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Stable motor cortex excitability in red and green lighting conditions
Neuroscience Letters 460 (2009) 32–35
Contents lists available at ScienceDirect
Neuroscience Letters journal homepage: www.elsevier.com/locate/neulet
Stable motor cortex excitability in red and green lighting conditions Berthold Langguth a,∗ , Peter Eichhammer a , Karin Pickert a , Ulrike Frank a , Martin Perna a,b , Michael Landgrebe a , Ulrich Frick a , Goeran Hajak a , Philipp Sand a a b
Department of Psychiatry, University of Regensburg, Universitaetsstrasse 84, 93053 Regensburg, Germany Department of Psychiatry, University of Brno, Czech Republic
a r t i c l e
i n f o
Article history: Received 11 March 2009 Received in revised form 29 April 2009 Accepted 12 May 2009 Keywords: Transcranial magnetic stimulation Cortical excitability Intracortical inhibition Colour blindness Colour stimulation
a b s t r a c t Illumination science has long established effects of coloured light on emotional state, cognitive performance, plus tactile, gustatory and olfactory perception. To explore the neurobiological mechanisms underlying these crossmodal phenomena, cortical excitability was addressed by single and paired-pulse transcranial magnetic stimulation (TMS) in 23 men with normal colour vision, and in 10 subjects with red–green blindness. Using a sequential challenge, excitability measures were recorded at baseline and during exposure to either red or green light. Dichromacy did not predict any of the electrophysiological parameters under study regardless of the spectral paradigm. In both dichromats and trichromats, red and green illumination did not induce any significant effects on resting motor threshold, short intracortical inhibition, intracortical facilitation and cortical silent periods. Our results suggest that motor cortex excitability as assessed by TMS is not sensitive to the modulatory effects of context-independent red and green light. © 2009 Elsevier Ireland Ltd. All rights reserved.
Our perception of the world integrates information delivered by multiple sensory modalities. Of these, colour vision plays a key role by acting on other sensory, motor and information processing systems [26], plus on emotional connotations. Coloured light may cause dizziness [20] and may shift circadian rhythms [22] leading to changes in body temperature and melatonin secretion [10]. In addition, colour-evoked changes in taste [13], appetite [27], mood [16] cognition [2], motor performance [11], and muscular strength [5] have been reported. Thus muscular power was increased in an anaerobic cycling test under ambient red light, and hand grip strength was decreased in blue light as compared to white light [5]. The interplay between colours and brain function may confer behavioral fitness that has served to select against non-trichromatic vision in primate evolution [21]. Occasionally, cross-talk between regions of the brain involved in colour-processing and those controlling other tasks can manifest as colour synesthesia. This rare condition is marked by co-stimulation of chromatic visual and non-visual sensory or cognitive pathways [23]. Supposedly, co-stimulation results from a disturbed balance in excitation and inhibition along feedback pathways in the brain [7]. Biological underpinnings of crossmodal phenomena, however, remain poorly explored. Specifically, little is known on the role played by cortical excitability in mediating the individual response to a given spectral environment. Transcranial magnetic stimula-
∗ Corresponding author. Tel.: +49 941 941 2099; fax: +49 941 941 2025. E-mail address: [email protected] (B. Langguth). 0304-3940/$ – see front matter © 2009 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.neulet.2009.05.034
tion (TMS) is a non-invasive technique for assessing excitability of the motor cortex that has been employed to visualize tactile [19], auditory [14], olfactory [24] and visual input [18]. The reported role of ambient coloured light on muscular power and strength [5] prompted us to employ TMS for measuring the impact of red and green light on motor cortex excitability. To test for specificity of effects, we compared parameters of cortical excitability from trichromats with those obtained in dichromats. Experiment 1. In the first experiment, motor cortex excitability was investigated under three ambient conditions (no visual stimulation, exposure to red light, and exposure to green light) in 10 men with red–green colour blindness (three subjects with protoanopia, seven subjects with deuteranopia; mean age = 27.9 ± 8.7 years, range = 20–44 years) and in 10 men with normal colour vision (mean age = 27.1 ± 4.3 years, range = 22–39 years). Colour vision was evaluated in all subjects by the Ishihara and the FarnsworthMunsell 100-hue test [3]. For the experiment, participants sat relaxed in a reclining armchair as visual stimuli were presented and measurements were obtained. Colours were generated in randomized order (red–dark–green, or green–dark–red) by video goggles (Sony personal LCD video Monitor PLM-A35E; two .55 in. LCDs with 800 × 255 pixel resolution, connected to Sony DVP-FX1) [17]. Red and green light was generated digitally and was matched for colour intensity and brightness. Following the exposure to coloured light, goggles were switched off (darkness condition). For all three visual conditions, motor cortex excitability measurements were performed after 10 min of adaptation. Excitability measurements lasted about 30 min, resulting in a total duration of about 40 min
B. Langguth et al. / Neuroscience Letters 460 (2009) 32–35
33
Fig. 1. Each experimental session consisted of three measurements of cortical excitability under different visual conditions (red light exposure, green light exposure, darkness). The control condition (darkness) was always second in order, the order of red and green light exposure was randomized. Measurements of cortical excitability included resting motor threshold (RMT), cortical silent period (CSP), short intracortical inhibition (SICI) and intracortical facilitation (ICF).
