730 IEEE TRANSACTIONS ON COGNITIVE AND DEVELOPMENTAL SYSTEMS, VOL. 14, NO.

2, JUNE 2022

Uncertainty Modeling for Multicenter Autism

Spectrum Disorder Classification Using
Takagi–Sugeno–Kang Fuzzy Systems
Zhongyi Hu , Senior Member, IEEE, Jun Wang , Chunxiang Zhang, Zhenzhen Luo, Xiaoqing Luo ,
Lei Xiao , and Jun Shi

Abstract—The resting-state functional magnetic resonance I. I NTRODUCTION

imaging (rs-fMRI) is a pivotal tool that can reveal brain
dysfunction in the computer-aided diagnosis of the autism spec-
trum disorder (ASD). However, the instability of data collection
devices, complexity of pathogenesis, and ambiguity in the causes
of the disease always introduce considerable uncertainty in
identifying ASD using rs-fMRI. Due to the strong ability of
Takagi–Sugeno–Kang fuzzy inference systems (TSK FISs) in han-
dling the uncertainty of knowledge and expression, we build an
ASD classification model based on TSK FISs and further propose
a novel multicenter ASD classification method FCG-MTGS-
TSK. Specifically, the correlation information of multiple imaging
centers is considered by introducing multitask group sparse
learning, and the features across multiple imaging centers are
thus jointly selected. An augmented lagrange multiplier (ALM)
method is further developed to find the optimal solution of the
model. Compared with the other existing methods, the proposed
method has the advantages of strong interpretability and high
classification accuracy. The experimental results also identify the
most discriminative functional connectivity in multicenter ASD
classification.
Index Terms—Autism spectrum disorder (ASD), joint group
sparsity, multicenter learning, resting-state functional magnetic
resonance imaging (rs-fMRI), TSK fuzzy system.
Manuscript received January 18, 2021; revised April 3, 2021; accepted
April 8, 2021. Date of publication April 15, 2021; date of current version
June 10, 2022. This work was supported in part by the Major Project of
Zhejiang Provincial Natural Science Foundation under Grant LD21F020001;
in part by the Science and Technology Commission of Shanghai Municipality
under Grant 20ZR1419900; in part by the National Natural Science
Foundation of China under Grant U1809209 and Grant 61772237; in
part by the Major Project of Wenzhou Natural Science Foundation under
Grant ZY2019020; in part by the Key Project of Zhejiang Provincial Natural
Science Foundation under Grant LZ20F020022; and in part by the Six Talent
Climax Foundation of Jiangsu under Grant XYDXX-030. (Corresponding
author: Jun Wang.)
Zhongyi Hu, Zhenzhen Luo, and Lei Xiao are with the Intelligent
Information Systems Institute, Wenzhou University, Wenzhou 325035, China.
Jun Wang and Jun Shi are with the Key Laboratory of Specialty Fiber
Optics and Optical Access Networks, Shanghai Institute for Advanced
Communication and Data Science, School of Communication and Information
Engineering, Shanghai University, Shanghai 200444, China, and also with
the Jiangsu Key Laboratory of Big Data Security and Intelligent Processing,
Nanjing University of Posts and Telecommunications, Nanjing 210023, China
(e-mail: wangjun_shu@shu.edu.cn).
Chunxiang Zhang and Xiaoqing Luo are with the School of Artificial
Intelligence and Computer Science, Jiangnan University, Wuxi 214122, China.
Color versions of one or more figures in this article are available at
https://doi.org/10.1109/TCDS.2021.3073368.
Digital Object Identifier 10.1109/TCDS.2021.3073368
UTISM spectrum disorder (ASD) is a lifelong neurode-
A velopmental disorder accompanied by many complica-
tions. Its main symptoms include social handicap, speech
communication disorders, and stereotypes of actions [1]–[3].
Since Dr. Leo Kanner published the first paper [4] on autism
in children during the 1940s, ASD has become one of the
most serious neurological development disorders in the world.
According to statistics, the prevalence of ASD in the United
States and China is 2.47% [5] and 1.19% [6], respectively,
and this proportion is increasing year by year. Furthermore,
two-thirds of ASD patients cannot live independently and
need attentive care during their entire lifetime. In other words,
autism is a public health problem that places a heavy economic
burden on families and society.
Previous, studies have shown that both behavioral and
cognitive deficits of ASD are closely related to the poten-
tial dysfunction of brain regions [7]–[12]. Resting-state
functional magnetic resonance imaging (rs-fMRI) is a piv-
otal tool that can reveal brain dysfunction based on the
blood-oxygen-level-dependent (BOLD) signals when the sub-
ject is placed in the resting state [13]–[15]. Most of the
rs-fMRI-based ASD classification methods are developed
using functional connectivity (FC) as features, in which
the Pearson correlation coefficient is calculated as FC by
using the average BOLD signals of two brain regions in
rs-fMRI [16], [17].
Thus, far, it has been reported that rs-fMRI is effec-
tive in ASD classification. Heinsfeld et al. [18] identified
ASD patients from an rs-fMRI data set based solely on the
brain activation patterns. Sherkatghanad et al. [19] focused
on the automated detection of ASD using a convolutional
neural network, with the most common rs-fMRI data from
the autism brain imaging data exchange (ABIDE) data set.
However, most of these classification methods are limited
to single imaging center, and it is common to acquire rs-
fMRI from multiple imaging centers in practice [20]–[23].
Besides, the multicenter data are collected by different scan-
ners and parameters, and the model learned from one imag-
ing center can hardly be directly applied to another. To
this end, it is necessary to develop a novel multicenter
ASD classification method by jointly using the multicenter
imaging data.

