The N400 Event Related Potential: An Overview

Dara Kelly, University of Connecticut

The event related potential (ERP) N400 component was originally characterized by Marta Kutas and Steven A. Hillyard in 1980 as a reaction to an unexpected or inappropriate, but syntactically correct, word at the end of a sentence. At that time the N400 waveform was defined as a negative deflection below the pre stimulus baseline, starting around 250 milliseconds and peaking around 400 milliseconds. However, it was officially characterized as occurring anywhere between 200 and 600 milliseconds (Kutas & Hillyard, 1980b). Kutas and Hillyard speculated at that time that the N400 revealed the “interruption of ongoing sentence processing by a semantically inappropriate word and the ‘reprocessing’ or ‘second look’ that occurs when people seek to extract meaning from senseless sentences” (Kutas & Hillyard, 1980b). Today, the N400 is determined by its characteristic morphology and change in amplitude relative to deviant or unexpected stimuli (Kutas & Federmeier, 2011). Unlike other event related potentials, this potential was originally recorded as subjects silently read sentence stimuli (visual EP). Each sentence was seven words in length, presented one word at a time on flashcards. Each word appeared for 100 milliseconds at a rate of one word per second. There were 16 experimental blocks that consisted of 10 sentences each. The ERP was recorded and averaged across the entire sentence (Kutas & Hillyard, 1980b), which was about an eight second time base (Kutas & Hillyard, 1980a). To look at the N400, the time window following the seventh word was analyzed (Kutas & Hillyard, 1980a). The amplitude component of the N400 is the most sensitive measure in regards to changes in stimuli; while the latency of this ERP stays relatively stable (Kutas & Federmeier, 2011). As a result, generally, experiments look at the N400 effect. This effect is calculated by subtracting the waveform of one condition from the waveform from another condition, revealing amplitude differences between the conditions and thus the amplitude of the N400 component. There are a number of paradigms typically used to elicit the N400 response including priming paradigms, reading or listening for comprehension, lexical decision, among others (Kutas & Federmeier, 2009). The N400 has been elicited in both conditions where attention is required as well as conditions where the participant’s attention is directed elsewhere. (Federmeier, 2011; Perrin & Garcia-Larrea, 2003) The amplitude of N400 is larger when stimulus is semantically inappropriate or incongruent and smaller when stimulus is semantically appropriate or congruent. The amplitude is thought to be larger in response to the unexpected stimuli because it takes more neural resources to process the unexpected stimuli as compared to the expected stimuli (Kutas & Federmeier, 2011). As previously stated, the amplitude of the N400 is highly sensitive to a word’s semantic expectancy; but it is not sensitive to simple grammatical errors such as “the dog has four leg” (as opposed to ‘legs’), to congruently but physically unexpected endings such as “The girl wore a red DRESS” (as opposed to ‘dress’), or to unexpected events in other structured events such as music (Kutas & Hillyard, 1980b). Since the initial characterization of the N400 by Kutas and Hillyard, the general consensus is that all potentially meaningful items, across multiple modalities including spoken language and American Sign Language, linguistic and non-linguistic as well as auditory and non-auditory stimuli, can elicit an N400 effect (Kutas & Federmeier, 2009). Examples of stimulus that elicit N400 effects for priming and crosspriming studies include: incongruent pairs of words or pictures (Keifer, 2001; Nigam, Hoffman, & Simons, 1992), line drawings (Ganis, Kutas, & Sereno, 1996), environmental sounds (Orgs, Lange, & Dombrowski, 2006), faces (Nelson & Nugent, 1990), videos (Sitnikova, Kuperberg, & Holcomb, 2003), and gestures (Kelly, Kravitz, & Hopkins, 2004; Özyürek, Willems, Kita, & Hagoort, 2007; Wu and Coulson, 2007). Topographic mapping from several studies has shown different laterality depending on stimuli. For example it has been shown that the N400 effect was more right dominant for word stimuli and more left dominant for environmental sounds (Van Petten & Rheinfelder, 1995). What is also clear is that there are multiple sources that contribute to this evoked potential (Kutas & Federmeier, 2011). To further the understanding of the neural resources contributing to this potential, more recently, intracranial recording techniques have been used. Results from these studies and techniques suggest that there are a number of brain regions and neural resources that contribute to the N400 as it is recorded at the scalp level (Kutas & Federmeier, 2011). These studies have found contributing sites include the anterior medial temporal lobe, the middle and superior temporal areas, interior temporal areas and prefrontal areas from both hemispheres. (Kutas & Federmeier, 2011) Similarly, MEG data has implicated similar areas as previously stated (Kutas & Federmeier, 2011). The N400 has been used in research to answer questions about topics such as how meaningful information is stored in the brain (semantic memory), and to compare how the human brain uses auditory language versus visual language (Kutas & Federmeier, 2011), but perhaps the most important aspect of the N400 are the current and future clinical uses of this evoked potential. The N400 has been applied to a number of patient populations with varying pathologies including developmental disorders, neurological disorders and psychiatric disorders (Duncan et al, 2009). Within the realm of clinical assessment, the N400 can aid in quantifying clinical assessment for patients who have suffered strokes or traumatic brain injuries resulting in semantic comprehension deficit, as well as aid in the decision making process regarding surgery for those patients who suffer from focal seizure disorders often characterized by abnormal tissue in the temporal lobe just to name a few (Duncan et al, 2009). It has also been proposed that in the future, the N400 could assist in diagnostic classification of diseases such as Alzheimer’s disease. Another possible clinical use is to use the N400 in neurocognitive analyses of complex symptoms in patients with schizophrenia, but data at this point is still not conclusive (Duncan et al, 2009). The N400 ERP has been a useful tool in research thus far and has great promise to continue helping researchers uncover how the human brain works. Hopefully in time, this potential will become of more clinical utility and will be used more routinely by researchers and clinicians alike.

