| | Visual event-related potential changes in multiple system atrophy: Delayed N2 latency in selective attention to a color taskReceived 11 December 2007; received in revised form 14 February 2008; accepted 18 February 2008. Abstract Recent studies demonstrated an altered P3 component and prolonged reaction time during the visual discrimination tasks in multiple system atrophy (MSA). In MSA, however, little is known about the N2 component which is known to be closely related to the visual discrimination process. We therefore compared the N2 component as well as the N1 and P3 components in 17 MSA patients with these components in 10 normal controls, by using a visual selective attention task to color or to shape. While the P3 in MSA was significantly delayed in selective attention to shape, the N2 in MSA was significantly delayed in selective attention to color. N1 was normally preserved both in attention to color and in attention to shape. Our electrophysiological results indicate that the color discrimination process during selective attention is impaired in MSA. 1. Introduction  Multiple system atrophy (MSA) is an adult onset neurodegenerative disease characterized by varying degrees of parkinsonism, cerebellar ataxia, and autonomic dysfunction. Although cognitive dysfunction was not considered a main feature of MSA, mild cognitive deficits, particularly in frontal lobe function, had been suspected by neuropsychological tests [1], [2], [3]. Robbins et al. found evidence of impairment in executive function, attention, and working memory [2]. However, motor involvement in MSA may interfere with such neuropsychological testing. This problem can be partly overcome using event-related potentials (ERPs), an index of cognitive function for assessment of cognitive processing, because ERPs are essentially independent of motor influence [4], [5]. Until now, numerous ERP studies have been done to evaluate the cognitive function in various neurodegenerative diseases. Especially much has been reported about the clinical application of P3. In the ERP components, the P3 component is the most well-known endogenous component, as an electrophysiological index of cognitive function in studying cognitive processing. As a matter of course, several reports paid attention to the P3 component, and showed the P3 abnormalities in MSA during visual discrimination tasks. The cognitive impairments in MSA were pointed out from an electrophysiological view [4], [5], [6]. The prolongation of visual P3 latency and the deterioration of P3 amplitude were shown in MSA, although ERP abnormalities in MSA were milder than those in corticobasal degeneration or in progressive supranuclear palsy [7]. Several negative components of ERPs, such as N2, are known to correlate with information processing stages. The N2 component as well as P3 has been given a profound psychological significance, and was useful in clinical application of ERPs [8], [9], [10], [11]. Traditional research on the N2 component focused on stimulus classification [12], [13] and stimulus deviance [14], [15], as determinants of N2 potentials. Recent years have seen an explosion of research on the N2 component of ERPs, a negative wave peaking between 200 and 350 ms after stimulus onset. The oddball N2 potential in the visual modality is known to belong to the family of attention-related N2 components, and to consist of an N2a component with posterior scalp distribution and an N2b component with frontocentral scalp distribution [16], [17]. We applied a visual selective attention task to elicit ERPs for MSA patients and age-matched controls and also measured several ERP components earlier than P3, because abnormalities of endogenous ERP components other than P3 have not been described in MSA. We now report N2 abnormalities in MSA during selective attention to color. Our electrophysiological data may contribute to the knowledge of cognitive dysfunction in MSA. 2. Methods  2.1. Subjects The subjects were 17 patients (9 men, 8 women) with a clinical diagnosis of MSA, and 10 elderly healthy volunteers (3 men, 7 women). The mean (standard deviation; SD) of age in the MSA group was 62.8 (7.6). The mean (SD) of age in the normal control group was 63.2 (9.3). All the control subjects showed normal neurological findings and had no specific neurological