Research ReportSpatio-temporal processing of words and nonwords: Hemispheric laterality and acute alcohol intoxication
Introduction
Reading comprehension emerges from dynamic interactions among cortical areas comprised by a broadly generic neurofunctional system that is engaged by letter strings differing in semantic, lexical and orthographic attributes. This multidimensional process has been investigated extensively with neuroimaging methods such as event-related potentials (ERPs) and functional magnetic resonance imaging (fMRI) that draw on their respective advantages in temporal dynamics vs. spatial mapping.
A huge body of ERP literature (Kutas and Federmeier, 2011) has explored a negative deflection peaking at ~400 ms (N400) which is sensitive to low-level lexical and orthographic factors, as well as semantic, mnemonic, and contextual aspects when reading single words, sentences, and discourse-level text (Hagoort and van Berkum, 2007, Halgren, 1990, Kutas and Federmeier, 2000, Osterhout and Holcomb, 1995). The N400 is modulated by a broad range of influences and may reflect an attempt to access lexicosemantic networks and integrate potentially meaningful stimuli into the current context (Bentin et al., 1985, Federmeier and Laszlo, 2009, Halgren, 1990, Holcomb, 1993, Kutas and Federmeier, 2000, Van Petten and Luka, 2006), see Kutas and Federmeier (2011) for an extensive discussion. The N400 amplitude is commonly greater to pseudowords, orthographically regular, pronounceable nonwords (PN) that carry no meaning (e.g. blont), as compared to real words (RW) (Bentin et al., 1985, Holcomb et al., 2002, Smith and Halgren, 1987, Ziegler et al., 1997). Under exceptional circumstances the N400 can also be elicited by orthographically illegal, nonpronounceable nonwords (NN, e.g. kdzv) (Laszlo et al., 2012). However, the neural basis of these effects is not well understood, prompting questions such as: to what degree are real words and pseudowords subserved by the same neurofunctional network; at which spatiotemporal processing stage does the divergence take place; are orthographically legal nonwords (PN) and illegal letter strings (NN) processed by different neural networks; are there hemispheric laterality differences in subserving different types of letter strings? Intracranial EEG evidence is limited in that regard (Nobre and McCarthy, 1995), but it suggests that, whereas the NN do not elicit the N400, the N400 generated by PN in the anterior temporal lobe is somewhat smaller than the negativity to real words. MEG evidence obtained with the equivalent current dipole modeling approach indicates that the RW and PN elicit stronger left-lateralized N400 magnetic equivalent (M400) than NN in the superior temporal cortex (Vartiainen et al., 2011). Functional MRI studies generally report that PN and RW activate the same left-lateralized fronto-temporal network, commonly with greater prefrontal activation to PW than RW (Clark and Wagner, 2003, Gold and Buckner, 2002, Mechelli et al., 2005). Evidence on NN is less clear but it appears that whereas the RW and PW elicit a strongly left-lateralized activity, the NN tend to evoke bilateral activation (Henson et al., 2002, Tagamets et al., 2000, Vigneau et al., 2005), but see Vinckier et al. (2007). However, even though the fMRI method is an excellent mapping tool, it cannot provide insight into the real time processing dynamics, making the correspondence between the observed activation patterns and the N400 ambiguous.