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 HU et al.: UNCERTAINTY MODELING FOR MULTICENTER ASD CLASSIFICATION
Fig. 1. Pipeline of ASD diagnosis using FCG-MTGS-TSK.
Another challenging problem in ASD classification using
rs-fMRI is data uncertainty, which is always caused by the
instability of data collection devices, complexity of patho-
genesis, and ambiguity in identifying medical causes. Due
to the strong ability of Takagi–Sugeno–Kang fuzzy inference
systems (TSK FISs) in handling the uncertainty of knowledge
and expression, it is effective to build an ASD classification
model based on TSK FISs [24]–[26].
Specifically, the data uncertainty in the rs-fMRI is handled
by the fuzzy sets in the IF part of fuzzy rules. Besides, the
final outputs of TSK-FIS are combined with the firing strength
that indicates how much each rule contributes to the predict
results.
In the literature, TSK-FISs have been fully investigated.
For example, Luo et al. [27] proposed a SparseFIS method,
which can considerably reduce the number of fuzzy rules
by constraining the sparsity of the consequent parameter
vector in the TSK fuzzy system. Juang and Chen [28]
proposed a TSK fuzzy system based on support vector
machine (SVM) in a principal component space for real-
time object detection. Khater et al. [29] proposed a novel
stable and fast nonlinear learning method called ATSKFC-
RACL based on an adaptive TSK fuzzy controller. Although
these methods have achieved satisfactory results in spe-
cific problems, they are not applicable to ASD classifi-
cation because of the high dimensionality of the features
extracted from neuroimaging data. Besides, they do not con-
sider the correlation between multiple imaging centers and
thus, cannot handle the multitask issues in multicenter ASD
classification.
In this study, we considered the multicenter ASD clas-
sification as a multitask learning problem and developed
a novel feature-correlation-guided multitask group sparse TSK
fuzzy system, in which the effective correlation information
among features was incorporated to provide more prior
knowledge for classification [30]. To combine the multicenter
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731
knowledge in the ASD classification, we imposed a novel
group sparse regularization on the consequent parameters of
all the fuzzy rules across multiple tasks. This new regu-
larization term encouraged the correlated tasks to share the
common knowledge in consequent parameters of fuzzy rules
across multiple tasks. To validate our method, extensive exper-
iments were conducted on the ABIDE database, and the
results indicated the promising performance of the proposed
method.
The pipeline of the proposed method includes two stages,
i.e., feature extraction and FCG-MTGS-TSK classification. In
the first stage of feature extraction, effective features were
extracted from the multicenter rs-fMRI data, and they were
then fed to the FCG-MTGS-TSK classifier. In the second stage
of classification, these features were classified by the FCG-
MTGS-TSK classifier, and the multicenter diagnosis results
were finally obtained. Fig. 1 shows the entire pipeline of the
method.
The remainder of this article is organized as follows.
In Section II, we mainly introduce the source of the data
sets, the data preprocessing, and the feature extraction of
the imaging data. In Section III, we review the TSK fuzzy
system and propose feature-correlation-guided multitask group
sparse learning method for multicenter ASD classification. In
Section IV, we use a set of simulated data sets and three groups
of medical data sets from different clustering centers to com-
pare the classification performance of the proposed algorithm
and analyze the corresponding results. Finally, we draw the
conclusions in Section V.
II. M ATERIALS
The data set used in this work was obtained from
ABIDE [31]. We used the data of UM_2, OLIN, and
LEUVEN_2 imaging centers, and the relevant information is
shown in Table I.
 732 IEEE TRANSACTIONS ON COGNITIVE AND DEVELOPMENTAL SYSTEMS, VOL. 14, NO. 2, JUNE 2022

