Results from the thalamus

Figure 4 (a) and (b) show results from seeding different parts of the visual system.In (a) the seed point was in the lateral geniculate nucleus (LGN), a thalamic nucleus which processes visual information. The connectivity distribution heads anteriorly into optic tract, and posteriorly into visual cortex, consistent with the known connections of the lgn in non-human primate [22,23]. However, when the seed is placed in the optic tract (b),two distinct pathways emerge. The two coronal scans in this figure show these two pathways just after they split (near the (coronal) level of lgn) and around 10mm posterior to the split. The righthand pathway follows the route of the pathway in (a). The left hand pathway (see the axial slice in Figure 4 (b)), heads inferior to lgn, round the posterior ventral edge of thalamus to the superior colliculus. These distributions correspond to the two known branches of the primate visual system ([23]); the optic radiations (via LGN) and the superior-collicular brachium.

Figure 4 (c,d) show connectivity distributions seeded in different areas in thalamus.(c) shows a distribution seeded in a medial dorsal area in thalamus. In primate, nuclei in the medial dorsal nuclear cluster of thalamus receive projections from anterior temporal lobe [24,25,26] and maintain reciprocal projections with prefrontal cortex [27,28]. The connectivity distribution in (c) progresses anteriorly into prefontal cortex, and initially posteriorly round the posterior edge of thalamus followed by anteriorly into anterior temporal lobe. (d) shows a distribution seeded in a ventral lateral area in thalamus. In primate thalamus, the ventral lateral nuclear group processes motor information, and maintains strong connections with other motor zones [29,30], such as primary motor cortex, and cerebellar cortex. The connectivity distribution in (d) progresses superiorly to primary motor cortex and inferiorly to cerebellar cortex and brainstem.

The interpretation issues discussed in the previous section are particularly relevant to the distributions shown in Figure 4 (a,b,c,d). (a) and (b) and (d), show pathways which mainly exist in large white matter pathways, with correspondingly low uncertainty in fiber direction. Hence the distributions seen in these figures are narrow. This should not be interpreted to mean that true connections from the seed voxel are necessarily correspondingly focused, but rather that the uncertainty on the pathway defined by the principal diffusion directions is low. The pathway seen in (c) spreads as it passes through a region of uncertainty while approaching temporal lobe, and also encounters uncertainty before entering prefrontal cortex. Again, this should be interpreted as uncertainty in the connection defined by the principal diffusion directions. To reiterate the point previously: In order to infer on diffuse connections from a single seed, the model of diffusion within a voxel must allow for multiple fibers passing through the voxel. However, as can be seen in (b) and (d), presence of local fiber divergence may well be reflected in the local pdf at, for example, branching points in the pathways. In these two examples, branches which are known to occur in primate brain, are found by accounting for uncertainty in principal diffusion direction.

To test the consistency of the results throughout the thalamus, we seeded every voxel in thalamus (manually outlined on the T1 weighted image), and classified the results by the cortical area with the highest probability of connection to the seed. Four cortical areas were manually outlined on the T1 image to correspond with the principal projection and reception sites of thalamic nuclear clusters in primate brain [23] (Figure 4 (e)):

Cortical Zone	Connected Nuclear Cluster in Primate	Color in Figure 4 (e)
Prefrontal-Temporal	medio-dorsal, ventral anterior	purple
Motor-Premotor	ventral lateral	orange
Sensory	ventral posterior	sky blue
Occipital	lateral geniculate, pulvinar (partly)	yellow

Figure 4 (f) shows the nuclei in human thalamus, as defined by histological staining [31] with, overlaid, a color map showing predictions derived from primate data of the strongest cortical connection sites.

We skull-stripped the diffusion weighted image [32], and performed affine registration between the diffusion weighted and T1 images [33],[34], taking care never to resample the diffusion image. We then ran probabilistic tractography seeded from every voxel in the structural scan, classifying the results as above. The results can be seen in figure 4 (g). The classification of thalamic seed voxels by their connectivity distributions, reveals a segmentation of thalamic nuclear clusters broadly consistent with the histological prediction (underlaid in figure 4 (g)), and most probable connected cortical zones consistent with predictions from primate data (overlaid in color in figure 4 (f)). Furthermore, the results show approximate bilateral symmetry in thalamic seed voxels.

These results are examined and extended in detail in [8] including a finer segmentation of the thalamic nuclei resulting from an increased number of cortical zones, and a detailed look at the information available in the probability values themselves.