per ambient condition (Fig. 1). This experimental setup allowed for comparison of recordings during red and green light exposure with recordings in darkness as the control condition. Experiment 2. In the second experiment, an additional 13 male subjects (mean age = 24.9 ± 2.4 years, range = 22–29 years) with normal colour vision were examined to address a possible order effect of colour exposure. Each subject underwent two sessions, one starting with green light exposure and other starting with red light exposure. The order of the two sessions was randomly assigned. Participants were recruited by advertisements and included medical students and hospital staff. All participants were free of medication and free of any DSM-IV diagnosis as verified during an interview by board-certified specialists (B.L. and M.L.). Written informed consent was obtained from each subject. The study protocol was approved by the local ethics committee. Excitability measurements included the assessment of resting and active motor threshold (RMT, AMT), cortical silent period (CSP), short intracortical inhibition (SICI) and intracortical facilitation (ICF). TMS was delivered over the optimal representation of the right abductor digiti minimi (ADM). TMS was performed using two Magstim 200 stimulators (Magstim Co., Whiteland, Dyfed, UK) connected via a Bistim module to a figure-of-eight coil (double circular 70 mm coil). The coil was held in the optimal position, i.e. with the junction of the two wings tangential to the skull and the handle pointing backwards and ∼45◦ away from the midline. Thus the induced current in the brain was directed about perpendicularly to the presumed direction of the central sulcus. We recorded motor-evoked potentials (MEPs) from the ADM at rest using surface electrodes in a belly-tendon montage (filters 20 Hz–10 kHz; A/D rate 5 kHz). 50 ms of prestimulus EMG were recorded to assess muscle relaxation. Reducing the stimulus intensity in steps of 1%, we defined the resting motor threshold (RMT) as the lowest intensity at which at least four of eight consecutive MEPs were ≥50 V in amplitude while the investigated muscle was at rest [25]. Audio–visual electromyographic feedback was provided to control for muscle relaxation. Active motor threshold (AMT) was determined as the lowest stimulation intensity that evoked a MEP ≥ 250 V in at least four of eight consecutive trials during voluntary abduction of the small finger. A constant level of voluntary contraction was maintained by audio–visual feedback of the EMG activity. MEP amplitudes were measured peak to peak. Cortical silent period (CSP) was measured in 10 trials at a stimulus intensity of 150% RMT with an inter-sweep interval of 5 s in the moderately active ADM (voluntary abduction with 30% of maximal force, monitored by audio–visual electromyographic feedback). CSP duration was defined as the interval between the end of the MEP and first reappearance of voluntary EMG activity. Measurements were obtained off-line on the non-rectified recording of every individual sweep and were then averaged. Intracortical excitability was measured using the paired-pulse paradigm consisting in a first subthreshold conditioning pulse fol-
lowed by a second suprathreshold test pulse [15]. The intensity of the first stimulus was set to 80% RMT while the intensity of the second stimulus was adjusted to produce an unconditioned MEP of ∼1 mV. Interstimulus intervals of 2, 3, 4, 5, 7, 8, 10, 15 and 20 ms were tested in random order using 10 or more recordings per interval. The interval between sweeps was 4 s. Measurements were performed off-line on the non-rectified recording of every individual sweep and were then averaged. The effect of conditioning stimuli on MEP amplitude at each ISI was determined as the ratio of the average amplitude of the conditioned MEP to the average amplitude of the unconditioned test MEP obtained in the same block of trials. As it was known from previous studies [15] that the conditioning stimulus exerts a suppressive effect on the control MEP at short ISIs (2, 3, 4, and 5 ms), and a facilitatory effect at longer ISIs (7, 8, 10, 15, and 20 ms), analyses of SICI and ICF were conducted separately for short vs. long ISIs. Separate analysis