TABLE I
I NFORMATION A BOUT THE DATA O BTAINED F ROM T HREE I MAGING the largest correlation with labels were selected and the
C ENTERS AND U SED IN T HIS S TUDY training data X(trn) ∈ RN×P are, therefore, obtained.
During the parameter optimization on the validation set
and the performance evaluation on the testing set, we also
completed the feature extraction of the data according to the
above steps. However, when it came to step (3), we directly
selected the corresponding features of column index pt instead
of calculating Pearson’s correlation. Finally, we could obtain
the validation data set X(val) and the testing data set X(tst)
successfully.

A. Data Preprocessing III. M ETHOD

The rs-fMRI data of each subject were preprocessed using A. Overview of TSK Fuzzy Systems
the data processing assistant for resting-state fMRI (DPARSF)
The TSK fuzzy system defines the rules in the form of “IF–
tool, and the detailed steps are as follows.
THEN.” Suppose that x = (x1 , x2 , . . . , xP )T ∈ RP is an input
1) Removal of the data of the first ten time points of the
feature vector, the rth fuzzy rule of the TSK fuzzy system can
functional magnetic resonance image sequence.
be expressed as follows:
2) Time-level and head motion correction.
3) Normalizing data into the Montreal Neurological IF x1 is Ar1 ∧ x2 is Ar2 ∧ · · · ∧ xP is ArP
Institute 152 (MNI152) standard space after the THEN y = wr0 + wr1 x1 + wr2 x2 + · · · + wrP xP (1)
T1-weighted image segmentation.
4) Dividing the brain into 116 regions by using the anatom- where Arp is the fuzzy subset for the rth fuzzy rule correspond-
ical automatic labeling (AAL) template, each of which ing to the pth element of the input variable x, r denotes the
was resampled according to 3 mm×3 mm×3 mm index of the fuzzy rule, P denotes the number of the variables,
voxels. and ∧ denotes the fuzzy conjunction operator. In this study, we
5) Spatial smoothing using half-height and full-width adopted the Gaussian membership function to express Arp (xp )
  2 
Gaussian kernels.   xp − crp
6) Eliminating noise with the application of a band-pass μArp xp = exp − (2)
2σrp
filter (0.01–0.1 Hz).
7) Removal of the linear drift and interference variables. where crp and σrp can be obtained by clustering or other parti-
8) Calculation of the average time series of each brain tioning methods. In general, we used the fuzzy c-means (FCM)
region. clustering algorithm to partition the data set, and both crp and
Our experiments were conducted based on ten folded cross- σrp could be calculated using
validation, which is a common validation scheme adopted in

N N
many studies [32]–[38]. To derive the data set for training, crp = urn xnp / urn (3)
validation, and testing, the subjects in each imaging center n=1 n=1
were first divided into ten groups: one for testing, one for

N
 2 
N
validation, and others for training. The training, validation, σrp = h · urn xnp −crp / urn (4)
and testing sets in each imaging center were then combined n=1 n=1
to generate the training, validation, and testing sets for the
where h is a parameter adjusted by users, xn =
entire multicenter data set.
(xn1 , xn2 , . . . , xnP )T ∈ RP is the nth feature vector in FCM,
and urn denotes the membership of xn belonging to the rth
B. Feature Extraction cluster.
Assume that we have determined the premise of the fuzzy
Feature extraction on the training data was performed as
rule. Given the input x, the output of the TSK fuzzy system
follows.
can be computed as the following procedure:
1) For each subject, the Pearson correlation coefficients
between the brain regions were calculated and the FC 
R

matrix Mi , i = 1, 2, . . . , N, is obtained. Each element ŷ = φr (x)lr (x) (5)

in Mi denotes the FC between two brain regions. r=1

2) Due to the symmetry of Mi , only the upper triangle is R

used, and the elements in the upper triangle of Mi were φr (x) = μr (x)/ μk (x) (6)
k=1
rearranged to a vector ai , i = 1, 2, . . . , N.
3) Let A(trn) = [a1 , a2 , . . . , aN ]T , in which each row rep- 
P
 
