Ординатура / Офтальмология / Английские материалы / The Neuropsychology of Vision_Fahle, Greenlee_2003

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Chapter 4

Functional magnetic resonance imaging and positron emission tomography studies of motion perception, eye movements, and reading

Mark W. Greenlee

Introduction

Functional brain imaging is a rapidly growing area of cognitive neuroscience. fMRI of the visual system is a specialized field, in which methods from neurophysiology, cognitive neuroscience, and psychophysics are combined to study activation of the visual cortex and related cortical areas. This Chapter focuses on recent findings from studies of visual motion processing, eye movements, and reading. As such it serves as a selective introduction to an expanding research area, a survey of which would surpass the aim of this Chapter.

The analysis of retinal image motion is an important feature of all biological visual systems. For example, object motion can be used to segment figure from ground. The relative paths of moving objects with respect to each other and the observer provide important cues for target localization in depth (i.e. motion parallax). Image motion is also evoked by the observer’s own eye, head and body movements. Such wide-field motions should be distinguished from local motion related to actual object displacements. Thus, the analysis of object motion involves retinal and extraretinal sources of information. Therefore, it comes as little surprise that biological visual systems have developed elaborated mechanisms for the precise encoding of object motion (Reichardt 1961; van Santen and Sperling 1985) and that a complex hierarchy of cortical areas has evolved to analyse image motion. Damage to the motion-specific cortical areas leads to an impairment in visual motion processing (see Chapter 7, this volume).

Visual motion-processing is believed to be primarily a function of the dorsal visual pathway (Zeki 1974, 1978; Van Essen et al. 1981; Albright 1984; Albright et al. 1984). Information about image motion passes to cortical regions in the parietal cortex as part of an analysis of spatial relationships between objects in the environment and the viewer (Andersen 1995, 1997; Colby 1998). Signals from the parietal cortex project to

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the frontal eye fields (FEF) in prefrontal cortex (lateral part of area 6) and are used in the preparation of saccadic and smooth-pursuit eye movements (Schiller et al. 1979; Bruce et al. 1985; Lynch 1987; Krauzlis and Stone 1999; Tehovnik et al. 2000). Thus, an elaborated hierarchy of visual and visuomotor areas underlies the analysis of visual motion. Functional imaging studies in human observers should provide essential information about which areas contribute to our percept of visual motion and to our oculomotor responses to visual motion.

In this chapter we review brain-imaging studies that have investigated cortical responses to visual motion. We also review the evidence for the existence of cortical areas responding during oculomotor tasks, such as those requiring saccades or smooth pursuit. Finally, we review studies that explore the cortical control of reading and evidence for the involvement of cortical areas in reading disabilities. The aim of all of these studies is to determine the extent to which these cortical responses, as indexed by stimulus-evoked changes in blood flow and tissue oxygenation, are specific to the form of visual cognition under investigation. We first review the current findings on functional imaging of human cortical responses to visual motion. We consider the effects related to stimulus properties such as spatiotemporal frequency, contrast, direction, speed, and motion coherence. The results of many groups suggest that several cortical areas respond selectively to visual motion. Different visual areas also respond to complex optic flow fields. Afterwards, we review the literature on task-related changes in the blood oxygen level-dependent (BOLD) response to visual motion. These findings suggest that changes in the subject’s attention can modify the BOLD response to visual stimulation. Attention to different aspects of moving stimuli can lead to differences in the response. The role of pursuit eye movements in motion perception and the resultant pattern of BOLD responses are also considered. The task-dependent effects of proand anti-saccades, variations in the amplitude and frequency of saccades, and the difference between saccadic eye movements and smooth pursuit are also reviewed. Finally, we discuss results related to reading and disorders of reading. Other reviews on these topics have been recently published (Greenlee 2000; Kanwisher and Wojciulik 2000; Culham et al. 2001).

Positron emission tomography studies of motion perception

Several groups have used positron emission tomography (PET) to study changes in regional cerebral blood flow (rCBF) evoked when subjects viewed visual motion. Zeki et al. (1991) used PET with the short-life radioactive tracer H215O to map cortical responses to random dot motion. The dot stimuli moved with a speed of 6 /second in one of eight directions. They found significant responses to visual motion in the human homologue of area V5/V5a. Watson et al. (1993) and Dupont et al. (1994) could replicate and expand these findings.

