Edited by: Kathleen S. Rockland, Boston University, United States
Reviewed by: Ettore Alberto Accolla, University of Fribourg, Switzerland; Masahiko Takada, Kyoto University, Japan
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Within the cortico basal ganglia (BG)–thalamic network, the direct and indirect pathways comprise of projections from the cortex to the striatum (STR), whereas the hyperdirect pathway(s) consist of cortical projections toward the subthalamic nucleus (STN). Each pathway possesses a functionally distinct role for action selection. The current study quantified and compared the structural connectivity between 17 distinct cortical areas with the STN and STR using 7 Tesla diffusion weighted magnetic resonance imaging (dMRI) and resting-state functional MRI (rs-fMRI) in healthy young subjects. The selection of these cortical areas was based on a literature search focusing on animal tracer studies. The results indicate that, relative to other cortical areas, both the STN and STR showed markedly weaker structural connections to areas assumed to be essential for action inhibition such as the inferior frontal cortex pars opercularis. Additionally, the cortical connectivity fingerprint of the STN and STR indicated relatively strong connections to areas related to voluntary motor initiation such as the cingulate motor area and supplementary motor area. Overall the results indicated that the cortical–STN connections were sparser compared to the STR. There were two notable exceptions, namely for the orbitofrontal cortex and ventral medial prefrontal cortex, where a higher tract strength was found for the STN. These two areas are thought to be involved in reward processing and action bias.
The basal ganglia (BG) collectively refer to a group of interconnected subcortical nuclei. The main BG components are the caudate and putamen, which together form the striatum (STR), the internal and external segments of the globus pallidus (GPi and GPe, respectively), the substantia nigra, and the subthalamic nucleus (STN) (
Therefore, both the STN and STR are considered as crucial input structures to the BG and are essential for both optimal and flexible adaptive motor control and action selection, which may arise from a number of scenarios, from goal-directed behaviors to habitual responses (
To the best of our knowledge, a quantitative comparison of the connectivity profiles between the frontal cortex and the STN and STR in humans has yet to be conducted. There have been numerous studies quantifying the diffusion weighted and resting-state functional MRI (rs-fMRI) connectivity patterns of the cortex, STN, and STR separately (e.g.,
Sixteen healthy participants (9 female, age range = 19–28, mean age = 23.13,
The structural data were obtained from a 7T whole body Siemens MAGNETOM using a 24 channel Nova head coil (NOVA Medical Inc., Wilmington, MA, United States) during two sessions. The first session consisted of a whole-brain MP2RAGE (
In a second structural scan session, DWI was acquired with a spin echo planar imaging sequence (
Finally, in a third MRI session, rs-fMRI was acquired using a 2D EPI sequence. A total of 76 slices were acquired interleaved in transversal direction, with a TA of 5:16 min, TR = 3330 ms, TE = 18 ms, voxel size = 1.5 mm isotropic, phase encoding A > P, GRAPPA acceleration factor 3, BW = 1086 Hz/Px, and echo spacing = 1.03 ms. To correct for distortions, a GRE field map with 57 slices was acquired in transversal direction with a TA of 4:53 min, TR = 1500, TE1 = 6.00 ms, TE2 = 7.02 ms, voxel size = 2.0 mm isotropic, FA = 68°, phase encoding A > P, and BW = 259 Hz/Px.
The STN and STR masks have been previously described in
Instead of testing the connectivity of the STN and STR with the entire cortex, we selected a number of cortical areas that have been identified in non-human primate (NHP) tracer studies as connecting to both the STN and STR. These connections were selected by conducting an empirical literature search using the PubMed database
Since a large number of studies used different nomenclature to refer to the same or similar brain regions (e.g., Brodmann, Walkers, Vogts, and “own labeling system”) we summarized these studies into a single cortical area using the anatomical description of the original study. The human homolog of each cortical area was then identified in standard MNI-space using a number of comparative anatomical atlases that are based on both human and NHPs (
Cortical areas that connect both to the STR and STN based on tracer studies in non-human primates.