diseases. None of the normal subjects had any history of medical or psychiatric disorders or any abnormal MRI findings. All subjects gave signed informed consent, after the purpose of the study and the protocol had been explained to them, and before any procedures were performed. All patients were diagnosed as having probable MSA on the basis of the MSA diagnostic criteria [18]. The MSA patients consisted of 5 patients with predominant parkinsonian features, 10 patients with predominant cerebellar features, and 2 patients with predominant autonomic features. Any patients with cerebral infarcts in the MRI study were excluded from the study. The duration of illness ranged from 1 to 9 years, with a mean (SD) of 3.6 (2.5). Eight patients did not need any assistance. Four patients needed assistance only when trying to stand or turn or when stepping up or down. Three patients needed assistance in walking. One patient was unable to walk and needed assistance in standing. One other patient was bedridden. The mean (SD) of scores on the Wechsler Adult Intelligence Scale-Revised test was 92(11) for the full-scale IQ, 99(16) for verbal IQ, and 86(8) for performance IQ. 2.2. Paradigms for ERPs Each subject performed a visual selective attention to a color task, with sustained attention to color, and a visual selective attention to a shape task, with sustained attention to shape. Subjects were instructed to maintain central fixation, and to look at four kinds of stimulus figures, each of which contained color and shape information (Fig. 1). The luminance of green targets was 0.23 cd/m2 and that of blue targets was 0.10 cd/m2. The luminance of the background screen was 0.05 cd/m2. During the visual selective attention to color task, subjects were instructed to respond, by pressing a button with their right thumb, whenever the rare target color, green, appeared, and to ignore any shape information (Fig. 1; left half). During the selective attention to shape task, subjects were instructed to respond whenever the rare target shape appeared, and to ignore any color information (Fig. 1; right half). 2.4. Statistics We used Student's t-test (unpaired) for comparison of the mean values of ERP and reaction time measurements between the MSA patients and the normal subjects. Differences between two groups were considered significant at p ≤ 0.05. 3. Results  All the normal subjects accurately performed the task. All the MSA patients could perform both selective attention tasks at an error rate not exceeding 5%. Grand average ERP waveforms were obtained from midline electrodes (Fig. 2). Table 1 shows the mean (SD) values of ERP peak latency, interpeak latency, peak amplitude and reaction time in MSA and normal subjects. During the visual selective attention to color task, we found the N2 latency delay and the prolongation of interpeak latency from N1 peak to N2 peak in MSA subjects, compared with normal control subjects. The P3 latency delay was found in MSA during a visual selective attention to shape task. We found no significant difference between MSA and normal subjects, for N1 latency at Oz, interpeak latency from N2 peak to P3 peak and reaction time. No significant difference was found between MSA and normal subjects, for N1 amplitude at Oz and P3 amplitude at Pz. 4. Discussion  Little is known about the ERP changes in MSA, except for abnormalities of the P3 component during a discrimination task. To examine the visual discrimination process in MSA patients more closely, we employed two kinds of selective attention tasks: a sustained visual attention to color task, and a sustained visual attention to shape task. We obtained several important results on ERP measurements by comparing between the MSA group and the age-matched control group. We found a significant prolongation of P3 latency during selective attention to the shape task. We further found a significant prolongation of N2 latency and interpeak latency between N1 and N2, during the selective attention to the color task in the MSA group. However, we did not find any significant prolongation of N2 latency during the selective attention to shape task, and also did not find the significant prolongation P3 latency during color task. Previously, we studied the ERP components during a visual oddball task in MSA [6]. We applied a