The human motion complex of occipitotemporal cortex

Because of a lack of sensitivity in PET studies, or because of the use of surface coils in fMRI that restrict the part of the brain explored, the initial imaging studies concentrated on a motion-sensitive region, located in the temporo-parieto-occipital junction. Zeki et al. (1991) compared the brain activity when subjects passively viewed a random-dot pattern that was stationary to one that was moving in one of eight possible directions. One extrastriate region in the temporo-parieto-occipital cortex stood out by being significantly more active for moving than for stationary stimuli. Zeki et al. (1991) proposed that this region was the human homolog of monkey MT/V5. It should be noted that this result, like those of most imaging studies, was obtained by statistical analysis: the human motion complex of occipito-temporal cortex (hMT/V5) appeared as a set of voxels in which the difference in activity between motion and control was statistically significant.

This has two implications. First, much depends on the control condition, and here Zeki et al. (1991) introduced the static pattern as a control condition. This allows one to dissociate the effect of the stimulus pattern (which is removed) from its movement (which remains). However, by comparing just two closely matched conditions, one can conclude only that there is a relative difference in activity. By adding a further, lower-order condition, an empty fixation condition, as introduced by Tootell et al. (1995b) (see below), one can ascertain whether motion and stationary conditions differ in activation from some baseline level. One can then infer that the neuronal population, the activity of which is reflected by the MR signals, increases its activity above spontaneous activity, that is, shows an excitatory response. Monkey fMRI has confirmed that this assertion indeed is valid for hMT/V5+ (see below). One does not know, however, to what extent this increased neuronal activity of the hMT/V5+ population reflects activity of inhibitory or excitatory neurons. The situation is analogous for single-cell studies, although some firing pattern criteria have been proposed to recognize inhibitory interneurons. Second, the statistical decision depends on the threshold chosen and the volume of search. The accepted standard is p < .05, but this can be applied to a region of interest (ROI) or to the whole brain. The ROI approach is the most sensitive, but it depends on the preliminary localizer scan to include all relevant voxels. Searching over the whole brain, on the other hand, requires correction for multiple comparisons and can be applied to a single subject or to a group of subjects. For a group analysis, one can use either a fixed-effect analysis (as in the Zeki et al., 1991, study), which allows one to draw conclusions only about the subjects tested, or a random effects analysis (Holmes and Friston, 1998), which allows inferences to be made about the general population.

In a subsequent study from the same laboratory (Watson et al., 1993) using a more sensitive camera, hMT/V5 was studied in single subjects as well as across the group. This allowed the investigators to demonstrate the variability of its anatomical localization in the different subjects, at least when using a fixed reference such as the Talairach coordinates (Fig. 83.1). The authors noted that hMT/V5+ was closely associated with the ascending branch of the inferior temporal sulcus (ITS), a finding which has been amply confirmed by subsequent studies (Dumoulin et al., 2000; Tootell et al., 1995b). They noted that this region corresponds to a cortical field that is heavily myelinated from birth. A third PET study from our group provided the first independent confirmation of these observations with control of eye movements (Dupont et al., 1994).

Figure 83.1..  

The cerebral hemispheres from four subjects, showing the hMT/V5+ of each as defined by PET activation experiments, superimposed on the individual's own MRI (rendered brain). Each subject occupies a row: the two hemispheres are shown as viewed at rotations of 50 and 90 degrees from the occipital pole. The Statistical Parametric Map (SPM) image is edited to leave only hMT/V5+. (From Watson et al., 1993.) (See color plate 64.)

The final identification of hMT/V5 was provided by Tootell et al. (1995b) using the greater spatial (5 to 10 mm rather than 15 to 20 mm in PET) and temporal resolution of fMRI. This technique not only has better resolution, but also allows a more complete functional investigation of a cortical region. Many tests can be performed on the same subject, because no radioactive tracer has to be injected. Tootell et al. provided evidence that hMT/V5 was not only motion sensitive, more so than V1 (Fig. 83.2), but also that it displayed three properties observed in monkey MT/V5: it was very sensitive to luminance contrast, it responded only weakly to equiluminant moving color stimuli, and it responded to ipsilateral stimulation. Because of the many functional similarities to monkey MT/V5, because of its localization with respect to retinotopic regions (Fig. 83.3), and owing to its distinct histological properties (Tootell and Taylor, 1995; see also Watson et al., 1993), this human cortical region was accepted as a distinct human cortical area. Work in the monkey has led to the consensus that several criteria need to be met for a region of cortex to be considered a separate area: retinotopic organization, connectivity, architectonics, and functional properties. Given the difficulty of obtaining detailed histological data in humans (but see Zilles et al., 1995), few visual cortical regions have achieved the status of distinct areas. hMT/V5, together with early regions V1, V2, V3, and V3A, is generally accepted as a separate cortical area.

Figure 83.2..  

Time courses of the MRI signal amplitude from V1 (A) and hMT/V5+ (B) of the same subject, sampled every 2 seconds during a 6-minute scan (average of two presentations). (From Tootell et al., 1995b.)

Figure 83.3..  

Location of hMT/V5+ with respect to the early retinotopic regions (A) and to the motion response of hV3A (B) on a flattened cortical surface from a single hemisphere. TOS, transverse occipital sulcus; IPS, intraparietal sulcus. C, D, Location of MT/V5 and satellites: schematic location of MT/V5, MSTv, MSTd, and FST in STS (modified from Orban, 1997) and actual activation of MT/V5, MSTv, and FST by moving random dots in monkey M4 (Vanduffel et al., unpublished). In panel C, P and C indicate peripheral and central visual field representation; scale bar = 5 mm. In panel D, stimuli were restricted to the central 7 degrees of the visual field, corresponding to the central representations in panel C. (A and B from Tootell et al., 1997.) (See color plate 65.)

