Applied Intelligence (2023) 53:6978–6991

https://doi.org/10.1007/s10489-022-03891-9

A unified framework of graph structure learning, graph generation

and classification for brain network analysis
Peng Cao1,2 · Guangqi Wen1,2 · Wenju Yang1,2 · Xiaoli Liu3 · Jinzhu Yang1 · Osmar Zaiane4

Accepted: 11 June 2022 / Published online: 13 July 2022

© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022

Abstract
Recently, functional brain networks have been employed for classifying neurological disorders, such as autism spectrum
disorders (ASDs). Graph convolutional networks (GCNs) have been shown to be successful in modeling applications with
graph structures. However, brain network data is in general of complex structure with small sample size, and the use of
GCNs on available datasets remains a big challenge. Driven by this important issue, three questions arise: 1) how to capture
the critical structures of brain networks by removing noisy connections, to facilitate the following GAN and GCN; 2) how to
generate graphs by generative adversarial networks (GANs) to preserve the local graph topology as well as the global data
distribution; 3) how to sufficiently leverage the real and generated graphs with domain gaps for improved classification. In
this paper, we proposed a three-stage framework, named BrainGC-Net, which coherently joins the power of graph pooling,
GAN and GCN for brain network generation and classification. Given the original brain network with a large number of
noisy connections, we propose graph pooling to enhance the important connections with a supervision scheme. Then, based
on the coarsened brain networks, we propose a graph GAN model, named EG-GAN, to focus on the global data distribution
in the embedding space and local graph topology in the graph space simultaneously. Finally, a domain consistent GCN
model is proposed to take sufficient advantage of the two domains rather than simply merging by incorporating multiple
consistent regularizations from view correlation, class correlation and sample correlation. With extensive experiments on
the ASD classification problem, we validate the effectiveness of our method and it achieves consistent improvements over
state-of-the-art methods on the public ABIDE dataset.

Keywords Brain network · Graph convolutional networks · Generative adversarial networks · Graph classification

1 Introduction the strength of the connection between those regions. This

Recent studies have shown that rs-fMRI based analysis of
brain functional connectivity (FC) is effective in helping
understand the pathology of brain diseases [1, 2]. The
functional network of the brain can be modeled as a graph
in which each node is a brain region and the edges represent
 Peng Cao
caopeng@cse.neu.edu.cn
1 College of Computer Science and Engineering, Northeastern
University, Shenyang, China
2 Key Laboratory of Intelligent Computing in Medical Image,
Northeastern University, Shenyang, China
3 Alibaba A.I. Labs, Hangzhou, China
4 Alberta Machine Intelligence Institute, University of Alberta,
Edmonton, Alberta, Canada
task can be seen as a graph classification problem. The
fundamental task of the graph classification problem is the
representation learning of graph-structured data. Motivated
by the success of the graph convolution network (GCN) [3]
in graph data, recent works [4–10] have applied GCN to the
functional network derived from rs-fMRI data to learn the
latent features from graphs.
Embedding learning for brain networks with GCN
requires a large collection of training data. However, the
major challenge is that the quantity of available labeled data
is usually very small in the clinical application, which limits
the classification performance. While recent attempts to
solve the limited data problem using generative adversarial
networks (GAN) have been successful in augmenting
training data by generating realistic images, most of them
are based on images. In this paper, we aim to address
the following challenges: (C.1) how to capture the critical
structures of brain network by removing noisy connection,

