Neuroimage: Sheng Zhang, Chiang-Shan R. Li

NeuroImage 59 (2012) 3548–3562
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NeuroImage
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Functional connectivity mapping of the human precuneus by resting state fMRI

Sheng Zhang a,⁎, Chiang-shan R. Li a, b, c
a
Department of Psychiatry, Yale University, New Haven, CT 06519, United States
b
Department of Neurobiology, Yale University, New Haven, CT 06520, United States
c
Interdepartmental Neuroscience Program, Yale University, New Haven, CT 06520, United States
a r t i c l e i n f o a b s t r a c t
Article history: Precuneus responds to a wide range of cognitive processes. Here, we examined how the patterns of resting
Received 12 May 2011 state connectivity may define functional subregions in the precuneus. Using a K-means algorithm to cluster
Revised 2 November 2011 the whole-brain “correlograms” of the precuneus in 225 adult individuals, we corroborated the dorsal-
Accepted 4 November 2011
anterior, dorsal-posterior, and ventral subregions, each involved in spatially guided behaviors, mental imagery,
Available online 12 November 2011
and episodic memory as well as self-related processing, with the ventral precuneus being part of the default
Keywords:
mode network, as described extensively in earlier work. Furthermore, we showed that the lateral/medial volumes
Functional connectivity of dorsal anterior and dorsal posterior precuneus are each connected with areas of motor execution/attention and
fMRI motor/visual imagery, respectively. Compared to the ventral precuneus, the dorsal precuneus showed greater
Resting state connectivity with occipital and posterior parietal cortices, but less connectivity with the medial superior frontal
Precuneus and orbitofrontal gyri, anterior cingulate cortex as well as the parahippocampus. Compared to dorsal-posterior
Default network and ventral precuneus, the dorsal-anterior precuneus showed greater connectivity with the somatomotor cortex,
as well as the insula, supramarginal, Heschl's, and superior temporal gyri, but less connectivity with the angular
gyrus. Compared to ventral and dorsal-anterior precuneus, dorsal-posterior precuneus showed greater connec-
tivity with the middle frontal gyrus. Notably, the precuneus as a whole has negative connectivity with the amyg-
dala and the lateral and inferior orbital frontal gyri. Finally, men and women differed in the connectivity of
precuneus. Men and women each showed greater connectivity with the dorsal precuneus in the cuneus and me-
dial thalamus, respectively. Women also showed greater connectivity with ventral precuneus in the hippocampus/
parahippocampus, middle/anterior cingulate gyrus, and middle occipital gyrus, compared to men. Taken together,
these new findings may provide a useful platform upon which to further investigate sex-specific functional neuro-
anatomy of the precuneus and to elucidate the pathology of many neurological illnesses.
© 2011 Elsevier Inc. All rights reserved.
Introduction with medial somatomotor regions (Morecraft et al., 2004); the posterior
precuneus with visual areas (Colby et al., 1988); and the ventral precu-
As part of the medial posterior parietal cortex, the precuneus is neus with the dorsolateral prefrontal cortex, the inferior parietal lobule,
engaged in reflective, self-related processing (Kjaer et al., 2002; Lou and the superior temporal sulcus (Morecraft et al., 2004; Pandya and
et al., 2004), awareness and conscious information processing (Kjaer Seltzer, 1982).
et al., 2001; Vogt and Laureys, 2005), episodic memory (Dorfel Numerous studies have suggested connectivity analysis of resting
et al., 2009; Lundstrom et al., 2003, 2005), and visuospatial processing state fMRI data as a useful alternative to characterize functional sub-
(Kawashima et al., 1995; Wenderoth et al., 2005), as well as showing divisions of a brain region. This approach parceled brain areas on the
greater activity during resting as compared to responding to an exter- basis that each subregion has a unique pattern of connectivities — a
nal task (Fransson and Marrelec, 2008) (see also (Cavanna, 2007; “functional fingerprint” (Passingham et al., 2002). Specifically, low
Cavanna and Trimble, 2006) for review). These different processes frequency blood oxygenation level dependent (BOLD) signal fluctua-
may selectively involve subregions within the precuneus. Indeed, axonal tions reflect connectivity between functionally related brain regions
tracings in macaque monkeys revealed distinct patterns of anatomical (Biswal et al., 1995; Fair et al., 2007; Fox and Raichle, 2007). Studies
connectivity for three subdivisions of the precuneus (Buckwalter et al., of this “spontaneous” activity have provided insight into the intrinsic
2008; Colby et al., 1988; Leichnetz, 2001; Morecraft et al., 2004; functional architecture of the brain and shown that the spontaneous
Pandya and Seltzer, 1982). The dorsal-anterior precuneus is connected fluctuations are present in many neuroanatomical systems, including
motor, visual, auditory, default mode, memory, language, dorsal at-
⁎ Corresponding author at: Connecticut Mental Health Center S103, 34 Park Street,
tention, and ventral attention systems (Fox and Raichle, 2007).
New Haven CT 06519, United States. Fax: + 1 203 974 7076. Based on the findings that regions with similar functionality tend to
E-mail address: sheng.zhang@yale.edu (S. Zhang). be correlated in their spontaneous BOLD activity, investigators
1053-8119/$ – see front matter © 2011 Elsevier Inc. All rights reserved.
doi:10.1016/j.neuroimage.2011.11.023
S. Zhang, C.R. Li / NeuroImage 59 (2012) 3548–3562 3549
described subareal boundaries for the thalamus (Zhang et al., 2008,