of variance (ANOVA) models were used for the respective motor excitability parameters (RMT, CSP, SICI and ICF) with chromatic vision (i.e. normal colour vision and colour blindness) as between-subjects factor (experiment 1) and lighting condition (i.e. red light, green light, and darkness) as within-subject factor (experiments 1 and 2). Age and order of lighting conditions (red first vs. green first) were entered as covariates. In addition, excitability parameters of both groups (experiment 1) in the control condition were compared by t-test. The level of significance was set at 0.05. Due to the exploratory character of this study, corrections for multiple comparisons were not performed. All experimental procedures were tolerated by the participants without any relevant side effects. At the 5% level of significance, dichromats and trichromats did not differ with regard to any of the excitability parameters in experiment 1 (Table 1; RMT: T = 0.00; d.f. = 18; p = 1.0; CSP: T = −0.13; d.f. = 18; p = 0.90; SICI: T = 0.18; d.f. = 18; p = 0.86; ICF: T = −0.23; d.f. = 18; p = 0.82). Similarly, exposure to coloured light did not elicit significant effects on any of these parameters (effect of lighting condition—RMT: F = 0.30; d.f. = 2, 30; p = 0.75; CSP: F = 0.19; d.f. = 2, 30; p = 0.83; SICI: F = 0.95; d.f. = 2, 30; p = 0.40; ICF: F = 0.48; d.f. = 2, 30; p = 0.62). Moreover, no significant interaction of chromatic vision and lighting condition was detected (interaction term—RMT: F = 0.52; d.f. = 2, 30; p = 0.60; CSP: F = 0.21; d.f. = 2, 30; p = 0.82; SICI: F = 1.03; d.f. = 2, 30; p = 0.37; ICF: F = 1.6; d.f. = 2, 30; p = 0.21). The order of lighting conditions per session, which was entered as a covariate in the analysis, emerged as a confounder of ICF (order × lighting condition: F = 7.6; d.f. = 2, 30; p = 0.002; chromatic vision × order × lighting condition: F = 3.59; d.f. = 2, 30; p = 0.04). Stimulus order did not affect the remaining parameters of cortical excitability. In experiment 2, excitability parameters were again resistant to effects of lighting colour (RMT: F = 0.36; d.f. = 2, 46; p = 0.70; CSP: F = 0.42; d.f. = 2, 46; p = 0.66; SICI: F = 0.14; d.f. = 2, 46; p = 0.87; ICF: F = 0.51; d.f. = 2, 46; p = 0.60). As opposed to experiment 1, we observed a significant interaction of stimulus order and lighting condition for RMT (F = 9.7; d.f. = 2, 46; p < 0.005). However, crosswise comparison of all conditions (red first, green first, red second,
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B. Langguth et al. / Neuroscience Letters 460 (2009) 32–35
Table 1 Motor cortex excitability measurements in experiments 1 and 2 under the respective lighting conditions. RMT: resting motor threshold; CSP: cortical silent period; SICI: short intracortical inhibition; ICF: intracortical facilitation. Group
Age
Experiment 1 Colour-blind
27.9 ± 8.7 years
Normal colour vision
Experiment 2 Normal colour vision
N
Light condition
Order
RMT
CSP
SICI
4 6 4 6 4 6
Darkness Darkness Red Red Green Green
r-d-g g-d-r r-d-g g-d-r r-d-g g-d-r
41.3 45.0 40.0 44.8 40.8 46.5
± ± ± ± ± ±
8.0 5.3 4.9 5.1 4.7 7.1
152 ± 15 160 ± 29 136 ± 14 156 ± 29 155 ± 20 157 ± 26
0.68 0.58 0.69 0.55 0.67 0.54
27.1 ± 4.3 years
5 5 5 5 5 5
Darkness Darkness Red Red Green Green
r-d-g g-d-r r-d-g g-d-r r-d-g g-d-r
43.2 43.8 42.6 43.0 40.8 44.2
± ± ± ± ± ±
3.7 7.7 4.3 5.4 1.3 8.2
134 183 125 183 131 192
± ± ± ± ± ±
25.1 ± 2.4 years
13 13 13 13 13 13
Darkness Darkness Red Red Green Green
r-d-g g-d-r r-d-g g-d-r r-d-g g-d-r
37.7 37.6 38.8 37.0 37.8 39.3
± ± ± ± ± ±
6.6 5.9 6.4 5.5 6.4 6.0
132 127 137 126 139 133
± ± ± ± ± ±
ICF ± ± ± ± ± ±
0.36 0.05 0.47 0.07 0.24 0.05
1.33 1.23 1.55 1.12 1.24 1.35
± ± ± ± ± ±
0.18 0.36 0.26 0.17 0.21 0.28
10 37 25 32 17 44
0.67 ± 0.21 0.53 ± 0.10 0.67 ± 0.17 0.58 ± 0.08 0.59 ± 0.13 0.48 ± 0.21
1.32 1.28 1.19 1.21 1.19 1.35
± ± ± ± ± ±
0.20 0.31 0.04 0.25 0.16 0.47
30 32 33 38 27 30
0.67 0.72 0.67 0.85 0.79 0.76
± ± ± ± ± ±
1.29 1.16 1.33 1.34 1.39 1.35
± ± ± ± ± ±
0.32 0.16 0.40 0.42 0.62 0.40
0.21 0.22 0.19 0.25 0.32 0.26
Excitability parameters proved stable with regard to chromatic vision (colour-blind vs. normal colour vision) and lighting conditions (red light vs. green light vs. darkness) (all p > 0.05).