μr (x) = μAip xp (7)
resents a sample and each column represented a feature.
In order to reduce the dimension of A(trn) , the corre-
p=1

lations between features and labels were first evaluated where wr = (wr0 , wr1 , . . . , wrP )T ∈ RP+1 and lr (x) =
with Pearson’s correlation. Then, P features that have wr0 + wr1 x1 + wr2 x2 + · · · + wrP xP = [1, xT ]wr represents

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 HU et al.: UNCERTAINTY MODELING FOR MULTICENTER ASD CLASSIFICATION 733

⎡ ⎤⎡ ⎤
the corresponding consequent part of the rth fuzzy rule, φr (x) 
ωr(00) 
ωr(01) . . . 
ωr(0P) mr0
⎢ 
ωr(11) . . . ⎥⎢ ⎥
is the firing strength indicating how much the rth fuzzy rule ⎢ ωr(10) 
ωr(1P) ⎥⎢ mr1 ⎥
=⎢ . .. . . .. ⎥⎢ .. ⎥
contributes to the prediction results. Note that (6) and (7) are ⎣ .. . . . ⎦⎣ . ⎦
effective when P is not very large. When the input data are ωr(P0) 
 ωr(P1) . . .  ωr(PP) mrP
high dimensional, we can select several features (attributes) ⎡ ⎤

ωr(00) mr0 + 
ωr(01) mr1 + · · · + 
ωr(0P) mrP
with the largest variance and then compute the firing strength ⎢ ⎥
based on these features. ⎢ ωr(10) mr0 + 
ωr(11) mr1 + · · · + 
ωr(1P) mrP ⎥
T =⎢ .. ⎥. (12)
Let D = {(xi T , yi ) ∈ RP+1 |xi = (xi1 , xi2 , . . . , xiP )T , yi ∈ ⎣ . ⎦
{0, 1}, i = 1, 2, . . . , N} denotes the original input-and-output ωr(P0) mr0 + 
 ωP1
r m + ··· +
r1 ωPP
r m
rP
data set, where y = (y1 , y2 , . . . , yN )T ∈ RN indicates the true
label of these samples. With the data set D proposed, the We defined vrp = ( ωr(0p) mrp , 
ωr(1p) mrp , . . . , 
ωr(Pp) mrp )T as
output of the TSK fuzzy system can be computed as follows: a latent vector that recorded the pth column in (13). Obviously,
each column vrp depended not only on the margin correlation

R
coefficient mrp but also on the correlation between all of the

y= φr wr = w (8)
(P + 1) features  ωr(ij) , i, j = 0, 1, . . . , P. In other words, if
r=1
mrp = 0, vrp would be zero irrespective of whether the pth
where  = (φ1 , φ2 , . . . , φR ) ∈ RN×R(P+1) feature was related to the other features or not; if mrp = 0,
T
w = (w1 T , w2 T , . . . , wR T ) ∈ RR(P+1) , and vrp always relied on the correlation between the pth feature
φr = diag(φr (x1 ), φr (x2 ), . . . , φr (xN ))Xe , and and the other features.
In the multicenter ASD classification, we considered learn-
Xe = (1, x1 , x2 , . . . , xN )T . ing in an independent imaging center as a separate clas-
sification task. Thus, the above derivation could be easily
B. Feature-Correlation-Guided Multitask Group Sparse extended to the multitask learning settings. We assumed that
Learning for Multicenter ASD Classification the subdictionary φs1 , φs2 , . . . , φsR of all the R rules in the sth
To show how to use the correlation information between (s = 1, 2, . . . , S) imaging center predicted the output variable
features in our model, we first considered single-task learning ŷrm by using the linear model as in (9), and the consequent
by using the framework of the TSK fuzzy system and then parameters in wsr were decomposed and constructed in the
generalized to the multitask case. form of (10)–(12). Considering the intertask correlation, we
Considering the single-task settings, we constructed the rearranged all of the consequent parameters across multiple
following linear model [39] to predict the output variable yr : tasks as a (P + 1) × (P + 1) × (R·S) tensor; Fig. 2 shows the
details. We, therefore, propose the following learning criterion

yr = φr wr + r (9)
for the feature-correlation-guided multitask group sparse TSK
where  yr ∈ RN is the output for the rth fuzzy rule and fuzzy system for multicenter ASD classification:
r = (1r , 2r , . . . , Nr )T ∈ RN is the error vector satisfying 
S 
2
 
 s  s s
R
E(nr ) = 0 and Var(nr ) = δr 2 for each 1 ≤ n ≤ N.
min  y − φ r r
w
Suppose that the rth fuzzy subdirectory φr is indepen- wtr  
s=1 r=1 F
dent of its error vector r . Denote mr = E(φr T yr /N) = P 
   2
(mr0 , mr1 , . . . , mrP )T ∈ RP+1 as the marginal correlation vec-  1 1 
+λ  v1p , v2p , . . . , v1Rp , . . . , vS1p , vS2p , . . . , vSRp 
tor between all of the (P + 1) features and output  yr . Using F
p=0
(9), we obtained the following:
    