13
A unified framework of graph structure learning, graph generation and classification for brain network analysis 6979

which is beneficial for the following GAN and GCN, superiority of our method over other competing methods on
(C.2) how to generate a realistic graph representation that the brain network classification for ASD diagnosis.
preserves local graph structures and globally consistent The main contributions of our work can be summarized
data distribution, and (C.3) how to alleviate the domain as follows:
adaption of both representations of graphs for improved
1) Graph structure learning: We propose an attention
classification. We propose a three-stage framework, named
based graph pooling, which is able to remove the
BrainGC-Net, which coherently joins the power of graph
noisy functional connections and alleviate the multi-
pooling, GAN and GCN for the brain network generation
center subject inconsistency. Under the proposed prior
and classification. In our work, we select a common disease
subnetwork knowledge guides, it is able to identify
called autism spectrum disorder (ASD) for evaluation.
the critical graph structure, which actually boosts the
ASD is a neurodevelopmental disorder characterized by
performance of the following graph generation and
communication, behavior and social interaction deficits in
classification procedures.
patients which may include repetitive behavior, irritability,
2) Graph generation learning: To improve the graph
and attention problems. Bajestani et al. [11, 12].
generation quality, we propose a graph GAN by deriv-
Due to the intrinsically complex structure of brain
ing two additional constraints: a local topological mea-
networks, few GAN models can be successfully applied
sure to preserve global structural properties and global
due to the complex graph structure, diverse interpolation
homeomorphic mapping to regularize the position of
incompatible with the original distribution, and the unstable
the generated samples. Most graph GAN models focus
optimization. To solve these challenges, we propose a graph
on the modeling of the underlying true connectivity dis-
pooling model to enhance the important connections and
tribution and produce the most indistinguishable fake
remove the irrelevant connections with the supervision
connections. To the best of our knowledge, the pro-
scheme. Moreover, we firstly propose a prior subnetwork
posed EG-GAN is the first work that applies GAN
structure regularization to guide the pooling procedure
on brain networks for augmenting data for improved
and ensure the accurate subnetwork identification. By
classification performance.
removing the noisy connection, the clean structure not
3) Graph embedding learning: To take sufficient advan-
only reduces computational complexity, but also facilitates
tage of the generated graphs, we propose a domain con-
the downstream classification tasks. Then, based on the
sistent GCN for graph embedding learning to alleviate
structure of α-GAN, we proposed a graph GAN model
the distribution shift between the real graph and gener-
focusing on both Embedding and Graph space, named
ate graph domains through the view consistency, class
EG-GAN, which incorporates a local topological measure
consistency and pairwise sample similarity consistency.
constraint from graph space and a distribution consistent
4) We draw a connection among the graph pooling, graph
homeomorphic mapping from the latent code space. The
generation and graph classification. For example, the
aim is to enable the generator to preserve global structural
graph pooling leads to a clean graph structure, which
properties and enforce the compatibility between latent
boosts the performance of the following models of
sample distances and the corresponding graph sample
graph generation and graph classification; our proposed
distances, both of which are important for the brain network
DC-GCN can reduce the distribution gap between the
neurological disorders. The proposed generative model is
real graphs and the generated graphs.
unsupervised through adversarial learning, which lacks
sufficiently discriminative ability for graph classification. The rest of the paper is organized as follows. Detailed
Moreover, it only generates the graph structure of brain mathematical formulations and descriptions of the proposed
networks without the node signal features. To alleviate the graph pooling, EG-GAN and DC-GCN are provided in
existing gap between the domains of real and generated Section 2. In Section 3, we evaluate the performance by
graphs, we propose a domain consistent GCN model to extensive experiments on the ABIDE datasets. We conclude
improve the graph classification performance via three this study in Section 4.
mechanisms: (1) cross-view consistency, (2) class center
consistency and (3) sample similarity consistency. The
proposed model is able to learn a consistent graph 2 Method
embedding by fully exploiting the correlation from the
perspectives of view correlation, domain correlation and 2.1 Overview
sample correlation through the training process. Extensive
ablation studies and comparison experiments conducted The notations and the corresponding descriptions are shown
on the ABIDE dataset have shown the effectiveness and in Table 1. Formally, given an original graph Gi = {Vi , Ai }

13
6980
Table 1 The notations and the
corresponding description Variable name
G / Ĝ
A / Â
n and c
Dr , Dg and Drg
h and Z
F Cluster indicator matrix
s The importance score of each node vi in graph G
R The set containing part of the brain regions
w The weight of edge eij in A
Gθ (·)
fw
Eφ (·)
fwc
Nr
Ng
and their corresponding label yi ∈ {−1, 1}, i = 1, . . . , Nr ,
we formulate our task as a graph classification task by
learning a mapping function f : X → Y in our study. Ai ∈
Rn×n denotes the corresponding adjacency matrix of Gi .
Each value of Ai is calculated between two brain regions
by Pearson’s correlation estimation. V = {v1 , v2 , ..., vn }
represents the set of nodes in G and each v contains one
dimensional signal.
Recently, deep learning methods have made a massive
breakthrough in medical applications. A large quantity of
data is the essential for training models. However, in the
medical domain, it is usually difficult to collect sufficient
data. To overcome these limitations, we proposed a data
augmentation method based on the coarsened graphs and
cast ASD diagnosis as a classification problem. Specifically,
we develop a unified three-stage learning framework for
brain network classification. It involves graph pooling for
structure learning, graph generation for data augmentation
and graph embedding learning for classification. The
framework is shown in Fig. 1.
2.2 Graph pooling
First, the highly noisy connections in the brain network lead
to poor classification performance. Second, inconsistencies
exits in the subjects from multi-sites. The inconsistency in
the brain network introduces a more significant challenge
to our classification task. Therefore, it is essential to
eliminate the inconsistency in FCs. Graph pooling is a
critical operation to coarsen an original graph with high
level noisy edges for graph representation learning in GCN.
The aim of the graph pooling procedure is to preserve the
global topology structure in brain networks and remove
the noisy edges. Attention has been widely used in recent
13
P. Cao et al.
Description
The original / coarsened brain network
Adjacent matrix of original / coarsened brain network
The node amounts of G and Ĝ
The datasets of real graphs, generated graphs and the mixed graphs
Graph embedding vector and node embedding matrix
Graph generator
Graph discriminator
Graph encoder
Code discriminator
The number of real graphs
The number of generated graphs
deep learning research. In our work, we propose a temporal
graph pooling with attention mechanism where weights
are determined by GCN. We formulate graph pooling as
a cluster assignment problem with attention mechanism.
By hiding the non-indicative edges and highlighting the
indicative edges, the nodes of an original graph are grouped
into some clusters. Formally, an original graph G is
transformed into a coarsened graph Ĝ = {V̂ , Â} with
a coarsened structure, where V̂ = {SN1 , SN2 , ..., SNc }
denotes the set of supernodes in Ĝ, Â ∈ Rc×c denotes
the corresponding weighted adjacency matrix of coarsened
graph Ĝ, and c denotes the number of supernodes. To
achieve this, we introduce a learnable parameter F ∈ Rn×c .
F indicates the membership of a node to a cluster. F is
formally defined as:

s , i ∈ SNj
Fij = i (1)
0, i ∈/ SNj
where si denotes the importance score of each node vi in
graph G.
With the optimized F , we can obtain a set of clusters
as supernodes V̂ = {SN1 , SN2 , ..., SNc } and the weighted
adjacency matrix of the supergraph  = F T AF ∈ Rc×c .
Then the nodes of a cluster are pooled as one supernode
to produce a coarsened graph. The superedge between
supernodes is the aggregation of edges multiplying with
the node importance. Each superedge eij in  is defined
as si ∗ wij ∗ sj , where wij denotes the weight of edge eij
in A. Therefore, the learned connection weights help us
identify the informative edges. The attention mechanisms
allow GCN to focus more on important connections through
learning a weight parameter. It is able to construct a
coarsened and clean graph structure with only important
edges by highlighting the critical connections and removing
A unified framework of graph structure learning, graph generation and classification for brain network analysis 6981