The haemodynamic correlates of the cortical response to optic flow fields were investigated in a study by De Jong et al. (1994) with H215O-PET. In their study, six subjects

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viewed simulated optic flow fields (consisting of small bright dots on a dark background) under binocular viewing conditions. Comparisons were made between displays with 100% coherent motion (radial expansion from a virtual horizon) and 0% coherent motion (same dots and speed gradients, but random direction). The average speed was 7.6 /s (coherent motion) and 17.8 /s (random condition). The reported Talairach coordinates (based on the stereotactic atlas of Talairach and Tournoux 1988) correspond to the human V5/V5a complex (MT/MST, also referred to as MT ) in the border region between areas 19 and 37, to the inferior cuneus in area 18 (the human homologue of V3), to the insular cortex, and to the lateral extent of the posterior precuneus in occipitoparietal cortex (areas 19/7). In a further PET study, Cheng et al. (1995) asked 10 subjects to monocularly view an 80 (virtual) field, while luminous dots moved coherently in one of eight directions. The control conditions consisted either of incoherent motion sequences or mere fixation. The authors used electrooculography (EOG) to control for eye movements during the PET scans. The results indicate that several visual areas respond to visual motion stimuli. Some of the occipitotemporal (V5/V5a, BA 19/37) and occipitoparietal (V3A, BA 7) responses were more pronounced during coherent motion perception, i.e. a condition under which all dots move in one direction. These pioneering PET studies of motion perception suggested at an early phase in this research that several extrastriate and associational visual areas respond selectively to visual motion. The stage is now set for comprehensive functional magnetic resonance imaging (fMRI) studies of human cortical processing of visual motion.

fMRI studies of motion perception

The anatomical location of V5/MT in human cortex

Anatomical MRI with sulci labelling has pointed to the ascending limb of the inferior temporal sulcus as the location of area MT/V5 in humans (Dumoulin et al. 2000). Although there is some variation among individual subjects regarding the position and form of this segment of the ITS (Anderson et al. 1996), there is considerable agreement across healthy brains.

The BOLD signal

fMRI is a relatively new procedure for assessing changes in brain activation (Roland 1993; Orrison et al. 1995; Hennig l998; Logothetis et al. 1999, 2001). The first fMRI measures were performed in 1990 in the rat (Ogawa et al. 1990). Belliveau et al. (1991) conducted the first fMRI measures in humans with the exogenous paramagnetic contrast agent gadolinium, which was given as an intravenous bolus during visual stimulation. Endogenous contrast effects have been found with the circulating blood haemoglobin. Deoxyhaemoglobin is paramagnetic in nature, whereas oxyhaemoglobin is diamagnetic. Perfusion-induced changes in the local amounts of these two forms of haemoglobin yield variations in the T2*-weighted MR-signal. This effect is called BOLD

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figure: (1) only a small subset of voxels are positively correlated above a predefined correlation threshold with the time course of stimulation, and (2) the time course of the T2*-signal is shifted by approximately 4–6 s. This shift reflects the delays associated with the haemodynamic response function. The time constant of the recovery is 2–3 times longer than the onset delay and, as such, represents a serious limitation in the temporal resolution of the BOLD signal. The exact relationship between the underlying neural activity (in the form of pre-and postsynaptic potentials and action potentials) and the BOLD response is only poorly understood (Logothetis et al. 2001; Heeger et al. 2000).

Stimulus-specific responses in visual cortex: contrast

In one of the first studies of fMRI in visual cortex, Tootell et al. (1995b) showed that the human V5 complex showed a selective response to motion, the amplitude of which already saturated at very low values of contrast (around 5%). Tootell et al. (1995b) mapped BOLD responses in striate and extrastriate visual areas to visual motion stimuli (expanding–contracting radial gratings). They found that the human V5/V5a (also referred to as MT/MST) region and V3a (Tootell et al. 1997) respond well to low stimulus contrast levels. Boynton et al. (1999) explored the contrast response in visual cortex to stimuli that varied in contrast. They found contrast-dependent BOLD responses that were correlated with the contrast discrimination performance of the subjects. Fahle et al. (2001) mapped visual contrast responses on to inflated cortical representations and found monotonic increases in the BOLD response with stimulus contrast that saturated at 10% contrast levels. These studies suggest that the BOLD response can, indeed, index the stimulus-evoked neural response to sensory events.