Cortical ROIs | Tracer studies | Cortical masks and corresponding atlas |
---|---|---|
(1) Primary motor cortex (M1) | M1 ( |
|
(2) Pre-motor cortex (pre-M1) | 6v, 6r ( |
|
(3) Supplementary motor area (SMA) | SMA and pre-SMA ( |
|
(4) Pre-supplementary motor area (pre-SMA) | ||
(5) Frontal eye fields (FEF) | 8A and 8B ( |
|
(6) Dorsolateral prefrontal cortex (DLPFC) | 46, 9, 9/46d, and 9/46v ( |
|
(7) Frontopolar area (FPA) | 10 ( |
|
(8) Ventromedial and lateral prefrontal cortex (VMPFC) | 47o, 47m, and 14m ( |
|
(9) Orbitofrontal cortex (OFC) | 11 and 11m ( |
|
(10) Inferior frontal sulcus (IFS) | IFS and IFJ ( |
|
(11) Inferior frontal junction (IFJ) | ||
(12) Inferior frontal gyrus pars opercularis (POP) | POP: 44d, 44v, and PTR: 45 ( |
|
(13) Inferior frontal gyrus pars triangularis (PTR) | ||
(14) Cingulate cortex (CIN) | 23ab and 24 ( |
|
(15) Cingulate motor area (CMA) | CCZ, RCZa, and RCZp ( |
|
(16) Perigenual area (PGA) | PGA: 32pl, 32d and SGA: 25 ( |
|
(17) Subgenual area (SGA) |
Representation of the cortical region of interests (ROIs). Based on the literature search, all areas have a non-human primate homolog and structurally connect to both the STN and STR in non-human primates. For visualization purposes only the ROIs in the left hemispheres are displayed. See
The average FLASH volume of the three TE’s was linearly registered to the MP2RAGE whole-brain second inversion volume using a mutual information function, trilinear interpolation, and 6 degrees of freedom (DoF) in FLIRT (FSL 5.0.9). The MP2RAGE slab image was linearly registered to the MP2RAGE whole-brain UNI volume using a correlation cost function, trilinear interpolation, and 6 DoF in FLIRT. The MP2RAGE whole-brain was registered to the average rs-fMRI volume using mutual information cost function, trilinear interpolation, and 6 DoF. The MP2RAGE whole-brain was registered to the
The skull stripped 1 mm MNI template was linearly registered to the MP2RAGE whole-brain UNI volume using a correlation cost function, trilinear interpolation, and 12 DoF in FLIRT. The resulting transformation matrix were concatenated with the transformation matrix of the whole-brain to either the
Diffusion weighted image pre-processing and all subsequent analyses were conducted using FSL (version 5.0.10). The four runs were concatenated and the data were corrected for eddy currents and motion. A single volume without diffusion weighting (
Summary statistics of the tract lengths between the cortical areas and the STN and STR averaged over hemispheres.
STN |
STR |
||||
---|---|---|---|---|---|
Mean | Mean | BF10 | |||
(1) Primary motor cortex (M1) | 104.3 | 22.76 | 107.3 | 20.88 | 0.85 |
(2) Pre-motor cortex (pre-M1) | 92.62 | 7.23 | 100.32 | 9.18 | 781.37 |
(3) Supplementary motor area (SMA) | 96.96 | 6.36 | 102.37 | 5.98 | 14.82 |
(4) Pre-supplementary motor area (pre-SMA) | 93.45 | 6.17 | 107.22 | 11.29 | ≥1000 |
(5) Frontal eye fields (FEF) | 95.56 | 7.51 | 104.21 | 10.84 | ≥1000 |
(6) Dorsolateral prefrontal cortex (DLPFC) | 94.36 | 9.59 | 97.92 | 12.6 | 1.44 |
(7) Frontopolar area (FPA) | 95.48 | 11.61 | 86.59 | 11.47 | ≥1000 |
(8) Ventromedial and lateral prefrontal cortex (VMPFC) | 70.62 | 20.28 | 45.08 | 14.02 | ≥1000 |