2010), basal ganglia (Barnes et al., 2010), medial superior frontal cor-
tex (Kim et al., 2010a; Zhang et al., 2011), anterior cingulate cortex
(Margulies et al., 2007), cerebellum (O'Reilly et al., 2010), as well as
precuneus (Cauda et al., 2010; Margulies et al., 2009).
In accord with anatomical studies, a recent work confirmed three
functional subdivisions of the precuneus in anesthetized monkeys
and awake humans on the basis of resting state connectivity analysis
of BOLD signals (Margulies et al., 2009). In the study, however, the
seed regions (spheres of 3 mm in radius) covered only the medial
wall of the precuneus and provided little information on brain volumes
laterally beyond the seeds. This is in contrast to a wider extent of precu-
neus activation (x= −23 to +15) during cognitive performance as has
been reported in the literature (Cavanna and Trimble, 2006). Another
recent study characterized functional connectivity of the posterior me-
dial cortex but similarly focused only on the medial wall of the precu-
neus (Cauda et al., 2010).
We have three specific aims in this study. First, we sought to in-
vestigate functional subdivisions of the entire precuneus by charac-
terizing both cortical and subcortical connectivities of a large resting
state fMRI data set. In particular, we characterized the connectivity
of the lateral versus medial parts of the precuneus and examined Fig. 1. A flow chart of data analysis in this study. FC: functional connectivity.
whether or which part of the precuneus belongs to the default
mode network. Second, we examined the differences in regional con-
nectivities and highlighted the opposing pattern of connectivities be- Individual structural image was normalized to an MNI (Montreal
tween the three precuneus subdivisions. Third, recent works Neurological Institute) EPI (echo-planar imaging) template with af-
suggested sex differences in functional connectivity of brain areas in- fine registration followed by nonlinear transformation (Ashburner
cluding those of the default mode network (Biswal et al., 2010; and Friston, 1999; Friston et al., 1995). The normalization parameters
Weissman-Fogel et al., 2010). We thus explored sex differences in determined for the structural volume were then applied to the corre-
precuenus connectivities. sponding functional image volumes for each subject. Finally, the im-
ages were smoothed with a Gaussian kernel of 8 mm at Full Width
Materials and methods at Half Maximum. In a separate analysis, we used 4 mm Gaussian ker-
nel smoothing and obtained nearly identical results (Supplementary
Resting state data materials).
Additional preprocessing was applied to reduce spurious BOLD
Resting-state fMRI scans were pooled from three datasets (Lei- variances that were unlikely to reflect neuronal activity (Fair et al.,
den_2180/Leiden_2200, Newark, and Beijing_Zang, n = 144) down- 2007; Fox and Raichle, 2007; Fox et al., 2005; Rombouts et al.,
loadable from the 1000 Functional Connectomes Project (Biswal 2003). The sources of spurious variance were removed through linear
et al., 2010) and our own data (n = 81). Individual subjects' images regression by including the signal from the ventricular system, the
were viewed one by one to ensure that the whole brain was covered. white matter, and the whole brain, in addition to the six parameters
A total of 225 healthy subjects' resting state data (3-Tesla magnet; obtained by rigid body head motion correction. First-order deriva-
18–53 (mean = 24) years of age; 109 men; one scan per participant; tives of the whole brain, ventricular and white matter signals were
duration: 4.5–10 min; eyes closed during resting) were analyzed also included in the regression.
(Table 1). Fig. 1 illustrates the analyses step by step with the details Cordes and colleagues suggested that BOLD fluctuations below a
described as follows. frequency of 0.1 Hz contribute to regionally specific BOLD correla-
tions (Cordes et al., 2001). The majority of resting state studies low-
Imaging data preprocessing pass filtered BOLD signal at a cut-off of 0.08 or 0.1 Hz (Fox and
Raichle, 2007). Thus, we applied a temporal band-pass filter
Brain imaging data were preprocessed using Statistical Parametric (0.009 Hz b f b 0.08 Hz) to the time course in order to obtain low-
Mapping (SPM 8, Wellcome Department of Imaging Neuroscience, frequency fluctuations (Fair et al., 2007; Fox and Raichle, 2007; Fox
University College London, U.K.), as described in our previous work et al., 2005; Lowe et al., 1998).
(Zhang et al., 2011). Briefly, images of each individual subject were
first realigned (motion corrected) and corrected for slice timing. Linear correlations with 116 anatomical masks
We used the anatomical parcelation algorithm to delineate 116

Table 1
Available demographic data and imaging parameters for the selected resting-state
anatomical masks from the Montreal Neurological Institute (MNI)
functional MRI datasets from the image repository for the 1000 Functional Connec- template (Tzourio-Mazoyer et al., 2002). The BOLD time courses
tomes Project and for our own dataset. were averaged spatially each for all 116 seed regions. We computed
the correlation coefficient between the averaged time course of
Dataset Subjects Ages Timepoints TR Slice acquisition
(years) (s) order each mask and the time courses of each individual voxels of the pre-
cuneus for individual subjects.
Beijing_Zang 31 M/66 F 18–26 225 2 Interleaved ascending
Leiden_2180 10 M/0 F 20–27 215 2.18 Sequential descending To assess and compare the resting state “correlograms,” we con-
Leiden_2200 11 M/8 F 18–28 215 2.2 Sequential descending verted these image maps, which were not normally distributed, to z
Newark 9 M/9 F 21–39 135 2 Interleaved ascending score maps by Fisher's z transform (Berry and Mielke, 2000; Charles
Our own 48 M/33 F 19–53 295 2 Interleaved ascending and Richardson, 2004; Jenkins and Watts, 1968): z = 0.5 log e[(1 + r)/
Note: M, males; F, females. (1− r)]. The z maps were used in group, random effect analyses
3550 S. Zhang, C.R. Li / NeuroImage 59 (2012) 3548–3562
(Penny et al., 2004). A one-sample t-test was applied to the “z maps” Given any two clustering number k's, the one with lower BIC value
across 225 subjects for each of the 116 correlograms for further analysis. was preferred. Furthermore, because the K-means algorithm is sensi-
tive to the initial, randomly selected cluster centers, we repeated this
Parcelation of the precuneus based on functional connectivity algorithm 1000 times to alleviate the effect of the initial conditions.
Furthermore, we also employed spectral clustering analysis,
Voxels within the precuneus mask, which was obtained from the which yielded similar results as K-means clustering (Supplementary
116 anatomical masks of an MNI template created by Tzourio- materials).
Mazoyer et al. (2002), were subject to functional connectivity based
segmentation, with each voxel represented by 116 t values. A K- Results
means algorithm was applied to cluster the voxels within the precu-
neus on the bases of the 116 t values. The results of 1000 runs of K-means clustering suggested an opti-
As an unsupervised learning algorithm, K-means clustering clas- mal cluster number of 8 according to the BIC (Supplementary Fig. 2a).
sifies a given data set into an a-priori set of K clusters by minimizing Figs. 2 and 3 each shows these 8 clusters and the t statistic connectivity
an objective squared error function as shown in Eq. (1): map of individual clusters.
To examine the relationship of the 8 clusters identified from K-
X
k X
n
‖ xði jÞ −cj ‖ means clustering, we applied hierarchical clustering to their connec-
2
J¼ ð1Þ
j¼1 i¼1 tivity maps (see Supplement for methodological details). The results
showed that the 8 clusters were broadly divided into the dorsal (clus-
where ‖xi(j) − cj‖ 2 is a distance measure between a data point xi(j) and ters 1–4) and ventral precuneus (clusters 5–8) (Supplementary Fig.
the cluster center cj (MacQueen, 1967). The algorithm was executed 2b). We thus re-ran K means clustering for two- and three- cluster so-
by: lutions. The results confirmed the findings that the precuneus could
be separated into dorsal and ventral parts, and the dorsal part could
1. Placing K points into the space represented by the objects that are be further separated into dorsal-anterior and dorsal-posterior subre-
being clustered. These points represent initial group centroids. gions (Supplementary Fig. 3).
2. Assigning each object to the group that has the closest centroid.
3. When all objects have been assigned, recalculating the positions of The dorsal precuneus (clusters 1–4)
the K centroids.
4. Repeating Steps 2 and 3 until the centroids no longer move. This The dorsal precuneus comprised the lateral dorsal-anterior precu-
produces a separation of the objects into groups from which the neus (cluster 4), the medial dorsal-anterior precuneus (cluster 2), the
metric to be minimized can be calculated. lateral dorsal-posterior precuneus (cluster 1), and the medial dorsal-
In order to determine the optimal number of clusters that best de- posterior precuneus (cluster 3) (Fig. 2).
scribed the data set, we used the Bayesian Information Criterion (BIC) The dorsal precuneus (clusters 1–4) showed positive connectivity
(Gentle et al., 2004; Schwarz, 1978), which is widely used for model with the superior parietal cortex, and negative connectivity with the
identification in time series and linear regression: middle, left medial, and right lateral parts of the orbital frontal gyri,
left superior frontal gyrus, orbital part of the inferior frontal gyrus,