However, even the identification of the motion-sensitive region in the ITS as the human homolog of MT/V5 may be premature. Monkey MT/V5 is joined by several satellites (Fig. 83.3) which are themselves selective for motion (Desimone and Ungerleider, 1986; for review see Orban, 1997). Thus, the human motion-sensitive region in the ITS may well correspond to the entire complex, including MT/V5 and its satellites, as suggested by DeYoe et al. (1996). This view has become generally accepted, and the region is referred to as hMT/V5+. Several authors have attempted to subdivide the complex using known properties of MST neurons: large ipsilateral overlap (Desimone and Ungerleider, 1986; Raiguel et al., 1997), responsiveness to optic flow patterns (Duffy and Wurtz, 1991; Lagae et al., 1994; Saito et al., 1986), and response during pursuit (Komatsu and Wurtz, 1988). hMT/V5+ responds to ipsilateral stimulation (Brandt et al., 2000; Ffytche et al., 2000; Tootell et al., 1998; Tootell et al., 1995b). Morrone et al. (2000) suggested that the parts of the hMT/V5+ complex that respond to translation and optic flow components are distinct entities. The part responsive to optic flow, presumed to be the homolog of MSTd, is located more ventrally and appears only when the flow stimuli are changing in time. This localization is in agreement with the results of an earlier passive study of optic flow by de Jong et al. (1994) and with these of a study from our group (Peuskens et al., 2001a) investigating the neural correlates of heading judgments based on optical flow. Both studies observed activity in a ventral satellite of hMT/V5+ related to expansion/contraction. On the other hand, Dukelow et al. (2001), using ipsilateral overlap and pursuit in the dark, reached a different conclusion: according to these authors, MSTd and MSTl are located anterior to MT/V5 proper in the human complex. This contradiction illustrates the difficulty of relating human imaging to monkey single-cell properties.

The recent study of Vanduffel et al. (2001) in the awake monkey makes this even more clear. Up to now, the hMT/V5 complex was believed to include homologs of the subregions of MST, in addition to MT/V5. Yet, when using the translating random-dot pattern typically used in human studies (Sunaert et al., 1999) in monkeys, Vanduffel et al. (2001) observed motion sensitivity in MT/V5, of course, as well as in MSTv and in FST, but not in MSTd (Figs. 83.3, 83.4). The advent of monkey fMRI has made it possible to identify the satellites in the human complex properly. One should scan the human complex at high resolution and test stimuli that differentiate the various parts of the motion complex in monkey fMRI. The aggregation of several functional regions into a single-motion complex may also explain some of the variability in its localization (Watson et al., 1993). As expected from single-cell studies, monkey MT/V5 was activated (above baseline) by both stationary and moving stimuli, but more so by motion. This activation translates into MR signals of opposite polarity in the standard BOLD (blood oxygen level dependent) fMRI and in contrast-enhanced fMRI, using MION (monocrystalline iron oxide nanoparticle) as the contrast agent (Fig. 83.4).

Figure 83.4..  

A, Comparison of BOLD and MION MR signals. Percent signal change in left and right MT/V5 (monkey M1) with respect to the no-stimulus (gray) condition for the three stimulus conditions: no stimulus, stationary, and moving random dots. Average of multiple time series with different order of conditions. Vertical lines indicate the standard error of the mean. Notice reversal of the MR signal sign in MION. B, SPMs of the two hemispheres of M3 on the coronal section trough caudal superior temporal sulcus (STS) for the comparison of moving versus stationary dots. Voxel size 2 × 2 × 2 mm. Lateral arrows, MT/V5; medial arrows, floor of STS: MSTv. (From Vanduffel et al., 2001.) (See color plate 66.)

One should note that the definition of hMT/V5+ in humans reflects a difference in the activity level of the hMT/V5+ population for the two types of stimuli. This is very different from the criterion used in single-cell studies, where regions are considered to be motion selective when they have large proportions of direction-selective cells. Even in monkey fMRI, which shows that the statistical definition of a motion-sensitive region indeed applies to MT/V5, this definition does not reflect the direction selectivity of the underlying neuronal population. In fact, it probably reflects the speed tuning of the population. Because of the small eye movements that occur during fixation, even a stationary stimulus produces extremely slow speeds on the retina (on the order of 0.1 to 0.2 deg/sec) (Stavenski et al., 1975), and most MT/V5 neurons are much less sensitive to these slow speeds than to the 4 to 6 deg/sec speed used in the motion condition of the fMRI studies (Cheng et al., 1994; Churchland and Lisberger, 2001; Lagae et al., 1993; Mikami et al., 1986). This view has received support from the study of Chawla et al. (1999a), who reported that motion MR responses over hMT/V5+ and hV3A displayed an inverted U shape when speed was manipulated in the 1 to 32 deg/sec range. Single-cell studies (Lagae et al., 1993; Orban et al., 1986) have suggested that speed tuning and direction selectivity tend to co-occur in neuronal populations. This may explain why Vanduffel et al. (2001) did observe a correlation, albeit a weak one, between motion sensitivity in the fMRI and the proportion of direction-selective neurons in the single-cell studies. Attempts have been made to use motion opponency as a direct indication of direction selectivity (Heeger et al., 1999), but this reflects the mutual inhibition between neurons tuned to opposite directions rather than direction selectivity as such. An alternative is to use unidirectional adaptation, as done by Tolias et al. (2001) in the anesthetized monkey. Because the reversal of direction after adaptation was not compared directly and statistically to the control event (phase shift in the same direction), this study remained inconclusive. Furthermore, Pack et al. (2001) have recently shown that responses of MT/V5 neurons to moving plaids are dependent on anesthesia.