The organization of the human striatum estimated by intrinsic functional connectivity

Abstract

The striatum is connected to the cerebral cortex through multiple anatomical loops that process sensory, limbic, and heteromodal information. Tract-tracing studies in the monkey reveal that these corticostriatal connections form stereotyped patterns in the striatum. Here the organization of the striatum was explored in the human with resting-state functional connectivity MRI (fcMRI). Data from 1,000 subjects were registered with nonlinear deformation of the striatum in combination with surface-based alignment of the cerebral cortex. fcMRI maps derived from seed regions placed in the foot and tongue representations of the motor cortex yielded the expected inverted somatotopy in the putamen. fcMRI maps derived from the supplementary motor area were located medially to the primary motor representation, also consistent with anatomical studies. The topography of the complete striatum was estimated and replicated by assigning each voxel in the striatum to its most strongly correlated cortical network in two independent groups of 500 subjects. The results revealed at least five cortical zones in the striatum linked to sensorimotor, premotor, limbic, and two association networks with a topography globally consistent with monkey anatomical studies. The majority of the human striatum was coupled to cortical association networks. Examining these association networks further revealed details that fractionated the five major networks. The resulting estimates of striatal organization provide a reference for exploring how the striatum contributes to processing motor, limbic, and heteromodal information through multiple large-scale corticostriatal circuits.

Figures

Fig. 1.

Examples of within-subject surface and volume extraction. Examples of the extracted cerebral cortex surface and striatal boundaries are shown for 3 typical subjects within their native space. The red line delineates the estimated boundary of the cerebral cortical surface between the gray and white matter. The green line shows the estimated edge of the striatum tailored to each individual subject's T1-weighted image. The green line is superimposed on the T2* images to illustrate deviations in the blood oxygenation level-dependent (BOLD) data. Imperfections are apparent in the BOLD data, particularly in the ventral striatum, which lies near to the signal dropout region of the orbital frontal cortex.

Fig. 2.

Examples of between-subject striatal alignment. Volumetric images are shown for the registered structural data from 3 typical subjects. The green line represents the striatal edge estimated from the group structural template and is superimposed identically across the subjects to illustrate each individual's registration to the group template. Each subject's striatum is well registered in relation to the template. Close examination reveals subtle differences between subjects reflecting alignment errors on the order of a few millimeters.

Fig. 3.

Signal-to-noise ratio (SNR) maps of the functional data from the full sample (N = 1,000). The mean estimate of the BOLD fMRI data SNR is illustrated for coronal (left), sagittal (center), and transverse (right) images. The sagittal sections are of the left hemisphere. A, anterior; P, posterior; M, medial; L, lateral; S, superior; I, inferior. The slice coordinate in the MNI atlas space is located at the bottom right of each panel. The estimate of the striatal edge from the group template is illustrated in green (similar to Fig. 2). Note the generally high and uniform SNR except for regions of ventral striatum.

Fig. 4.

Functional connectivity reveals the inverted somatomotor topography within the posterior putamen that is comparable to monkey anatomy and task-evoked estimates. A: a representative case of the inverted somatomotor topography in the monkey putamen revealed by tracer injections in the foot (green) or tongue (blue) representation of the primary motor cortex. Adapted from Flaherty and Graybiel (1993) with permission (see Table 3 under Motor foot). B: coronal sections (left, y = −8) and left sagittal sections (right, x = −28) display the inverted somatomotor topography in the task-evoked (top) and functional connectivity (bottom) data. Green color indicates foot representation; blue color indicates tongue representation. The functional connectivity images were produced from the replication sample (n = 500) using seed regions in the foot- and tongue-specific motor cortex representations from the task-evoked data. C: functional connectivity from the foot- and tongue-specific representations in the putamen (seed regions shown in B, bottom) show specific correlations with the foot and tongue regions of the motor cortex. A threshold of 0.4 was used for the task data, z(r) > 0.035 for the motor foot and z(r) > 0.045 for the motor tongue striatal functional connectivity MRI (fcMRI) data, and z(r) > 0.09 for the cortical fcMRI data. Seed region coordinates are reported in Table 1. Monkey corticostriatal projection tracings shown here and in subsequent figures were redrawn for conformity. Original tracings showed terminal labeling; redrawings included both dense and diffuse projections. Original tracings of the right striatum were flipped in the redrawings for conformity.

Fig. 5.

Functional connectivity reveals the lateral-medial topography of the primary motor and supplementary motor cortices within the putamen that is comparable to monkey anatomy. A: a representative case of the lateral-medial topography of the primary motor cortex and supplementary motor area (SMA) in the monkey putamen revealed by tracer injections in the motor (blue) and SMA (purple) forelimb representations. Adapted from Takada et al. (1998a) with permission (see Table 3 under SMA). B: a coronal section (y = −8) displays the lateral-medial topography in the functional connectivity data produced from the replication sample (n = 500) using seed regions of the task-evoked motor hand representation and the estimated human SMA homolog. Thresholds of z(r) > 0.04 and 0.09 were applied for the motor hand and estimated SMA striatal fcMRI maps, respectively. C: functional connectivity maps from the motor- and SMA-specific striatal seed regions (regions shown in B) illustrate their preferential correlations with primary motor cortex and SMA. A threshold of z(r) > 0.07 was applied. Seed region coordinates are reported in Table 1. Note that there is also correlation with insular regions that fall near to the striatum. We suspect that these are residual artifacts of limited resolution that are not fully handled by our methods (see text).