RSS medial superior frontal gyrus, gyrus rectus, amygdala, as well as cere-
BIC ¼ n ln þ k lnðnÞ ð2Þ
n bellar lobule IX and right cerebellar lobule VII (Schmahmann et al.,
1999; Schmahmann et al., 2000) (Fig. 3 and Supplementary Table 1).
where n is the number of observations (=116); k is the number of Other than these connectivities shared by all four clusters of the
class; RSS is the residual sum of squares from the K-means model. dorsal precuneus, the dorsal-anterior precuneus (clusters 2 and 4)
Fig. 2. K-means clustering segments the precuneus based on functional connectivities of individual voxels within the region. Eight clusters were represented in axial, sagittal, and
coronal sections with different colors.
Fig. 3. Group results of voxel-wise functional connectivity of each of the eight clusters of the precuneus. Positive (warm color) and negative (cold color) correlations were super-
imposed on axial slices at Z = −35, −25, −15, −5, 5, 15, 25, 35, 45, 55, 65 mm of a structural image. n = 225, p b 0.05, corrected for family-wise error or FWE of multiple comparisons.
Color scales reflect T values of one-sample t test.
also showed positive connectivity with the supplementary motor rolandic operculum, postcentral lobule, left supramarginal gyrus,
area, right supramarginal gyrus and paracentral lobule, and negative Heschl's and superior temporal gyri; between the medial dorsal-
connectivity with the left lateral part of the orbital frontal gyrus, left anterior precuneus (cluster 2) and the middle and posterior cingulate
triangular part of inferior frontal gyrus, right medial part of the orbital cortices, cuneus, superior occipital gyrus, and cerebellar vermis lobule
frontal gyrus, left angular gyrus, inferior temporal gyrus, and right III; between the lateral dorsal-posterior precuneus (cluster 1) and the
cerebellar crus II and lobule VIIb. The dorsal-posterior precuneus middle occipital gyrus, intraparietal sulcus, and right paracentral lobule;
(clusters 1 and 3) showed positive connectivity with the right poste- and between the medial dorsal-posterior precuneus (cluster 3) and the
rior cingulate cortex, right cuneus and superior occipital gyrus, and middle and posterior cingulate cortices, calcarine sulcus, cuneus, lin-
negative connectivity with the rolandic operculum, insula, Heschl's gual, right angular, and cerebellar vermis lobules III, IV, V (Fig. 3 and
gyrus, superior and middle temporal gyri and temporal pole, as well Supplementary Table 1).
as left cerebellar lobule X and cerebellar vermis lobules VI, VII, VII, Negative connectivity was observed between the lateral dorsal-
IX, X (Fig. 3 and Supplementary Table 1). anterior precuneus (cluster 4) and middle frontal gyrus, right trian-
Positive connectivity was observed between the lateral dorsal- gular part of inferior frontal gyrus, left posterior cingulate cortex,
anterior precuneus (cluster 4) and the right primary motor cortex, right angular, anterior cingulate cortex, and right cerebellar crus II;
between the medial dorsal-anterior precuneus (cluster 2) and the left Functional connectivity with subcortical regions
primary motor cortex, left opercular part of the inferior frontal gyrus,
left hippocampus and parahippocampus, inferior occipital gyrus, left We used a subcortical mask that encompassed the thalamus, cau-
middle temporal gyrus and temporal pole, left cerebellar lobules VII, date, putamen, and pallidum to describe subcortical connectivities of
X, and vermis lobules VII, IX, X; between the lateral dorsal-posterior each of 8 clusters (Fig. 5). Overall, the precuneus showed positive
precuneus (cluster 1) and the left olfactory bulb, right medial part connectivity with the pulvinar and little or negative connectivity
of the orbital frontal gyrus, anterior cingulate cortex and parahippo- with the sensory thalamic nuclei as documented in studies of non-
campus; and between the medial dorsal-posterior precuneus (cluster human primates (Schmahmann and Pandya, 1990; Yeterian and
3) and the primary motor cortex, right superior frontal gyrus, left lat- Pandya, 1993). Furthermore, the medial dorsal-anterior precuneus
eral part of orbital frontal gyrus, opercular and triangular parts of the (cluster 2), medial dorsal-posterior precuneus (cluster 3), and the
inferior frontal gyri, supplementary motor area, hippocampus, inferi- ventral-posterior precuneus (clusters 5, 7, and 8 but not cluster 6)
or occipital gyrus, postcentral gyrus, supramarginal gyrus, left para- showed positive connectivity with the mediodorsal (MD) nucleus of
central lobule, inferior temporal gyrus, and cerebellar lobules VII, X. the thalamus.
In the basal ganglia, we observed negative connectivity between
middle and dorsal parts of caudate and all eight clusters, and positive
connectivity between the ventral part of the caudate and clusters 5
The ventral precuneus (clusters 5–8) and 8 of ventral precuneus. The ventral (clusters 5–8) as well as
dorsal-posterior precuneus (clusters 1 and 3) also had negative con-
The ventral precuneus (clusters 5–8) showed positive connectivi- nectivity with the putamen and pallidum.
ty with the left medial part of the orbital frontal gyrus, posterior cin-
gulate cortex, calcarine sulcus, cuneus, left cerebellar lobules IV, V and
Differences in functional connectivity between the three precuneus clusters
cerebellar vermis lobules III, IV, V, and negative connectivity with the
left primary motor cortex, lateral part of the orbital frontal gyrus,
