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Nat Neurosci. Author manuscript; available in PMC 2016 September 01.
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Published in final edited form as:

Nat Neurosci. 2015 November ; 18(11): 1664–1671. doi:10.1038/nn.4135.

Functional connectome fingerprinting: Identifying individuals

based on patterns of brain connectivity
Emily S. Finn1,*, Xilin Shen2,*, Dustin Scheinost2, Monica D. Rosenberg3, Jessica Huang2,
Marvin M. Chun1,3,4, Xenophon Papademetris2,5, and R. Todd Constable1,2,6
1Interdepartmental Neuroscience Program, Yale University, New Haven, CT USA
2Department of Diagnostic Radiology, Yale School of Medicine, New Haven, CT USA
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3Department of Psychology, Yale University, New Haven, CT USA

4Department of Neurobiology, Yale University, New Haven, CT USA
5Department of Biomedical Engineering, Yale University, New Haven, CT USA
6Department of Neurosurgery, Yale School of Medicine, New Haven, CT USA

Abstract
While fMRI studies typically collapse data from many subjects, brain functional organization
varies between individuals. Here, we establish that this individual variability is both robust and
reliable, using data from the Human Connectome Project to demonstrate that functional
connectivity profiles act as a “fingerprint” that can accurately identify subjects from a large group.
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Identification was successful across scan sessions and even between task and rest conditions,
indicating that an individual’s connectivity profile is intrinsic, and can be used to distinguish that
individual regardless of how the brain is engaged during imaging. Characteristic connectivity
patterns were distributed throughout the brain, but notably, the frontoparietal network emerged as
most distinctive. Furthermore, we show that connectivity profiles predict levels of fluid
intelligence; the same networks that were most discriminating of individuals were also most
predictive of cognitive behavior. Results indicate the potential to draw inferences about single
subjects based on functional connectivity fMRI.

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Address correspondence to: Emily S. Finn ([email protected]).

*These authors contributed equally to this work.
Author contributions
ESF, XS, DS, XP and RTC conceptualized the study. XS designed and performed the identification analyses with support from ESF
and DS. ESF designed and performed the behavioral analyses with support from MDR and JH. XS and XP contributed unpublished
data analysis tools and visualization software. XP, MMC and RTC provided support and guidance with data interpretation. ESF wrote
the manuscript, with contributions from XS and comments from all other authors.
Competing Financial Interests Statement
The authors declare no competing financial interests.
Code availability
The 268-node functional parcellation is available online on the BioImage Suite NITRC page (https://www.nitrc.org/frs/?group_id=51).
Matlab scripts were written to perform the analyses described; this code is available from the authors upon request.
Supplementary methods checklist
A supplementary methods checklist is available.
 Finn et al. Page 2

Introduction
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We are all unique individuals. Nevertheless, human neuroimaging studies have traditionally
collapsed data from many subjects to draw inferences about general patterns of brain activity
that are common across people. Studies that contrast two populations—such as patients and
healthy controls—typically ignore the considerable heterogeneity within each group.

Despite the predominance of such population-level inferences, researchers have long

recognized that even among the neurologically healthy, brain structure1–3 and function4–6
show high individual variability. In terms of function, variability is found in activation
patterns during cognitive tasks4–6 as well as intrinsic organization as measured by functional
connectivity analyses of data acquired while subjects are simply resting7. Recently, the
Human Connectome Project (HCP) set out to map the connections in the human brain by
acquiring high-quality structural and functional MRI scans from a large number of healthy
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subjects8. Many of the early analyses of HCP data have focused on elucidating the general
blueprint for brain connectivity that is shared across people. Yet despite the gross
similarities, there is reason to believe that a substantial portion of the brain connectome is
unique to each individual9.

An open question is whether this uniqueness is sufficiently observable by fMRI to enable a

transition from population-level studies to investigations of single subjects. Here, we show
that functional connectivity profiles act as an identifying “fingerprint,” proving that
individual variability in connectivity is both substantial and reproducible. Using HCP data
from 126 subjects, each scanned during six separate sessions across two days, we
demonstrate that a functional connectivity profile obtained from one session can be used to
uniquely identify a given individual from the set of profiles obtained from the second
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session. We show that identification is successful between rest sessions, task sessions and
even across rest and task. Results indicate that while changes in brain state may modulate
connectivity patterns to some degree, an individual’s underlying intrinsic functional
architecture is reliable enough across sessions and distinct enough from that of other
individuals to identify him or her from the group regardless of how the brain is engaged
during imaging.

Furthermore, we establish the relevance of these connectivity profiles to behavior by

demonstrating, in a fully cross-validated analysis, that functional connectivity profiles can be
used to predict the fundamental cognitive trait of fluid intelligence in novel subjects. These
results provide a critical foundation for future work to begin to test inferences about single
subjects, to reveal how individual functional brain organization relates to distinct behavioral
phenotypes.
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Results
Data for this study consisted of scans from 126 subjects provided in the Q2 data release of
the Human Connectome Project8. Each subject was scanned over a period of two days. Here,
we used data from six separate imaging conditions: two rest sessions (one on each of the two
days) and four task sessions (working memory, emotion, motor and language; two on each

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day). Functional connectivity was assessed using a functional brain atlas10 consisting of 268
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nodes covering the whole brain; this atlas was defined based on a separate population of
healthy subjects (see Online Methods for Yale dataset description). The Pearson correlation
coefficient between the timecourses of each possible pair of nodes was calculated and used
to construct 268×268 symmetrical connectivity matrices where each element represents a
connection strength, or edge, between two nodes. This was done for each subject for each
condition separately, such that each subject had a total of six matrices reflecting connectivity
patterns during each of the different scan sessions.

Identification was performed across pairs of scans consisting of one “target” and one
“database” session, with the requirement that the target and database sessions be taken from
different days: for example, day 1 rest matrices were used as the target and compared to a
database of day 2 rest matrices (see Fig. 1a for a schematic). In an iterative process, one
individual’s connectivity matrix was selected from the target set and compared against each
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of the connectivity matrices in the database to find the matrix that was maximally similar
(Fig. 1b). Similarity was defined as the Pearson correlation coefficient between vectors of
edge values taken from the target matrix and each of the database matrices. Once an identity
had been predicted, the true identity of the target matrix was decoded and that iteration was
scored 1 if the predicted identity matched the true identity, 0 if it did not. Within a target-
database pair, each individual target connectivity matrix was tested against the database in
an independent trial.