Fig. 1 The overall architecture S1 S5

of our proposed three-stage S8
S1 S5
S2 S6 S7 S8
BrainGC-Net framework S9 S2 S6 S7
S9
S3 S10 S3 S10 s-GCN
S11 S11
S4 S4

Original Graph Coarsened Graph

Graph pooling
Cross-view consistency

Coarsened Graphs

Real
Node temporal
Graph set feature learning f-GCN
Dr

EG-GraphGAN Ar
Generated
Graph set
s-GCN
Dg Ag

j
Gi Gj Dg+ Dg- Dr+ Dr-
Class semantic consistency
Graph space Embedding space
Pairwise similarity consistency

DC-GCN

the irrelevant connections. Meanwhile, all the dynamic
brain network series data become consistent. Furthermore,
to constrain the consistency of temporal multi-graph, we
perform graph pooling on all the graphs with a shared F .
The aim of the graph pooling is to identify the
indicative edges for our task. However, with the optimized
F , the pooling may neglect the potentially important
subnetworks. In order to address this, we consider the prior
information of subnetworks and incorporate the knowledge
into the proposed model to encourage the edges within the
important subnetwork with higher weights. Hence, the prior
subnetwork knowledge regularization is:
⎛ ⎞
 graph space simultaneously. At first, in order to effectively
1
Rsub = −log ⎝ 2
si sj ⎠
Rprior i,j ∈Rprior
where Rprior contains the brain regions in the subnetwork.
We choose six common networks including DMN (default
mode network), AN (auditory network), SN (salience net-
work), SMN (somato-motor network), VN (visual network)
and CEN (central executive network). The regularization
helps our model identify potential subnetworks that are most
predictive of ASD diagnosis.
2.3 EG-GraphGAN
2.3.1 Architecture
Recently, generative adversarial networks (GANs) [13]
have achieved state-of-the-art performance in the field of
image generation producing very realistic images in an
unsupervised setting. In this study, we propose a graph
GAN model focusing on the global data distribution in
the embedding space and local graph topology in the
(2) address the mode collapse problem of GANs, we introduce
additional autoencoder and code discriminator networks
on top of the existing generator and discriminator. Instead
of using the code discriminator from α-GAN or KL loss
from VAE-GAN, we introduce WGANs that minimize an
approximation of the Wasserstein distance between the real
distributions and the distribution of the generated samples
[14, 15]. Similar to any typical GAN architecture, our

13
6982 P. Cao et al.

GAN consists of four main components - graph generator generated samples.

Gθ , graph discriminator fw , graph encoder Eφ and code
discriminator fwc . The graph generator network Gθ (·) is 1 r  N
1    Ng
g g
trained to learn a function Gθ (·) : h(r) → G mapping Ld = fw Ĝi − fw Gθ hi(r) + Lgp
m m
each point in the latent embedding space to a graph sample i=1 i=1
in the graph space. h(r) is the real graph embedding (7)
vector. A graph encoder network Eφ (·) is trained to learn where Nr is the number of real graphs and Ng is the number
a function Eφ (·) : G → h(e) , mapping each real graph of generated graphs.
sample to a point in the latent space. h(e) is the generated During the graph encoding stage, the graph convolu-
graph embedding vector. These networks are trained in
tandem with two discriminator networks, fwc and fw , which  function is used for each layer as follows: Eφ (·) :
tion
1 1
φ D̃ − 2 ÃD̃ − 2 Z (l) W (l) , where Z (l) is the node embed-
learn to discriminate abilities between real and generated
samples and latent points, respectively. Figure 2 illustrates dings of the layer l. During the graph generation stage,
the overall architecture of the EG-GAN framework. the link prediction function is defined as follows: p(Â |
First, the basic total loss of the graph generative Ẑ) = ni=1 nj=1 p(Aˆij | ẑi , ẑj ), with p(Aˆij | ẑi , ẑj ) =
T
adversarial model is determined by: σ (f ẑi · f (ẑj )), where  and Ẑ are the adajcent matrix
and node embeddings of the generated graph Ĝgen . We
eg g g
Ladv = Leenc + Led + Lgen + Ld (3) also incorporate the addition of reconstruction terms, that
discourages mode collapse as Gθ (·) needs to be able to
where: reconstruct every input graph Ĝ. In the graph space, we
choose a pointwise reconstruction term with L1 distance to
1) Lcenc is the loss of the graph encoder module: match the distributions of Ĝ and Ĝrec = Gθ (h(e) ). More-
over, we propose another reconstruction term for the graph
1 
Nr  embedding from the embedding space. Both reconstruction
Lcenc = − fwc Eφ (Ĝi ) (4)
Nr losses consider the graph space and latent embedding space,
i=1
respectively. The reconstruction loss is calculated as:
2) Lcd is the loss of the graph discriminator module by
treating h(r) as real and the encoder Eφ (·) output h(e) 1  
Ng   2  2 
   