visual discrimination task to elicit ERPs, in which three kinds of figures were presented one by one in random sequence, and the subjects were instructed to discriminate shapes of the figures presented. Since all the presented stimuli were of the same color (white), the “color” factor of those stimuli did not exert any influence on the discrimination in this task. We obtained results that showed significantly prolonged P3 latency and preserved N2 latency in MSA [6]. These results of our previous study are similar to our results during the selective attention to shape task which also showed significantly prolonged P3 latency and preserved N2 latency in MSA. We found a significant prolongation of N2 latency during the selective attention to the color task in the MSA group, although all of our MSA patients executed the color task accurately with a low rate of mistakes, less than 5%. Prolonged N2 latency in the selective attention to color task suggests that MSA patients may have subclinical impairment of color discrimination and that they discriminated or detected the target color stimuli more slowly than normal controls, although, as far as we know, impairment of color discrimination has not been reported in MSA. Abnormal color discrimination has frequently been reported in Parkinson disease (PD) patients [19]. The color impairment in PD is most prominent in the tritan (blue–yellow) axis [20], [21]. The cause of impaired color vision in PD is thought to be related to dopamine depletion, because the abnormality of color vision seen in PD can be reversed by treatment with levodopa and other dopaminergic drugs [22]. Muller et al. reported that the color vision abnormalities in PD did not correlate with dopaminergic nigral degeneration as measured by I123 β-CIT single-photon emission tomography of the dopamine transporter [23]. From these results, they suggested that this visual abnormality seen in PD is extranigral in origin [23]. Some people questioned whether abnormalities of color discrimination in PD are real or just an epiphenomenon related to the motor disability of PD patients. The participation of motor disability in execution of the color discrimination task was denied and the validity of color dysfunction in PD was supported by the additional evidence that abnormalities of the visual-evoked potentials (VEPs) produced by color pattern stimuli are more responsive to levodopa therapy than are those evoked by black-and-white stimuli [24]. PD patients have abnormal VEPs and pattern electroretinograms (ERGs), attributed to dopaminergic transmission deficiency in the visual pathway, probably the retina [25]. VEP abnormalities are not reported in MSA. Sartucci et al. studied the chromatic pattern-reversal ERGs in PD and MSA patients. Their results indicate that both chromatic and achromatic pattern-reversal ERGs are unaffected in MSA, whereas in early PD they are clearly impaired, suggesting different pathogenic retinal mechanisms between MSA and PD [25]. On the basis of our present ERP study, not only PD but also MSA might have some abnormality in color vision. N2 latency during selective attention to the color task showed significant prolongation, whereas N1 latency during the same task was not prolonged in MSA. Generally, the N1 component has been interpreted as an evaluative process for external stimuli and N1 amplitude was related to the degree of the attention to external stimuli. N1 latency is unaffected by discriminative processing [26]. The N2 is thought to reflect a later stage of selective processing [27], [28], and to be an endogenous potential. Interpeak latency from the N1 peak to the N2 peak during selective attention to color task was significantly increased in MSA, while N1 latency showed no difference between the MSA group and the normal controls. Therefore, N2 delay during this color task indicates impaired visual discrimination processing for color and preservation of the evaluative process for visual external stimuli in MSA patients. Although the color processing pathway in humans has not been elucidated completely, it is thought that color information is confined mainly to pathways which convey information from V1, through V2 and V4, to the inferior temporal lobe [29]. Le et al. conducted a functional MRI study in normal human subjects during