Identification was tested across all the various pairs of scan sessions (Fig. 1a; nine pairs,
each with two possible configurations created by exchanging the roles of target and database
session). In each case, the success rate was measured as the percentage of subjects whose
identity was correctly predicted out of the total number of subjects.
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Connectivity-based identification of individual subjects

Whole-brain identification
As a first pass, identification was performed using the whole-brain connectivity matrix (268
nodes; 35,778 edges), with no a priori network definitions. The success rate was 117/126
(92.9%) and 119/126 (94.4%) based on a target-to-database of Rest1-to-Rest2 and the
reverse Rest2-to-Rest1, respectively. The success rate ranged from68/126 (54.0%) to110/126
(87.3%) based on other database and target pairs including rest-to-task and task-to-task
comparisons (see Fig. 2a, rightmost bar in each graph).

Given that the 126 identification trials are not independent from one another, we performed
non-parametric permutation testing to assess the statistical significance of these results (see
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Online Methods). Across 1,000 iterations, the highest success rate achieved was 6/126, or
roughly 5%. Thus the p value associated with obtaining at least 68 correct identifications
(the minimum rate achieved above) is 0.

Network-based identification
We next tested identification accuracy based on each of eight specific functional networks to
test the hypothesis that certain brain networks contribute more to individual subject

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discriminability than others. These networks were derived from the same set of healthy
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subjects used to define the 268-node atlas (Fig. 1c). Two networks emerged as the most
successful in individual subject identification; these were the medial frontal (network 1) and
frontoparietal network (network 2), both comprised of higher-order association cortices in
the frontal, parietal and temporal lobes. A combination of these two networks was also
tested to determine if this combination might afford even higher predictive power than each
network on its own. Figure 2a shows identification rates based on each network separately,
the combination of networks 1 and 2 as well as the whole brain for each of the nine database
and target pairs. We also highlight identification based on the combination of networks 1 and
2, referred to for convenience as the frontoparietal networks, in Fig. 2b. Frontoparietal-based
identification was extremely high between Rest1 and Rest2 (98–99%). Accuracy dropped
slightly when identification was performed between rest and task, or between two task
conditions, but remained highly significant (80–90% for most condition pairs). The
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combination of these two frontoparietal networks significantly outperformed either network

on its own, as well as the whole brain, across all 18 database-to-target pairs (one-tailed
paired t-test versus network 1: t17 = 10.4, p < 10e−9; versus network 2: t17 = 1.97, p = 0.03;
versus whole brain: t17 = 5.1, p < 10e−5).

Factors affecting identification accuracy

We next explored several factors affecting identification accuracy, including quantifying
contributions of individual edges to subject discriminability, varying the length of the
timecourses used to calculate connectivity matrices, expanding the database set from one
matrix to two, comparing different node and network schemes, and ruling out potential
confounds (motion and anatomic differences).
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Quantifying edgewise contributions to identification

To quantify the extent to which different edges contribute to subject identification, we
derived two measures: the differential power (DP) and the group consistency (Φ). DP
reflects each edge’s ability to distinguish an individual subject by quantifying how
“characteristic” that edge tends to be, such that edges with a high DP tend to have similar
values within an individual across conditions, but different values across individuals
regardless of condition. Φ quantifies the consistency of a connection within a subject and
across the group (see Online Methods for details of how DP and Φ were calculated).

Restricting analysis to the two rest sessions, DP and Φ were calculated for all edges in the
brain, and edges in the 99.5 percentile of DP and Φ are visualized in Figure 3a. The majority
of high-DP edges are in the frontal, temporal, and parietal lobes and involve nodes in the
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frontoparietal networks (1 and 2) or default mode (network 3). (This result was stable across
percentile thresholds; see Supplementary Table 1.) This data-driven mathematical definition
of characteristic edges recapitulates the results of our network-based analysis, showing that
in general, connections involving higher-order association cortices are the most
discriminating of subjects. Approximately 28% of the edges with high DP were within and
between the two frontoparietal networks. Another 48% were edges linking these two
networks to other networks (Fig. 3a, top right), suggesting that levels of interaction and

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integration between the frontoparietal networks and the rest of the brain are also highly
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discriminating.

Conversely, the majority of high-Φ edges connect cross-hemisphere homologsin the

occipital and parietal lobes (Fig. 3a, bottom left). Many of these edges were within the
motor network (network 5) or the primary visual network (network 6; Fig. 3a, bottom right).
These edges are highly consistent both within and across subjects, and thus do not contribute
substantially to individual subject identification.

Identification using shorter timecourses

Scan sessions differed in duration, meaning that the amount of data used to compute the
connectivity profiles varied between sessions. The two rest sessions contained two runs of
1,200 brain volumes (time points) each, which is substantially longer than the working
memory scan (two runs with 405 time points), the language scan (316), the motor scan
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(284), or the emotion scan (176). To investigate the effect of the number of time points on
identification power, we performed frontoparietal-based identification between the two rest
sessions while varying the number of time points used to calculate connectivity matrices
between 100 and 1,100. Results indicate that longer timecourses are preferable in preserving
individual characteristics in connectivity profiles (Fig. 3b), and that temporal variability in
the connectivity profiles degrades identification based on shorter timecourses, especially
those under approximately 500 time points.

Identification based on two-matrix database

Results in Fig.2 indicate, as expected, that individual identification is more challenging
when performed across connectivity matrices obtained from different task conditions, or
across task and rest (even after taking into account the fact that task runs contain fewer
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timepoints). It is well known that connectivity patterns can be modulated by different

imaging conditions11–13, and such modulation contributes to the intra-subject variation,
making identification more difficult. In an effort to capture the intra-subject variation, we
performed identification using an expanded database that included two connectivity matrices
per subject (one rest session and one task session from the same day, with the target matrix
from a task session on the other day; the frontoparietal networks were used for this analysis).
In all cases, accuracy was improved using the two-matrix database over a database of either
the rest or task session alone (Mann Whitney U test, versus rest alone: rank sum = 68, two-
sided p = 0.004; versus task alone: rank sum = 100, two-sided p = 0.0002). The average
success rate increased to 97.2%, with a maximum rate of 100% (compare to an average rate
of 82.1% using a task-only database, and 86.9% using a rest-only database; see Fig. 3c).
This suggests that the within-subject variability is well captured by a linear model that
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includes a baseline (connectivity at rest) and a deviation introduced by an independent task

(connectivity during task).