Studies in healthy social drinkers indicate that acute alcohol intoxication impairs cognitive control (Field et al., 2010, Finn, 2000). Neuroimaging evidence indicates that the anterior cingulate cortex (ACC), as a central node subserving conflict processing, is uniquely sensitive to alcohol intoxication in conflict-inducing tasks such as the Stroop task (Kovacevic et al., 2012, Marinkovic et al., 2012a). In a recent companion paper, we have reported that alcohol attenuates event-related theta power estimated to ACC during response conflict in a double-duty lexical decision task (Marinkovic et al., 2012b). Moreover, in agreement with their sensitivity to memory processes (Klimesch et al., 2001), theta oscillations seem to reflect lexicosemantic retrieval of word meaning as they are greater to RW in comparison to meaningless but orthographically legal PN. Acute alcohol intoxication attenuates theta power to RW but not PN, suggesting that it selectively affects lexicosemantic processing (Marinkovic et al., 2012b). This is consistent with behavioral evidence of alcohol effects on semantic memory access (Acheson et al., 1998, Maylor et al., 1990). There have been no reports, however, on whether N400 deflections to letter strings differing in meaning and orthographic legality are dissociated under alcohol intoxication. A single previous ERP study that examined acute alcohol effects on language processing used only real words in a priming paradigm (Marinkovic et al., 2004b). The reported alcohol-induced attenuation of the posterior N180 is suggestive of deficient prelexical processing whereas an amplified N400 may indicate increased difficulty in accessing lexicosemantic representations of real words. Whether real words and different types of nonwords would be differentially affected by alcohol remains an outstanding question, along with the need to gain more precise insight into the neural basis of such effects.
The principal objective of the current study was to examine spatiotemporal stages of processing of words and nonwords as a function of acute alcohol intoxication. To that end, we employed an anatomically-constrained MEG method that combines distributed source modeling of the MEG signal with structural MRI. The resulting “brain movies”, statistical parametric maps of estimated cortical activity across time, provide estimates of the anatomical distribution of the underlying neural networks in a time-sensitive manner (Dale et al., 2000, Dhond et al., 2001, Marinkovic et al., 2003). Scalp EEG was recorded simultaneously with MEG from a limited montage for comparison purposes. Healthy social drinkers (N=22) participated in a lexical decision task under both alcohol and placebo conditions in a counterbalanced design. They were asked to detect real words while ignoring nonwords consisting of both PN and NN (Fig. 1). In this double-duty paradigm, response conflict was induced by an additional requirement to respond to all real words that also referred to animals (AW). The design made it possible to investigate effects of meaning, orthographic regularity, and decision conflict on the underlying neural dynamics. This approach can reveal what type of information is accessed at different stages of reading and could contribute to the long-standing discussion of the models of reading (Coltheart et al., 2001, Harm and Seidenberg, 2004). Furthermore, pharmacological manipulation of alcohol could facilitate parsing different aspects of word/nonword processing and indicate whether lexicosemantic access is selectively vulnerable to the effects of intoxication.
Section snippets
Task performance
Performance accuracy differed across the four letter string types as indicated by the main effect of condition, F[3,63]=20.0, p<0.00001, with percent accuracy means (±SD) as follows: RW: 91.1 (±7.2), AW: 83.2 (±9.5), PN: 93.0% (±13.0), and NN: 98.4% (±3.5), Fig. 2. Accuracy was the lowest to AW, F[1,21]=55.7, p<0.00001 and the highest to NN as compared to other conditions, F[1,21]=56.8, p<0.00001. Subjects tended to be slower to respond to AW than to RW, F[1,21]=3.9, p=0.06, with means (±SD) of
Discussion
The overall spatiotemporal pattern of activity to real words and pseudowords observed in this study is consistent with the highly replicable left-lateralized visual word processing activity that starts in the occipital cortex, advances along the ventral visual stream and engages lateral temporal and anteroventral prefrontal cortices (Dale et al., 2000, Dhond et al., 2001, Dhond et al., 2003, Halgren et al., 2002, Marinkovic et al., 2003). In contrast, orthographically illegal letter strings
Participants
All sessions of the experiment were completed by twenty-two participants (12 men, mean±SD age=24.9±4.5 years) who were all healthy, right-handed, non-smoking native English speakers. Prior to the study, all prospective participants were carefully screened on a number of criteria and were excluded if they were left-handed, if they were under 21 years of age, if they were not native speakers of English, if they were on any medication, if they had a history of seizures or heady injury leading to
Acknowledgments
This research was supported by Funds from the National Institutes of Health (K01-AA13402 and R01-AA016624 (to KM), K01-MH079146 (to DJH), RR031599), and MIND Institute. The data were collected at Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA. We thank Jonathan Dan, Jason Sherfey, and Sanja Kovacevic for assistance.
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