Lerec (Ĝ, Ĝrec ) = Eφ Ĝi − Eφ Ĝirec  + Ĝi − Ĝirec 
as fake : m 2 1
i=1
(8)
1  c i 
Ng
1 r N
Lcd = fw h(r) − fwc hi(e) + Lcgp (5)
m m
i=1 i=1

g
2.3.2 Topology loss
3) Lgen is the loss of the graph generator module:
The previously introduced EG-GraphGAN only considers
Ng
1   the global graph connectivity structure generation with
g
Lgen =− fw Gθ (hi(r) ) (6) an adversarial learning scheme (i.e., graph connectivity
m
i=1 structure) and ignores the local topology at the node scale of
a graph (e.g., how central a node is in the graph). To solve
g
4) Ld is the loss of the graph discriminator module which this, we introduce a local topology loss to regularize the
aims to distinguish the real graph data Ĝ from the generators. In our study, we choose the proximity centrality

Fig. 2 Our framework involves Graph Generator

four modules: graph encoder, ReLU

graph generator, graph FC
Softplus
discriminator and code (Z, ZT) Generated graph

discriminator
Real
Real or
Real Gaussian Fake?
Distribu on Fake
or Reconstructed graph
Code
Fake? Embedding
Convolutional Operation

Original graph

Code Discriminator Graph Encoder Graph Discriminator

13
A unified framework of graph structure learning, graph generation and classification for brain network analysis
used in graph theory as the common measure. Closeness
centrality directly relates to the cardinality of the shortest
path between two nodes. It is calculated as: CC(i) =
 c−1 , where d(i, j ) defines the distance between two
d(i,j )
j  =i
supernodes i and j , and c is the number of supernodes. It
has a reflection of the whole connectivity in the network
structures. The topology loss is defined as follows:
g

m
Ltp = MAE (CC(i), CC(j )) .
i=1
2.3.3 Distribution consistency loss
A high-quality generative model should be able to
synthesize graphs that preserve global distribution of
realistic graphs. To prevent the generator from producing
diverse graph samples of which the corresponding latent
codes are close, we further propose a consistent loss to
encourage the graphs reconstructed by the decoder as the
nearby latent vectors to be consistently closer. It guarantees
that interpolating between samples in the latent space
leads to semantic interpolation in the graph space further
improving the mapping h(r) → G. More specifically, we
add a homeomorphic mapping to the model. We attempt
to random sample hij along the line between pairs of
points vector hi and hj . With the reconstructed graph data
(i,j ) (i,j )
Ĝrec , it is desirable that Ĝrec is consistently closer to
i j
the reconstructed Ĝrec and Ĝrec . The loss enables us to
achieve smooth interpolations of generated fake samples.
The homeomorphic mapping loss can be written as:
 
(i,j ) j (i,j )
Lehom = Lerec Ĝirec , Ĝrec + Lerec Ĝrec , Ĝrec (10)
2.3.4 Overall loss
The training is proceeded in terms of four kinds of losses:
adversarial loss, reconstruction loss, topology loss and
distribution-consistency loss. The overall losses for our
EG-GraphGAN are as follows,
eg eg g
LGAN = Ladv + λ11 Ltp + λ12 Lehom + λ13 Lerec
Under the unified objective of the multiple losses in GAN,
the benefits of the graph generation model can be exploited
and the generation performance improves. The adversarial
loss forces the decoder to generate graphs that are likely
to fool the discriminator in its task to distinguish between
real and reconstructed graphs, while both topology loss and
homeomorphic mapping loss aim to improve the generation
performance from two aspects of local graph topology and
global embedding distribution.
6983
2.4 Domain consistent GCN, DC-GCN
The adversarial loss defined in the previous section forces
the model to generate realistic samples, but does not
guarantee to provide discriminative information for graph
classification of ASD and normal control (NC) due to
the domain gap. To alleviate the existing gap between the
domains of real and generated graphs, our aim is to improve
the graph classification performance via three mechanisms:
(9) (1) cross-view consistency, (2) class center consistency
and (3) sample similarity consistency. Dr = {Vir , Ari }N r
i=1
denotes the real graphs, where V r = {v1 , v2 , ..., vc }
represents the set of nodes with BOLD signal series and
c indicates the number of subjects and brain supernodes.
g Ng
Drg = {{Ari }Ni=1 ; {Aj }j =1 } denotes the mixed graph dataset
r
with the real and generated graphs, only the graph structure
of which is considered. To this end, we train two GCN
models, f -GCN and s-GCN on Dr and Drg for learning
the graph embeddings with two specific graph convolution
modules.
2.4.1 Node spatio-temporal features learning in f -GCN
We are interested in the dynamic functional connectivity
analysis and focus on the design of a unified model that
is capable of handling spatio-temporal data for capturing
the dynamic functional connectivity. In Dr , we aim to
jointly learn the node spatio-temporal features involving
the temporal features in the BOLD signal and the spatial
features of the graph structures. In order to learn a
representation of the temporal dynamics contained in rs-
fMRI time series, we employ the gating mechanism gated
linear units (GLU) [16] to capture dynamic temporal
features. The output through 1D convolutional layer is
divided into two equal parts, namely P and Q, which are
the outputs of the first and the second half convolution
kernels individually. The temporal gated convolution can be
(t+1)
defined as: fT = P ⊗ σ (Q), where ⊗ is the Hadamard
product operator. The convolution kernel is designed to map
(t)
the input fT to a single output element [P , Q]. With the
temporal features, we employ a stack of graph convolutional
layers to capture the spatial features of the graph structures.
(11)
2.4.2 Multiple consistency regularization
Through the graph generation by our EG-GAN, the two
graph domains from the real graph dataset and the generated
graph dataset are nearly aligned from a distribution
perspective. However, it only enforces the alignment of
global distribution through adversarial learning, but it
ignores the local embedding alignment and the class
semantic alignment. Additionally, the two GCN models
proposed for focusing on capturing the different graph
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6984
properties on Dr and Drg lack the correlation between
each other. The two GCNs are desirable to be reinforced
by each other through collaboratively learning. To this
end, we propose a domain consistent GCN, named DC-
GCN, to find low-dimensional graph embedding from
multi-view multi-domain data via three mechanisms: (1)
cross-view consistency, (2) class center consistency and
(3) sample similarity consistency. In order to fully exploit
the correlation of the two view embeddings, we develop
a collaborative learning framework for the two graph
convolution modules with multiple regularizations from the
perspective of the multi-views from the same graph, the real
and the generated graph data distributions and the graph
data correlation. The main idea of collaborative learning is
that each sample can learn a consistent graph embedding
from multi-view and multi-domain but also from the whole
population through the training process.
Cross-view consistency For the real graph data, the cross-
view pairs of the same graph are captured by the
two different GCN models. Now we have two specific
embeddings hf and hs for each real graph with feature
embedding. In order to fully exploit the correlation of the
two view embedding, we propose a cross-view consistency
for the two graph convolution modules. We introduce a
cross-view consistency with contrastive loss, which takes
into account the consistency between embeddings by the
f -GCN and s-GCN, which gives rise to the following
constraint:
1 1
Lcv = I d 2 + (1 − I ) {max(0, md − d)}2 (12)
2 2
where I indicates whether the paired cross-view embed-
dings are for the same subject(if matched, I = 1; otherwise,
I = 0); and d is the Euclidean distance between feature
descriptors hf and hs learned by the two GCNs, respec-
tively. Such feature consistency loss encourages the feature
descriptors of matching pairs to be close and non-matching
pairs to be separated by a distance of at least a margin
md . Equation 12 encourages the cross-view embeddings to
be close in the embedding space, and punishes the non
cross-view embeddings that are margin md away.
Class semantic consistency In addition to the cross-view
relationship, we also consider the possible consistency of
the class semantic across domains of Dr and Dg . The
graph generation is independently conducted on the two
classes of ASD and NC, which results in the possible
indiscrimination between the two classes in the graph
dataset of Dg . To explicitly alleviate the negative influence
of those generated noisy samples and enforce the cross-
domain category consistency, we propose a regularization
to enforce the semantic alignment of the two domains
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P. Cao et al.
distribution. It helps alleviate these domain gap issues by
GAN and facilitates the graph embedding by guaranteeing
that samples from different domains with the same class
label will be mapped nearby in the feature space. We denote
Cr+ , Cr− , Cg+ and Cg− as the class centroids of the two
domains of the Dr and Dg . Aligning the distribution of
Dr and Dg is able to guide the s-GCN model to produce
a consistent graph embedding for the two domains. We
align the synthesized sample distribution to the real sample
distribution with the Euclidean distance as follows.
 2  2
   