opercular, triangular, and orbital parts of inferior frontal gyri, supple- We quantified the differences in functional connectivity of the
mentary motor area, insula, amygdala, supramarginal gyrus, superior dorsal-anterior, dorsal-posterior, and ventral precuneus. To better
temporal pole, cerebellar lobule VII (Fig. 3 and Supplementary Table represent the results, we separated the whole brain into 116 regions
1). Clusters 5, 7, and 8 shared a similar pattern of connectivity (Sup- based on the AAL atlas and examined the differences in functional
plementary Fig. 2b), showing positive connectivity with the right me- connectivity with each region with paired t tests across the entire co-
dial part of the orbital frontal gyrus and angular gyrus, and negative hort of subjects. Results were summarized in Fig. 4, and Supplemen-
connectivity with the right primary motor cortex, rolandic operculum, tary Tables 2–4. In the following, we described those brain regions
inferior occipital gyrus, postcentral lobule, left paracentral lobule, Hes- showing not only significant differences but also an opposite pattern
chl's gyrus, superior temporal gyrus, right middle temporal pole, right of connectivity between the three precuneus subdivisions (Figs. 4D–F,
cerebellar crus II, and cerebellar vermis lobules VII, IX, X (Fig. 3 and Sup- and Table 2).
plementary Table 1). Compared to both the dorsal-posterior and ventral precuneus, the
Positive connectivity can be found in the right olfactory bulb, dorsal-anterior precuneus showed greater connectivity with the right
gyrus rectus, parahippocampus, lingual, superior occipital gyrus, fusi- primary motor cortex (PMC), rolandic operculum, SMA, right insula,
form gyrus, cerebellar hemisphere lobules III, IV, V, and left cerebellar postcentral gyrus, supramarginal gyrus, Heschl's gyrus, superior tem-
lobule VI for the medial–ventral part of ventral precuneus (cluster 5); poral gyrus, as well as less connectivity with the right angular gyrus.
in the rectus gyrus, parahippocampus, lingual, superior, middle, and Compared to ventral precuneus, both dorsal-anterior and dorsal-
inferior occipital gyri, fusiform gyrus, cerebellar lobules III, IV, V, VI, posterior precuneus showed greater connectivity with middle occipital,
X as well as vermis lobules I, II, VI for lateral–ventral part of ventral inferior/superior parietal, and paracentral gyri. Conversely, compared
precuneus (cluster 6); in the middle cingulate cortex and left superior to the dorsal precuneus, the ventral precuneus showed greater connec-
occipital gyrus for dorsal part of ventral precuneus (cluster 7); and in tivity in middle part of orbital frontal gyrus, olfactory bulb, medial supe-
the middle part of the orbital frontal gyrus, olfactory bulb, medial su- rior frontal gyrus, medial part of orbital frontal gyrus, gyrus rectus, left
perior frontal gyrus, rectus gyrus, middle cingulate cortex, parahippo- anterior cingulate gyrus, parahippocampal, left angular, and fusiform
campus, and cerebellar lobules III, IV, V for middle part of ventral gyri, as well as right cerebellar lobule III and left cerebellar lobule X.
precuneus (cluster 8) (Fig. 3 and Supplementary Table 1). Negative Compared to the dorsal-anterior and ventral precuneus, the dorsal-
connectivity was observed in the superior and middle frontal gyri, su- posterior precuneus showed greater connectivity in the middle frontal
perior parietal gyurs, intraparietal sulcus, left middle temporal gyrus, gyrus. Compared to the ventral precuneus, the dorsal-anterior precu-
inferior temporal gyrus, left cerebellar crus II, and cerebellar lobules neus showed less connectivity in the left cerebellar lobule III and the
VIIb, IX for medial–ventral part of ventral precuneus (cluster 5); in dorsal-posterior precuneus showed less connectivity in the right cere-
the superior and middle frontal gyri, medial superior frontal gyrus, bellar lobule X and vermis lobules I, II.
anterior and middle cingulate cortices, intraparietal sulcus, left cere-
bellar crus II, and right cerebellar lobule VIIb for lateral–ventral part Sex differences in precuneus connectivity
of ventral precuneus (cluster 6); in the right hippocampus, left mid-
dle occipital gyrus, left middle temporal gyrus and temporal pole, We examined the functional connectivities of the precuneus sepa-
right inferior temporal gyrus, cerebellar crus I and lobules VI, IX, as rately for men (n = 109) and women (n = 116). Although men
well as vermis lobules VI, VII for dorsal part of ventral precuneus showed an optimal cluster number of 6 rather than 8, the patterns
(cluster 7); and in the right middle frontal gyrus, middle occipital of connectivity of the major clusters were very similar between men
gyrus, superior parietal gyrus, intraparietal sulcus, cerebellar crus I, and women and to those obtained with men and women combined
II and lobules VI, VIIb and vermis lobules VI, VII for middle part of ven- (Supplementary Figs. 4 and 5). Thus, to compare precuneus connec-
tral precuneus (cluster 8). tivity between men and women, we focused on the two-cluster solu-
Notably, all eight precuneus clusters showed negative connectivi- tion of dorsal (clusters 1–4) and ventral (clusters 5–8) precuneus, as
ty with right lateral part of the orbital frontal gyrus, orbital part of in- well as the three-cluster solution with additional subdivisions of the
ferior frontal gyrus, amygdala, and right cerebellar lobule VII (Figs. 3 dorsal-posterior (clusters 1 and 3) and dorsal-anterior precuneus
and 4G and Supplementary Table 1). (clusters 2 and 4).