Sources

1. Duncan, C. C., Barry, R. J., Connolly, J. F., Fischer, C., Michie, P. T., Näätänen, R., & Van Petten, C. (2009). Event-related potentials in clinical research: guidelines for eliciting, recording, and quantifying mismatch negativity, P300, and N400. Clinical Neurophysiology, 120(11), 1883-1908.
2. Ganis, G., Kutas, M., & Sereno, M. I. (1996). The search for “common sense”: An electrophysiological study of the comprehension of words and pictures in reading. Journal of Cognitive Neuroscience, 8(2), 89-106.
3. Kelly, S. D., Kravitz, C., & Hopkins, M. (2004). Neural correlates of bimodal speech and gesture comprehension. Brain and language, 89(1), 253-260.
4. Kiefer, M. (2001). Perceptual and semantic sources of category-specific effects: Event-related potentials during picture and word categorization. Memory & Cognition, 29(1), 100-116.
5. Kutas, M &Federmeier, K. D. (2009) N400. Scholarpedia, 4(10):7790.
6. Kutas, M., & Federmeier, K. D. (2011). Thirty years and counting: finding meaning in the N400 component of the event-related brain potential (ERP).Annual review of psychology, 62, 621-647.
7. Kutas, M., & Hillyard, S. A. (1980a). Event-related brain potentials to semantically inappropriate and surprisingly large words. Biological Psychology,11(2), 99-116.
8. Kutas, M., & Hillyard, S. A. (1980b). Reading senseless sentences: Brain potentials reflect semantic incongruity. Science, 207(4427), 203-205.
9. Nelson, C. A., & Nugent, K. M. (1990). Recognition memory and resource allocation as revealed by children’s event-related potential responses to happy and angry faces. Developmental Psychology, 26(2), 171.
10. Nigam, A., Hoffman, J. E., & Simons, R. F. (1992). N400 to semantically anomalous pictures and words. Journal of cognitive neuroscience, 4(1), 15-22.
11. Orgs, G., Lange, K., Dombrowski, J. H., & Heil, M. (2006). Conceptual priming for environmental sounds and words: An ERP study. Brain and cognition, 62(3), 267-272.
12. Özyürek, A., Willems, R. M., Kita, S., & Hagoort, P. (2007). On-line integration of semantic information from speech and gesture: Insights from event-related brain potentials. Journal of Cognitive Neuroscience, 19(4), 605-616.
13. Perrin, F., & García-Larrea, L. (2003). Modulation of the N400 potential during auditory phonological/semantic interaction. Cognitive Brain Research.
14. Sitnikova, T., Kuperberg, G., & Holcomb, P. J. (2003). Semantic integration in videos of real–world events: An electrophysiological investigation.Psychophysiology, 40(1), 160-164.
15. Van Petten, C., & Rheinfelder, H. (1995). Conceptual relationships between spoken words and environmental sounds: Event-related brain potential measures. Neuropsychologia, 33(4), 485-508. Wu, Y. C., & Coulson, S. (2007). Iconic gestures prime related concepts: An ERP study. Psychonomic bulletin & review, 14(1), 57-63.