Fig. 6.

Reliability of human striatal maps based on functional connectivity. Each voxel in the striatum is assigned a color corresponding to its most strongly correlated cerebral network according to the legends below of the 7 (left)- and 17 (right)-network cortical parcellations (from Yeo et al. 2011). The 7- and 17-network parcellations were each produced in the discovery sample (n = 500) and replicated in the replication sample (n = 500). For example, the blue regions of the striatum include those voxels that are more strongly correlated with the blue cerebral network (involving somatosensory and motor cortices) than any other network. Note that the discovery and replication maps are highly similar (voxel overlap was 90.2% and 87.1% for the 7- and 17-network estimates, respectively).

Fig. 7.

A map of the human striatum based on functional connectivity to 7 major networks in the cerebrum. Each voxel in the striatum is assigned a color corresponding to its most strongly correlated cerebral network in the 7-network cortical parcellation shown at bottom (from Yeo et al. 2011). The full sample of 1,000 subjects was used to create a best estimate of the map. The sections display coronal (left), sagittal (center), and transverse (right) images. A, anterior; P, posterior; M, medial; L, lateral; S, superior; I, inferior. The slice coordinate in the MNI atlas space is located at the bottom right of each panel.

Fig. 8.

A fine-parcellated map of the human striatum based on functional connectivity to 17 networks in the cerebrum. The format and use of abbreviations are the same as in Fig. 7 but in this instance in relation to a finer cerebral parcellation involving 17 networks (from Yeo et al. 2011). These data are from the full sample of 1,000 subjects. Note that this method identifies the correct locations of the foot (blue) and tongue (aqua) regions in the posterior putamen. As discussed in the text, some features of the parcellation are uncertain, as illustrated by the asterisk in the putamen (labeled as the pink network).

Fig. 9.

Confidence of the parcellation estimates. Confidence values for each voxel of the striatum with respect to its assigned network vs. second-choice network are displayed for the 7 (left)- and 17 (right)-network estimates from 1,000 subjects. Network boundaries are generally associated with lower confidence values.

Fig. 10.

Distinct regions of the posterior ventral striatum are coupled to motor and association cortical networks. Seed regions placed in the motor (A) and default (B) network assignments of the left posterior ventral striatum in the 7-network parcellation reveal correlation with the motor and default cortical networks, respectively, in the replication sample (n = 500). The 7-network cortical parcellation is also displayed to show that these corticostriatal fcMRI correlations are minimally influenced by signal bleeding from the adjacent cortex.

Fig. 11.

Evidence for preferential patterns of corticostriatal functional connectivity involving association and limbic networks. Left hemisphere cortical functional connectivity maps derived from the replication sample (n = 500) are shown for seed regions placed in high-confidence regions of the striatum from the discovery sample (n = 500) for the frontoparietal control (A), default (B), and limbic (C) networks. Seed regions are shown in the center image (Table 2). Separate regions of the striatum are correlated with distinct cerebral networks underlying cognitive and limbic function.

Fig. 12.

Quantitative evaluation of the specificity of corticostriatal circuits involving association and limbic networks. A–C: the 3 polar plots display the functional connectivity correlation values derived from the replication sample (n = 500) for each of the striatal seed regions (Table 2) from Fig. 11 with cortical seed regions placed in distributed regions of cortical networks, shown in the center image. Polar scale ranges from r = −0.25 (center) to r = 0.35 (outer boundary) in 0.2-step increments. Each polar plot has a distinct connectivity profile.

Fig. 13.

Regression of cortical signal from the striatum. The effects of regressing out the adjacent cortical signal from the striatum are shown with the full sample of 1,000 subjects. A–D: posterior striatum (y = −8). E–H: anterior striatum (y = 12). First 2 columns show the 7-network parcellation (A, E) and an fcMRI map of a proximal insula seed region (B, F) with no cortical signal regression from the striatum (see methods for seed region coordinate). Third and fourth columns show the 7-network parcellation (C, G) and fcMRI maps of the same seed region (D, H) with regression of cortical signal from the striatum (not applied to cortex). Note how the parcellations are dominated by the network labeled by violet. When regression is applied, a more plausible parcellation results. The contrast between the functional connectivity patterns within the striatum before (e.g., F) and after (e.g., H) regression of adjacent cortical signal illustrates that bleeding of signal from cortex to striatum is mitigated but not fully removed. Signal bleeding minimally affects the major portions of the caudate and ventral striatum. Parcellation estimates within the putamen are less certain.

