Neuropsychology and neuropharmacology of P3a and P3b

doi:10.1016/j.ijpsycho.2005.12.012

International Journal of Psychophysiology

Volume 60, Issue 2, May 2006, Pages 172-185

https://doi.org/10.1016/j.ijpsycho.2005.12.012 Get rights and content

Abstract

Perspectives on the P300 event-related brain potential (ERP) are reviewed by outlining the distinction between the P3a and P3b subcomponents. The critical factor for eliciting P3a is how target/standard discrimination difficulty rather than novelty modulates task processing. The neural loci of P3a and P3b generation are sketched and a theoretical model is developed. P3a originates from stimulus-driven disruption of frontal attention engagement during task processing. P3b originates when temporal–parietal mechanisms process the stimulus information for memory storage. The neuropharmacological implications of this view are then outlined by evaluating how acute and chronic use of ethanol, marijuana, and nicotine affect P3a and P3b. The findings suggest that the circuit underlying ERP generation is influenced in a different ways for acute intake and varies between chronic use levels across drugs. Theoretical implications are assessed.

Introduction

The P300 was discovered over 40 years ago and has provided much fundamental information on the neural underpinnings of cognition (Sutton et al., 1965; for a superb review of the original work, see Bashore and van der Molen, 1991). Despite many studies, the usefulness of P300 as a practical assessment tool has been limited because its neural generators are still unclear. However, recent advances on the underlying processing mechanisms of the P3a and P3b subcomponents have suggested a plausible approach. The present paper reviews these issues and outlines how human neuropharmacological findings can contribute to P300 theory. The paper is organized into sections: First, a theoretical overview for P300 is presented. Second, the neuropsychological background of the P3a and P3b subcomponent distinction is sketched. Third, the effects of neuropharmacological challenges on P3a and P3b are outlined. Fourth, the implications of the neuropharmacological associations are highlighted for alcohol, marijuana, and tobacco. The findings are discussed in terms of underlying mechanisms.

Section snippets

P300 theory

Fig. 1 schematically illustrates variants of the “oddball” paradigm, which is often used to elicit the P300. In the single-stimulus task, the target is presented infrequently in time with no other stimuli (top). In the traditional two-stimulus oddball, an infrequent target occurs in a background of frequent standard stimuli (middle). In the three-stimulus oddball, the target is presented infrequently in a background of frequently occurring standard stimuli and infrequently occurring distracter

P3a and P3b

An infrequent tone presented with physically different frequent tones in the absence of a task can produce a positive waveform having a central/parietal maximum amplitude distribution and relatively short peak latency. This component has been dubbed the “P3a” to distinguish it from the task-relevant target “P3b” potential (Squires et al., 1975, Snyder and Hillyard, 1976). P3a from auditory stimuli can be observed directly during oddball task processing in 10–20% of normal young adults (Polich,

Theoretical considerations

Different stimulus/task conditions appear to determine P300 scalp topography outcomes in a fashion that suggests overlapping neural activations are engaged, with the functional distinction between an initial frontal/central P3a and subsequent parietal P3b emerging (He et al., 2001, Spencer et al., 2001, Gaeta et al., 2003, Yago et al., 2003). Stimulus context as defined by the degree of physical similarity between stimuli determines task difficulty (Demiralp et al., 2001, Hagen et al., 2006),

Neuropsychology of P300

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 (Soltani and Knight, 2000). 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. These recordings suggested that at least some portion of the

Neuropharmacology and P300

The neurotransmitters systems underlying P300 generation are as yet unclear, although various mechanisms have been implicated (Frodl-Bauch et al., 1999, Hansenne, 2000). Given distinct P3a and P3b neuropsychological origins, 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

Common drugs and P300

The ERP studies outlined below employed this approach by assessing young adults who were empirically defined as “low” or “high” use individuals for different substances based on normative data from thousands of drug-use surveys of the same population. Low-use and high-use generally reflect the bottom and upper 30% of each subject group in terms of various quantification measures. Additional criteria were employed to eliminate drug-dependent or substantial poly-drug users. Placebo and

Acknowledgements

This work was supported by RO1-DA018262, RO1-DA11737, RO1-DA08363, and 3 P50 AA06420. The second author was supported by the Clark Fellowship in Neurophysiology from Scripps Clinic. We thank Quetzal A. Class and Brian A. Lopez for their superlative assistance and perceptive comments.

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Neuropsychology and neuropharmacology of P3a and P3b

Abstract

Introduction

Section snippets

P300 theory

P3a and P3b

Theoretical considerations

Neuropsychology of P300

Neuropharmacology and P300

Common drugs and P300

Acknowledgements

Cogn. Brain Res.

Brain Cogn.

Int. J. Psychophysiol.

Pharmacol. Biochem. Behav.

Pharmacol. Biochem. Behav.

Biol. Psychol.

Electroencephalogr. Clin. Neurophysiol.

Electroencephalogr. Clin. Neurophysiol.

Prim. Care

Neuroimage

Eur. J. Pharmacol.

Brain Res.

Biol. Psychol.

Biol. Psychol.

Cogn. Brain Res.

Clin. Neurophysiol.

Electroencephalogr. Clin. Neurophysiol.

Neuropsychologia

Electroencephalogr. Clin. Neurophysiol.

Neuroscience

Int. J. Psychophysiol.

Cogn. Brain Res.

Trends Neurosci.

Brain Cogn.

Electroencephalogr. Clin. Neurophysiol.

Cogn. Brain Res.

Int. J. Psychophysiol.

Neurophysiol. Clin.

Electroencephalogr. Clin. Neurophysiol.

Biol. Psychiatry

Biol. Psychiatry

Intelligence

Int. J. Psychophysiol.

Clin. Neurophysiol.

P300 hemispheric amplitude asymmetries from a visual oddball task

Psychophysiology

The P300 brain potential is reduced in smokers

Psychopharmacology (Berl)

Low doses of ethanol disrupt sensory responses to brain noradrenergic neurons

Nature

Prefrontal modulation of visual processing in humans

Nat. Neurosci.

Evidence that tobacco smoking increases the density of (−)-[3H] nicotine binding sites in human brain

J. Neurochem.

Bottom-up influences on working memory: behavioral and electrophysiological distraction varies with distractor strength

Exp. Psychol.

Cannabinoid receptors and modulation of cyclic AMP accumulation in the rat brain

J. Neurochem.

Localizing P300 generators in visual target and distractor processing: a combined event-related potential and functional magnetic resonance imaging study

J. Neurosci.

Effect of smoking history on (3H) nicotine binding in human postmortem brain

J. Pharmacol. Exp. Ther.

Rewarding actions of phencyclidine and related drugs in nucleus accumbens shell and frontal cortex

J. Neurosci.

Effects of smoked marijuana on human performance: a critical review

Sensitivity to nicotine and brain nicotinic receptors area altered by chronic nicotine and mecamylamine infusion

J. Pharmacol. Exp. Ther.

Disruption of attention to novel events after frontal lobe injury in humans

J. Neurol. Neurosurg. Psychiatry

The central role of the prefrontal cortex in directing attention to novel events

Brain

An electrophysiological index of stimulus unfamiliarity

Psychophysiology

Wavelet analysis of P3a and P3b

Brain Topogr.