Fig. 4. Differences in functional connectivity between dorsal-anterior (DA), dorsal-posterior (DP), and ventral (V) precuneus. (A–C, upper row) Connectivities with each of the 116
AAL masks was examined with pairwise paired t tests. Results at p b 0.00014 (p b 0.05, corrected for multiple comparisons) are superimposed on axial slices at Z = − 30, − 20, − 10,
0, 10, 20, 30, 40, 50 mm of a structural image. Red: DA > DP (A), DA > V (B), and DP > V (C); blue: DP > DA, V > DA, and V > DP. (D–F, bottom row) Significant differences are shown
only for regions with an opposite pattern of connectivity between DA and DP (D), DA and V (E), and DP and V (F). See Supplementary Tables 1–3 for additional information. (G)
Brain regions with negative connectivity with all eight precuneus clusters. Frontal_Inf_Orb: inferior part of the orbital frontal gyrus; Frontal_Orb_Lat: lateral part of the orbital fron-
tal gyrus; Cerebelum_8: cerebellum part 8.
The results of two-sample t tests (cluster-level threshold of dorsal-anterior, dorsal-posterior, and ventral precuneus, consistent
P b 0.05, FWE corrected) are shown in Fig. 6 and Table 3. Compared with previous anatomical and functional mappings (Buckwalter
to women, men showed greater connectivity in the cuneus for dorsal et al., 2008; Cauda et al., 2010; Colby et al., 1988; Leichnetz, 2001;
precuneus. Conversely, compared to men, women showed greater Margulies et al., 2009; Morecraft et al., 2004; Pandya and Seltzer,
connectivity in the thalamus and hypothalamus for dorsal precuneus 1982). The three subdivisions not only showed statistically significant
and in hippocampus, parahippocampus, middle/anterior cingulate differences in but sometimes an opposing pattern of regional connec-
gyrus, and middle occipital gyrus for ventral precuneus. tivities. Furthermore, women and men differed in these connectivi-
ties. Altogether, these results highlighted anatomical and functional
Discussion heterogeneity of the precuneus and suggested the utility of connec-
tivity mapping in the delineation of functional divisions of a brain
We presented resting state functional connectivity maps of the area. We summarize the pattern of connectivities in Fig. 7 and dis-
human precuneus. The patterns of connectivity were distinct for the cussed the main findings in the following.
Fig. 5. Group results of each of the 8 clusters, masked to show the subcortical connectivities. Positive (warm color) and negative (cold color) correlations were superimposed on
eight axial slices at Z = −10, −5, 0, 5, 10, 15, 20, 25 mm of a structural image. n = 225, p b 0.05, corrected for family-wise error or FWE of multiple comparisons. Color scales represent
T values of one-sample t test.
The dorsal-anterior/posterior precuneus Furthermore, extending previous work, we described distinct con-
nectivities of the lateral and medial precuneus. The lateral dorsal-
We observed significant functional connectivity of the dorsal- anterior region showed negative or little correlation, while the medial
anterior precuneus (clusters 2 and 4) with the superior parietal cor- region showed positive correlation, with the posterior cingulate cor-
tex, consistent with co-activation of these structures in the execution tex, suggesting that the medial but not the lateral precuneus plays a
or preparation of spatially guided behaviors (Cavanna and Trimble, role of a transition from the parieto-occipital to parieto-limbic cortex
2006; Wenderoth et al., 2005). Both lateral (cluster 1) and medial (Cavanna and Trimble, 2006; Margulies et al., 2009). The primary
(cluster 3) dorsal-posterior precuneus showed strong connections motor cortex showed strong connection with the lateral dorsal-
with the superior occipital and parietal cortices, known to be involved anterior precuneus (cluster 4) but not with the medial dorsal-
in visual–spatial information processing (Cavada and Goldman-Rakic, anterior precuneus (cluster 2), while the anterior cingulate cortex
1989; Leichnetz, 2001), and responded to imagery during visual rota- showed connection with the medial dorsal-anterior precuneus but
tion (Suchan et al., 2002), deductive reasoning (Knauff et al., 2003), not with the lateral dorsal-anterior precuneus. These contrasting pat-
music processing (Platel et al., 1997; Satoh et al., 2001), spatial navi- terns of connectivity suggest that the lateral and medial dorsal-
gation (Ghaem et al., 1997), as well as motor imagery (Hanakawa anterior precuneus may each play a more important role in the exe-
et al., 2003; Malouin et al., 2003; Ogiso et al., 2000). Altogether, the cution and attentional monitoring of spatial behavior. Imaging studies
dorsal-anterior and dorsal-posterior precuneus are each connected support these functional distinctions (Astafiev et al., 2003; Simon
with networks involved in spatially guided behaviors and mental et al., 2002). For instance, an earlier study showed that the lateral supe-
imagery. rior parietal cortex and precuneus responded to saccadic eye movements
Table 2
Differences in functional connectivity (p b 0.00014, or p b 0.05, corrected for multiple comparisons) between the dorsal-anterior and dorsal-posterior precuneus (DA vs. DP), be-
tween dorsal-anterior and ventral precuneus (DA vs. V), and between dorsal-posterior and ventral precuneus (DP vs. V). Only brain regions showing an opposite pattern of con-
nectivity between the two respective clusters are shown here. “>” indicates DA > DP, DA > V, or DP > V, and “b” indicates DA b DP, DA b V, or DP b V.
DA vs. DP DA vs. V DP vs. V
Right primary motor cortex > >

