Brain Advance Access originally published online on July 12, 2007
Brain 2007 130(11):e83; doi:10.1093/brain/awm153
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
A few remarks on assessing magnocellular sensitivity in Schizophrenic patients
1Skottun Research, Oakland, California, USA, 2Centre for Mathematics and Physics in the Life Sciences and Experimental Biology (CoMPLEX), University College London, London and 3Centre for Philosophy of Natural and Social Science, London School of Economics, London, UK
Correspondence to: John R. Skoyles, PhD, Centre for Philosophy of Natural and Social Science, Lakatos Building, London School of Economics, Houghton Street, London, WC2A 2AE, UK E-mail: j.skoyles{at}ucl.ac.uk
Received February 23, 2007. Revised April 24, 2007. Accepted June 8, 2007.
Sir, Butler and colleagues (2007
) recorded event-related potentials in an attempt to isolate magnocellular activity in individuals with schizophrenia, and concluded that, these individuals ‘show significant and substantial deficits in early visual processing affecting the subcortical magnocellular pathway’ (Butler et al., 2007, p. 428). In their experiments, Butler et al. (2007) relied upon two stimulus manipulations to isolate magnocellular responses: (i) spatial frequency, and (ii) contrast. With regard to these two stimulus dimensions Butler et al. (2007, p. 418) wrote: ‘[r]ecent visual evoked potential work in humans with magnocellular and parvocellular preferential stimuli demonstrates that the spatial characteristics and contrast dependence of these pathways are similar to those found in monkeys ...’. We wish to comment upon these manipulations in light of this statement.
The first stimulus manipulation used by Butler and colleagues (2007), ‘spatial frequency’, can be used to reliably differentiate magno- and parvocellular activity at contrast thresholds because there is evidence to indicate that contrast detection is mediated by the magnocellular system below about 1.5 cycle/degree and by the parvocellular system above this frequency (Skottun, 2000). Rather than using threshold stimuli, Butler et al. (2007), however, used gratings of 80% contrast.
Butler et al. (2007) used centrally fixated stimuli of 6.1 degreesx 4.6 degrees. Levitt et al. (2001) have reported that for neurons with receptive fields within the central 5.0 degrees, the average characteristic frequencies, for the two cell types, are 3.55 cycle/degree and 4.57 cycle/degree, respectively. Kaplan and Shapley (1982) and Spear et al. (1994) have found little difference between magno- and parvocellular neurons with regard to spatial resolution. Blakemore and Vital-Durand (1986, see their Fig. 6) found essentially identical spatial resolution for magno- and parvocellular neurons. It seems, therefore, that a 5.0 cycle/degree grating of 80% contrast (as was used by Butler and colleagues) would have activated many magnocellular neurons and that, given the small amount of low frequency attenuation in LGN cells (Derrington and Lennie, 1984; Levitt et al., 2001), a 1.0 cycle/degree grating would have activated many parvocellular neurons. Thus, both of the stimuli used by Butler et al. (2007), even though they were biased for the magno- and parvocellular systems, would be expected to have activated both magno- and parvocellular neurons.
In addition, the use of centrally fixated stimuli may have favored the activation of parvocellular neurons. In the case of the sample of Levitt et al. (2001) going from the overall sample, which included receptive fields out to 14 degrees, to only cells within the central 5 degrees reduced the numbers of magnocellular neurons from 75 to 33 cells but only from 84 to 82 cells in the case of parvocellular neurons. Thus, the use of centrally fixated stimuli may have boosted the parvocellular response relative to the magnocellular response.
The modest low frequency attenuation in subcortical neurons (Derrington and Lennie, 1984; Levitt et al., 2001) and the relatively small difference in spatial frequency tuning between magno- and parvocellular cells (Blakemore and Vital-Durand, 1986; Spear et al., 1994; Levitt et al., 2001) makes the use of spatial frequency of high contrast stimuli a poor technique for differentiating magno- and parvocellular neurons. The small low frequency attenuation at the subcortical level, however, stands in marked contrast to the spatial tuning of cortical cells which show pronounced bandpass characteristics, i.e. have substantial low frequency attenuation (De Valois et al., 1982). It appears therefore that effects that are specific to certain spatial frequencies (such as the effects depicted in Fig. 5 of Butler et al., 2007) ought to be sought in terms of cortical mechanisms rather than in terms of the subcortical magno- and parvocellular systems.