green second) by t-tests did not reveal any significant effect. For the other excitability measures, no interaction of order and lighting condition was observed (CSP: F = 0.26; d.f. = 2, 46; p = 0.77; SICI: F = 1.55; d.f. = 2, 46; p = 0.22; ICF: F = 0.51; d.f. = 2, 46; p = 0.60). When data from experiments 1 and 2 were combined, the interaction of stimulus order and lighting condition for RMT no longer reached significance (RMT: F = 2.58; d.f. = 2, 82; p = 0.08). Using four electrophysiological parameters, no significant differences were detected in excitability profiles of dichromats and sex- and age-matched trichromats. An apparent effect of stimulus order on ICF in experiment 1 was most probably caused by limited group size and disappeared in experiment 2. Likewise, the observed interaction of lighting condition and stimulus order in experiment 2 disappeared when data from both experiments were pooled. The decrease in RMT is best explained by increasing muscle tension over the course of the second experiment. Our findings count against a motor cortical functionality of red and green light in otherwise healthy individuals. Moreover, as red and green stimuli failed to elicit a distinct motor cortical response in trichromats, it appears unlikely that compensatory mechanisms may have obscured any effects specific to colour-blind individuals. Overall, our data refer to 46 experimental sessions in 10 colourblind subjects and in 23 subjects with normal chromatic vision (of these, 13 subjects participated in both experiments). Due to the relatively small sample size of both groups in experiment 1, however, and in view of the known variability in measures of motor cortex excitability [29], minor effects of dichromacy may have gone unnoticed. Earlier assessments of primary visual cortex excitability by visually evoked potentials under red light conditions have led to mixed results [28,1,4] but crossmodal effects of red and green light have not been systematically addressed. Specifically, it is not known whether effects of coloured light may be compared to effects observed with other forms of colour presentation that are dependent on contextual information. E.g., green colour may reduce subjective loudness perception depending on the extent to which the green colour is associated to natural elements, such as leaves of a tree [6]. In another study, motor cortex excitability was only modified by smell in case of congruence of the sniffed odour and the observed grasped food [24]. Similarly, a role for colours on motor
behavior has been evidenced in specific contextual situations [9]. Thus it is conceivable that effect size is reduced in context-free exposure to coloured light as performed in our experiment. Regarding motor cortical excitability, only one previous study has used a visual challenge paradigm similar but not identical to our settings [18]. In the investigation by Leon-Sarmiento et al., motorevoked potentials and short intracortical inhibition were sensitive to darkness as caused by the blindfolding of eyes with a mask. The light stimulus was defined as a standard room lighting condition [18]. No such effects were seen when the “goggles-off” condition was compared to “goggles-on” conditions using coloured light in our study. Differences may be explained by the settings employed to examine illumination colours and cone-mediated stimuli, rather than darkness vs. illumination, i.e. mostly rod-mediated effects. In conclusion, we have shown similar motor cortex responses in dichromats and trichromats, and negligible crossmodal effects of both red and green light in healthy subjects. The outcome may serve to reassure those who are routinely exposed to contextindependent ambient red or green light. Many nocturnal tasks of astronomers, military air crew and other professionals are performed under red light conditions to avoid desensitization of rod cells [8]. Insight into the cortical effects of coloured light may be used to further improve safety, or to enhance productivity at the workplace [12]. Further investigations are invited to address context specificity, plus putative crossmodal effects of blue light, and to explore motor cortical excitability in subjects with colour synesthesia. Acknowledgements We gratefully acknowledge helpful discussions with Dr. R. Remmel and Dr. C. Dardenne, Dardenne Eye Clinic, Bad Godesberg. We also want to thank Helene Niebling and Sandra Pflügl for technical assistance. References [1] J. Afra, A. Ambrosini, R. Genicot, A. Albert, J. Schoenen, Influence of colors on habituation of visual evoked potentials in patients with migraine with aura and in healthy volunteers, Headache 40 (2000) 36–40.