Direction-specific responses

Motion stimuli can be defined by the spatiotemporal characteristics of the display components. For example, kinetic patterns can be defined by alternate columns of dots, each moving in opposite directions, thereby forming so-called motion borders. Responses to kinetically defined borders were described early on by Reppas et al. (1997) and van Oostende et al. (1997). Surprisingly, the V5/V5a (MT ) area did not respond selectively to motion-defined contours, although it did respond to the global motion in the stimuli. Van Oostende et al. (1997) describe the kinetic occipital (KO) region in the lateral extrastriate cortex, which responded selectively to kinetic contours. This ventral posterior visual area appears to respond to borders defined by the relative directions of moving dots. As such, this area might be involved in the analysis of image motion related to self-motion of the observer (see below).

Several extensive studies have been conducted on the effects of direction and speed of frontoplanar dot motion, using PET and fMRI methods (Dupont et al. 1994, 1997; van Oostende et al. 1997; Cornette et al. 1998; Orban et al. 1998). Subjects performed psychophysical tasks of direction and speed discrimination during scanning. Careful documentation of the visual areas responding to various forms of dot motion suggests that, in addition to V5/V5a, several extrastriate areas (e.g. lingual gyrus and cuneus) show

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selective responses to the direction and speed of visual motion. These responses are enhanced when subjects perform psychophysical tasks in the scanner (see below). As mentioned above, Orban and colleagues identified an area in the ventral portion of extrastriate cortex, which they refer to as the KO cortex (Dupont et al. 1994; van Oostende et al. 1997). KO responds well to motion-defined borders within complex motion displays.

Visual motion is not only defined by displacement of luminance contours, but can also be defined by the displacement of contrast, texture, or flickering contours (Smith 1994). This latter form of visual motion has been referred to as second-order motion. fMRI has been recently used to explore the cortical regions underlying the processing of secondorder motion. Smith et al. (1998) compared BOLD responses to motion stimuli yielding firstand second-order motion. Using retinotopic mapping techniques to define area borders, these authors showed that most striate and extrastriate regions responded to both types of motion. Smith et al. (1998) found that the lateral posterior region corresponds to the KO region reported by van Oostende et al. (1997). Smith et al. (1998) refer to this area as V3b, and show that it responds well to second-order motion. Selective activation to second-order motion of plaids has been found in V3 using PET (Wenderoth et al. 1999). Significant activations in striate and extrastriate cortex to colourand motion-defined patterns have also been reported (Skiera et al. 2000). The results of these studies suggest that several visual areas are involved in the analysis of visual motion. Structure from motion can be evoked by patterns of motion coherence, and these motion borders elicit activation in some of these areas. A critical feature of a motion detector is its directional selectivity, i.e. the extent to which the activity of the detector is affected by the direction of the stimulus. Since any given voxel will contain neurons coding all possible stimulus directions, fMRI methods will not necessarily be able to reveal the microstructure of motion analysis. However, a given area might show evidence for direction-specific interactions, like motion opponency, which point to the existence of direction-specific coding strategies. Evidence for this phenomenon is outlined next.

Selectivity for stimulus speed/drift frequency and motion opponency

A counterphase flickering sinewave grating can be constructed by superimposing two equal contrast gratings of the same spatial frequency and orientation that drift at the same speed but in opposite directions. By comparing responses to drifting and counterphase flickering stimuli, Heeger et al. (1999) showed that the MT region exhibited lower responses to flickering than to drifting gratings. The differences in BOLD responses led the authors to suggest the presence of ‘motion opponency’ in area MT , which would reflect mutual inhibition of neurons tuned to opposite directions. Further evidence for motion opponency was found in a comparison of single-unit responses in the primate V5 region (Heeger et al. 1999). The effects of motion opponency could underlie the higher responses found for coherently moving dot patterns compared to random dot motion. A small, but reliable, effect of motion coherence

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processing. In a PET study with light-point figures (Johansson 1975), Bonda et al. (1996) explored responses to coherent versus random motion sequences. Compared to random motion, body movements evoked greater activity in the STS region and the amygdala. Subjects had to perform a postscan memory test, which might explain the involvement of the amygdala and entorhinal cortex. Responses to the movements of the eyes and mouth were compared to that evoked by a radial grating (Puce et al. 1998). The number of significantly activated voxels was compared for the different stimuli in selected regions of interest. They found that radial gratings evoked a large activation in V5 but little or no activation in the superior temporal sulcus (STS) region. In contrast, mouth and eye motion evoked activation in the STS but less activation in V5/MT . Responses in the STS to optic flow stimuli have also been reported (see below). Taken together, these studies suggest the existence of a cortical area that preferentially responds to biological motion. It remains open whether these responses are related to the analysis of visual motion as such or to the preparation for possible imitation (such as the activity described in ‘mirror neurons’; see Iacoboni et al. 2001).