(9) Orbitofrontal cortex (OFC) | 61.28 | 14.68 | 37.0 | 11.39 | ≥1000 |
(10) Inferior frontal sulcus (IFS) | 99.85 | 8.46 | 107.13 | 11.78 | 45.70 |
(11) Inferior frontal junction (IFJ) | 103.38 | 10.8 | 104.81 | 14.09 | 0.25 |
(12) Pars opercularis (POP) | 76.97 | 18.53 | 95.07 | 13.55 | ≥1000 |
(13) Pars triangularis (PTR) | 79.25 | 17.55 | 94.35 | 14.07 | ≥1000 |
(14) Cingulate cortex (CIN) | 93.77 | 15.25 | 92.25 | 12.15 | 0.24 |
(15) Cingulate motor area (CMA) | 86.47 | 6.85 | 91.14 | 4.82 | 33.16 |
(16) Perigenual area (PGA) | 88.86 | 11.5 | 87.12 | 15.47 | 0.26 |
(17) Subgenual area (SGA) | 44.63 | 25.48 | 48.36 | 11.59 | 0.30 |
To remove any spurious connections, the resulting seed images were thresholded so that only voxels which had at least 50 samples were kept. The resulting thresholded masks were divided by the number of samples (
Tract seed ratio can be informative to show differences in connectivity between regions it does not take differences in volume into account. Therefore, in addition to tract seed ratio we also calculate tract strength. To remove any spurious connections, the resulting seed image was thresholded so that only voxels which had at least 50 samples were kept. The number of non-zero voxels was then divided by the total number of voxels in the seed mask, resulting in a ratio indicating the proportion of seed mask voxels that was probabilistically connected to the target mask. This ratio is relative to the volume of the seed mask and compensates for the volumetric differences between the STN and STR. Tract strength was defined as the average of the two ratios that resulted from the seed-to-target tractography and target-to-seed tractography (
The rs-fMRI data were corrected for
The outlier criteria were three times the interquartile range. All statistics were done using the Bayesian tests implemented in the BayesFactor toolbox (
Suggested categories for interpreting the Bayes factors.
Bayes factor BF10 | Interpretation | ||
---|---|---|---|
> | 100 | Decisive evidence for H1 | |
30 | – | 100 | Very strong evidence for H1 |
10 | – | 30 | Strong evidence for H1 |
3 | – | 10 | Substantial evidence for H1 |
1 | – | 3 | Anecdotal evidence for H1 |
1 | No evidence | ||
1/3 | – | 1 | Anecdotal evidence for H0 |
1/10 | – | 1/3 | Substantial evidence for H0 |
1/30 | – | 1/10 | Strong evidence for H0 |
1/100 | – | 1/30 | Very strong evidence for H0 |
< | 1/00 | Decisive evidence for H0 |
All corresponding analysis scripts can be found on
The outlier analysis indicated that for a single tract [STN – orbitofrontal cortex (OFC)] there were four outliers. These data points were removed from any further analysis. The JZS Bayesian mixed effect model revealed that the model with main effects for subcortical structure and cortical structures, as well as an interaction between these two variables, is preferred over the model without the interaction, by a Bayes factor of >1000. Therefore, the data provide decisive evidence that the average number of samples reaching the target is generally higher for the tracts between the STN and cortex than for the STR. Pairwise
Summary statistics of the average seed ratios for the STN and STR to cortex averaged over hemispheres.