Bilateral middle part of orbital frontal gyrus b b
Right middle frontal gyrus b >
Bilateral rolandic operculum > >
Bilateral supplementary motor area > >
Bilateral olfactory bulb b b
Bilateral medial superior frontal gyrus b b
Bilateral medial part of orbital frontal gyrus b b
Bilateral gyrus rectus b b
Right insula > >
Left anterior cingulated gyrus b b
Bilateral parahippocampal b b
Bilateral middle occipital gyrus > >
Bilateral fusiform gyrus b b
Bilateral postcentral gyrus > >
Bilateral superior parietal lobule > >
Bilateral intraparietal sulcus > >
Bilateral supramarginal gyrus > >
Left angular b b
Right angular b b
Bilateral paracentral gyrus > >
Bilateral heschl's gyrus > >
Bilateral superior temporal gyrus > >
Left cerebellum part 3 b
Right cerebellum part 3 b b
Left cerebellum part 10 b b
Right cerebellum part 10 b
Vermis parts 1 and 2 b
and manual pointing, but the left medial dorsal-anterior precuneus perspective taking (den Ouden et al., 2005; Farrow et al., 2001; Kircher
responded during attention to a peripheral visual target (Simon et al., 2002; Ochsner et al., 2004; Ruby and Decety, 2001) activated mid-
et al., 2002). dle part of ventral precuneus (cluster 8).
The lateral dorsal-posterior precuneus (cluster 1) was particularly Notably, clusters 5, 6, 8 and part of the cluster 7 (Brodmann area
responsive during motor imagery. For instance, in an fMRI study, 31) are often suggested to belong to both posterior cingulate and pre-
Hanakawa et al. (2003) identified lateral dorsal-posterior precuneus cuneate cortices and appear to be a cortical transition zone from the
activation during imagery as compared to execution of visually guid- medial parietal areas to the posterior cingulate cortex (Cavanna,
ed sequential finger-tapping. In a PET study, Malouin et al. (2003) 2007). Our results confirmed this view by demonstrating strong func-
showed activation in lateral dorsal-posterior precuneus during men- tional connectivity of the ventral precuneus with the posterior cingu-
tal simulation of locomotion. Using magnetoencephalographic re- late cortex.
cording, (Ogiso et al., 2000) localized the dipole source in lateral
dorsal-posterior precuneus when participants imagined themselves
hurdling in self-centered space. The precuneus and the default network
Taken together, the current results extended the roles of the dor-
sal anterior and posterior precuneus in spatially guided behavior and We observed a distinct pattern of positive connectivity with the
mental imagery: the medial/lateral dorsal anterior precuens are each default network for ventral but not dorsal precuneus, replicating
specific to attentional monitoring/execution of spatially guided be- Cauda et al. (2010). This is also consistent with our recent study of in-
havior; and the medial/lateral dorsal posterior precuens are each spe- dependent component analyses delineating two networks each in-
cific to visual/motor imagery. volving the dorsal (cuneus–precuneus network) and ventral
(default network) precuneus (Zhang and Li, 2011). Similarly,
Buckner et al. (2008) suggested that the dorsal precuneus, or Brod-
The ventral precuneus mann area 7, may not be part of the default network. A recent study
also supported this view by showing decreased regional cerebral
In reviewing functional imaging findings, Cavanna and Trimble blood flow (CBF) in the posterior cingulate gyrus, medial frontal cor-
(2006) suggested a central role for the precuneus in episodic memory tex and ventral but not dorsal precuneus, in participants performing a
retrieval and self-related processing. The MNI coordinates of the brain spatial working memory task, as compared to rest (Pfefferbaum et al.,
regions ∞ed in Cavanna and Trimble (2006) were mostly within the 2011). In contrast, our previous work suggested a role of the dorsal
ventral precuneus (especially clusters 7 and 8, as described here). precuneus in mediating behavioral engagement (Zhang and Li,
For instance, recognition of meaningful sentences (Tulving et al., 2010). We observed that the fractional amplitude of low frequency
1994), and retrieval of word-pairs (Shallice et al., 1994) as well as au- fluctuation (fALFF) of the dorsal precuneus accounted for approxi-
tobiographical information (Addis et al., 2004; Gilboa et al., 2004) ac- mately 10% of the variance in prefrontal activations related to atten-
tivated dorsal part of ventral precuneus (cluster 7); recollection of tional monitoring and response inhibition in a stop signal task.
previously studied words (Henson et al., 1999), retrieval of musical Thus, although both the dorsal and ventral precuneus appear to be in-
melody (Platel et al., 2003), and self-related processes such as empa- volved in behavioral engagement to an external task, their specific
thy, intentionality judgment, attribution of emotional state and roles remained to be specified.
Fig. 6. Gender differences (109 men vs. 116 women) in the functional connectivity of the precuneus (cluster-level threshold: p b 0.05, FWE corrected). Significant regional differences
were identified for dorsal precuneus of men > women (cuneus) and of women > men (area of the hypothalamus, mamillary body, fornix, and thalamus), as well as for ventral precuneus
of women> men (middle/anterior cingulated gyrus, middle occipital gyrus, and hippocampus/para hippocampus) as shown in Table 3.
Precuneus connectivity with the inferior parietal lobule intraparietal sulcus responded differently to task difficulty in mental
arithmetic, consistent with its integral role in the default network
We observed a distinct pattern of functional connectivity with the (Wu et al., 2009). During cue-directed spatial attention the intraparietal
inferior parietal lobule, suggesting functional differentiation of the sulcus showed greater activation during the early than late phase of the
supramarginal gyrus, angular gyrus, and intraparietal sulcus task while the opposite was true of the ventral precuneus (Schultz and
(Caspers et al., 2006, 2008; Uddin et al., 2010; Wu et al., 2009). The Lennert, 2009). Moreover, in a learning task, the intraparietal sulcus
ventral precuneus was positively connected with the angular gyrus responded more to untrained than trained epochs, while ventral precu-
but not with other parts of the inferior parietal lobule. With the ex- neus as well as angular gyrus responded more to the opposite contrast
ception of the medial dorsal-anterior precuneus, the dorsal and ven- (Delazer et al., 2005). In a task of object and place recognition, the ven-
tral precuneus were each positively and negatively connected with tral precuneus and intraparietal sulcus each responded more to place
the intraparietal sulcus. and object (Sugiura et al., 2005). Additionally, many studies showed
The angular gyrus was a key parietal node of the default network that supramarginal gyrus, intraparietal sulcus, and dorsal precuneus, but
as described in both fMRI and positron emission tomography studies not the angular gyrus or ventral precuneus, often activated concurrently
(Greicius et al., 2003; Raichle et al., 2001; Uddin et al., 2009, 2010). A to the same contrasts, under a variety of different experimental con-
recent study showed that the angular but not supramarginal gyrus or texts (Filimon et al., 2009; Loayza et al., 2011; Stilla et al., 2007; Van
Table 3
Gender differences in functional connectivity of the dorsal precuneus (clusters 1–4) and ventral precuneus (clusters 5–8); cluster-level threshold: p b 0.05, FWE corrected.
Cluster size Voxel Z MNI coordinate (mm) Identified region and