Effects of parcellation scheme

To investigate the sensitivity of identification to the specific choice of parcellation atlas and
network definitions, we repeated the identification experiments using connectivity matrices
calculated from the 68-node FreeSurfer atlas14, grouped into seven networks based on Yeo et

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al.’s network scheme15 (where networks 3, 4 and 6 represent the frontoparietal networks).
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Between the two rest sessions, the identification rate based on this atlas was about 89%
using the whole brain, and about 75% using the frontoparietal networks (Fig. 4a). Reduction
in identification accuracy compared to our 268-node functional parcellation and
corresponding network definitions, especially in the case of frontoparietal-based
identification, suggests that a relatively high-resolution parcellation contributes to the
detection of individual variability and boosts identification rate.

To further investigate the difference in identification accuracy, correlations between

connectivity matrices of all 126 subjects from Rest1 and Rest2 were calculated based on our
atlas and network scheme and based on the FreeSurfer and Yeo scheme. Figure 4b compares
the raw cross-subject correlation coefficients for the frontoparietal networks. The diagonal
elements in Figure 4b represent correlation coefficients between matched subjects, while the
off-diagonal elements are from unmatched subjects. Successful individual identification
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requires the diagonal elements to be the largest. The comparison shows that using the
FreeSurfer and Yeo scheme, the raw coefficients are larger for both diagonal (t250 = −4.3, p
< 10e−5) and off-diagonal (t31,750 = −18.0, p < 10e−72) elements (Fig. 4b, bottom), which is
uninformative in explaining the difference in identification accuracy. To control for equal
global distribution of correlation coefficients, we normalized both matrices (Fig. 4c). After
normalization, there was no difference between schemes in off-diagonal elements (t31,750 =
0.27, p = 0.79), however using our parcellation and network scheme, the diagonal elements
were significantly larger than using the FreeSurfer and Yeo scheme (t250 = 14.6, p < 10e−35),
underpinning the increase in identification rate. In Fig.4c (top), the diagonal line is visually
more prominent in the matrix on the left compared to the matrix on the right.

Effects of head motion

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As head motion is a known confound of connectivity analyses16, we tested if subjects could

be identified based on their distribution of frame-to-frame motion during functional scans
(see Online Methods). Identification based on each subject’s motion distribution had an
average success rate of 2.4%, which is well below the identification accuracy achieved using
connectivity profiles. Thus it is unlikely that identification power is based on idiosyncratic
patterns related to motion in the scanner.

Effects of anatomic differences

HCP provides functional data that has been normalized to a common space. Despite this, the
influence of individual brain anatomy is hard to eliminate completely from functional data
and may contribute to individual identification, for example via registration conferring a
preference between the same subject on two different days. Nonetheless any such influence
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from anatomy should remain largely static, and should not be modulated by task conditions.

To confirm that identification power came from true differences in functional connectivity
rather than anatomic idiosyncrasies, we recalculated connectivity matrices using different
smoothing kernels for the BOLD data (4 mm, 6 mm and 8 mm). With larger smoothing
kernels, the registration advantages for the same brain compared to a different brain should
be vastly reduced or eliminated. Yet we saw only a very slight drop in identification power:

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based on Rest1/Rest2 pairs, identification using the frontoparietal networks remained above
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96% for all three smoothing levels (see Supplementary Table 2).

We also investigated whether individuals could be identified by BOLD signal variance in

each node (see Online Methods). While BOLD variance likely reflects metabolic function to
a substantial degree, it could also be influenced by anatomic factors such as differing
number of gray-matter voxels per node across subjects. This identification was successful—
ranging from 48–87% across different combinations of database and target sessions—but in
all cases, it was less successful than connectivity-based identification (see Supplementary
Table 3, compare to Fig. 2b). Crucially, if BOLD variance were driven mostly by anatomic
properties, it should be fairly constant regardless of how the brain is engaged during
imaging, and thus the accuracy of variance-based identification should not differ according
to brain state. That there was considerable variability with brain state further suggests that
functional rather than anatomic features are responsible for the high degree of identification
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accuracy observed.

Connectivity profiles predict cognitive behavior

To determine whether individual differences in functional connectivity are relevant to
individual differences in behavior, we tested whether connectivity profiles could be used to
predict subjects’ level of fluid intelligence. Fluid intelligence (gF) is the capacity for on-the-
spot reasoning to discern patterns and solve problems, independent of acquired
knowledge17. Levels of gF vary widely in the population18 and correlate with many other
cognitive abilities and life outcomes19–22; investigating the biological basis of gF is of
interest since it is considered to reflect intrinsic cognitive ability. In the HCP protocol, fluid
intelligence (gF) was assessed using a form of Raven’s progressive matrices with 24 items23
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(scores are integers indicating number of correct items).

We used leave-one-subject-out cross-validation to demonstrate that gF can be predicted

based solely on the connectivity profile of a previously unseen individual. In this iterative
process, data from one subject is set aside as the test set, and data from the remaining n−1
subjects is used as the training set. Each iteration consisted of three steps: (1) feature
selection, in which edges with a significant relationship to gF are identified in the training
set and separated into two tails according to sign (positive and negative); (2) model building,
in which training data is used to fit two simple linear regressions between gF and a summary
statistic of connectivity strength in the positive- and negative-feature network, respectively;
and (3) prediction, in which data from the excluded subject is input into each model to
generate a predicted gF score (see Online Methods for further details). Following all
iterations, we assessed the predictive power of each model by correlating predicted and
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observed gF scores across all subjects. Data from the day 1 rest session was used here.

Similar to the identification analysis, as a first pass, we tested whether whole-brain

connectivity could predict gF in novel subjects. Based on a feature-selection threshold of p <
0.01, the correlation between predicted and observed gF scores was r = 0.50 (p < 10e−9) for
the positive-feature model (Fig. 5a) and r = 0.26 (p = 0.005) for the negative-feature model.
While both models generated significant predictions, the positive model was more accurate

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than the negative model (z = 2.15, two-tailed p = 0.03). Prediction was significant across all
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three feature-selection thresholds tested: all r > 0.29, p ≤ 0.001 for the positive tail; all r >
0.22, p ≤ 0.01 for the negative tail. (Note, though, that the predicted range is narrower than
the observed range in Fig. 5a; thus the model is most successful at generating predictions of
gF level relative to other subjects.)