P
mr = E φr T yr /N = E φr T φr wr /N s.t. wsr = vsrp , s = 1, 2, . . . , S (13)
 
+ E φr T r /N =  r wr (10) p=0

where ys is the label vector in the sth task, sr and wsr repre-
where  r ∈ R(P+1)×(P+1) is the covariance matrix of φr . Then,
sent the subdictionaries and the consequent parameters of the
we obtained the following:
rth rule in the sth task, respectively, and λ > 0 is a regulariza-
wr =  r −1 mr . (11) tion coefficient. Moreover, as highlighted in Fig. 2, the matrix
[(v11p , v12p , . . . , v1Rp ), . . . , (vS1p , vS2p , . . . , vSRp )] ∈ R(P+1)×(R·S)
For the ease of description, we used r to denote  r −1 . To
recorded all of the pth latent vectors across multiple
make the algorithm more robust to noise, we used the graph- 2
r ∈ R(P+1)×(P+1) that tasks. When (v11p , v12p , . . . , v1Rp ), . . . , (vS1p , vS2p , . . . , vSRp ) =
ical Lasso method [40] to construct  F
0, the pth joint group of S tasks was excluded. When
recorded the significant partial correlations in r . Therefore, 2
we obtained wr ≈  r mr , which could be further expanded as (v11p , v12p , . . . , v1Rp ), . . . , (vS1p , vS2p , . . . , vSRp ) = 0, the ele-
F
follows: ments in the group were not all 0s, vsrp was jointly determined
⎡ ⎤ by msrp and the pth feature and its correlated features.
wr0 All in all, minimizing the regularization term
⎢ wr1 ⎥ P
⎢ ⎥ 2
p=0 (v1p , v2p , . . . , vRp ), . . . , (v1p , v2p , . . . , vRp )F jointly
1 1 1 S S S
wr ≈ ⎢ . ⎥
⎣ .. ⎦ selected the consequent parameters in different fuzzy rules
wrP across different imaging centers.

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 734 IEEE TRANSACTIONS ON COGNITIVE AND DEVELOPMENTAL SYSTEMS, VOL. 14, NO. 2, JUNE 2022

 −1

R  T
w = 2
2
φ2r φ2r 2 + ρ2
r=1
⎛ ⎞
R  T 
R 
P
× ⎝2 φ2r φ2r y2 + ρ φ2r v2rp ⎠ (18)
r=1 r=1 p=0
...
 −1

R  T
w = 2
S
φSr φSr S + ρS
r=1
⎛ ⎞
R  T 
R 
P
× ⎝2 φSr φSr yS + ρ φSr vSrp ⎠ (19)
r=1 r=1 p=0

where s = (φs1 , φs2 , . . . , φsR ), s = 1, . . . , S.

Similar to the above steps, we executed (20)–(22) in the kth
iteration and obtained the following output of v1rp , v2rp , . . . , vSrp :
Fig. 2. Consequent parameters of fuzzy rules in FCG-MTGS-TSK.
ρ 2 (P+1)w1r
ρw1r − 2λ+ρ(P+1)
v1rp = (20)
2λ
C. Optimization ρ 2 (P+1)w2r
ρw2r − 2λ+ρ(P+1)
We used an alternative optimization method to solve the v2rp = (21)
problem in (13). By taking advantage of the augmented 2λ
Lagrange multiplier (ALM) method [41], we transformed ..
.
the objective of (13) into the following, where the penalty ρ 2 (P+1)wSr
ρwSr −
coefficient ρ> 0 is a very large number: vSrp =
2λ+ρ(P+1)
. (22)
S 
 2 2λ
   
 s  s s
R
Lρ w , vrp =
s s
y − φr wr  Eventually, the final w1 , w2 , . . . , wS was the approximate
  solution of problem (14). Considering that this was a binary
s=1 r=1 2
   classification problem, for the testing data set X(tst) , we let