sustained attention to color task, and showed activation of the inferior temporal gyrus, fusiform gyrus, and lingual gyrus [30] which corresponded to these color processing pathways. Although our results do not add essential information on pathogenesis or clinical presentation of MSA, and on electrophysiological–clinical correlates, we would like to emphasize, however, that our study is the first which found a significant prolongation of N2 latency during the selective attention to the color task in MSA. Electrophysiological data may facilitate differential diagnosis between MSA and PD. Pattern VEPs and ERGs are unaffected in MSA, whereas in PD they are impaired. Color discrimination is clinically unaffected in MSA, whereas in PD it is impaired. Our most important finding is a prolonged N2 latency in the selective attention to color task. On behavioral observations, no significant difference was observed in an error rate or reaction time between MSA and normal controls. Since ophthalmological function and N1 component as an index of visual cortex activity were normally preserved, we interpreted a prolonged N2 latency as subclinical impairment of color discrimination as an impaired cognitive function caused by structural or neurotransmitter abnormalities in the brain of MSA. An attention-related N2 component has been known as an index of information processing stages. We should further look for additional scientific or clinical benefits of this electrophysiological index in future investigations. In summary, we compared N2 as well as N1 and P3 in MSA patients with these components in normal controls, by using visual selective attention tasks. While the P3 in MSA was delayed in selective attention to shape, the N2 in MSA was delayed in selective attention to color. N1 was normally preserved. Our electrophysiological results during selective attention to a color task indicate abnormalities of attentional processing of color in MSA. References  [1]. [1]Berent S, Giordani B, Gilman S, Junck L, Lehtinen S, Markel DS, et al. Neuropsychological changes in olivopontocerebellar atrophy. Arch Neurol. 1990;47:997–1001. MEDLINE [2]. [2]Robbins TW, James M, Lange KW, Owen AM, Quinn NP, Marsden CD. Cognitive performance in multiple system atrophy. Brain. 1992;115:271–291. [3]. [3]Krishnan S, Mathuranath PS, Sarma S, Kishore A. Neuropsychological functions in progressive supranuclear palsy, multiple system atrophy and Parkinson's disease. Psychophysiology. 2006;54:268–272. [4]. [4]Kamitani T, Kuroiwa Y, Wang L, Li M, Suzuki Y, Takahashi T, et al. Visual event-related potential changes in two subtypes of multiple system atrophy, MSA-C and MSA-P. J Neurol. 2002;249:975–982. MEDLINE |
CrossRef
[5]. [5]Kamitani T, Kuroiwa Y, Wang L, Li M, Ikegami T, Matsubara S. Event-related potentials during visual S1-S2 paradigm in multiple system atrophy: relation to morphologic changes on brain MRI measurement. Parkinsonism Relat Disord. 2003;10:93–100. Abstract | Full Text |
Full-Text PDF (265 KB)
|
CrossRef
[6]. [6]Deguchi K, Takeuchi H, Sasaki I, Tsukaguchi M, Touge T, Nishioka M. Impaired novelty P3 potentials in multiple system atrophy – correlation with orthostatic hypotension. J Neurol Sci. 2001;190:61–67. |
CrossRef
[7]. [7]Pirtosek Z, Jahanshahi M, Barrett G, Lees AJ. Attention and cognition in bradykinetic-rigid syndromes: an event-related potential study. Ann Neurol. 2001;50:567–573. MEDLINE |
CrossRef
[8]. [8]Brecher M, Porjesz B, Begleiter H. The N2 component of the event-related potential in schizophrenic patients. Electroencephalogr Clin Neurophysiol. 1987;66:369–375. Abstract |
Full-Text PDF (486 KB)
|
CrossRef
[9]. [9]Enoki H, Sanada S, Ohtahara S. P300 in children: developmental change and its clinical application. Electroencephalogr Clin Neurophysiol. 1990;76:104. [10]. [10]Porjesz B, Begleiter H, Bihari B, Kissin B. The N2 component of the event-related brain potentials in abstinent alcoholics. Electroencephalogr Clin Neurophysiol. 1987;66:121–131. Abstract |
Full-Text PDF (802 KB)
|
CrossRef
[11]. [11]Towey J, Rist F, Hakerem G, Ruchkin DS, Sutton S. N250 latency and decision time. Bull Psychon Soc. 1980;15:365–368. [12]. [12]Ritter W, Simson R, Vaughan HG, Friedman DA. A brain event related to the making of a sensory discrimination. Science. 1979;203:1358–1361. MEDLINE [13]. [13]Ritter W, Simson R, Vaughan HG. Event-related potential correlates of two stages of information processing in physical and semantic discrimination task. Psychophysiology. 1983;20:168–179. MEDLINE |