(voxels) value approximate BA
x y z
Dorsal precuneus: men > women

289 4.53 3 − 88 37 Cuneus, BA 18/19
Dorsal precuneus: women > men

116 4.99 0 − 10 − 14 Area of the hypothalamus, MB, Fx
4.14 0 − 13 1 Thalamus
Ventral precuneus: men > women

None
Ventral precuneus: women > men

104 5.02 0 −1 25 Middle/anterior cingulate G, BA 24
154 4.74 − 36 − 76 40 Middle occipital G, BA 7/19
197 4.37 − 24 − 19 − 14 Hippocampus, BA 20
4.18 − 21 − 34 − 11 Para hippocampus, BA 30
Note: P b 0.001, uncorrected, and 20 voxels in extent of activation. G, gyrus; BA, Brodmann area; MB: mamillary body; Fx: fornix.
de Winckel et al., 2005). Taken together, these studies suggested that et al., 2009; Schmahmann and Pandya, 1990; Yeterian and Pandya,
the ventral precuneus and angular gyrus belong to a functional network 1993; Zhang et al., 2008, 2010). The precuneus projects to dorsal thala-
in distinction to the one that comprises the dorsal precuneus, supra- mus, the intralaminar nucleus, and pulvinar, but not sensory thalamus,
marginal gyrus, and intraparietal sulcus. such as the ventral posterior lateral nucleus (Cavanna and Trimble,
2006; Parvizi et al., 2006; Schmahmann and Pandya, 1990; Yeterian
Subcortical connectivity of the precuneus and Pandya, 1993; Zhang et al., 2008). In accord with these previous
studies, the current findings suggested that the precuneus does not
By interconnecting with cortical areas, subcortical structures play share the thalamic connectivity with the parietal somatosensory corti-
an important role in motor and cognitive control (Barnes et al., cal regions (Cavanna and Trimble, 2006). As with Cauda et al. (2010),
2010; Draganski et al., 2008; Lehericy et al., 2004a, 2004b; Robinson we also showed positive connectivity between the ventral precuneus
Fig. 7. A summary of functional connectivity of the dorsal-anterior (DA, red), dorsal-posterior (DP, green), and ventral (V, yellow) precuneus, with blue indicating connectivity with
all three regions. Positive and negative connectivities are each indicated by solid and dashed line. Abbreviations: PMC: primary motor cortex; Frontal Sup: superior frontal gyrus;
Frontal Orb Mid: middle part of orbital frontal gyrus; Frontal Mid: middle frontal gyrus; Frontal Orb Lat: lateral part of orbital frontal gyrus; Frontal Inf Oper: opercular part of in-
ferior frontal gyrus; Frontal Inf Tri: triangular part of inferior frontal gyrus; Frontal Inf Orb: orbital part of inferior frontal gyrus; Rolandic Oper: rolandic operculum; SMA: supple-
mentary motor area; Frontal Sup Med: medial superior frontal gyrus; Frontal Orb Med: medial part of orbital frontal gyrus; Rectus: gyrus rectus; Cingulum Ant: anterior cingulated
gyrus; Cingulum Mid: middle cingulated gyrus; Cingulum Post: posterior cingulated gyrus; Occipital Sup: superior occipital gyrus; Occipital Mid: middle occipital gyrus; Occipital
Inf: inferior occipital gyrus; Postcentral: postcentral gyrus; Parietal Sup: superior parietal lobule; IPS: intraparietal sulcus; SupraMarginal: supramarginal gyrus; Paracentral: para-
central gyrus; Heschl: Heschl's gyrus; Temporal Sup: superior temporal gyrus; Temporal Pole Sup: superior temporal pole; Temporal Mid: middle temporal gyrus; Temporal Pole
Mid: middle temporal pole; Temporal Inf: inferior temporal gyrus.
and mediodorsal thalamus, and negative connectivity between the ven- Weissenbacher et al., 2009). On the other hand, it has also been demon-
tral precuneus and sensory thalamic nuclei. We observed positive con- strated that the multiple characteristics of anti-correlation networks,
nectivity between the precuneus (all 8 clusters) and the pulvinar, which include cross-subject consistency, spatial distribution, as well
consistent with both human and monkey tract-tracing studies (Parvizi as presence with modified whole brain masks and before global signal
et al., 2006; Zhang et al., 2008, 2010). regression, are not determined by global regression (Fox et al., 2009).
We observed positive connectivity between ventral precuneus We also examined this issue by repeating the same analysis only with-
(clusters 5 and 8) and the ventral caudate, and negative connectivity out the global signal regression in our previous work using the same
between all precuneus clusters and middle/dorsal caudate, as well as data set as we used in this study (Zhang et al., 2011). The results
between ventral precuneus (clusters 5–8) and dorsal-posterior pre- showed a very similar pattern of functional connectivity as in the an-
cuneus (clusters 1 and 3) and the putamen/pallidum, in line with re- alyses with global signal regression, suggesting that the negative
cent findings (Barnes et al., 2010; Cauda et al., 2010; Di Martino et al., connectivities are not a result of image preprocessing (e.g., global
2008; Draganski et al., 2008; Leh et al., 2007; Parvizi et al., 2006; signal regression).
Yeterian and Pandya, 1991). For instance, Di Martino et al. (2008) Furthermore, these negative connectivities are represented ana-
showed that the dorsal caudate was positively connected with the tomically in tract tracing studies of monkey. For instance, amygdala,
dorsolateral prefrontal cortex (DLPFC) and negatively connected which showed negative connections with all eight precuneus clusters,
with the precuneus, while the ventral caudate was positively con- was connected with both dorsal (Leichnetz, 2001) and ventral
nected with the ventrolateral prefrontal cortex (VLPFC), ventral pre- (Parvizi et al., 2006) precuneus in macaques. Orbitofrontal and ven-
cuneus, as well as the limbic areas. The VLPFC but not the DLPFC tromedial prefrontal cortices were connected with the dorsal precu-
appears to have a specific role in memory retrieval (Kostopoulos neus (Parvizi et al., 2006), while the superior temporal cortex was
and Petrides, 2003; Petrides, 2002), which is consistent with the connected with the ventral precuneus (Morris et al., 1999). Connec-
role of the ventral precuneus. Other studies reported that the puta- tions with putamen were also observed in monkeys for dorsal precu-
men and dorsal caudate activated, while ventral precuneus deacti- neus (Cavada and Goldman-Rakic, 1991; Leichnetz, 2001; Parvizi et al.,
vated to positive emotions (Bartels and Zeki, 2000, 2004). During 2006). Overall, the findings suggested that both positive and negative
working memory of spatial and nonspatial aspects of a visual scene, functional connectivity are represented anatomically.
precuneus responded more to spatial than nonspatial cues, while dor-
sal caudate demonstrated the opposite pattern of responses
Sex differences of the functional connectivity in precuneus
(Wallentin et al., 2006). Taken together, these results are in line
with our findings of negative connectivity between the ventral precu-
Sex differences in regional brain activation of the precuneus have
neus and dorsal caudate/putamen.
been observed in word generation (Bell et al., 2006; Gizewski et al.,
2006), spatial attention (Bell et al., 2006), visual word learning
Global connectivity of the precuneus
(Chen et al., 2007), working memory (Bell et al., 2006; Goldstein
et al., 2005; Mitchell, 2007; Schweinsburg et al., 2005), execution of
All eight clusters of the precuneus showed negative connectivity
a visuospatial plan (Boghi et al., 2006; Unterrainer et al., 2005), spa-
with the lateral and inferior orbital frontal gyri, and the amygdala.