Due to the nature of our cross-validated approach, a slightly different set of edges was
selected in each iteration. To explore which networks contributed the most predictive power,
for each of the eight networks, we calculated the average number of within-network edges
selected across all iterations and normalized by the total number of within-network edges (to
control for differences in overall network sizes). Networks 1 and 2 contributed the highest
fraction of edges to the positive model, while network 3 contributed the highest fraction of
edges to the negative model; this was consistent across statistical thresholds for feature
selection (Fig. 5b). Thus, edges that show a consistent positive correlation with gF are
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disproportionately located in the frontoparietal networks, and edges that show a consistent
negative correlation with gF are mostly in the default-mode network.

As a second-pass analysis, we directly tested whether predictive power varied across the
different networks; specifically, whether the networks that performed best for identification
(the frontoparietal networks) also performed best for predicting cognitive behavior. To do
this, we repeated the leave-one-subject-out cross-validated procedure described above, this
time restricting the feature selection step to features (within-network edges) from each of the
eight networks in turn. We also tested a combination of networks 1 and 2. Thus, nine sets of
predicted gF scores were generated. Each of these was correlated with observed gF scores to
assess the predictive power of each network or network combination. Results are shown in
Figure5c and 5d.
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As hypothesized, predictive power based on the positive features was highest for the
frontoparietal networks (at a feature-selection threshold of p < 0.01: r = 0.42, p < 10e−6 and r
= 0.39, p = < 10e−5 for networks 1 and 2 respectively, r = 0.50, p < 10e−9 for the
combination of the two networks; this pattern was consistent across different statistical
thresholds used for feature selection). The subcortical-cerebellar network (network 4) also
had significant predictive power at a feature-selection threshold of p < 0.01 (r = 0.22, p =
0.01, though this result was less consistent across feature-selection thresholds). Based on the
negative features, only the default mode (network 3) had significant predictive power (r =
0.35, p < 10e−5 at p < 0.01; this result was consistent across feature-selection thresholds).

These results reinforce the functional relevance of our identification analyses, in that the
networks most discriminating of individuals are also the most relevant to individual
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differences in behavior. Crucially, the relationship between connectivity and cognitive ability
is sufficiently robust to generalize to previously unseen subjects.

Discussion
Here we show that an individual’s functional brain connectivity profile is both unique and
reliable, analogous to a fingerprint. We demonstrate that it is possible, with near-perfect

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accuracy, to identify individuals from a large group of subjects based solely on their
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connectivity matrix. While inter-individual consistency in functional brain networks has

been well characterized across both task and rest conditions24,25, and even across states of
consciousness26, the remarkable intra-individual reliability observed here suggests that while
the general blueprint may be shared, functional organization within individual subjects is
idiosyncratic, relatively robust to changes in brain state, and provides meaningful
information above and beyond the common template27.

We also demonstrate that this individual variability is relevant to individual differences in

behavior, in that connectivity profiles can be used to predict the fundamental cognitive trait
of fluid intelligence in novel subjects. These results underscore the potential to discover
fMRI-based connectivity “neuromarkers” of present or future behavior that may eventually
be used to personalize educational and clinical practices, improving outcomes28–30.
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Anatomic loci of distinguishing connectivity features

Although identification based on the whole-brain connectivity matrix was highly successful,
performance was best using a combination of the two frontoparietal networks. These
networks are comprised of higher-order association cortices rather than primary sensory
regions; these cortical regions are also the most evolutionarily recent31 and show the highest
inter-subject variance7,32,33.

That the frontoparietal networks were most distinguishing of individuals—and the most
predictive of behavior—is consistent with the role these networks play in cognition. Nodes
in these networks tend to act as flexible hubs, switching connectivity patterns according to
task demands34. Additionally, broadly distributed across-network connectivity has been
reported in these same regions35, suggesting a role in large-scale coordination of brain
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activity. Although the frontoparietal network is particularly active in tasks requiring a high
degree of cognitive control, here we show that it can identify individuals regardless of
whether the data is collected during task or at rest. Training cross-subject classifiers based
on frontoparietal connectivity to predict which task a subject is performing yields
classification accuracy that is statistically significant but still quite low34; the present
findings of high inter-individual variability may help explain these results. In light of this,
future work might use within-subject classification to explore how the frontoparietal
networks reorganize according to task demands in individual subjects.

Similarly, the frontoparietal networks emerged as most predictive of gF, which is consistent
with previous reports that structural and functional properties of these networks relate to
intelligence36–38. Also of interest, aberrant functional connectivity in the frontoparietal
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networks has been linked to a variety of neuropsychiatric illnesses39,40. The work presented
here, while focused on healthy subjects, suggests that sensitivity may be compromised in
studies of disease if inferences are drawn only at the group level. New insights into
neuropsychiatric illnesses may be gained from an approach that links individual functional
connectivity profiles to a spectrum of behavioral and symptom measures rather than a single
diagnosis41,42.

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Additional considerations
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Note that the discriminating power of connectivity profiles here is a result of integrating over
a relatively long period of time (i.e., runs that last several minutes). There is a growing body
of literature43 showing that in the resting state, functional connectivity is dynamic and varies
considerably over short periods of time (i.e., intervals less than one minute). Future work
may seek to characterize individuals based on properties of these dynamic fluctuations,
however, the current results indicate that single measures of time-averaged functional
connectivity, based on relatively long scan sessions, provide meaningful information about
individuals.

Note also that the cross-session identification performed here was between sessions
separated by a single day; it remains unclear to what degree individual connectivity profiles
are consistent across the lifespan. Cross-sectional studies have shown changes in functional
connectivity with age44–46, but future work should employ longitudinal designs to test the
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stability or evolution of the functional connectivity “fingerprint” over the course of months
or years rather than days.