CrossRef
[14]. [14]Näätänen R, Simpson M, Loveless NE. Stimulus deviance and evoked potentials. Biol Psychol. 1982;14:53–98. MEDLINE |
CrossRef
[15]. [15]Näätänen R, Picton TW. N2 and autonomic and controlled processes. In: McCallum WC, Zapoli R, Denoth F editor. Cerebral psychophysiology: studies in event-related potentials. EEG J. Suppl. 38:Amsterdam: Elsevier; 1986;p. 169–186. [16]. [16]Renaut B, Lesévre N. Topographical study of the emitted potential obtained after the omission of an expected visual stimulus. In: Otto D editors. Multidisciplinary perspectives in event-related brain potential research. Washington, DC, U.S.: Government Printing Office; 1978;. [17]. [17]Folstein JR, Van Petten C. Influence of cognitive control and mechanism on the N2 component of the ERP: a review. Psychophysiology. 2007 Sep 10;. [18]. [18]Gilman S, Low PA, Quinn N, Albanese A, Ben Shlomo Y, Fowler CJ, et al. Consensus statement on the diagnosis of multiple system atrophy. J Neurol Sci. 1999;163:94–98. |
CrossRef
[19]. [19]Büttner T, Kuhn W, Klotz P, Stainberg R, Voss L, Bulgaru D, et al. Disturbance of colour perception in Parkinson's disease. J Neural Transm Park Dis Dement Sect. 1993;6:11–15. MEDLINE |
CrossRef
[20]. [20]Haug BA, Kolle RU, Trenkwalder C, Oertel WH, Paulus W. Predominant affection of the blue cone pathway in Parkinson's disease. Brain. 1995;118:771–778. [21]. [21]Birch J, Kolle RU, Kunkel M, Paulus W, Upandhyay P. Acquired colour deficiency in patients with Parkinson's disease. Vision Res. 1998;38:3421–3426. MEDLINE |
CrossRef
[22]. [22]Büttner T, Kuhn W, Patzold T, Przuntek H. l-Dopa improves colour vision in Pakinson's disease. J Neural Transm Park Dis Dement Sect. 1994;7:13–19. MEDLINE |
CrossRef
[23]. [23]Müller T, Kuhn W, Büttner T, Eising E, Coenen H, Haas M, et al. Colour vision abnormalities do not correlate with dopaminergic nigrostriatal degeneration in Parkinson's disease. J Neurol. 1998;245:659–664. MEDLINE |
CrossRef
[24]. [24]Barbate L, Rinalduzzi S, Laurenti M, Ruggieri S, Accornero N. Color VEPs in Parkinson's disease. Electroencepharogr Clin Neuophysiol. 1994;92:169–172. [25]. [25]Sartucci F, Orlandi G, Bonuccelli U, Borghetti D, Murri L, Orsini C, et al. Chromatic pattern-reversal electroretinograms (ChPERGs) are spared in multiple system atrophy compared with Parkinson's disease. Neurol Sci. 2006;26:395–401. MEDLINE |
CrossRef
[26]. [26]Fitzgerald PG, Picton TW. Event-related potentials recorded during the discrimination of improbable stimuli. Biol Psychol. 1983;17:241–276. MEDLINE |
CrossRef
[27]. [27]Kenemans JL, Kok A, Smulders FT. Event-related potentials to conjunctions of spatial frequency and orientation as a function of stimulus parameters and response requirements. Electroencephalogr Clin Neurophysiol. 1993;88:51–63. MEDLINE [28]. [28]Wijers AA, Mulder G, Okita T, Mulder LJ. Event-related potentials during memory search and selective attention to letter size and conjunctions of letter size and color. Psychophysiology. 1989;26:529–547. MEDLINE |
CrossRef
[29]. [29]Lennie P. Color vision. In: Kandel ER, Schwartz JH, Jessell TM editor. Principles of neuroscience. 4th ed.. New York, U.S.: McGraw-Hill Health professions Division; 2000;p. 583. [30]. [30]Le TH, Pardo JV, Hu X. 4T-fMRI study of nonspatial shifting of selective attention: cerebellar and parietal contributions. J Neurophysiol. 1998;79:1535–1548. MEDLINE a Department of Clinical Neurology, Graduate School of Medical Sciences, Yokohama City University, 3-9 Fukuura, Kanazawaku, Yokohama 236-0004, Japan b Department of Stroke Medicine, Graduate School of Medical Sciences, Yokohama City University, 3-9 Fukuura, Kanazawaku, Yokohama 236-0004, Japan c Department of Neurology, National Hospital Organization Saitama Hospital, 2-1 Suwa, Wako-shi, Saitama 351-0102, Japan Corresponding author. Department of Clinical Neurology, Graduate School of Medical Sciences, Yokohama City University, 3-9 Fukuura, Kanazawaku, Yokohama 236-0004, Japan. Tel.: +81 45 787 2725; fax: +81 45 788 6041.
PII: S1353-8020(08)00091-6 doi:10.1016/j.parkreldis.2008.02.009 © 2008 Elsevier Ltd. All rights reserved. | |
|