STN |
STR |
||||
---|---|---|---|---|---|
Mean | Mean | BF10 | |||
(1) Primary motor cortex (M1) | 0.21 | 0.02 | 0.18 | 0.01 | ≥1000 |
(2) Pre-motor cortex (pre-M1) | 0.18 | 0.01 | 0.16 | 0.01 | ≥1000 |
(3) Supplementary motor area (SMA) | 0.19 | 0.01 | 0.16 | 0.01 | ≥1000 |
(4) Pre-supplementary motor area (pre-SMA) | 0.18 | 0.01 | 0.16 | 0.01 | ≥1000 |
(5) Frontal eye fields (FEF) | 0.19 | 0.02 | 0.17 | 0.02 | ≥1000 |
(6) Dorsolateral prefrontal cortex (DLPFC) | 0.18 | 0.01 | 0.16 | 0.01 | ≥1000 |
(7) Frontopolar area (FPA) | 0.18 | 0.02 | 0.15 | 0.01 | ≥1000 |
(8) Ventromedial and lateral prefrontal cortex (VMPFC) | 0.15 | 0.02 | 0.14 | 0.01 | 17.56 |
(9) Orbitofrontal cortex (OFC) | 0.15 | 0.01 | 0.15 | 0.01 | 0.24 |
(10) Inferior frontal sulcus (IFS) | 0.19 | 0.02 | 0.17 | 0.02 | ≥1000 |
(11) Inferior frontal junction (IFJ) | 0.20 | 0.02 | 0.17 | 0.02 | ≥1000 |
(12) Pars opercularis (POP) | 0.17 | 0.02 | 0.17 | 0.02 | 0.19 |
(13) Pars triangularis (PTR) | 0.17 | 0.02 | 0.17 | 0.02 | 0.19 |
(14) Cingulate cortex (CIN) | 0.19 | 0.02 | 0.17 | 0.01 | ≥1000 |
(15) Cingulate motor area (CMA) | 0.17 | 0.01 | 0.16 | 0.01 | ≥1000 |
(16) Perigenual area (PGA) | 0.17 | 0.02 | 0.16 | 0.01 | 909.18 |
(17) Subgenual area (SGA) | 0.13 | 0.04 | 0.14 | 0.02 | 0.52 |
The outlier analysis indicated that for a single tract [STR – perigenual area (PGA)] there was a single outlier. This data point was removed from any further analysis. The JZS Bayesian mixed effect model revealed that the model with main effects for subcortical structure and cortical structures, as well as an interaction between these two variables, is preferred to the model without the interaction with a Bayes factor of >1000. Therefore, the data provide decisive evidence that the tract strength between the STN and cortex is generally lower than for the STR and the cortex. Note that this was the case even though the absolute number of samples reaching the target was higher for the STN.
The
Summary statistics of the tract strengths for the STN and STR to cortex averaged over hemispheres.
STN |
STR |
||||
---|---|---|---|---|---|
Mean | Mean | BF10 | |||
(1) Primary motor cortex (M1) | 0.71 | 0.1 | 0.84 | 0.09 | ≥1000 |
(2) Pre-motor cortex (pre-M1) | 0.64 | 0.06 | 0.69 | 0.07 | 139.30 |
(3) Supplementary motor area (SMA) | 0.77 | 0.08 | 0.83 | 0.07 | 132.52 |
(4) Pre-supplementary motor area (pre-SMA) | 0.74 | 0.06 | 0.73 | 0.09 | 0.27 |
(5) Frontal eye fields (FEF) | 0.43 | 0.2 | 0.65 | 0.12 | ≥1000 |
(6) Dorsolateral prefrontal cortex (DLPFC) | 0.67 | 0.07 | 0.76 | 0.09 | ≥1000 |
(7) Frontopolar area (FPA) | 0.7 | 0.09 | 0.79 | 0.11 | 131.73 |
(8) Ventromedial and lateral prefrontal cortex (VMPFC) | 0.57 | 0.2 | 0.39 | 0.12 | ≥1000 |
(9) Orbitofrontal cortex (OFC) | 0.45 | 0.18 | 0.3 | 0.08 | ≥1000 |
(10) Inferior frontal sulcus (IFS) | 0.7 | 0.09 | 0.76 | 0.1 | 10.87 |
(11) Inferior frontal junction (IFJ) | 0.61 | 0.12 | 0.73 | 0.07 | ≥1000 |
(12) Pars opercularis (POP) | 0.48 | 0.15 | 0.7 | 0.07 | ≥1000 |
(13) Pars triangularis (PTR) | 0.63 | 0.18 | 0.71 | 0.08 | 7.0 |
(14) Cingulate cortex (CIN) | 0.64 | 0.08 | 0.78 | 0.08 | ≥1000 |
(15) Cingulate motor area (CMA) | 0.76 | 0.07 | 0.84 | 0.06 | 721.13 |
(16) Perigenual area (PGA) | 0.75 | 0.11 | 0.78 | 0.11 | 0.37 |
(17) Subgenual area (SGA) | 0.22 | 0.2 | 0.27 | 0.11 | 0.55 |
Star plots of the tract strengths between the STN, STR, and the different cortical regions per participant. The STN is color coded using blue, the STR using orange, and both tracts are plotted with 50% opacity. Each segment corresponds to an individual participant.
The main effect of cortical areas and the interaction indicated that various cortical areas have different tract strengths to the subcortex and that this tract strength varied per cortical area and subcortical structure.