Butler et al. (2007) further found abnormal C1, P1 and N1 amplitudes when using low spatial frequency stimuli (see their Fig. 6). According to these authors, the C1 amplitude ‘is driven more strongly by parvocellular than magnocellular inputs’ (Butler et al., 2007, p. 418); the P1 amplitude ‘has dual underlying generators including a dorsal generator within dorsolateral extrastriate cortex (e.g. V3a) and a ventral source within ventrolateral extrastriate cortex (e.g. V4) ... The dorsal generator is driven predominantly by magnocellular input and the ventral generator by parvocellular input ...’ (Butler et al., 2007, p. 418); and the N1 amplitude ‘appears to reflect primarily ventral stream sources’ (Butler et al., 2007, p. 419). Given that Butler et al. (2007) associate the ventral cortical stream with parvocellular activity it thus appears that two of the three amplitudes at which they observed abnormalities, according to their reasoning, are associated predominantly with the parvocellular system (via the ventral stream) and the third amplitude is associated with a combination of the magno- and the parvocellular systems. This seems at odds with their conclusion that the abnormalities are of magnocellular origin.
In addition to measuring amplitudes Butler et al. (2007) recorded latencies to the various amplitudes. They found two statistically significant results (see Table 1 of Butler et al., 2007). In the first case, the schizophrenic individuals had longer C1 latencies (91.2 ms versus 81.5 ms) to the low spatial frequency stimuli. In the second case, the patients had longer P1 latencies to the high spatial frequency stimuli (158.0 ms versus 148.5 ms). Given that C1 ‘is driven more strongly by parvocellular than magnocellular input’ and P1 has ‘dual underlying generators including a dorsal generator’ (Butler et al., 2007, p. 418) these observations do not point to a specifically magnocellular deficit even if we were to accept the assumption of Butler et al. (2007) that low and high spatial frequencies bias the stimuli, respectively, for the magno- and parvocellular systems.
Given the very high contrast (80%) in combination with the spatial frequencies (1.0 and 5.0 cycle/degree) used in these experiments, it is difficult to be confident that the two frequencies would have made any large difference in the activation of the magno- versus the parvocellular system. The results of Butler et al. (2007) are reminiscent in this regard of the observations of Slaghuis (1998) who found both sustained and transient system deficits in schizophrenic individuals.
With regard to the second stimulus manipulation involved, ‘contrast’, Butler et al. (2007, p. 419) wrote: ‘Parvocellular neurons respond poorly to low-stimulus contrast (<16%), so that cortical responses to low-contrast stimuli reflect activity driven primarily by magnocellular input’ and that ‘[t]he parvocellular system ... does not respond to contrast levels below 
10% ...’ (Butler et al., 2007, p. 418). On this basis, they held that using low-contrast stimuli should isolate magnocellular activity.
The view that the magnocellular system has a lower contrast threshold than the parvocellular system is based on recordings from single neurons (Shapley et al., 1981; Derrington and Lennie 1984; Hicks et al., 1983; Kaplan and Shapley, 1982, 1986; Schiller and Colby, 1983). However, studies in which lesions have been placed in either the magnocellular or the parvocellular layers of the lateral geniculate nucleus (LGN) have found that the largest deficits in contrast sensitivity in fact occur following parvocellular lesions. In comparison, the reductions in contrast sensitivity following lesions in the magnocellular layers are mainly confined to cases where stimuli of both low spatial and high temporal frequency are employed (Schiller et al., 1990a, b; Merigan and Maunsell, 1990, 1993; Merigan et al., 1991a, b). Also, supporting this, psychophysical studies in humans suggest that the magnocellular system only mediates contrast detection at low spatial frequencies (see, e.g. Legge, 1978; Tolhurst, 1975), and that at frequencies above (about) 1.5 cycle/degree detection is mediated by the parvocellular system (Skottun, 2000). Legge (1978) found contrast thresholds as low as 0.13% for 3 cycle/degree gratings associated with the parvocellular system (at the time called the ‘sustained system’). (For comparison, the lowest contrast used by Butler et al., 2007, and which was supposed to specifically activate the magnocellular system, was 4%.) These findings indicate that under most conditions, it is the parvocellular system, not the magnocellular system, that responds to the lowest contrast. It appears, therefore, that with regard to the roles of the magnocellular and parvocellular systems in contrast sensitivity that there is a fundamental inconsistency between behavioral performance and human psychophysics on the one hand and estimates based on the responses of single neurons on the other. Given these findings, researchers need to be cautious about attributing responses generated by low-contrast stimuli to the magnocellular pathway. (There may be at least two reasons for the discrepancy between single cells and behavioral performance: (i) probability summation—there are about 10 times as many parvocellular neurons as magnocellular neurons, and (ii) differences in integration time—parvocellular neurons integrate information over longer periods.)