B. Langguth et al. / Neuroscience Letters 460 (2009) 32–35 [2] J.S. Bedwell, D.M. Orem, The effect of red light on backward masking in individuals with psychometrically defined schizotypy, Cogn. Neuropsychiatry 13 (2008) 491–504. [3] B.L. Cole, Assessment of inherited colour vision defects in clinical practice, Clin. Exp. Optom. 90 (2007) 157–175. [4] R.L. Cowan, B.B. Frederick, M. Rainey, J.M. Levin, L.C. Maas, J. Bang, J. Hennen, S.E. Lukas, P.F. Renshaw, Sex differences in response to red and blue light in human primary visual cortex: a bold fMRI study, Psychiatry Res. 100 (2000) 129–138. [5] D.K. Crane, R.W. Hensarling, A.P. Jung, C.D. Sands, J.K. Petrella, The effect of light color on muscular strength and power, Percept. Motor Skills 106 (2008) 958–962. [6] H. Fastl, Audio–visual interactions in loudness evaluation, in: Proc. 18th International Congress on Acoustics, Kyoto, Japan, 2004, pp. 1161–1166. [7] P.G. Grossenbacher, C.T. Lovelace, Mechanisms of synesthesia: cognitive and physiological constraints, Trends Cogn. Sci. 5 (2001) 36–41. [8] D.P. Hightower, S.H. Thomas, C.K. Stone, S. Brinkley, D.F. Brown, Red cabin lights impair air medical crew performance of color-dependent tasks, Air Med. J. 14 (1995) 75–78. [9] R.A. Hill, R.A. Barton, Psychology: red enhances human performance in contests, Nature 435 (2005) 293. [10] G. Hoffmann, V. Gufler, A. Griesmacher, C. Bartenbach, M. Canazei, S. Staggl, W. Schobersberger, Effects of variable lighting intensities and colour temperatures on sulphatoxymelatonin and subjective mood in an experimental office workplace, Appl. Ergon. 39 (2008) 719–728. [11] M. Imhof, Effects of color stimulation on handwriting performance of children with ADHD without and with additional learning disabilities, Eur. Child Adolesc. Psychiatry 13 (2004) 191–198. [12] H.T. Juslen, M.C. Wouters, A.D. Tenner, Lighting level and productivity: a field study in the electronics industry, Ergonomics 50 (2007) 615–624. [13] T. Katsuura, X. Jin, Y. Baba, Y. Shimomura, K. Iwanaga, Effects of color temperature of illumination on physiological functions, J. Physiol. Anthropol. Appl. Hum. Sci. 24 (2005) 321–325. [14] A.A. Kuhn, A. Sharott, T. Trottenberg, A. Kupsch, P. Brown, Motor cortex inhibition induced by acoustic stimulation, Exp. Brain Res. 158 (2004) 120–124. [15] T. Kujirai, M.D. Caramia, J.C. Rothwell, B.L. Day, P.D. Thompson, A. Ferbert, S. Wroe, P. Asselman, C.D. Marsden, Corticocortical inhibition in human motor cortex, J. Physiol. 471 (1993) 501–519.
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Contents lists available at ScienceDirect
Neuroscience Letters journal homepage: www.elsevier.com/locate/neulet
Stable motor cortex excitability in red and green lighting conditions Berthold Langguth a,∗ , Peter Eichhammer a , Karin Pickert a , Ulrike Frank a , Martin Perna a,b , Michael Landgrebe a , Ulrich Frick a , Goeran Hajak a , Philipp Sand a a b
Department of Psychiatry, University of Regensburg, Universitaetsstrasse 84, 93053 Regensburg, Germany Department of Psychiatry, University of Brno, Czech Republic
a r t i c l e
i n f o
Article history: Received 11 March 2009 Received in revised form 29 April 2009 Accepted 12 May 2009 Keywords: Transcranial magnetic stimulation Cortical excitability Intracortical inhibition Colour blindness Colour stimulation
a b s t r a c t Illumination science has long established effects of coloured light on emotional state, cognitive performance, plus tactile, gustatory and olfactory perception. To explore the neurobiological mechanisms underlying these crossmodal phenomena, cortical excitability was addressed by single and paired-pulse transcranial magnetic stimulation (TMS) in 23 men with normal colour vision, and in 10 subjects with red–green blindness. Using a sequential challenge, excitability measures were recorded at baseline and during exposure to either red or green light. Dichromacy did not predict any of the electrophysiological parameters under study regardless of the spectral paradigm. In both dichromats and trichromats, red and green illumination did not induce any significant effects on resting motor threshold, short intracortical inhibition, intracortical facilitation and cortical silent periods. Our results suggest that motor cortex excitability as assessed by TMS is not sensitive to the modulatory effects of context-independent red and green light. © 2009 Elsevier Ireland Ltd. All rights reserved.
Our perception of the world integrates information delivered by multiple sensory modalities. Of these, colour vision plays a key role by acting on other sensory, motor and information processing systems [26], plus on emotional connotations. Coloured light may cause dizziness [20] and may shift circadian rhythms [22] leading to changes in body temperature and melatonin secretion [10]. In addition, colour-evoked changes in taste [13], appetite [27], mood [16] cognition [2], motor performance [11], and muscular strength [5] have been reported. Thus muscular power was increased in an anaerobic cycling test under ambient red light, and hand grip strength was decreased in blue light as compared to white light [5]. The interplay between colours and brain function may confer behavioral fitness that has served to select against non-trichromatic vision in primate evolution [21]. Occasionally, cross-talk between regions of the brain involved in colour-processing and those controlling other tasks can manifest as colour synesthesia. This rare condition is marked by co-stimulation of chromatic visual and non-visual sensory or cognitive pathways [23]. Supposedly, co-stimulation results from a disturbed balance in excitation and inhibition along feedback pathways in the brain [7]. Biological underpinnings of crossmodal phenomena, however, remain poorly explored. Specifically, little is known on the role played by cortical excitability in mediating the individual response to a given spectral environment. Transcranial magnetic stimula-