From a methodological perspective, the scale of the node atlas appears to influence
identification accuracy. The parcellation used in our primary analysis consisted of 268 nodes
across the whole brain, with each node optimized to contain voxels with similar resting-state
timecourses10. This number is consistent with the range postulated by other groups47,48, but
represents a more fine-grained scheme than other atlases such as the automatic anatomic
labeling atlas (90 nodes)49 or the FreeSurfer atlas (68 nodes). In a comparison of
identification rates, network definitions based on our high-resolution parcellation
outperformed networks based on the FreeSurfer atlas; the coarser node size of the latter
likely diminishes accuracy by averaging out individual variability.
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Conclusion
Together, these advances suggest that analysis of individual fMRI data is possible, and
indeed, desirable. Given this foundation, human neuroimaging studies have an opportunity
to move beyond population-level inferences, in which general networks are derived from the
whole sample, to inferences about single subjects, examining how individuals’ networks are
functionally organized in unique ways and relating this functional organization to behavioral
phenotypes in both health and disease.

Online Methods
Subject information
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The primary dataset used in this work is from the Human Connectome Project (HCP). A
second dataset, acquired at Yale, was used for node and network definitions. These two
datasets are described in turn below.

HCP data—We used the Q2 HCP data release, which was all the HCP data publicly
available at the time that this project was begun. The full Q2 release contains 142 healthy
subjects; we restricted our analysis to subjects for whom all six fMRI sessions were

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available (n = 126; 40 males, age 22 to 35). This represents a relatively large sample size
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compared to most neuroimaging studies and has the advantage of being an open-source
dataset, facilitating replication and extension of this work by other researchers. Note that
most subjects have at least one blood relative in the group, with many sets of twins. A more
heterogeneous population should make the identification problem easier, and therefore the
high accuracy rate observed here, despite the homogeneity of the sample, underscores the
power of functional connectivity-based identification.

The resting-state runs (rfMRI_REST1 and rfMRI_REST2) were acquired in separate

sessions on two different days. Task runs included the following: working memory
(tfMRI_WM), motor (tfMRI_MOTOR), language (tfMRI_LANGUAGE, including both a
story listening and arithmetic task) and emotion (tfMRI_EMOTION). The working memory
task and motor task were acquired on the first day, and the language task and emotion task
were acquired on the second day. In total, there were six conditions: day 1 rest, day 2 rest,
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working memory, motor, language, and emotion. The HCP scanning protocol was approved
by the local Institutional Review Board at Washington University in St. Louis. For all
sessions, data from both the left-right (LR) and right-left (RL) phase-encoding runs were
used to calculate connectivity matrices. Full details on the HCP dataset can be found
elsewhere8.

Yale data—This dataset consisted of 45 healthy subjects scanned on a Siemens 3T Tim

Trio at Yale University (28 males; age= 31 ± 7.3, range 19–50). Resting-state fMRI data was
acquired using a multiband gradient echo EPI sequence with similar parameters to the HCP
acquisition (FOV = 210 mm, matrix size 84 × 84, TR = 0.956 ms, TE = 30 ms, resolution =
2.5 mm3). Eight 5.6 minute runs were acquired, totaling 45 minutes of data. Additionally, an
MPRAGE image (TR = 2530 ms, TE = 2.77 ms, TI = 1,100 ms, flip angle = 7 degrees,
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resolution = 1 mm3) and a two-dimensional anatomical T1 image (TR = 285 ms, TE = 2.61
ms, resolution = 2.5 mm3) were acquired for registration purposes. All participants provided
written informed consent in accordance with a protocol approved by the Human Research
Protection Program of Yale University.

Preprocessing
The HCP minimal preprocessing pipeline was used50 for the HCP dataset. This pipeline
includes artifact removal, motion correction, and registration to standard space. For the Yale
dataset, images were motion corrected using SPM8 and were warped to common space
using a series of linear and non-linear transformations as previously described10.

For both the HCP and Yale datasets, standard preprocessing procedures were applied to the
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fMRI data, including removing linear components related to the six motion parameters (Yale
data) or 12 motion parameters (HCP data; these include first derivatives, given as
Movement_Regressors_dt.txt), regressing the mean time courses of the white matter and
cerebro-spinal fluid as well as the global signal, removing the linear trend, and low-pass
filtering. For the HCP dataset, we investigated a range of spatial smoothing Gaussian kernel
sizes—from no smoothing to a full-width half-max (FWHM) of 4 mm, 6 mm or 8 mm—and
found that smoothing level had essentially no effect on identification accuracy (see

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 Finn et al. Page 12

Supplementary Table 2); thus results based on data with no spatial smoothing are presented
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in the main text. (Note that our node-based analysis, in contrast to a voxel-wise analysis,
contains a considerable degree of inherent smoothing because the timecourses of many
contiguous voxels are averaged into a single node.)

Image preprocessing and calculation of connectivity matrices was done using BioImage
Suite software51. Pearson correlation coefficients between pairs of node timecourses were
calculated and normalized to z scores using the Fisher transformation, resulting in a 268 ×
268 symmetric connectivity matrix for each session for each subject. Connectivity matrices
were not thresholded or binarized in any way.

Functional parcellation and network definition

Using the 45 subjects in the Yale dataset, a 268-node functional atlas was constructed using
a group-wise spectral clustering algorithm10. The two hemispheres were segmented
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separately into a target number of 150 regions. The final parcellation was examined to
ensure each node contained a reasonable number of voxels. Note that this single whole-brain
parcellation atlas was defined in MNI space, and was applied to all subjects in the HCP
dataset via traditional registration techniques. The parcellation image is publicly available on
the BioImage Suite NITRC page (https://www.nitrc.org/frs/?group_id=51).

In addition to parcellating the brain into 268 functionally coherent nodes, we further
clustered these nodes into large-scale networks. To define the networks, the same group-wise
spectral clustering algorithm was applied to connectivity matrices from the45 Yale subjects
to group the 268 nodes into eight networks10. The eight networks were evaluated and
compared visually to existing definitions of resting-state networks published by other
groups15,25. Despite the fact that we included subcortical regions and cerebellum, whereas
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other definitions excluded these regions, our network configuration matched well with these
other network definitions. Our eight clusters represent approximately the following
networks: 1) medial frontal, 2) frontoparietal, 3) default mode, 4) subcortical/cerebellum, 5)
motor, 6) visual I, 7) visual II, 8) visual association (see Fig. 1c).

