Psychophysiological correlates of coping and quality of life in patients with ALS

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Highlights

  • N400 event-related potentials can be reliably elicited in patients with amyotrophic lateral sclerosis and quality of life modulates the N400 amplitude in response to incongruent disease-related words.

  • Healthy subjects do not show this effect.

  • N400 modulation might serve as a psychophysiological correlate of quality of life.

Abstract

Objective

Self-regulation models of coping suggest that patients with chronic diseases reporting low quality of life (QoL), an indicator of failed coping efforts, should show facilitated access to disease related words. Here we investigated whether a reduced N400 amplitude within an incongruent, i.e. unpredictable disease-related context would be a correlate of this facilitated access.

Methods

ERPs were recorded in N = 18 patients with amyotrophic lateral sclerosis (ALS) and N = 20 age-matched healthy controls during reading of sentences, ending either with congruent or incongruent words. Incongruent and congruent words were disease related or disease unrelated. Mean N400 amplitudes were analyzed with mixed models.

Results

Generally, incongruent words elicited a more negative N400 amplitude than congruent words in all groups and conditions, i.e. an N400 effect. In patients with high QoL this N400 effect did not differ between disease related and unrelated words. In patients with low QoL, however, the N400 effect was significantly smaller for disease related than for disease unrelated words. In healthy controls N400 amplitudes showed no such interaction between congruence, disease relatedness and QoL. Results remained stable when controlling for disease severity, duration and depression.

Conclusion

The N400 indicates increased accessibility to disease related information in ALS patients with low QoL. The increased access may imply a constantly activated disease related context which is linked to low QoL.

Significance

N400 modulation by disease related information may serve as a psychophysiological correlate of coping and the patient’s QoL.

Introduction

Amyotrophic lateral sclerosis (ALS) is a rare degenerative disorder marked by progressive paralysis and ultimately death. However, many studies have demonstrated that subjective quality of life (QoL), an important indicator of the impact of, or coping with, a disease, can be rather high in patients with ALS. Moreover, QoL was found to be relatively independent of medical aspects of the ALS, such as disease severity or duration (Kübler et al., 2005, Rabkin et al., 2000, Robbins et al., 2001), but strongly influenced by psychosocial factors (Lulé et al., 2009, Matuz et al., 2010, McDonald et al., 1994, Plahuta et al., 2002). In the present study, we aimed at establishing a psychophysiological correlate of subjective QoL and thus, coping with a severe and terminal disease.

Subjective QoL may be defined as “the difference between the hopes and expectations of the individual and that individual’s present experiences” (Calman, 1984). It is low if the difference is large, e.g. because of a serious disease, and high if the difference is low, e.g. due to successful coping (Lazarus and Folkman, 2008, Rapkin and Schwartz, 2004). The relation between these differences and the use of coping strategies has been described (Cameron and Leventhal, 2002) with reference to a simple feedback loop (TOTE model: test-operate-test-exit; Miller et al., 1986): Individuals first test for the presence of a difference between their expectations and their experiences and then engage in various operations to reduce this difference. The difference is then tested again, and the cycle iterates until expectations and experiences match. This model predicts that individuals who report low QoL repeatedly compare their experiences with their expectations but might be unsuccessful in effectively reducing the difference between the two. In the context of a severe disease, patients who report low QoL might therefore tend to compare their experiences with their expectancies repeatedly, without being able to bridge the gap between their hopes and their current situation.

To test this hypothesis we examined the N400 event related potential (ERP) to disease related and disease unrelated words in patients with ALS and healthy controls. The N400 is a negative ERP deflection with a peak latency about 400 ms after the onset of a meaningful stimulus (usually, a word) that is incongruent with the preceding context (Kutas and Hillyard, 1980). However, the absolute value of the N400 does not need to be negative. It is, therefore, typically examined by evaluating a difference ERP created by subtracting the EEG signal in one condition from the signal in another condition (Kutas and Federmeier, 2011). Besides semantic congruence, predictability in general has been found to modulate the N400, with larger amplitudes following non-predictable sentence endings even when the ending itself is semantically congruent with the sentence content (Kutas and Hillyard, 1984, Lau et al., 2008). N400 effects are further modulated by word frequency such that unpredictable high frequency words elicit a smaller N400 amplitude than unpredictable low frequency words (Allen et al., 2003, van Petten and Kutas, 1990).

In summary, applying the TOTE model to coping with diseases suggests that disease related concepts are repeatedly processed in patients reporting low QoL. When such concepts are presented in a sentence context, amplitudes of the N400 potential are inversely related to the ease of lexical access, with lower amplitudes reflecting facilitated access to the mental lexicon. ALS patients who report low QoL should be confronted with disease specific concepts more often than patients who report high QoL. This should make the processing of disease related words easier in ALS patients with poor QoL than in patients with high QoL. Therefore, an N400 effect between incongruent and congruent disease related words should be reduced in patients with low QoL as compared to patients with high QoL. Further, these differences should be specific for disease-related material, and not be obtained for disease unrelated words, i.e. N400 effects to disease unrelated words should be independent of QoL. To ensure that our proposed results would be truly disease related, healthy age-matched volunteers served as controls. Healthy controls were expected to show only an effect of congruence, but not an interaction of congruence, disease relatedness, and QoL.

Section snippets

Participants

Patients were recruited at the ALS outpatient clinic of the Department of Neurology, University Hospital of Würzburg. The initial patient sample comprised N = 21 patients fulfilling the revised El Escorial criteria of clinically definite or clinically probable ALS (Brooks et al., 2000). Exclusion criteria were a history of any other neurological or psychiatric disorder and disease duration of less than 3 months. The three-month criterion was chosen because coping processes in the acute phase

Description of samples

Sample characteristics are shown in Table 1. Patients and controls did not differ in age, t(36) = 0.15, p = .89, or quality of life t(24.77) = −1.22, p = .23, but patients showed a trend towards higher depression scores in the BDI-II, t(35) = 1.83, p = .07, and significantly higher scores in the ADI-12, t(35) = 3.99, p < .01.

Grand mean ERP waveforms of congruent vs. incongruent, and disease related vs. disease unrelated target words are presented in Fig. 1, separately for patients (top) and healthy controls

Discussion

In this study, the accessibility of disease related words was investigated in patients with a severe and terminal disease. N400 effects were examined as a function of self-reported QoL to determine if N400 effects could serve as an psychophysiological correlate of coping with a disease. Theoretically, our approach is based on models and previous research, according to which QoL serves as a measure of coping with a disease (Matuz et al., 2010). In line with this view, patients who have

Conflict of interest statement

The authors declare no competing financial interests.

Acknowledgements

R. Real received a grant by the Graduate School of Life Sciences of the University of Würzburg (RTG 1253/1). Funded by FP7-ICT-2009-4, Grant 247919 (DECODER). B. Kotchoubey was supported by German Research Society (Deutsche Forschungsgemeinschaft) Grant KO-1753-10.

This work was supported by the European ICT Program Project FP7-247919. Possible inaccuracies of information are under the responsibility of the project team. The text reflects solely the views of its authors. The European Commission

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