∗ Corresponding author. Tel.: +49 941 941 2099; fax: +49 941 941 2025. E-mail address: [email protected] (B. Langguth). 0304-3940/$ – see front matter © 2009 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.neulet.2009.05.034
tion (TMS) is a non-invasive technique for assessing excitability of the motor cortex that has been employed to visualize tactile [19], auditory [14], olfactory [24] and visual input [18]. The reported role of ambient coloured light on muscular power and strength [5] prompted us to employ TMS for measuring the impact of red and green light on motor cortex excitability. To test for specificity of effects, we compared parameters of cortical excitability from trichromats with those obtained in dichromats. Experiment 1. In the first experiment, motor cortex excitability was investigated under three ambient conditions (no visual stimulation, exposure to red light, and exposure to green light) in 10 men with red–green colour blindness (three subjects with protoanopia, seven subjects with deuteranopia; mean age = 27.9 ± 8.7 years, range = 20–44 years) and in 10 men with normal colour vision (mean age = 27.1 ± 4.3 years, range = 22–39 years). Colour vision was evaluated in all subjects by the Ishihara and the FarnsworthMunsell 100-hue test [3]. For the experiment, participants sat relaxed in a reclining armchair as visual stimuli were presented and measurements were obtained. Colours were generated in randomized order (red–dark–green, or green–dark–red) by video goggles (Sony personal LCD video Monitor PLM-A35E; two .55 in. LCDs with 800 × 255 pixel resolution, connected to Sony DVP-FX1) [17]. Red and green light was generated digitally and was matched for colour intensity and brightness. Following the exposure to coloured light, goggles were switched off (darkness condition). For all three visual conditions, motor cortex excitability measurements were performed after 10 min of adaptation. Excitability measurements lasted about 30 min, resulting in a total duration of about 40 min
B. Langguth et al. / Neuroscience Letters 460 (2009) 32–35
33
Fig. 1. Each experimental session consisted of three measurements of cortical excitability under different visual conditions (red light exposure, green light exposure, darkness). The control condition (darkness) was always second in order, the order of red and green light exposure was randomized. Measurements of cortical excitability included resting motor threshold (RMT), cortical silent period (CSP), short intracortical inhibition (SICI) and intracortical facilitation (ICF).
per ambient condition (Fig. 1). This experimental setup allowed for comparison of recordings during red and green light exposure with recordings in darkness as the control condition. Experiment 2. In the second experiment, an additional 13 male subjects (mean age = 24.9 ± 2.4 years, range = 22–29 years) with normal colour vision were examined to address a possible order effect of colour exposure. Each subject underwent two sessions, one starting with green light exposure and other starting with red light exposure. The order of the two sessions was randomly assigned. Participants were recruited by advertisements and included medical students and hospital staff. All participants were free of medication and free of any DSM-IV diagnosis as verified during an interview by board-certified specialists (B.L. and M.L.). Written informed consent was obtained from each subject. The study protocol was approved by the local ethics committee. Excitability measurements included the assessment of resting and active motor threshold (RMT, AMT), cortical silent period (CSP), short intracortical inhibition (SICI) and intracortical facilitation (ICF). TMS was delivered over the optimal representation of the right abductor digiti minimi (ADM). TMS was performed using two Magstim 200 stimulators (Magstim Co., Whiteland, Dyfed, UK) connected via a Bistim module to a figure-of-eight coil (double circular 70 mm coil). The coil was held in the optimal position, i.e. with the junction of the two wings tangential to the skull and the handle pointing backwards and ∼45◦ away from the midline. Thus the induced current in the brain was directed about perpendicularly to the presumed direction of the central sulcus. We recorded motor-evoked potentials (MEPs) from the ADM at rest using surface electrodes in a belly-tendon montage (filters 20 Hz–10 kHz; A/D rate 5 kHz). 50 ms of prestimulus EMG were recorded to assess muscle relaxation. Reducing the stimulus intensity in steps of 1%, we defined the resting motor threshold (RMT) as the lowest intensity at which at least four of eight consecutive MEPs were ≥50 V in amplitude while the investigated muscle was at rest [25]. Audio–visual electromyographic feedback was provided to control for muscle relaxation. Active motor threshold (AMT) was determined as the lowest stimulation intensity that evoked a MEP ≥ 250 V in at least four of eight consecutive trials during voluntary abduction of the small finger. A constant level of voluntary contraction was maintained by audio–visual feedback of the EMG activity. MEP amplitudes were measured peak to peak. Cortical silent period (CSP) was measured in 10 trials at a stimulus intensity of 150% RMT with an inter-sweep interval of 5 s in the moderately active ADM (voluntary abduction with 30% of maximal force, monitored by audio–visual electromyographic feedback). CSP duration was defined as the interval between the end of the MEP and first reappearance of voluntary EMG activity. Measurements were obtained off-line on the non-rectified recording of every individual sweep and were then averaged. Intracortical excitability was measured using the paired-pulse paradigm consisting in a first subthreshold conditioning pulse fol-