Lcs = (Cr+ − Cg+ ) − (Cr− − Cg− )2  (13)
2 2
Pairwise similarity consistency The previous regularization
considers the consistency from the perspective of global
distribution ignoring the local pairwise similarity consis-
tency. The local pairwise similarity consistency requires that
the graph data with the similar graph structure should be
mapped close. Incorporating and preserving the local con-
sistency can promote to learn a better embedding of the
brain network. To this end, all the training samples are
treated as a global graph to exploit the association in the
subjects. Given the mixed data Drg , we construct an undi-
rected global graph Ḡrg = V̄rg , Ārg , where Ārg describes
the pairwise similarities between each pair of subjects with
brain networks and each subject is represented by a vertex v̄
associated with a graph.
In our work, we adopt the graph Laplacian regularizer,
which is defined based on an undirected weighted graph
Ḡrg . The definition of the graph’s edges is critical in order
to capture the underlying structure of the data and explain
the similarities between each pair samples. In this setting,
a kernel K : G × G → R is called a graph kernel, which
can capture the inherent similarity in the graph structure
and is reasonably efficient to evaluate. Similar to kernels on
vector spaces, graph kernels can be calculated implicitly by
computing K. The similarity between two original graphs
Ĝi and Ĝj is calculated as:
n n 
i j p q
ij p=1 q=1 wp wq k vi , vj
Ārg = K(Ĝi , Ĝj ) = n n j
, (14)
i
p=1 wp q=1 wq
p q
where vi and vj denote the p-th and q-th node features
(Pearson’s correlation vector) of the i-th and j -th original
graphs, wpi = n k(v1
p u and k(·, ·) denotes a RBF kernel.
,v )
u=1 i i
By minimizing the term Lps in (15), we expect that if two
samples Gi and Gj have similar graph structures, hi and hj
are mapped close to each other through:

Lps = T r H T L̄rg H (15)
A unified framework of graph structure learning, graph generation and classification for brain network analysis 6985

where L̄rg is the graph Laplacian matrix and L̄rg = D̄rg −
Ārg , H is the learned graph embeddings of the domains of
Dr and Dg .
Finally, the overall loss function for our graph classifica-
tion can be formulated as:
LGCN = Lce + λ21 Lcv + λ22 Lcs + λ23 Lps
where Lce indicates the cross entropy loss, λ21 , λ22 and λ23
are regularization parameters.
3 Experiments
The ABIDE database (Autism Brain Imaging Data
Exchange) which investigates the neural basis of autism
[17] aggregates data from 17 different acquisition sites
and openly shares rs-fMRI and phenotypic data of 1112
subjects. In this work, the images analyzed were those
preprocessed with the Connectome Computation System
(CCS).
based methods (Eigenpooling GCN [18], BrainGNN [7]
and Population GCN [6]) and the autoencoder based
method (ASDdiagNet [19]). Moreover, the network based
feature is a linear classification using a ridge classifier.
We also compare BrainGC-Net with four state-of-the-
art methods, including 4 topology-based approaches (i.e.,
(16) Clustering Coefficient (CC), t-BNE [20], NAG-FS [21]
and MC-NFE [10]), and 2 subgraph-based approaches (i.e.,
Graph Boosting, and Ordinal Pattern [22]). To make a fair
comparison, their originally released codes and published
settings are used in the experiment. Compared with all
baselines, the proposed BrainGC-Net achieves the best
performance in terms of all metrics. It demonstrates that our
BrainGC-Net is effective for graph classification with brain
disorder diagnosis. We observe consistent improvements
from the proposed graph pooling. It can actually boost the
performance of graph generation and graph classification.
The fact implies the necessity to develop a consistent
coarsened graph structure to tackle graph related problems.
3.2 Discussion on the EG-GraphGAN

3.1 Comparison with the state-of-the-art methods
To demonstrate the overall performance of brain network
classification, we compare the proposed method with other
state-of-the-art methods. The performance in terms of
accuracy is shown in Table 2. To more comprehensively
evaluate our model, we compare BrainGC-Net with two
types of state-of-the-art neural network based methods:
the covering CNN based method (BrainNetCNN), GCN
To demonstrate the effectiveness of our EG-GAN, we
compare EG-GAN with its three variants and three state-
of-the-art graph generation methods on the original graphs
and coarsened graphs, respectively. VAEGAN [24] uses
the analytical KL loss to minimize the distance between
the prior and the posterior of the latents; AAE [25] is
a probabilistic autoencoder that uses GAN to perform
variational inference by matching the aggregated posterior
of the hidden code vector of the autoencoder with an

Table 2 Performance comparison of various methods

Methods ACC AUC Specificity Sensitivity

Network based feature 0.559±0.001∗ 0.602±0.002∗ 0.578±0.001∗ 0.537±0.001∗

CC [22] 0.607±0.002∗ 0.624±0.003∗ 0.587±0.001∗ 0.559±0.004∗
t-BNE [20] 0.655±0.001∗ 0.708±0.001∗ 0.621±0.002∗ 0.608±0.002∗
Graph Boosting 0.646±0.002∗ 0.725±0.003∗ 0.639±0.003∗ 0.617±0.003∗
NAG-FS [21] 0.618±0.006∗ 0.599±0.006∗ 0.607±0.005∗ 0.588±0.005∗
MC-NFE [10] 0.684±0.003∗ 0.693±0.005∗ 0.636±0.003∗ 0.701±0.006∗
Ordinal Pattern [22] 0.641±0.002∗ 0.729±0.002∗ 0.628±0.001∗ 0.611±0.002∗
ASDdiagNet [19] 0.665±0.002∗ 0.721±0.003∗ 0.675±0.002∗ 0.653±0.003∗
BrainNetCNN [23] 0.651±0.003∗ 0.728±0.002∗ 0.656±0.003∗ 0.624±0.005∗
Eigenpooling GCN [18] 0.586±0.001∗ 0.655±0.003∗ 0.596±0.001∗ 0.574±0.001∗
BrainGNN [7] 0.671±0.003 0.743±0.003 0.681±0.003 0.659±0.003
MVS-GCN [9] 0.699±0.005 0.691±0.003 0.631±0.005 0.702±0.007
Population GCN [6] 0.635±0.002∗ 0.675±0.002∗ 0.651±0.002∗ 0.617±0.002∗
BrainGC-Net 0.728 ± 0.008 0.787 ± 0.003 0.708 ± 0.003 0.749 ± 0.003
BrainGC-Net w/o pooling 0.649±0.018 0.678±0.013∗ 0.622±0.017∗ 0.674±0.009∗

Each experiment is run 10 times and the average classification performance is reported. The best results are in bold. The values marked by ∗

indicate that our method achieves significantly different results compared with the competing methods

13
6986 P. Cao et al.

Table 3 Performance evaluation of compared algorithms regarding

graph statistical properties

Models Degree Edges Centrality

Real LCC CPL REDE CC

8.00 1.59 0.75 0.028
ARGA-VAE 1.61 0.31 0.10 0.046
α-GAN 1.74 0.32 0.12 0.051
VAEGAN 1.75 0.31 0.09 0.026
EG-GrapGAN 1.76 0.28 0.06 0.024

The real row includes the values of real graphs, while the rest are
the absolute values of differences between graphs generated by each
algorithm and the real graphs. LCC: Size of the largest connected
component; CPL: characteristic path length: REDE: Relative edge
distribution entropy; CC: clustering coefficient