Identification analysis
Fig. 1b illustrates the prediction procedure. First, a database was created that consisted of all
the individual subjects’ connectivity matrices from a single condition, D = [Xi, i = 1, …,
126], where Xi is a 268 × 268 correlation matrix and the subscript i denotes subject. In the
identification step, the identity of the target matrix was predicted using a correlation matrix
obtained from a different session. To predict the subject identity, the similarity between the
current target matrix Yi and all other matrices in D was computed, and the predicted identity
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was that with the maximal similarity score. Similarity was defined as the Pearson correlation
between two vectors of edge values taken from the target matrix and each of the database
matrices. Note that we performed prediction with replacement, such that the algorithm was
not forced to predict a unique subject on each iteration within a condition.

To assess the statistical significance of identification accuracy, we performed non-parametric

permutation testing. In each iteration, we first randomly selected one condition from day 1 to

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 Finn et al. Page 13

serve as the database set, and a second condition from day 2 to serve as the target set. Next,
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subject identity was permuted—such that each subject in the target set was assigned a
“correct” identity corresponding to a different subject in the database set—and identification
performed. Then the roles of database and target sets were reversed. This procedure was
repeated 1,000 times.

To investigate the contributions of individual networks (as described above) to identification

accuracy, a sub-matrix was used corresponding to a single network or combination of
networks. If we denote the set of nodes belonging to network j as Vj = [vjk, k = 1, …, Kj],
where Kj is the total number of nodes in network j, the sub-matrix of network j is X(Vj, Vj),
thus only connections within the selected network(s) are included.

Quantifying edgewise contributions to identification

Edge-based analyses were performed to determine if specific edges contribute more to
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individual identification than other edges. When performing subject identification, the
Pearson correlation coefficients were computed between the target connectivity pattern and
all connectivity patterns in the database, and the subject identity was chosen to be the one
that had the largest correlation coefficient. Computationally, the Pearson correlation of two
vectors is the sum of element-wise products, given that the two vectors are z-score
normalized (zero-mean with unit standard deviation). Therefore, this score can be broken
down to quantify the individual amount contributed from each entry in the vector, where
some edges contribute positively to the total coefficient and others contribute negatively.

Given two sets of connectivity matrices obtained from Rest1 and Rest2 runs
after z-score normalization, we computed the corresponding edge-wise product vector (φi),
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Where i indexes subject, e indexes edge and M is the total number of edges in the selected
network (or the whole brain). The sum of φi over all edges ∑eφi(e) is the correlation between
and . The group consistency measure (Φ) was computed as the mean of φi across
all subjects. Large positive entries in Φ are edges that are consistent both within a subject
and across the group.

In the same way, we can calculate φi between patterns from different subjects, e.g.:
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It is possible that an edge e is equally correlated within the same subject and between
different subjects. In other words, φij(e) (when subject subscript is not matched) and φii(e)
(when subject subscript is matched) are of similar value. Therefore, such an edge will not
contribute to distinguishing an individual from the other subjects.

For an edge to be truly helpful in individual identification, the following property must hold,

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 Finn et al. Page 14
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In this way, the particular edge contributes to maximize the correlation between connectivity
patterns from matched subjects. To quantify the differential power of an edge for the purpose
of subject identification, we computed an empirical probability, Pi(e),

We defined Pi(e) in this way so that it can be interpreted similarly as the p value in a
standard statistical test. The smaller the Pi(e)value the better differential power the edge has
to identify a single subject i. The overall differential power of an edge across all subjects is
then defined by the differential power measure (DP),
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The results of these edgewise analyses are visualized in Fig. 3a.

Identification using shorter timecourses

Scan sessions differed in duration: rest sessions were substantially longer than task sessions,
and thus the discrepancy in amount of data could at least partially account for the differences
in identification accuracy between rest-rest, rest-task and task-task pairs. To explore this
possibility, we tested frontoparietal-based identification between the two rest sessions while
varying the number of time points used to calculate connectivity matrices between 100 and
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1,100 in increments of 100. For each number of time points n, identification accuracy was
tested for each of 500 randomizations; these randomizations were generated by choosing
among 50 starting points for each of the two rest runs and using n brain volumes beginning
with that starting point to calculate matrices. Results based on a database and target of Rest1
and Rest2, respectively, are shown in Fig. 3b; results based on reversing the database and
target were extremely similar.

Identification based on two-matrix database

We also tested a database design option where two matrices were included for each subject.
The current design of the database and target set makes identification challenging because
the two sets of data were not only acquired on separate days, but also under different
conditions (except for the Rest1 and Rest2 pair) with the brain engaged in a different
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cognitive task. Inputting additional information about the difference between task and rest
could potentially improve identification performance. Therefore, we created a database that
included a connectivity matrix obtained from a resting-state session and another matrix
obtained from a task session acquired on the same day: . For
identification, we always required that the target matrix be obtained on a different day. To
predict the subject identity, we projected the current target matrix Yi to the subspace

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 Finn et al. Page 15

spanned by the pair , to obtain a projection Ỹi, and then computed the similarity
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between Ỹi and Yi to find the best match. Results are shown in Fig. 3c.

Effects of parcellation scheme

To investigate the effect of brain parcellation and network assignment on identification
accuracy, we also computed correlation matrices based on the 68-node FreeSurfer atlas
included as part of the HCP data. We used Yeo et al.’s previously published seven-network
definition15 which included the following networks: 1) visual, 2) motor, 3) pre-motor/
parietal (dorsal attention), 4) ventral attention, 5) ventromedial prefrontal, 6) frontal-parietal
control, 7) default mode. These networks do not include subcortical structures or
cerebellum. Network labels were assigned to each node in the FreeSurfer atlas as follows.
Given a node, we counted the number of voxels belonging to each of the seven networks.
The network with the largest number of voxels is assigned as the primary network label for
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the given node. Because the 68-node parcellation is created independently from the seven
networks, their boundaries do not align in a one-to-one manner. Therefore, we also allowed
a secondary network association for a node when the number of voxels in this network
ranked second and the proportion to the total number of voxels in the node exceeded 30
percent. All 68 nodes have at least one primary network association. When defining a sub-
matrix that represents a single network, we included nodes for which the target network was
either the primary or secondary label.

Comparisons of identification accuracy between the Shen and FreeSurfer and Yeo schemes
are shown in Fig. 4.