As illustrated in
A probability map of three representative cortical regions projecting to the subcortex. For the pars triangularis (PTR), frontal eye fields (FEF), and pre-supplementary motor area (pre-SMA), a probability map was created using the individual thresholded seed masks. The thresholded seed masks only include those voxels which contained at least 50 samples in the tractography analysis. To be able to compare the results across participants, the thresholded seed masks were transformed back into MNI-standard space using the inverted transformation matrices. The color intensity indicates the overlap across participants. In red-yellow the probability map of the thresholded seed masks toward the STR; in blue the probability map of the thresholded seed masks toward the STN. The
To test for differences between tracts connecting subcortical areas, i.e., STN and STR, with the cortex, Bayesian paired
Paired
M1 | Pre-M1 | SMA | Pre-SMA | FEF | DLPFC | FPA | VMPFC | OFC | IFS | IFJ | POP | PTR | CIN | CMA | PGA | SGA | |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
M1 | – | 15.17 | 18.65 | 0.46 | ≥1000 | 0.67 | 0.2 | 133.02 | ≥1000 | 0.2 | 67.37 | ≥1000 | 1.56 | 60 | 250.31 | 1.19 | ≥1000 |
Pre-M1 | 15.17 | – | ≥1000 | ≥1000 | ≥1000 | 2.15 | 9.66 | 1.05 | ≥1000 | 34.54 | 0.44 | ≥1000 | 0.2 | 0.19 | ≥1000 | 324.43 | ≥1000 |
SMA | 18.65 | ≥1000 | – | 0.38 | ≥1000 | 457.49 | 5.39 | ≥1000 | ≥1000 | 2.93 | ≥1000 | ≥1000 | 97.17 | ≥1000 | 0.21 | 0.25 | ≥1000 |
Pre-SMA | 0.46 | ≥1000 | 0.38 | – | ≥1000 | ≥1000 | 0.83 | 248.91 | ≥1000 | 1.96 | ≥1000 | ≥1000 | 10.66 | 359.66 | 0.26 | 0.19 | ≥1000 |
FEF | ≥1000 | ≥1000 | ≥1000 | ≥1000 | – | ≥1000 | ≥1000 | 2.2 | 0.21 | ≥1000 | 32.15 | 0.34 | 133.78 | ≥1000 | ≥1000 | ≥1000 | 49.93 |
DLPFC | 0.67 | 2.15 | 457.49 | ≥1000 | ≥1000 | – | 1.17 | 5.25 | ≥1000 | 1.62 | 4.59 | ≥1000 | 0.43 | 0.63 | 291.21 | 6.37 | ≥1000 |
FPA | 0.2 | 9.66 | 5.39 | 0.83 | ≥1000 | 1.17 | – | 140.69 | ≥1000 | 0.19 | 10.67 | ≥1000 | 2.51 | 31.77 | 18.82 | 2.09 | ≥1000 |
VMPFC | 133.02 | 1.05 | ≥1000 | 248.91 | 2.2 | 5.25 | 140.69 | – | ≥1000 | 18.65 | 0.34 | 1.28 | 0.9 | 1.21 | ≥1000 | ≥1000 | ≥1000 |
OFC | ≥1000 | ≥1000 | ≥1000 | ≥1000 | 0.21 | ≥1000 | ≥1000 | ≥1000 | – | ≥1000 | 90.73 | 0.29 | ≥1000 | ≥1000 | ≥1000 | ≥1000 | ≥1000 |
IFS | 0.2 | 34.54 | 2.93 | 1.96 | ≥1000 | 1.62 | 0.19 | 18.65 | ≥1000 | – | 227.44 | ≥1000 | 1.44 | 3.98 | 2.47 | 0.58 | ≥1000 |
IFJ | 67.37 | 0.44 | ≥1000 | ≥1000 | 32.15 | 4.59 | 10.67 | 0.34 | 90.73 | 227.44 | – | 67.98 | 0.2 | 0.3 | ≥1000 | 243.21 | ≥1000 |
POP | ≥1000 | ≥1000 | ≥1000 | ≥1000 | 0.34 | ≥1000 | ≥1000 | 1.28 | 0.29 | ≥1000 | 67.98 | – | 883.01 | ≥1000 | ≥1000 | ≥1000 | ≥1000 |
PTR | 1.56 | 0.2 | 97.17 | 10.66 | 133.78 | 0.43 | 2.51 | 0.9 | ≥1000 | 1.44 | 0.2 | 883.01 | – | 0.2 | 215.06 | 13.3 | ≥1000 |
CIN | 60 | 0.19 | ≥1000 | 359.66 | ≥1000 | 0.63 | 31.77 | 1.21 | ≥1000 | 3.98 | 0.3 | ≥1000 | 0.2 | – | ≥1000 | ≥1000 | ≥1000 |