Fig. 14.

Alternative regression method for removing cortical signal from the striatum. The 7-network parcellation results are shown for the anterior striatum (y = 12) using the regression method applied in this paper (A; see methods and Fig. 13) in which the signal from a unitary cortical mask is regressed from all striatal voxels. An alternative regression method is shown in which for each striatal voxel the signal of neighboring cortical voxels within 9 mm is regressed out (B). Asterisk indicates the region of low confidence similar to Fig. 8. The full sample of 1,000 subjects was used.

Fig. 15.

Functional connectivity reveals the distinct topography of motor, association, and limbic networks. A: 5 regions with replicated monkey tract-tracings and putative human homologs were selected for comparison: dorsolateral prefrontal cortex (PFClp), medial prefrontal cortex (PFCmd), estimated subgenual cingulate area 25 (scg25), motor cortex, and SMA. All estimated homologies here and in subsequent figures are uncertain but reasonable approximations based on the available literature. B: a representative anatomical tract-tracing case for each region. Cases illustrated are listed in Table 3. C: coronal slices show the corresponding functional connectivity generated from the replication sample (n = 500) using the seed regions depicted in A. Slice atlas coordinates are displayed at bottom right. Note the similarity of the patterns between the anatomy and functional connectivity, as well as their correspondence with the motor (blue), ventral attention (violet), frontoparietal control (orange), default (red), and limbic (cream) parcellations in the 7-network parcellation. Anatomical tract-tracing cases were adapted for conformity as described in Fig. 4 from the following with permission: motor (Liles and Updyke 1985), SMA (Inase et al. 1999), PFClp (Selemon and Goldman-Rakic 1985), scg25 (Haber et al. 2006), and PFCmd (Ferry et al. 2000). Original tracings from Ferry et al. (2000; PFCmd and Fig. 17 PFCa) showed the density of axonal synaptic boutons. The redrawing for PFCmd included only the overlapping circles in the original tracing.

Fig. 16.

Functional connectivity reveals that distributed cortical regions within the frontoparietal control network couple to similar zones of the striatum. A: PFClp, anterior area PG (PGa), and dorsomedial prefrontal cortex (PFCmp) were chosen as distributed cortical regions within the frontoparietal control network in order to compare human functional connectivity with monkey anatomy within a single network. B: a representative anatomical tract-tracing case for each region. Cases illustrated are listed in Table 3. C: coronal slices show the corresponding functional connectivity generated from the replication sample (n = 500) using the seed regions depicted in A. Slice atlas coordinates are displayed at bottom right. Note the broad similarity of the patterns both across the regions and between the monkey anatomy and human functional connectivity. Anatomical tract-tracing cases were adapted as described in Fig. 4 from Selemon and Goldman-Rakic (1985) with permission.

Fig. 17.

Functional connectivity reveals that distributed cortical regions within the default network couple to similar zones of the striatum. A: 5 regions, the superior temporal sulcus (STS), the central portion of area PG (PGc), posterior cingulate cortex (PCC), PFCmd, and PFCa in the frontal pole, with replicated monkey tract-tracings and putative human homologs were selected to compare functional connectivity with monkey anatomy within the default network (red). Cases illustrated are adapted from cases in Table 3. B: a representative anatomical tract-tracing case for each region. C: coronal slices show the corresponding functional connectivity generated from the replication sample (n = 500) using the seed regions depicted in A. Slice atlas coordinates are displayed at bottom right. Note the general similarity of the patterns both across the regions and between the monkey anatomy and human functional connectivity. However, several discrepancies are also notable including the differences between PGc and PCC and STS. Anatomical tract-tracing cases were adapted as described in Figs. 4 and 15 from the following with permission: STS (Selemon and Goldman-Rakic 1985), PGc (Cavada and Goldman-Rakic 1991), PCC (Baleydier and Mauguiere 1980), and PFCmd (Yeterian and Pandya 1991) and PFCa (Ferry et al. 2000).

Fig. 18.

Functional connectivity reveals that interdigitated cerebral association networks couple to nearby but preferentially distinct zones of the striatum. Two association networks that each comprise distributed regions within the cortex (labeled red and yellow) in the 17-network parcellation were selected to examine fine-grained features of corticostriatal organization. Center: 3 seed regions distributed across the brain for each network (Table 4). Seed regions were obtained from Yeo et al. (2011) except for ventral anterior area PG (PGav) and the dorsal posterior portion of posterior area PG (PGpdp). Functional connectivity was computed with the replication sample (n = 500). A: the functional connectivity of PFCdp, PFCv, and PGav from the red association network converge on similar zones of dorsal caudate head (shown in coronal slice y = 12). B: by contrast, the functional connectivity of PGpdp, PCC, and PFCm from the yellow association network converge upon similar zones of the ventral caudate head. Note that spatially juxtaposed cerebral regions (e.g., PGav and PGpdp) coupled to distinct striatal zones consistent with their belonging to separate large-scale cerebral networks.