arbitrary prior distribution; ARGA-VAE [26] encodes
the topological structure and node content in a graph
to a compact representation, on which a decoder is
trained to reconstruct the graph structure. Furthermore,
the latent representation is enforced to match a prior
distribution via an adversarial training scheme. We measure
the generated graphs from different GAN models in
Table 3. Compared to the state-of-the-art methods on the
original graphs and coarsened graphs, our method achieves
better stability, balance, and competitive classification
performance (Fig. 3). We show that the proposed EG-
GAN could enrich data to make it more beneficial for
the graph classification. The results indicate that the local
measure and global mapping regularization enables our
GAN model to achieve improved graph generation quality.
The results suggest that the graph GANs are not able to
learn a graph representation without additional constraints.
It can be observed that the performances of all the GAN
models are poor on the original graphs, due to the large
number of noisy and irrelevant connections, which limit the
performance of the graph generation. The results in Table 3
show that our proposed EG-GAN model leads to producing
CLassification Metrics Value
Fig. 4 t-SNE results of generated samples by comparable GAN
models
graphs preserving local topology properties that are similar
to the original graphs. A high-quality generative model
should be able to synthesize graphs that are consistent with
the original graph distribution.
3.3 The qualitative results of the comparable GANs
To intuitively understand the learning stability of EG-GAN,
we further illustrate the data distribution of the original
and generated two class samples in two dimensional space.
We also present qualitative comparisons with the αGAN,
ARGA-VAE and VAEGAN in Fig. 4. Figure 4 shows the
scatter plot results of t-SNE, with each point representing
a data sample. We apply t-SNE analyses to both the
original and synthetic datasets. This visualizes how closely
the distribution of generated samples resembles that of
the original in 2-dimensional space, giving a qualitative
assessment. From Fig. 4, it can be observed that our
GAN is able to synthesize graphs that are consistent

80
70
60
[%]

50
ACC AUC ACC AUC
Original Graph Coarsened Graph
CONDGEN VAEGAN
AAE ARGA-VA
EG-GAN w/o tp EG-GAN w/o consistency
EG-GAN
Fig. 5 The difference in the data distribution of the original and
Fig. 3 The comparison study of graph generation models on the generated graphs with the distribution consistency loss (a) or without
original graph and the coarsened graph for the graph classification it (b) in our GAN

13
A unified framework of graph structure learning, graph generation and classification for brain network analysis 6987

CLassification Metrics Value [%] 85
83
81
79
77
75
73
71
69
67
65
ACC
f-GCN on Dr
DC-GCN w/o any regularization DC-GCN（only cv）
DC-GCN（only cs）
DC-GCN
Fig. 6 Ablation study of DC-GCN model for the graph classification
with the original graph distribution with the help of our
homeomorphic interpolation mapping.
The advantage of adopting the distribution consistency
loss with homeomorphic mapping is that it enables us to
achieve smooth interpolations of generated fake samples.
Figure 5 illustrates the embedded representation of the
generated and true data with and without distribution
consistency mechanism. From Fig. 5, it can be observed that
the distribution consistency loss is able to synthesize graphs
that are consistent with the original graph distribution
with the help of our homeomorphic interpolation mapping,
suggesting the strong ability of our method to improve the
modeling distribution of complex data.
3.4 Discussion on the DC-GCN
In addition to the above-mentioned results, we are also
interested in the effectiveness of each component in the
proposed DC-GCN model. Accordingly, we conduct an
ablation study on the multiple regularization separately
to investigate how these components would affect the
segmentation performance. From the results in Fig. 6, we
can find that compared with all baselines, the proposed
DC-GCN generally achieves the best performance with
respect to all the metrics. It also demonstrates that exploiting
the complementary consistency is important for the graph
data augmentation. It can be seen that DC-GCN w/o any
regularization performs worst. It actually further confirms
our finding that there exists inconsistency between the real
graphs and the generated graphs. The result demonstrates
that our proposed DC-GCN module is able to alleviate
the distribution gap between the two domains. The results
suggest that the distribution gap should be considered to
improve the classification performance when augmenting
data. Most previous work on data augmentation ignores the
AUC issue of distribution gaps.
s-GCN on Drg
3.5 The effectiveness of graph pooling
DC-GCN（only ps）
In this paper, we attempt to improve explainability by
identifying the critical subnetwork through the indicative
edges learned. For instance, we visually explore the
coarsened graphs generated by the graph pooling module
and compare them with the original graphs. Two groups
of samples, including ASD and normal controls, were
selected and visualized. The results are presented in Fig. 5.
By observing them individually, the original graphs of
each subject are highly irregular in the view. However,
the inconsistency of each object is alleviated with the
process of graph pooling. Therefore, our results seem
to yield solid evidence that imposing a graph pooling
method during training the network is a viable method for
improving GCN performances for diagnosis. We can also
find that most of the edges in the brain network are non-
indicative of the final classification task. Through graph
pooling, the indicative edges are highlighted. Furthermore,
by comparing the results in Fig. 4(a) and (b), it is apparent
to see that the difference between the original graph of ASD
individuals and normal controls is difficult to differentiate.
In contrast, the difference between ASD individuals and
normal controls with respect to the coarsened graphs is
strengthened by the graph pooling.
3.6 The influence of the hyperparameters
of BrainGC-Net
In addition, we are also interested in the influence of the
model hyperparameters. To evaluate the impact of the loss
weights on BrainGC-Net, we conducted six experiments

72.0

69.5 69.5

71.5
Value

Value

Value

69.0 ACC(%) ACC(%) ACC(%)

69.0
AUC(%) AUC(%) AUC(%)
71.0

68.5
68.5 70.5

0.00 0.25 0.50 0.75 1.00 0.00 0.25 0.50 0.75 1.00 0.2 0.4 0.6 0.8 1.0
Weight Value Weight Value Weight Value

Fig. 7 Classification performance for different weight values (λ11 : the weight value of topology loss, λ12 : the weight value of distribution
consistency loss and λ13 : the weight value of reconstruction loss) of EG-GAN losses

13
6988 P. Cao et al.