lowed by a second suprathreshold test pulse [15]. The intensity of the first stimulus was set to 80% RMT while the intensity of the second stimulus was adjusted to produce an unconditioned MEP of ∼1 mV. Interstimulus intervals of 2, 3, 4, 5, 7, 8, 10, 15 and 20 ms were tested in random order using 10 or more recordings per interval. The interval between sweeps was 4 s. Measurements were performed off-line on the non-rectified recording of every individual sweep and were then averaged. The effect of conditioning stimuli on MEP amplitude at each ISI was determined as the ratio of the average amplitude of the conditioned MEP to the average amplitude of the unconditioned test MEP obtained in the same block of trials. As it was known from previous studies [15] that the conditioning stimulus exerts a suppressive effect on the control MEP at short ISIs (2, 3, 4, and 5 ms), and a facilitatory effect at longer ISIs (7, 8, 10, 15, and 20 ms), analyses of SICI and ICF were conducted separately for short vs. long ISIs. Separate analysis of variance (ANOVA) models were used for the respective motor excitability parameters (RMT, CSP, SICI and ICF) with chromatic vision (i.e. normal colour vision and colour blindness) as between-subjects factor (experiment 1) and lighting condition (i.e. red light, green light, and darkness) as within-subject factor (experiments 1 and 2). Age and order of lighting conditions (red first vs. green first) were entered as covariates. In addition, excitability parameters of both groups (experiment 1) in the control condition were compared by t-test. The level of significance was set at 0.05. Due to the exploratory character of this study, corrections for multiple comparisons were not performed. All experimental procedures were tolerated by the participants without any relevant side effects. At the 5% level of significance, dichromats and trichromats did not differ with regard to any of the excitability parameters in experiment 1 (Table 1; RMT: T = 0.00; d.f. = 18; p = 1.0; CSP: T = −0.13; d.f. = 18; p = 0.90; SICI: T = 0.18; d.f. = 18; p = 0.86; ICF: T = −0.23; d.f. = 18; p = 0.82). Similarly, exposure to coloured light did not elicit significant effects on any of these parameters (effect of lighting condition—RMT: F = 0.30; d.f. = 2, 30; p = 0.75; CSP: F = 0.19; d.f. = 2, 30; p = 0.83; SICI: F = 0.95; d.f. = 2, 30; p = 0.40; ICF: F = 0.48; d.f. = 2, 30; p = 0.62). Moreover, no significant interaction of chromatic vision and lighting condition was detected (interaction term—RMT: F = 0.52; d.f. = 2, 30; p = 0.60; CSP: F = 0.21; d.f. = 2, 30; p = 0.82; SICI: F = 1.03; d.f. = 2, 30; p = 0.37; ICF: F = 1.6; d.f. = 2, 30; p = 0.21). The order of lighting conditions per session, which was entered as a covariate in the analysis, emerged as a confounder of ICF (order × lighting condition: F = 7.6; d.f. = 2, 30; p = 0.002; chromatic vision × order × lighting condition: F = 3.59; d.f. = 2, 30; p = 0.04). Stimulus order did not affect the remaining parameters of cortical excitability. In experiment 2, excitability parameters were again resistant to effects of lighting colour (RMT: F = 0.36; d.f. = 2, 46; p = 0.70; CSP: F = 0.42; d.f. = 2, 46; p = 0.66; SICI: F = 0.14; d.f. = 2, 46; p = 0.87; ICF: F = 0.51; d.f. = 2, 46; p = 0.60). As opposed to experiment 1, we observed a significant interaction of stimulus order and lighting condition for RMT (F = 9.7; d.f. = 2, 46; p < 0.005). However, crosswise comparison of all conditions (red first, green first, red second,
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B. Langguth et al. / Neuroscience Letters 460 (2009) 32–35
Table 1 Motor cortex excitability measurements in experiments 1 and 2 under the respective lighting conditions. RMT: resting motor threshold; CSP: cortical silent period; SICI: short intracortical inhibition; ICF: intracortical facilitation. Group
Age
Experiment 1 Colour-blind
27.9 ± 8.7 years
Normal colour vision
Experiment 2 Normal colour vision
N
Light condition
Order
RMT
CSP
SICI
4 6 4 6 4 6
Darkness Darkness Red Red Green Green
r-d-g g-d-r r-d-g g-d-r r-d-g g-d-r
41.3 45.0 40.0 44.8 40.8 46.5
± ± ± ± ± ±
8.0 5.3 4.9 5.1 4.7 7.1
152 ± 15 160 ± 29 136 ± 14 156 ± 29 155 ± 20 157 ± 26
0.68 0.58 0.69 0.55 0.67 0.54
27.1 ± 4.3 years
5 5 5 5 5 5
Darkness Darkness Red Red Green Green
r-d-g g-d-r r-d-g g-d-r r-d-g g-d-r
43.2 43.8 42.6 43.0 40.8 44.2
± ± ± ± ± ±
3.7 7.7 4.3 5.4 1.3 8.2
134 183 125 183 131 192
± ± ± ± ± ±
25.1 ± 2.4 years
13 13 13 13 13 13
Darkness Darkness Red Red Green Green
r-d-g g-d-r r-d-g g-d-r r-d-g g-d-r
37.7 37.6 38.8 37.0 37.8 39.3
± ± ± ± ± ±
6.6 5.9 6.4 5.5 6.4 6.0
132 127 137 126 139 133
± ± ± ± ± ±
ICF ± ± ± ± ± ±
0.36 0.05 0.47 0.07 0.24 0.05
1.33 1.23 1.55 1.12 1.24 1.35
± ± ± ± ± ±
0.18 0.36 0.26 0.17 0.21 0.28
10 37 25 32 17 44
0.67 ± 0.21 0.53 ± 0.10 0.67 ± 0.17 0.58 ± 0.08 0.59 ± 0.13 0.48 ± 0.21
1.32 1.28 1.19 1.21 1.19 1.35
± ± ± ± ± ±
0.20 0.31 0.04 0.25 0.16 0.47
30 32 33 38 27 30
0.67 0.72 0.67 0.85 0.79 0.76
± ± ± ± ± ±
1.29 1.16 1.33 1.34 1.39 1.35
± ± ± ± ± ±
0.32 0.16 0.40 0.42 0.62 0.40
0.21 0.22 0.19 0.25 0.32 0.26
Excitability parameters proved stable with regard to chromatic vision (colour-blind vs. normal colour vision) and lighting conditions (red light vs. green light vs. darkness) (all p > 0.05).
