Reduced resource optimization in male alcoholics: N400 in a lexical decision paradigm

Abstract

Background: Event Related Potential (ERP) studies have highlighted some measures, notably P3 amplitude, that are associated with both state and trait deficits in alcoholism, while studies examining N400 amplitude in alcoholism are few. The present study aims to examine differences in the N400 component, an electrophysiological correlate of semantic priming, in event-related potentials from a lexical decision task in 87 alcohol dependent subjects and 57 community controls.

Methods: Each subject was presented with 300 stimuli sequentially in a quasi-randomized design, where 150 stimuli were words and 150 were non-words. The subjects made a lexical decision indicating the word/non-word status with a button press. Among the words, 50 words (primed) were always preceded by their antonyms (prime, n=50), whereas the remaining 50 words were unrelated. N400 amplitude and latency measures were compiled from ERPs to the primed and unprimed words. Corresponding reaction time (RT) and response characteristics were also analyzed.

Results: Control subjects revealed a significant attenuation of the N400 response to the primed word when compared to the unprimed word. Significantly less attenuation was observed in alcohol dependent subjects. No significant group differences were seen for latency and behavioral measures. All subjects had slower RT for unprimed words compared to primed words; however significantly less RT savings between the unprimed and primed condition was noted for alcoholics.

Conclusions: These results suggest a reduced flexibility in the cognitive networks and a lack of resource optimization in alcoholics. The reduced attenuation of N400 during the primed condition in the alcohol dependent subjects may reflect an inability to engage similar neuronal substrates associated with semantic relatedness as seen in the controls. As diminished N400 attenuation during priming is observed in both alcoholics and high risk subjects, it may be a marker of risk and a good endophenotype for alcoholism.

Figure 1

Sample of words used in the task, its corresponding priming condition and the order of presentation.

Figure 2

Grand average waveforms for alcoholics and controls for the primed and unprimed condition.

Figure 3

ERP waveform in primed and unprimed condition illustrating the N400 component for alcoholics and controls

Figure 4

CSD (current source density) map in alcoholics and controls describing the source (red) and sink (blue) for primed (P) and unprimed (U) conditions from a fixed latency slice at 325 ms near the peak N400 response.