P
+ λ  v11p , v12p , · · · , v1Rp , . . . y(tst) = sigmoid((tst) w) denote the prediction results, where
p=0 the sigmoid function was defined with a threshold of 0.5 as
 2 follows:

vS1p , vS2p , . . . , vSRp  1
 2
F f (x) = . (23)
  1 + e−x
ρ   
S P
+ ws − vsrp 
 r  . (14) The algorithm can be described as follows.
s=1  
2
p=0 2
For the sth task and fixing the values of vsrp
and wsr , we D. Computation Complexity
calculated the partial derivatives of the variables wsr and vsrp , The complexity of the training procedure of FCG-MTGS-
respectively, and set them to 0, i.e., TSK is determined by both FCM clustering algorithm for
  ⎛ ⎞ the antecedent parameters and the procedure of computing
∂L  s T s  R P
the consequent parameters in each task. The complexity of
= 2 −φr y − φsr wsr +ρ ⎝wsr − vsrp ⎠ = 0
∂wsr FCM is O(NRPT), where N is the total number of subjects,
r=1 p=0
R is the rule number, P is the feature number, and T is the
(15)
⎛ ⎞ iteration number in FCM. On the other hand, the complexity
∂L 
P of computing the conqsequent parameters ws in the sth task is
= 2λvsrp − ρ ⎝wsr − vsrp ⎠ = 0. (16) O(Ns 2 R(P + 1) + Ns 3 + Ns R2 (P + 1)2 ), where Ns is the subject
∂vsrp
p=0 number in the sth task.
Therefore, with regard to all of the S tasks, we computed
w1 , . . . , wS using (17)–(19) in each iteration and obtained the IV. E XPERIMENT
following output of w1 , w2 , . . . , wS : A. Experimental Settings
 R −1
  T In this section, we will use the accuracy (ACC), sensitiv-
w = 2
1
φr φr  + ρ
1 1 1 1
ity (SEN), specificity (SPE), area under the curve (AUC), and
r=1
⎛ ⎞ receiver operating characteristic (ROC) curves [42] to mea-
R  T 
R 
P sure the classification performance of all the methods involved.
× ⎝2 φ1r φ1r y1 + ρ φ1r v1rp ⎠ (17) These four metrics have been used in many machine learning
r=1 r=1 p=0 works [43]–[45]. The definitions of ACC, SEN, and SPE are

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 HU et al.: UNCERTAINTY MODELING FOR MULTICENTER ASD CLASSIFICATION 735

TABLE II
Algorithm 1 Feature-Correlation-Guided Multitask Group D ETAILED PARAMETER S ETTINGS IN A LL M ETHODS
Sparse Takagi–Sugeuo–Kang Fuzzy Systems (FCG-MTGS-
TSK)
Input: Training dataset D1 , D2 , . . . , DS number of fuzzy rules
R, regularization parameter λ, ρ
Output: w1 , w2 , . . . , wS
Step 1: Extract the antecedent part of a fuzzy rule.
Step 1.1: Partition the datasets D1 , D2 , . . . , DS into R clusters
with the FCM clustering algorithm.
Step 1.2: Compute csrp and σrp s in the Gauss membership func-

tion of the s-th imaging center by using Eqs. (3) and (4),
s = 1, . . . , S
Step 1.3: Determine the membership function μsArp (xp ) of the
s-th imaging center by using Eq. (2);
Step 1.4: Select 5 features (attriubtes) with the largest variance,
and compute the firing strength of the rules based on these
features using Eqs. (6) and (7).
Step 1.5: Generate s = (φs1 , φs2 , . . . , φsR )- Step 2: Joint group
sparse learning of consequent parameters across multiple tasks.
Step2.1: Initialize w1 = w2 = · · · = wS = 1 and
v1rp , v2rp , . . . , vsrp by using Eqs. (20)- (22), p = 0, 1, . . . , P,
r = 1, 2, . . . , R.
Step 2.2: Update w1 , w2 , . . . , wS by using Eqs.
(17)-(19).
Step 2.3: Update v1rp , v2rp , . . . , vsrp by using Eqs.
(20)-(22).
Step 2.4: Break if the convergence conditions are satisfied.
Step 3: Return w1 , w2 , . . . , wS .

