptic effect of the LC-NE system (reflected by the P3). The P3 component is thought to originate from neuronal inhibitory signals that inhibit unrelated neural activity to promote processing efficiency of task-relevant stimuli, thereby yielding large P3 amplitudes [13]. Correspondingly, activation of the LC-NE system in response to an important stimulus sends a "network reset" signal to the brain that interrupts the activity of the ongoing functional networks and facilitates their reorganization to promote rapid behavioral adaptation [18,55].…”

“…It is probable that only in the group of responders, because of differences in network connectivity and interactions with other neuromodulators, the VNS-induced activation of the LC-NE system results in a stronger inhibition and network reorganization that causes the antiepileptic effect. The P3 amplitude is proposed to reflect the LC-NE inhibition [13] and this could explain why the amplitude is increased only in responders. Nonetheless, this remains a hypothetical explanation and further research is necessary to clarify the different effects of VNS on cognition and seizure control.…”

“…In this cognitive paradigm, low-probability target stimuli ("oddballs", e.g., low frequency tones) are embedded in a train of highprobability nontarget stimuli ("standards", e.g., highfrequency tones). After the presentation of the infrequent target stimuli a large P3 can be measured at parietal midline electrodes [13,14].…”