CMA | 250.31 | ≥1000 | 0.21 | 0.26 | ≥1000 | 291.21 | 18.82 | ≥1000 | ≥1000 | 2.47 | ≥1000 | ≥1000 | 215.06 | ≥1000 | – | 0.28 | ≥1000 |
PGA | 1.19 | 324.43 | 0.25 | 0.19 | ≥1000 | 6.37 | 2.09 | ≥1000 | ≥1000 | 0.58 | 243.21 | ≥1000 | 13.3 | ≥1000 | 0.28 | – | ≥1000 |
SGA | ≥1000 | ≥1000 | ≥1000 | ≥1000 | 49.93 | ≥1000 | ≥1000 | ≥1000 | ≥1000 | ≥1000 | ≥1000 | ≥1000 | ≥1000 | ≥1000 | ≥1000 | ≥1000 | – |
Compared to other cortical areas, the SGA, frontal eye fields (FEF), OFC, and the pars opercularis of the inferior frontal gyrus (POP) had lower tract strengths toward the STN (SGA: 16 out of 16 paired
There were also a number of cortical areas that had relatively higher tract strengths toward both the STN and STR. Compared to the other cortical areas, the SMA, cingulate motor area (CMA), PGA, and pre-SMA had higher tract strengths toward the STN (SMA: 12 out of 16 paired
There were no outliers for the rs-fMRI correlations. The JZS Bayesian mixed effect model revealed that the model with main effects for subcortical structures and cortical structures, as well as an interaction between these two variables, is preferred to the model without the interaction with a Bayes factor of 130.74. The data therefore provide decisive evidence that the resting-state BOLD correlation between the STN and cortex is generally lower than for the STR and cortex.
The
Summary statistics of rs-fMRI correlation coefficient for the STN and STR to cortex averaged over hemispheres.
STN |
STR |
||||
---|---|---|---|---|---|
Mean | Mean | BF10 | |||
(1) Primary motor cortex (M1) | 0.12 | 0.19 | 0.41 | 0.43 | 743.67 |
(2) Pre-motor cortex (pre-M1) | 0.15 | 0.17 | 0.44 | 0.22 | >1000 |
(3) Supplementary motor area (SMA) | 0.18 | 0.18 | 0.36 | 0.27 | 7.26 |
(4) Pre-supplementary motor area (pre-SMA) | 0.04 | 0.21 | 0.39 | 0.22 | >1000 |
(5) Frontal eye fields (FEF) | –0.02 | 0.23 | 0.38 | 0.21 | >1000 |
(6) Dorsolateral prefrontal cortex (DLPFC) | 0.04 | 0.22 | 0.54 | 0.21 | >1000 |
(7) Frontopolar area (FPA) | 0.08 | 0.21 | 0.54 | 0.21 | >1000 |
(8) Ventromedial and lateral prefrontal cortex (VMPFC) | 0.16 | 0.23 | 0.63 | 0.21 | >1000 |
(9) Orbitofrontal cortex (OFC) | 0.1 | 0.24 | 0.59 | 0.21 | >1000 |
(10) Inferior frontal sulcus (IFS) | 0.07 | 0.23 | 0.45 | 0.23 | >1000 |
(11) Inferior frontal junction (IFJ) | 0.07 | 0.19 | 0.43 | 0.16 | >1000 |
(12) Pars opercularis (POP) | 0.13 | 0.18 | 0.46 | 0.21 | >1000 |
(13) Pars triangularis (PTR) | 0.15 | 0.2 | 0.45 | 0.23 | >1000 |
(14) Cingulate cortex (CIN) | 0.13 | 0.23 | 0.58 | 0.21 | >1000 |
(15) Cingulate motor area (CMA) | 0.15 | 0.19 | 0.55 | 0.19 | >1000 |
(16) Perigenual area (PGA) | 0.1 | 0.19 | 0.45 | 0.24 | >1000 |
(17) Subgenual area (SGA) | 0.12 | 0.2 | 0.52 | 0.26 | >1000 |
Violin plots of the rs-fMRI correlation between STN, STR, and the different cortical regions per participant. The STN is color coded using blue and the STR using orange. The black circles correspond to the individual participants.