shown as (24)–(26), where TP, FN, FP, and TN denote the true
positive, false negative, false positive, and the true negative,
respectively
TP
SEN = (24)
TP + FN
TN
SPE = (25)
TN + FP
TP + TN
ACC = . (26)
TP + FN + TN + FP
B. Summary of Competing Methods
We conducted comprehensive experiments to validate the
effectiveness of the proposed FCG-MTGS-TSK. The ASD
patients were labeled as “1” and normal controls as “0.”
We used the SVM as the baseline, which is a popular
method in the machine learning field [46]–[51]. It was trained
and tested on a single imaging center.
We regarded the multicenter ASD diagnosis as a multi-
task classification problem. The mt-LASSO [52], mt-L21 [53],
[54], and RMTFL [55] were used for comparison. They were
all from the MALSAR 1.1 (multitask learning via struc-
tural regularization) [56] toolkit, which is a multitask learning
software package based on structural regularization. Both mt-
L2TSKFS and FCG-MTGS-TSK were the nonlinear classifi-
cation methods based on the TSK fuzzy system. The parameter
settings of all the above methods are shown in Table II.
We compared the proposed method with some deep learning
methods, including deep belief network (DBN) and stacked
autoencoder (SAE), both of which have been successfully
applied in the diagnosis of brain diseases [57], [58].
In the training procedure of both mt-L2TSKFS [59] and
FCG-MTGS-TSK, we combined the multicenter training
data together and then extracted fuzzy rules from the com-
bined data. This strategy made all the fuzzy rules share premise
parameters, which were also used in validation and testing.
For fair comparison, we combined the multicenter training
data together and fed them into both DBN and SAE, respec-
tively. Table III summarizes the details of the methods used
in the experiments.
C. Classification Results and Analysis
Tables IV–VI show the classification results obtained by
different methods on each imaging center in the experiments.
Fig. 3 also plots the ROC curves.
The results in Tables IV–VI and Fig. 3 show that
the proposed FCG-MTGS-TSK effectively improved the
performance of multicenter ASD classification. Compared
with conventional multitask classification methods mt-LASSO,
mt-L21, and RMTFL, multitask fuzzy systems, including
both mt-L2TSKFS and FCG-MTGS-TSK, had better results,
which indicated that TSK fuzzy systems have better nonlinear
approximation ability in handling uncertainty for ASD diag-
nosis. Comparing the performance of FCG-MTGS-TSK with

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 736 IEEE TRANSACTIONS ON COGNITIVE AND DEVELOPMENTAL SYSTEMS, VOL. 14, NO. 2, JUNE 2022
TABLE III
S UMMARY OF THE M ETHODS FOR C OMPARISON
TABLE IV
C LASSIFICATION R ESULTS ON UM_2
TABLE V
C LASSIFICATION R ESULTS ON OLIN
mt-L2TSKFS, one may observe that the average AUC results
(i.e., 0.7334, 0.6704, and 0.7581) of FCG-MTGS-TSK on
three imaging centers were better than those of mt-L2TSKFS
(i.e., 0.7112, 0.6652, and 0.7669). We consider the reason lies
in the fact that feature correlation provided more knowledge
in multitask fuzzy modeling to enhance the performance of
FCG-MTGS-TSK, especially when the training samples were
inadequate.
Regarding the results of DBN and SAE, one may observe
that both of them could not obtain satisfactory classification
results as FCG-MTGS-TSK could. DBN even classified all
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TABLE VI
C LASSIFICATION R ESULTS ON LEUVEN_2
Fig. 3. ROC curves of different methods on UM2 , OLIN, and LEUVEN2 .
Fig. 4. Convergence curve of FCG-MTGS-TSK method.
the subjects into normal controls. This is because training
both DBN and SAE required a large number of training sam-
ples. However, we could not provide adequate training samples
for them.
Fig. 4 further plot the value of objective function when
FCG-MTGS-TSK was optimized. One may observe that the
FCG-MTGS-TSK convergences in a limited number of itera-
tions, which indicated that our method is efficient.
Both mt-L21 and FCG-MTGS-TSK introduced regular-
ization terms, which led to group sparsity in multitask
classification. However, FCG-MTGS-TSK was better than the
 HU et al.: UNCERTAINTY MODELING FOR MULTICENTER ASD CLASSIFICATION 737

TABLE VII
T OP I NTERREGIONAL F UNCTIONAL F EATURES S ELECTED F ROM RS - F MRI

Fig. 5. Top 30 discriminative rs-fMRI connections selected using the

proposed method.

mt-L21 method in general. The reason was that, in addi-

tion to the unique advantages of the TSK fuzzy system
for handling uncertainty issues, the specific regularization
term in FCG-MTGS-TSK helped to improve the results. By
integrating precision matrix in TSK fuzzy modeling, the FCG-
MTGS-TSK guided the selection of common information
across multiple imaging centers, and effectively improved the
performance of multicenter ASD classification.