In Experiment 1, Butler et al. (2007) recorded responses to arrays of isolated checks at five contrast levels (4, 8, 16, 32 and 64%) and found that the schizophrenic individuals had reduced amplitudes at most contrast levels. This was interpreted as ‘indicating decreased amplification of the contrast response function ... in patients with schizophrenia, which has been primarily associated with functioning of magnocellular neurons in primates’ (Butler et al., 2007, p. 422). However, given that event-related potentials are recorded from the scalp above the visual cortex, and thus reflect mainly cortical activity, reductions in these potentials could be the result of deficiencies anywhere along the visual pathways (i.e. in the visual optics, photoreceptors, retinal ganglion cells and LGN cells) including the visual cortex. The finding that the responses saturate at low contrasts in a way similar to magnocellular neurons does not necessarily mean that they reflect magnocellular activity since there are cortical neurons which have similar contrast-response relationships, e.g. neurons in cortical area MT (Sclar et al., 1990).
Butler et al. (2007) found some of the largest response reductions at the very highest contrast (see the C1 and P1 responses in Fig. 4 of Butler et al., 2007). It is difficult on the basis of such reductions to differentiate magno- and parvocellular deficits.
In the case of isolated check stimuli, Butler et al. (2007) found a ‘robust P1 that was dramatically reduced in amplitude in patients compared with controls’ (p. 420–421). Given, as was noted above, that P1, has dual generators only one of which is supposed to have a predominantly magnocellular input this is hardly unequivocal evidence for a magnocellular deficit.
We carried out a 2–D Fourier analysis on stimuli of the kind used in Experiment 1 by Butler et al. (2007) (i.e. ‘isolated checks’, see Fig. 1A). The results are shown in Fig. 1B where it can be seen that the main amplitudes are at 1.3 cycle/degree with secondary peaks of considerable energy at 2.7 cycle/degree, 4.0 cycle/degree and 5.3 cycle/degree along the horizontal and vertical dimensions with a further peak at the oblique at 1.9 cycle/degree. The primary component at 1.3 cycle/degree is very close to the frequency (approximately 1.5 cycle/degree) at which magno- and parvocellular neurons are equally sensitive (Skottun, 2000). This means that this component would have activated the two cell types almost equally. The higher components have smaller amplitudes than the fundamental component but would still, particularly at higher contrasts, have sizable amplitudes. These would almost certainly have activated parvocellular neurons (in addition to magnocellular neurons, presumably). One would, therefore, expect that these stimuli would activate both magno- and parvocellular systems about equally.
|
In conclusion, Butler et al. (2007
) relied upon spatial frequency and contrast in order to separate magno- from parvocellular activity in event-related potentials. (i) With regard to spatial frequency, when using high contrast this is not a particularly useful stimulus dimension given that the magno- and parvocellular systems, in comparison to cortical neurons, are not particularly selective with regard to spatial frequency and have largely overlapping tuning functions. (ii) In the case of using low contrast to isolate magnocellular responses, this faces the problem that behavioral contrast sensitivity is mediated by the parvocellular system under many, if not most, conditions. Furthermore, some of the largest deficits, such as the reduced amplitudes in the contrast-response function (Butler et al., 2007, Fig. 4), were with regard to the P1 amplitude. Given that this amplitude was held to reflect dorsal stream as well as ventral stream activity, this would suggest that the deficits could be in either one or both of these cortical streams rather than in the subcortical magnocellular systems. [One needs to make a distinction between the subcortical magno- and parvocellular systems and the dorsal and ventral cortical streams (Skottun and Skoyles, 2006).] That the deficits may be (in part at least) in the ventral stream is further suggested by the observation that also the C1 and N1 amplitudes are abnormal (Butler et al., 2007, Figs 5 and 6).
It is important to be able to assess magnocellular activity in schizophrenic patients since if schizophrenia were connected to magnocellular deficits this would have significant implications for our understanding of this condition and its etiology. While it has been previously suggested that schizophrenia is closely associated with deficits in the magnocellular portion of the visual system (e.g. Green et al., 1994; Keri et al., 2004), the data are conflicting (e.g. Slaghuis, 1998). The study of Butler et al. (2007) does not resolve this situation since the stimuli they used fail to differentiate magnocellular contributions from parvocellular ones and subcortical influences from cortical ones. Also, even if one were to accept the assertion of Butler et al. (2007) that the stimuli could isolate magnocellular activity, their data would not have pointed unequivocally to a magnocellular deficit. For these reasons, it is hard to draw any conclusions on the basis of the data of Butler et al. (2007) specifically with regard to the magnocellular system in schizophrenic patients.
 |
References |
|---|
 Top References |
|---|
Blakemore C, Vital-Durand F. Organization and post-natal development of monkey's lateral geniculate nucleus. J Physiol (1986) 380:543–491.