To test which of the resting-state correlations between the subcortical areas and cortex differed from each other, Bayesian paired
Contrary to the tract strengths, most of the rs-fMRI correlations between the STN and cortical ROIs did not differ from each other (see
Paired
M1 | Pre-M1 | SMA | Pre-SMA | FEF | DLPFC | FPA | VMPFC | OFC | IFS | IFJ | POP | PTR | CIN | CMA | PGA | SGA | |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
M1 | – | 0.30 | 0.43 | 0.22 | 0.24 | 14.0 | 9.74 | 579.85 | 107.47 | 0.26 | 0.20 | 0.41 | 0.29 | 436.16 | 78.01 | 0.27 | 0.65 |
Pre-M1 | 0.33 | – | 1.12 | 0.43 | 0.53 | 6.44 | 6.36 | 443.40 | 29.55 | 0.19 | 0.22 | 0.21 | 0.20 | 208.54 | 36.44 | 0.20 | 0.41 |
SMA | 0.88 | 0.27 | – | 0.21 | 0.20 | 40.49 | 39.79 | >1000 | 259.12 | 0.56 | 0.52 | 1.33 | 0.64 | 947.16 | >1000 | 0.90 | 2.18 |
Pre-SMA | 7.15 | 44.56 | 34.68 | – | 0.20 | 65.09 | 55.20 | >1000 | 539.04 | 0.52 | 0.37 | 0.69 | 0.47 | >1000 | 182.56 | 0.43 | 1.15 |
FEF | 34.56 | 770.56 | >1000 | 4.18 | – | >1000 | 205.76 | >1000 | >1000 | 1.51 | 0.52 | 1.35 | 0.80 | >1000 | >1000 | 0.69 | 1.83 |
DLPFC | 1.50 | 12.87 | 32 | 0.19 | 1.44 | – | 0.19 | 73.41 | 1.50 | 881.33 | 199.80 | 261.95 | 41.51 | 1.84 | 0.19 | 28.53 | 0.20 |
FPA | 0.27 | 0.85 | 3.33 | 0.30 | 5.25 | 1.27 | – | 202.08 | 1.03 | 27.91 | 59.36 | 5.09 | 7.47 | 1.09 | 0.20 | 12.71 | 0.20 |
VMPFC | 0.30 | 0.19 | 0.20 | 5.88 | 72.59 | 41.10 | 3.61 | – | 0.66 | >1000 | >1000 | >1000 | >1000 | 0.61 | 5.25 | >1000 | 1.10 |
OFC | 0.20 | 0.33 | 0.72 | 0.51 | 6.54 | 1.09 | 0.24 | 4.69 | – | >1000 | >1000 | >1000 | 750.84 | 0.19 | 0.70 | 163.26 | 0.45 |
IFS | 0.31 | 1.68 | 2.21 | 0.21 | 0.88 | 0.28 | 0.20 | 22.21 | 0.29 | – | 0.24 | 0.20 | 0.19 | 668.59 | 6.72 | 0.19 | 0.43 |
IFJ | 0.46 | 9.82 | 2.73 | 0.26 | 1.90 | 0.27 | 0.20 | 3.65 | 0.26 | 0.19 | – | 0.39 | 0.25 | >1000 | 870.92 | 0.25 | 0.78 |
POP | 0.21 | 0.28 | 0.38 | 6.26 | 123.63 | 10.06 | 0.43 | 0.28 | 0.24 | 0.88 | 2.64 | – | 0.18 | >1000 | 133.48 | 0.19 | 0.38 |
PTR | 0.25 | 0.19 | 0.22 | 2.83 | 24.36 | 11.48 | 0.81 | 0.20 | 0.36 | 10.85 | 2.75 | 0.26 | – | 281.89 | 6.38 | 0.19 | 0.44 |
CIN | 0.20 | 0.22 | 0.43 | 1.71 | 48.83 | 16.92 | 0.89 | 0.41 | 0.35 | 0.86 | 0.59 | 0.19 | 0.22 | – | 2.15 | >1000 | 0.34 |
CMA | 0.32 | 0.19 | 0.30 | 15.22 | 589.96 | 48.74 | 1.58 | 0.20 | 0.67 | 1.41 | 1.81 | 0.23 | 0.19 | 0.32 | – | 9.46 | 0.21 |
PGA | 0.21 | 0.57 | 1.19 | 0.45 | 4.85 | 1.03 | 0.23 | 1.38 | 0.19 | 0.35 | 0.27 | 0.30 | 0.71 | 0.34 | 0.64 | – | 0.45 |
SGA | 0.19 | 0.24 | 0.36 | 0.52 | 3.20 | 0.65 | 0.27 | 0.28 | 0.21 | 0.35 | 0.47 | 0.19 | 0.23 | 0.19 | 0.23 | 0.22 | – |
Contrary to the STN, the rs-fMRI correlations between the STR and the cortical ROIs seemed more heterogeneous. Compared to the other cortical areas, there were a number of regions which had a higher rs-fMRI correlation with the STR such as the ventral medial prefrontal cortex (VMPFC; 13 out of 16 paired