D. Discriminative Interregional Features

In order to identify the brain regions that were the most
conducive to the diagnosis of ASD, the total weight of each
FC was computed by adding their absolute values in all the
rules across multiple tasks. The normalized weights are then
obtained by dividing the largest weights values. Thrity pairs
of the most discriminative brain regions were selected based
on the most important functional connectivities, which were
determined by the normalized weights.
Table VII shows 30 most discriminative functional connec-
tivities, together with the normalized weights. The numbers
in the parentheses on the right indicate the index of the
functional regions in the AAL-Label template. Furthermore,
Fig. 5 illustrates the discriminative connections between the
brain regions, which are computed based on the multitask
FIS. Each circle in the figure denotes a brain region, and
their correlations are denoted by arcs. We used green and red
to distinguish between the left and the right brain regions,
respectively, while the others were plotted in yellow. The
intrahemisphere connections in both the left and the right
hemispheres were plotted in blue, while the interhemisphere
connections were plotted in black. In addition, the thickness
which uncertainty of rs-fMRI data in ASD classification can be
of lines represents the weights in the diagnosis.
described by the fuzzy sets in the fuzzy rules. Besides, the final
outputs of the TSK-FIS are combined with the firing strength
V. D ISCUSSION φr (x), which indicates how much each rule contributes to the
There have been many works that used machine learn- predict results.
ing methods to classify ASD. Representative methods The only work reported to classify ASD using TSK-FIS
included kernel methods [60], sparse learning [61], multitask is by Wang et al. [25], in which a multioutput TSK fuzzy
learning [62], multiview learning [16], [63], and deep neural system (MO-TSK) was developed to extract discriminant fea-
networks [64]. However, these works ignored the uncertainty tures in ASD classification. Since it handled uncertainty issue
issue in rs-fMRI. To this end, this article proposes a mul- using fuzzy sets, the method is robust than existing methods.
ticenter ASD classification method based on TSK FISs, in However, it did not consider the correlation between multiple

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 738 IEEE TRANSACTIONS ON COGNITIVE AND DEVELOPMENTAL SYSTEMS, VOL. 14, NO. 2, JUNE 2022
imaging centers and thus cannot handle the multitask issues
in multicenter ASD classification.
In the literature, there have been several multicenter ASD
classification methods reported. One pioneer work for multi-
center ASD classification is proposed by Nielsen et al. [20],
in which the linear model was used. However, it did not
consider the correlation between centers and thus, obtain
poor results on some imaging centers. To this end, Wang
et al. [62] proposed M3CC for multicenter ASD classification;
Huang et al. [61] proposed the self-weighted adaptive structure
learning model to obtain informative features and used multi-
template ensemble strategy for multicenter ASD classification;
and Wang et al. [65] proposed low-rank representation in mul-
ticenter ASD classification. All these methods considered the
correlation between imaging centers, and the performance of
multicenter ASD classification thus improved. However, these
works ignored the uncertainty issue in ASD classification. To
this end, this article handles the uncertainty in multicenter
ASD classification using multitask TSK fuzzy systems, which
opens a door in neuroimaging studies.
There are issues that require further investigation. For exam-
ple, the proposed method generated the antecedent parts of the
fuzzy rules by performing FCM across all tasks. This strategy
makes the antecedent part share the common knowledge across
multiple tasks, and however, ignores the individual characteris-
tics of each task. In our future work, we will further investigate
effective methods to generate more reasonable fuzzy parti-
tions, which makes the antecedent part of fuzzy rules both
share common knowledge across tasks and keep the individual
characteristics of individual task.
VI. C ONCLUSION
In this article, we proposed a novel feature-correlation-
guided multitask group sparse classifier under the framework
of the TSK fuzzy system. The effective correlation among
features was considered in the learning of the consequent
parameters. To combine the multicenter knowledge in the ASD
classification, we imposed a novel group sparse regulariza-
tion term on the consequent parameters of all fuzzy rules
across multiple tasks, which effectively encouraged these cor-
related tasks to share the common consequent parameters. Our
FCG-MTGS-TSK method has strong interpretability and high
classification accuracy. The experimental results also indicated
the effectiveness of selecting discriminative brain regions in
the assistant diagnosis of ASD.
ACKNOWLEDGMENT
The authors would like to thank the efforts and constructive
comments of respected editor and anonymous reviewers.
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