green second) by t-tests did not reveal any significant effect. For the other excitability measures, no interaction of order and lighting condition was observed (CSP: F = 0.26; d.f. = 2, 46; p = 0.77; SICI: F = 1.55; d.f. = 2, 46; p = 0.22; ICF: F = 0.51; d.f. = 2, 46; p = 0.60). When data from experiments 1 and 2 were combined, the interaction of stimulus order and lighting condition for RMT no longer reached significance (RMT: F = 2.58; d.f. = 2, 82; p = 0.08). Using four electrophysiological parameters, no significant differences were detected in excitability profiles of dichromats and sex- and age-matched trichromats. An apparent effect of stimulus order on ICF in experiment 1 was most probably caused by limited group size and disappeared in experiment 2. Likewise, the observed interaction of lighting condition and stimulus order in experiment 2 disappeared when data from both experiments were pooled. The decrease in RMT is best explained by increasing muscle tension over the course of the second experiment. Our findings count against a motor cortical functionality of red and green light in otherwise healthy individuals. Moreover, as red and green stimuli failed to elicit a distinct motor cortical response in trichromats, it appears unlikely that compensatory mechanisms may have obscured any effects specific to colour-blind individuals. Overall, our data refer to 46 experimental sessions in 10 colourblind subjects and in 23 subjects with normal chromatic vision (of these, 13 subjects participated in both experiments). Due to the relatively small sample size of both groups in experiment 1, however, and in view of the known variability in measures of motor cortex excitability [29], minor effects of dichromacy may have gone unnoticed. Earlier assessments of primary visual cortex excitability by visually evoked potentials under red light conditions have led to mixed results [28,1,4] but crossmodal effects of red and green light have not been systematically addressed. Specifically, it is not known whether effects of coloured light may be compared to effects observed with other forms of colour presentation that are dependent on contextual information. E.g., green colour may reduce subjective loudness perception depending on the extent to which the green colour is associated to natural elements, such as leaves of a tree [6]. In another study, motor cortex excitability was only modified by smell in case of congruence of the sniffed odour and the observed grasped food [24]. Similarly, a role for colours on motor
behavior has been evidenced in specific contextual situations [9]. Thus it is conceivable that effect size is reduced in context-free exposure to coloured light as performed in our experiment. Regarding motor cortical excitability, only one previous study has used a visual challenge paradigm similar but not identical to our settings [18]. In the investigation by Leon-Sarmiento et al., motorevoked potentials and short intracortical inhibition were sensitive to darkness as caused by the blindfolding of eyes with a mask. The light stimulus was defined as a standard room lighting condition [18]. No such effects were seen when the “goggles-off” condition was compared to “goggles-on” conditions using coloured light in our study. Differences may be explained by the settings employed to examine illumination colours and cone-mediated stimuli, rather than darkness vs. illumination, i.e. mostly rod-mediated effects. In conclusion, we have shown similar motor cortex responses in dichromats and trichromats, and negligible crossmodal effects of both red and green light in healthy subjects. The outcome may serve to reassure those who are routinely exposed to contextindependent ambient red or green light. Many nocturnal tasks of astronomers, military air crew and other professionals are performed under red light conditions to avoid desensitization of rod cells [8]. Insight into the cortical effects of coloured light may be used to further improve safety, or to enhance productivity at the workplace [12]. Further investigations are invited to address context specificity, plus putative crossmodal effects of blue light, and to explore motor cortical excitability in subjects with colour synesthesia. Acknowledgements We gratefully acknowledge helpful discussions with Dr. R. Remmel and Dr. C. Dardenne, Dardenne Eye Clinic, Bad Godesberg. We also want to thank Helene Niebling and Sandra Pflügl for technical assistance. References [1] J. Afra, A. Ambrosini, R. Genicot, A. Albert, J. Schoenen, Influence of colors on habituation of visual evoked potentials in patients with migraine with aura and in healthy volunteers, Headache 40 (2000) 36–40.
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