Effects of head motion

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In order to rule out the possibility that successful identification was driven simply by
characteristic movement patterns leading to predictable motion artifacts, we performed
prediction using motion estimates only. HCP data collection provides an estimate of frame-
to-frame displacement for each run (Movement_RelativeRMS.txt). This data was used to
generate a discrete motion distribution vector from each of the six Relative RMS vectors
(from the six conditions, using data from the left-right phase encoding run). We computed
the mean and standard deviation of the Relative RMS across all conditions and subjects. We
then specified 60 bins that spanned three standard deviations below and above the grand
mean, and the motion distribution vectors were calculated accordingly. The motion
distribution vectors were then used in the same way as the correlation matrices for individual
identity prediction purposes.

Effects of anatomic differences

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While connectivity calculations are based on functional BOLD data, subtle effects of
anatomic variability could potentially confer a preference between the same subject on two
different days when it comes to applying the 268-node parcellation, defined in standard
space, to each individual subject. To help rule out confounds of anatomy introduced at the
registration step, we recalculated connectivity matrices based on BOLD data smoothed with
three different kernel sizes (4 mm, 6 mm and 8 mm, keeping all other preprocessing steps
the same), and re-performed the identification analysis; at higher levels of smoothing, any

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 Finn et al. Page 16

registration advantage for the same brain relative to a different brain should be eliminated or
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vastly reduced. The resulting identification accuracies are presented in Supplementary Table
2.

We also performed a second analysis to help rule out the possibility that identification is
driven mainly by anatomic rather than functional differences between subjects. Rather than
connectivity between pairs of nodes, we tested whether individuals could be identified based
simply on a measure of BOLD variance in each node (calculation described below). In
theory, while BOLD variance likely reflects baseline metabolic function to a substantial
degree, it could also be influenced by anatomic factors such as partial volume effects
introduced by the gray/white-matter segmentation and/or differing numbers of gray-matter
voxels per node due to underlying variation in regional tissue volumes and gyral folding
patterns. This analysis helps to address these potential confounds. BOLD variance was
calculated and identification performed as follows:
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1. Within each node, we computed the mean BOLD signal in each frame.
This yields an N×268 matrix of node-wise mean BOLD intensities for
each subject for each condition, where N is the number of frames (1,200
for the resting-state runs and fewer for the task runs). (This is identical to
the first step in calculating connectivity matrices. Note that the mean
across the time dimension is zero because of the drift removal and band-
pass steps.)

2. For each node, using its N×1 timecourse vector, we compute its variance
as follows:
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This results in a single 1 × 268 vector of node-wise BOLD variances for

each brain state for each subject. In signal processing terms, this variance
is also known as “mean energy.”

3. We then performed identification by computing the correlation between

these mean BOLD variance vectors across the different conditions (states)
and sessions (days).

The results of this analysis are presented in Supplementary Table 3.

Behavioral prediction
In the HCP protocol, fluid intelligence (gF) was assessed using a form of Raven’s
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progressive matrices with 24 items23 (scores are integers indicating number of correct items;
mean = 16.8, s.d. = 4.7, median = 18, mode = 20, range 5–24; HCP: PMAT24_A_CR).

In light of evidence that head motion is a substantial confound in functional connectivity

analyses, we first checked for any correlation between head motion and gF score. In the full
sample of n = 126, this correlation was trending toward significance (r = −0.15, p = 0.09).
Upon further examination, we found that this relationship was driven by a small number of

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 Finn et al. Page 17

individuals with both high head motion and low gF score. Thus, for purposes of the
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behavioral analysis, we excluded subjects with particularly high motion during the Rest1
run; specifically, eight subjects with > 0.14 frame-to-frame head motion estimate (averaged
across both day 1 rest runs; HCP: Movement_RelativeRMS_mean) were excluded. There
was no correlation between head motion and gF in the remaining set of n = 118 subjects (r =
−0.05, p = 0.55).

Leave-one-subject-out cross-validation was used for the prediction analysis. In this iterative
analysis, features are selected and a predictive model is built based on n−1 subjects (the
training set) and the model is then tested on the remaining subject (the test set). Each subject
is left out once. Each iteration consisted of 1) feature selection, 2) model building, and 3)
prediction, described in turn below.

In the feature-selection step, Pearson correlation was performed between each edge in in the
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connectivity matrices andgF score across subjects in the training set. (Note that it is not
necessary to correct for multiple comparisons in this step because the nature of a predictive
analysis includes a built-in guard against false positives: if the proportion of false positives
in the feature-selection step is high, the model should not generalize well to independent
data.) Based on the signs of the resulting correlation values, edges were separated into two
tails: those positively correlated with gF and those inversely correlated with gF. Edges were
then thresholded based on the statistical significance of their correlation with gF, resulting in
two sets of features (positive and negative). Because the choice of statistical threshold at this
step is somewhat arbitrary, a range of thresholds was tested — p < 0.01, 0.05, 0.10 — to
ensure that results were consistent.

In the model-building step, we first defined a single-subject summary statistic, “network

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strength,” by summing values of all edges in each feature set in individual connectivity
matrices. In graph-theoretic terms, this statistic can be thought of as a type of weighted
degree for each feature network52. This summary statistic can be represented as follows:

Where c is an individual s’s connectivity matrix, and m(+) and m(-) are binary matrices
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indexing the edges (i,j) that are significantly positively or negatively correlated with gF,
respectively.

After obtaining network strength for each subject in the training set, simple linear regression
was used to model the relationship between network strength (the explanatory variable) and
gF (the dependent variable). Two models were built: one based on strength in the positive-
feature network, and a second based on strength in the negative-feature network. Each model

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 Finn et al. Page 18

—positive and negative—consisted of a first-degree polynomial that fit the training data best
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in a least-squares sense:

Finally, in the prediction step, positive and negative network strengths from the excluded
subject were calculated and input into each of the two respective models to generate
predicted gF scores for that subject.

These three steps were repeated iteratively such that each subject was excluded once.
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Finally, we assessed predictive power of both models by correlating observed versus

predicted gF scores across all subjects. Results are shown in Fig. 5.

Supplementary Material
Refer to Web version on PubMed Central for supplementary material.