This study set out to investigate the connectivity fingerprint of the STN and STR with the cortex using diffusion and rs-fMRI. The tract strengths indicate that for most cortical areas tested, the STR exhibits relatively higher tract strengths than the STN. It is unlikely that the lower tract strength for the STN was due to higher noise in the tractography as the absolute seed ratios were actually higher for the STN. For the rs-fMRI data, the correlations between the cortical ROI’s and the STR were also consistently found to be higher than those for the STN. This finding is in line with the previous literature that notes that while the STN and STR are indeed directly connected to similar cortical areas, STN connections are more sparsely present (
There were, however, two notable exceptions for tract strengths. Namely for the OFC and VMPFC, where a higher tract strength was found for the STN relative to the STR. The OFC and VMPFC are two cortical regions thought to be essential for reward processing, choice bias, and mood (
Overall the relative structural connectivity fingerprint of the cortex toward the STN is very similar to the STR. Compared to the other tested cortical areas, both subcortical areas have relatively low tract strengths toward the SGA, FEF, OFC, and POP. Both the SGA and OFC are thought to be involved in limbic processing. The FEF are largely governed by attentional mechanisms (
Relatedly, we found a lack of white matter connectivity between the STN, STR, and the inferior frontal gyrus pars opercularis. This was somewhat surprising given the functional significance of the inferior frontal gyrus associated with response inhibition (
There were also a number of cortical areas such as the CMA and SMA that compared to the other cortical areas had a stronger structural connectivity toward the subcortex. Both the CMA and SMA are thought to be crucial in voluntary based motor processes and highlight the role of the BG in action generation (
The cortical regions were selected based on their connection with both the STN and STR as identified in NHP tracer studies. Additionally, the cortical ROIs were created using atlases that parcellated the human cortex in terms of their structural and functional homolog with NHPs using DTI (
There are several limitations that need to be addressed. Even with a high spatial resolution of 1 mm isotropic DWI data, it remains a challenge to precisely identify where the white matter tract exactly enters the cortex resulting in the so-called “gyral biases” (
A final limitation is the anatomical specificity of the cortical ROIs used in this study and the relevance for computational models. Computational models have allowed us to generate quantifiable predictions about the role of the different structures in the cortico-BG-thalamic loops (
Using multimodal UHF MRI we show that compared to other tested cortical areas, the STN and STR have a relatively lower connectivity to areas thought to be involved in response inhibition and stronger connectivity to areas associated with voluntary based motor actions. Overall our results are consistent with previous literature in that the STN and STR are connected to similar cortical areas.
BI designed the study, analyzed the data, and wrote the paper. BF designed the study and wrote the paper. YT designed the study and wrote the paper. MK designed the study, analyzed the data, and wrote the paper.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
We thank SURFsara (