Butler PD, Martinez A, Foxe J, Kim D, Zemon V, Slipo G, et al. Subcortical visual dysfunction in schizophrenia drives secondary cortical impairments. Brain (2007) 130:417–30.
Derrington AM, Lennie P. Spatial and temporal contrast sensitivities of neurones in lateral geniculate nucleus of macaque. J Physiol (1984) 357:219–40.
De Valois RL, Albrecht DG, Thorell LG. Spatial frequency selectivity of cells in macaque visual cortex. Vis Res (1982) 22:545–59.[CrossRef][Web of Science][Medline]
Green MF, Nuechterlein KH, Mintz J. Backward masking in schizophrenia and mania, II: specifying the visual channel. Arch Gen Psychiatr (1994) 51:945–51.
Hicks TP, Lee BB, Vidyasagar TR. The responses of cells in macaque lateral geniculate nucleus to sinusoidal gratings. J Physiol (1983) 337:183–200.
Kaplan E, Shapley RM. X and Y cells in the lateral geniculate nucleus of macaque monkeys. J Physiol (1982) 330:125–43.
Kaplan E, Shapley RM. The primate retina contains two types of ganglion cells, with high and low contrast sensitivity. Proc Natl Acad Sci USA (1986) 83:2755–7.
Keri S, Kelemen O, Benedek G, Janka Z. Vernier threshold in patients with schizophrenia and their unaffected siblings. Neuropsychology (2004) 18:537–42.[CrossRef][Web of Science][Medline]
Legge GE. Sustained and transient mechanisms in human vision: temporal and spatial properties. Vis Res (1978) 18:69–81.[CrossRef][Web of Science][Medline]
Levitt JB, Schumer RA, Sherman SM, Spear PD, Movshon JA. Visual response properties of neurons in the LGN of normally reared and visually deprived macaque monkeys. J Neurophysiol (2001) 85:2111–29.
Merigan WH, Byrne CE, Maunsell JHR. Does primate motion perception depend on the magnocellular pathway? J Neurosci (1991a) 11:3422–9.[Abstract]
Merigan WH, Katz LM, Maunsell JHR. The effects of parvocellular lateral geniculate lesions on the acuity and contrast sensitivity of macaque monkeys. J Neurosci (1991b) 11:994–1001.[Abstract]
Merigan WH, Maunsell JHR. Macaque vision after magnocellular lateral geniculate lesions. Vis Neurosci (1990) 9:776–83.
Merigan WH, Maunsell JHR. How parallel are the primate visual pathways? Ann Rev Neurosci (1993) 16:369–402.[Web of Science][Medline]
Schiller PH, Colby CL. The responses of single cells in the lateral geniculate nucleus of the rhesus monkey to color and luminance contrast. Vis Res (1983) 23:1631–41.[CrossRef][Web of Science][Medline]
Schiller PH, Logothetis NK, Charles ER. Functions of the colour-opponent and broad-band channels of the visual system. Nature (1990a) 343:68–70.[CrossRef][Medline]
Schiller PH, Logothetis NK, Charles ER. Role of the color-opponent and broad-band channels in vision. Vis Neurosci (1990b) 5:392–8.
Sclar G, Maunsell JH, Lennie P. Coding of image contrast in central visual pathways of the macaque monkey. Vis Res (1990) 30:1–10.[CrossRef][Web of Science][Medline]
Shapley R, Kaplan E, Soodak R. Spatial summation and contrast sensitivity of X and Y cells in the lateral geniculate nucleus of the macaque. Nature (1981) 292:543–5.[CrossRef][Medline]
Skottun BC. The magnocellular deficit theory of dyslexia: the evidence from contrast sensitivity. Vis Res (2000) 40:111–27.[CrossRef][Web of Science][Medline]
Skottun BC, Skoyles JR. Is coherent motion an appropriate test for magnocellular sensitivity? Brain Cogn (2006) 61:172–80.[CrossRef][Web of Science][Medline]
Slaghuis WL. Contrast sensitivity for stationary and drifting spatial frequency gratings in positive- and negative symptom schizophrenia. J Abnorm Psychol (1998) 107:49–62.[CrossRef][Web of Science][Medline]
Spear PD, Moore RJ, Kim CBY, Xue JT, Tumosa N. Effect of aging on the primate visual system: spatial and temporal processing by lateral geniculate neurons in young adult and old rhesus monkeys. J Neurophysiol (1994) 72:402–20.
Tolhurst DJ. Reaction times in the detection of gratings by human observers: a probabilistic mechanism. Vis Res (1975) 15:1143–9.[CrossRef][Web of Science][Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||