tial navigation (Maguire et al., 1999), and target and novelty detec-
These results are consistent with earlier reports identifying negative
tion (Gur et al., 2007), covering sensory motor processing and
connectivities between the precuneus and amygdala (Hahn et al.,
complex cognitive and emotive functions (Hamann and Canli, 2004;
2011; Kim et al., 2010b; Roy et al., 2009; Xie et al., 2011; Yan et al.,
Kaiser et al., 2008; Li et al., 2006, 2009; Wager and Ochsner, 2005;
2009), between the precuneus and lateral/inferior orbital frontal
Wager et al., 2003). For instance, men showed greater precuneus ac-
gyrus (Fox et al., 2005; Liu et al., 2010; Xie et al., 2011; Yan et al.,
tivation than women during cognitive planning in the Tower of Lon-
2009), as well as positive connectivities between the amygdala and
don task (Boghi et al., 2006), and during spatial perspective taking
lateral/inferior orbital frontal gyrus (Dannlowski et al., 2009; Lang
(Kaiser et al., 2008). On the other hand, while some investigators
et al., 2009; Robinson et al., 2010; Roy et al., 2009). Notably, in a
reported decreased connectivity between the precuneus and other
study of contextual conditioning and extinction, amygdala responded
structures in the default network (Qiu et al., 2010), others do not
more to acquisition of contextual cues than extinction, while precu-
(Weissman-Fogel et al., 2010).
neus responded more to the opposite contrast (Lang et al., 2009). An-
Here, we observed greater connectivity in men than women between
other study showed activation of the precuneus and inhibition of the
the hippocampus/parahippocampus and the ventral precuneus — a struc-
amygdala and orbital frontal gyrus during virtual violence in a first-
ture implicated in episodic memory and self-related processing (see dis-
person shooter game (Mathiak and Weber, 2006). Using resting state
cussions in the above), consistent with sex differences in the role of
functional connectivity MRI, recent studies showed that the precuneus,
hippocampus in learning and memory (Cahill, 2006; Jackson et al.,
amygdala, as well as orbital frontal gyrus are the major cortical and sub-
2006; Maren et al., 1994; Rucker et al., 2004). Women also showed great-
cortical hubs or the brain's most globally connected areas (Cole et al.,
er connectivity between dorsal precuneus and thalamus/hypothalamus,
2010; Tomasi and Volkow, 2011). Taken together, these findings sug-
consistent with earlier studies (Swaab et al., 2001, 2003; Tomasi et al.,
gest a general role of the opposing functional connectivity between
2008; Wager et al., 2003), although the functional implications of this
the precuneus and amygdale/orbitofrontal cortex in mediating cognitive
finding remained to be established.
and affective functions.
A methodological note on negative connectivity Methodological and anatomical considerations
In addition to positive correlations between functionally related A potential issue of the medial/lateral differences concerned the
brain regions, negative correlations have also been observed between 8 mm Gaussian kernel used on data smoothing, which may induce
brain regions with theoretically opposed functional roles (Fox et al., artefactual results far more laterally than the precuneus itself. We
2005; Fransson, 2005; Greicius et al., 2003; Kelly et al., 2008; Uddin thus ran the analyses using the data smoothed with a 4 mm Gaussian
et al., 2009; Wang et al., 2006). However, recent studies suggested kernel and provided the results in Supplementary Fig. 6. Although the
that the global signal regression, a common data preprocessing step best cluster number was 7 instead 8 according to the BIC, the results
in seed region based functional connectivity analyses, is a likely of the 7- and 8- cluster solutions both suggested differences between
cause of anti-correlation functional networks (Murphy et al., 2009; the medial and lateral precuneus.
Another issue concerns that the precuneus is primarily a medial Astafiev, S.V., Shulman, G.L., Stanley, C.M., Snyder, A.Z., Van Essen, D.C., Corbetta, M.,
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Gass, A., Kappos, L., Matthews, P.M., Nichols, T.E., Radue, E.W., Borgwardt, S.J., 2009.
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Association of regional gray matter volume loss and progression of white matter le-
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Seidler, R.D., Siegle, G.J., Sorg, C., Teng, G.J., Veijola, J., Villringer, A., Walter, M.,
Wang, L., Weng, X.C., Whitfield-Gabrieli, S., Williamson, P., Windischberger, C.,
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line at doi:10.1016/j.neuroimage.2011.11.023. Chen, C., Xue, G., Dong, Q., Jin, Z., Li, T., Xue, F., Zhao, L., Guo, Y., 2007. Sex determines the
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Cohen-Adad, J., Benner, T., Greve, D., Kinkel, R.P., Radding, A., Fischl, B., Rosen, B.R.,
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Acknowledgments multiple sclerosis at 7T: A surface-based analysis. Neuroimage 57 (1), 55–62.
Colby, C.L., Gattass, R., Olson, C.R., Gross, C.G., 1988. Topographical organization of cor-
This study was supported by NIH grants R01DA023248, tical afferents to extrastriate visual area PO in the macaque: a dual tracer study. J.
Comp. Neurol. 269, 392–413.
K02DA026990, and R21AA018004. The NIH had no further role in Cole, M.W., Pathak, S., Schneider, W., 2010. Identifying the brain's most globally con-
study design; in the collection, analysis and interpretation of data; nected regions. Neuroimage 49, 3132–3148.
in the writing of the report; or in the decision to submit the paper Cordes, D., Haughton, V.M., Arfanakis, K., Carew, J.D., Turski, P.A., Moritz, C.H., Quigley,
M.A., Meyerand, M.E., 2001. Frequencies contributing to functional connectivity in
for publication. We thank investigators of the 1000 Functional Con- the cerebral cortex in “resting-state” data. AJNR Am. J. Neuroradiol. 22, 1326–1333.
nectomes Project and those who shared the data set for making this Dai, W., Lopez, O.L., Carmichael, O.T., Becker, J.T., Kuller, L.H., Gach, H.M., 2009. Mild
study possible, and Olivia Hendrick and Sarah Bednarski for their cognitive impairment and alzheimer disease: patterns of altered cerebral blood
flow at MR imaging. Radiology 250, 856–866.
help in editing the manuscript. Dannlowski, U., Ohrmann, P., Konrad, C., Domschke, K., Bauer, J., Kugel, H., Hohoff, C.,
Schoning, S., Kersting, A., Baune, B.T., Mortensen, L.S., Arolt, V., Zwitserlood, P.,
Deckert, J., Heindel, W., Suslow, T., 2009. Reduced amygdala-prefrontal coupling
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NeuroImage 59 (2012) 3548–3562

Contents lists available at SciVerse ScienceDirect

Functional connectivity mapping of the human precuneus by resting state fMRI

described subareal boundaries for the thalamus (Zhang et al., 2008,

We used the anatomical parcelation algorithm to delineate 116

DA vs. DP DA vs. V DP vs. V

Right primary motor cortex > >

Cluster size Voxel Z MNI coordinate (mm) Identiﬁed region and

Dorsal precuneus: men > women

Dorsal precuneus: women > men

Ventral precuneus: men > women

Ventral precuneus: women > men

A methodological note on negative connectivity Methodological and anatomical considerations

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