Task-related activation in motion-sensitive areas

Effects of attention

The effects of selective and divided attention have been studied using both PET and fMRI methods. In an early PET study, Corbetta et al. (1991) had subjects attend either to the speed, colour, or shape of sparse, randomly moving blocks. Two conditions were compared. In the selective attention condition, subjects were instructed to attend to one of the three stimulus dimensions and the stimuli differed only along that dimension. In the divided attention condition, the stimuli could differ along any one of the three dimensions and the subjects had to detect whether or not a change occurred. In the selective attention condition, the authors found a shift in activation depending on the stimulus dimension to which the subject attended. When subjects attended to the speed of the moving stimuli the activation occurred in lateral occipitotemporal cortex (probably in the V5/V5a region, but also in more anterior regions in Brodmann areas (BA) 21 and BA22).

The subject’s attention level has been shown to affect the BOLD response in fMRI experiments. In an fMRI study on the effects of selective attention on the response to visual motion, subjects viewed complex motion displays, in which random dot motion was sequentially interleaved with motion containing a circular annulus of coherently moving dots (Beauchamp et al. 1997). The subjects were instructed either to attend to the central fixation point, to both the location and speed of the dots within the annulus, or only to the colour of the dots within the annulus. The BOLD signal in the human homologue of V5/V5a was highest for the condition with attention to both speed and location, and the response decreased to 60 and 45% of this value when attention was shifted to the dot colour or to the fixation point, respectively.

Independent evidence for the claim that shifts of attention can modulate the response to visual motion was presented by O’Craven et al. (1997). They instructed subjects to

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attend either to moving or static random dots (black dots moving among static white dots). This dynamic stimulus remained constant during the entire MR-image acquisition period. Following instructions, subjects attended either to the static or the dynamic dots. The authors found a modulation in the BOLD signal depending on which instruction set the subjects followed. Attention to the dynamic components of the displays led to larger responses in the V5/V5a region. Alternating attention to left or right grating targets led to modulations in the BOLD response (Gandhi et al. 1999). The effect was about 25% of the stimulus-evoked response (driven by left–right physical alternation of the grating stimulus). Similar effects have been reported for spatial attention to flickering bar stimuli presented in one of the four visual quadrants (Tootell et al. 1998).

Using fMRI, Shulman et al. (1999) studied the effects of direction-cueing on cortical activation in a coherent motion paradigm. Comparing block and event-related designs, these authors could isolate response components related to the processing of the cue information (neutral, one of four directions), to the preparation of a motor response (button press when coherent motion was present, no response when absent), and to the processing/detection of noise and noise plus coherent motion. Since subjects responded only on trials where they thought they saw coherent motion, the design could not disentangle the BOLD signals related to the motor aspects of the response from the visual processing of the coherent motion. V5/MT and area V3B/KO showed little effect of motion coherence (Fig. 6 in Shulman et al. 1999). Interestingly, V5/MT responded during the cue period, although only stationary dots and a static cue were present. This anticipatory response suggests that expectation can lead to significant haemodynamic responses despite the absence of adequate stimuli (cf. Kastner et al. 1999), and as such points to substantial ‘top–down’ modulation in early visual areas. Cued trials also led to larger responses during the noise motion periods (Fig. 7 in Shulman et al. 1999). The use of spatial cues (left, right) in association with the parametric effect of motion coherence level was employed by Rees et al. (2000). Overall, these authors report a linear increase in BOLD signal with increasing motion coherence.

In summary, the effects of attention tend to enhance the BOLD signal in association with the visual stimulus. The effects reported so far vary between 25 and 50% of the stimulus-evoked response. Similar effects have been reported for static patterns (Kastner et al. 1998). Based on the results of the studies reviewed above, attention appears to modulate a stimulus-evoked response, but it has not been shown to evoke responses in otherwise silent areas. Evidence reported by Smith et al. (2000) suggests that attention might act to reduce spontaneous activity in non-attended regions of the visual field, thereby increasing the signal-to-noise ratio within the attended region.

Caveat: Can attention modulate activation in primary visual cortex (area VI)?

Although there is considerable controversy concerning the role of attention in the response in primary visual cortex to visual stimuli, recent work by Martinez et al. (1999, 2001) suggests that attention can indeed modulate V1 activity. These authors compared