78

76
76 76

74

Value
Value
Value
ACC(%) ACC(%) 74 ACC(%)
74 AUC(%)
AUC(%) AUC(%)
72
72

72
70
70
0.00 0.25 0.50 0.75 1.00 0.00 0.25 0.50 0.75 1.00 0.00 0.25 0.50 0.75 1.00
Weight Value Weight Value Weight Value

Fig. 8 Classification performance for different weight values (λ21 : the weight value of cross-view consistency loss, λ22 : the weight value of class
semantic consistency loss and λ23 : the weight value of pairwise similarity consistency loss) of classification losses

with varied values for the weights, including λ11 , λ12 , significant impact on the classification performance, which
λ13 , λ21 , λ22 and λ23 , which are illustrated in Figs. 7 and demonstrates that the loss weights are important factors for
8. For each experiment, we fix the weights of the other the model.
losses and individually adjust the impact of the current
hyperparameter on classification performance. Notability, 3.7 Interpretability
Fig. 7 is the results of varied values: λ11 , λ12 and λ13 for EG-
GAN. Meanwhile, Fig. 8 is the results of λ21 , λ22 and λ23 for To better understand the cortical circuitry underlying the
the classification. We can find that the weight values have a connectivity between large-scale neural networks, we evaluate

Fig. 9 The top 3 subnetworks

identified by BrainGC-Net

DMN

SN

CEN

13
A unified framework of graph structure learning, graph generation and classification for brain network analysis
our model to investigate the potential intrinsic subnetworks
from a data driven perspective. In this experiment, we
also empirically investigate the effectiveness of subnetwork
and inter-subnetwork connection identification. The top
3 subnetworks selected by our BrainGC-Net are shown
in Fig. 9. We found that the subnetworks identified by
BrainGC-Net yielded promising patterns that are expected
from prior knowledge on neuroimaging and cognition.
These included the CEN, DMN and SN. Moreover, the
prior knowledge regularization is essential for identifying
the biomarkers and understanding the characteristic patterns
of the disease.
4 Conclusion
Functional connectivity networks constructed from the rs-
fMRI hold great promise for distinguishing the disorder
patients from NCs. We developed a unified three-stage
learning framework for brain network classification, involv-
ing graph structure learning, graph generation and graph
classification. By combining the strengths of these net-
works, the proposed approach significantly improves the
state-of-the-art results in ASD classification on the bench-
mark dataset. Here we focused on a three-stage learning
framework; however, the end-to-end collaborative learn-
ing is more interesting and challenging. Moreover, we aim
to investigate whether our framework is transferable and
generalizable across disorder diseases with insufficient data.
Acknowledgements This research was supported by the National
Natural Science Foundation of China (No.62076059) and the Science
Project of Liaoning province (2021-MS-105).
Data Availability The datasets generated during and/or analysed
during the current study are available in the ABIDE repository, https://
fcon 1000.projects.nitrc.org/indi/abide/.
Declarations
Conflict of Interests The authors declare that they have no conflicts of
interest.
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Publisher’s note Springer Nature remains neutral with regard to
jurisdictional claims in published maps and institutional affiliations.
Peng Cao is an associate
professor of Key Laboratory
of Intelligent Computing in
Medical Image, Ministry of
Education. He earned his
Ph.D. degree in computer
application in 2014 at North-
eastern University, China.
His research interests include
brain network analysis,
machine learning for medical
data. His research papers have
been published in or accepted
by journals or conference
including Pattern Recogni-
tion, Computer Methods and
Programs in Biomedicine, Medical Image Computing and Computer
Assisted Intervention (MICCAI) and Thirty-Sixth AAAI Conference
on Artificial Intelligence (AAAI-22).
Guangqi Wen is currently a
Ph.D. candidate in Key Labo-
ratory of Medical Image Com-
puting of Ministry of Edu-
cation, Northeastern Univer-
sity, China. The objectives
of his research are (i) to
assist in the diagnosis of
brain diseases by leveraging
machine learning methods and
to explore information on the
critical biomarkers of brain
disease occurrence and (ii)
graph embedding learning in
the brain network.
13
P. Cao et al.
Wenju Yang is currently a
Ph.D. candidate in Key Labo-
ratory of Medical Image Com-
puting of Ministry of Edu-
cation, Northeastern Univer-
sity, China. The objectives of
his research are brain disease
diagnosis, time series analysis
and speech emotion recogni-
tion.
Xiaoli Liu is a senior
researcher of DAMO
Academy, Alibaba Group.
She earned her Ph.D. degree
at Northeastern University,
China. Her research interests
include machine learning,
computer vision.
Jinzhu Yang received the
Ph.D. degree in pattern recog-
nition and intelligent system
from the Northeastern Uni-
versity, Shenyang, China, in
2007. He is a professor and
director of Key Laboratory
of Intelligent Computing in
Medical Image, Ministry
of Education. His research
interest focuses on the image
processing and analysis, arti-
ficial intelligence and pattern
recognition and data analysis.
His research papers have been
published in or accepted by
journals including Magnetic Resonance Imaging, BMC Bioinformat-
ics, Proceedings of the National Academy of Sciences of the United
States of America(PNAS).
A unified framework of graph structure learning, graph generation and classification for brain network analysis 6991

Osmar Zaiane is a professor

in Computing Science at the
University of Alberta, Canada,
and Scientific Director of the
Alberta Innovates Centre for
Machine Learning. He is asso-
ciate Editor of many Interna-
tional Journals on data mining
and data analytics and served
as program chair and general
chair for scores of international
conferences in the field of
knowledge discovery and data
mining. His current research
interests include data mining,
healthcare informatics.

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