Acknowledgments
Data were provided in part by the Human Connectome Project, WU-MinnConsortium (Principal Investigators:
David Van Essen and Kamil Ugurbil;1U54MH091657) funded by the 16 NIH Institutes and Centers that support the
NIH Blueprint for Neuroscience Research; and by the McDonnell Center for Systems Neuroscience at Washington
University. This work was also supported by NIH EB009666 (RTC), T32 DA022975 (DS), and the NSF Graduate
Research Fellowship Program (ESF and MDR).
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Figure 1. Identification analysis procedure and network definitions

a) Database and target design. Each subject had six sessions of fMRI data: a resting-state
session (R1), a working memory task (WM) and a motor task (Mt) on day 1, and a resting-
state session (R2), a language task (Lg) and an emotion task (Em) onday2. For
identification, we used a set of connectivity matrices from one session for the database, and
connectivity matrices from a second session acquired on a different day as the target set. All
possible combinations of database and target sessions are indicated by the arrows connecting
session pairs. b) Identification procedure. Given a query connectivity matrix from the target
set, we computed the correlations between this matrix and all the connectivity matrices in
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the database. The predicted identity (ID*) is the one with the highest correlation coefficient.
c) Node and network definitions. We used a 268-node functional atlas defined on an
independent dataset of healthy control subjects using a group-wise spectral clustering
algorithm. Nodes were further grouped into eight networks using the same clustering
algorithm, and these networks were named according to their correspondence to other
existing resting-state network definitions.

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Figure 2. Identification accuracy across session pairs and networks

a) Identification accuracy based on all nine database and target pairs, where each row has the
same database session and each column has the same target session. Each graph shows
accuracy based on each individual network as well as a combination of networks 1 and 2
(the frontoparietal networks) and the whole brain (“All”). Bar shading (black or gray)
indicates which session was used as the database (with the other session serving as the
target). b) Identification results from the combined frontoparietal networks (top) are
highlighted in color-coded matrices (bottom) to more readily compare accuracy across rest-
rest, rest-task and task-task session pairs. Identification was most successful between the
rest-rest pair, with a slight drop in accuracy for both rest-task and task-task pairs.
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Figure 3. Factors affecting identification accuracy

a) Highly unique (DP, top row, red) and highly consistent (Φ, bottom row, blue) edges in
individual connectivity profiles. For visualization, both sets of edges were thresholded at the
99.5 percentile. In the circle plots (left), the 268 nodes (inner circle) are organized into a
lobe scheme (outer circle) roughly reflecting brain anatomy from anterior (top of circle) to
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posterior (bottom of circle), and split into left and right hemispheres; lines indicate edges. In
the colored matrices (right), the same data are plotted as percentage of edges within and
between each pair of networks; a darkly shaded cell indicates a relative over-representation
of that network pair in the DP (top) or Φ (bottom) masks. PFC, prefrontal; Mot, motor; Ins,
insula; Par, parietal; Tem, temporal; Occ, occipital; Lim, limbic (including cingulate cortex,
amygdala and hippocampus); Cer, cerebellum; Sub, subcortical (including thalamus and
striatum); Bsm, brainstem; L, left hemisphere; R, right hemisphere. b) Longer timeseries
improve identification accuracy. To control for the fact that task sessions contained fewer
time points than rest sessions, we recalculated rest connectivity matrices using truncated
timeseries containing between 100 and 1,100 time points. Results shown are from 500
randomizations using Rest1 and Rest2 as the database and target sessions, respectively. Box
represents median with 25 and 75th percentiles; whiskers represent range. c) Use of a two-
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matrix database improves identification rate relative to a single matrix (task or rest). Dots
and error bars represent mean and range of identification rate across all possible database
and target pairs, where the target matrix was always from a task session and the database
consisted of a rest-task pair (n = 8 combinations), task only (n = 8) or rest only (n = 4). *p <
0.01, Mann Whitney U test.

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Figure 4. Effect of node and network scheme on identification accuracy

a) Comparison of identification accuracy using the Shen node atlas and network definitions
(left) versus the FreeSurfer (FS) node atlas and Yeo network definitions (right). Accuracy is
numerically higher using the Shen scheme; the difference is exaggerated when using just the
frontoparietal networks (black lines) relative to the whole brain (gray lines). b) Raw
126×126 cross-subject correlations of frontoparietal connectivity patterns from Rest 1 and
Rest 2 (top; scale bar indicates r value). Row and column subject order is symmetric; thus,
diagonal elements are correlation scores from matched subjects. Mean correlation
coefficients for both diagonal (matched) and off-diagonal (unmatched) elements are shown
in the bar graph at bottom (error bars represent ± s.d.). The overall correlation coefficients
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are higher using the FS+Yeo scheme, for both diagonal elements (n = 126) and off-diagonal
elements (n = 15,876). **p < 10−5, two-tailed t-test. c) Cross-subject correlation matrices
after z score normalization (top; scale bar indicates z score). The global difference in
correlation values is eliminated since there is no significant difference in the off-diagonal z
scores. However, correlations between diagonal elements are significantly higher using the
Shen scheme than the FS+Yeo scheme (bottom; error bars represent ± s.d.), which helps
account for the increase in identification accuracy using the Shen scheme. **p < 10−5, two-
tailed t-test.
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Figure 5. Individual connectivity profiles predict cognitive behavior

a) Results from a leave-one-subject-out cross-validation (LOOCV) analysis comparing
predicted and observed fluid intelligence (gF) scores (n = 118 subjects). Scatter plot shows
predictions based on the whole brain in the positive-feature network at a feature-selection
threshold of p < 0.01. Each dot is one subject; gray area represents 95% confidence interval
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for best-fit line, used to assess predictive power of the model. b) Mean fraction of within-
network edges selected in the whole-brain positive-feature (left, red) and negative-feature
(right, blue) models, shown at a range of statistical thresholds for feature selection. Y-axis
indicates mean fraction of edges selected across all LOOCV iterations; x-axis indicates
network label (see Fig. 1c). c) Results from a LOOCV analysis in which feature selection
was restricted to within-network edges in the frontoparietal networks (1 and 2), at a feature-
selection threshold of p < 0.01. As in (a), each dot is one subject; gray area represents 95%
confidence interval for best-fit line. d) Results from nine separate LOOCV analyses in
which feature selection was restricted to within-network edges in each of the eight networks
plus a combination of networks 1 and 2. Y-axis indicates correlation between predicted and
observed gF scores; x-axis indicates network label. Asterisks indicate correlations significant
at p < 0.05 (uncorrected). Results based on a range of feature-selection thresholds (p-values)
are shown to demonstrate consistency across thresholds. Note that for some networks, no
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features passed the statistical thresholding step, and thus it was not possible to generate
predictions; this is reflected by missing bars.

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