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• Clinical Article •
Abnormalities in static and dynamic amplitude of low-frequency fluctuations and their spatial correlations with the dopamine / 5-hydroxytryptamine systems in patients with autism spectrum disorder
TAN Jinsha  HAN Chao  SI Yuning  ZHANG Shuting  WANG Meiyun 

Cite this article as: TAN J S, HAN C, SI Y N, et al. Abnormalities in static and dynamic amplitude of low-frequency fluctuations and their spatial correlations with the dopamine / 5-hydroxytryptamine systems in patients with autism spectrum disorder[J]. Chin J Magn Reson Imaging, 2026, 17(9): 55-61, 68. DOI:10.12015/issn.1674-8034.2026.09.008.


[Abstract] Objective To investigate the abnormal characteristics of static amplitude of low-frequency fluctuations (sALFF) and dynamic amplitude of low-frequency fluctuations (dALFF) in resting-state functional magnetic resonance imaging (rs-fMRI) among adolescents with autism spectrum disorder (ASD), and to analyze their associations with clinical symptoms and the distribution of neurotransmitter systems.Materials and Methods This was a retrospective case-control study. Fifty-seven adolescents with ASD and 71 age- and sex-matched healthy controls (HC) were retrospectively screened from the Autism Brain Imaging Data Exchange (ABIDE) database as study subjects. After standard preprocessing, whole-brain sALFF and dALFF (calculated using a sliding-window approach) were derived. After controlling for age, gender, mean framewise displacement, and full-scale IQ, two-sample t-tests were performed for intergroup comparisons, followed by Gaussian Random Field (GRF) correction. Pearson correlation analyses were conducted to assess relationships between altered brain activity and stereotyped behavior scores from the Autism Diagnostic Observation Schedule (ADOS). Spatial correlation analyses between case-control difference maps and templates of 10 neurotransmitter receptors / transporters were performed using the JuSpace toolbox with correction for multiple comparisons.Results Compared with the HC group, the ASD group exhibited significantly decreased sALFF in the left medial orbital superior frontal gyrus (peak t = -4.347, GRF corrected, P < 0.05) and significantly increased dALFF in the left middle frontal gyrus (peak t = 4.429, GRF corrected, P < 0.05) and orbital part of the left middle frontal gyrus (peak t = 5.327, GRF corrected, P < 0.05). The reduced sALFF in the left medial orbital superior frontal gyrus showed a positive correlational trend with ADOS stereotyped behavior scores (r = 0.263, uncorrected P = 0.048), while increased dALFF in the orbital part of the left middle frontal gyrus showed a stronger positive correlation trend (r = 0.294, uncorrected P = 0.026). Spatial correlation analysis revealed that sALFF alterations were negatively correlated with dopamine D1 receptor density (r = -0.73, q < 0.01) and positively correlated with dopamine D2 receptor density (r = 0.92, q < 0.01). In contrast, dALFF alterations were positively correlated with serotonin 5-HT4 receptor (r = 0.43, q < 0.01) and dopamine D1 receptor density (r = 0.42, q < 0.01), and negatively correlated with serotonin 5-HT1a receptor (r = -0.23, q < 0.05), dopamine D2 receptor density (r = -0.65, q < 0.01) and 18F-FDOPA uptake distribution (r = -0.50, q < 0.01).Conclusions Adolescents with ASD exhibit distinct abnormalities in both static and dynamic local brain activity within the prefrontal cortex. Dynamic alterations show stronger associations with stereotyped behaviors. These functional abnormalities are closely related to dopaminergic and serotonergic systems, suggesting that dALFF may serve as a putative neuroimaging biomarker reflecting the neurobiological mechanisms of ASD.
[Keywords] autism spectrum disorder；resting-state functional magnetic resonance imaging；magnetic resonance imaging；amplitude of low-frequency fluctuations；dopamine receptors；serotonin receptors；molecular imaging

TAN Jinsha1, 2   HAN Chao3   SI Yuning1, 2   ZHANG Shuting1, 2   WANG Meiyun1, 2*  

1 Department of Radiology, People's Hopspital of Zhengzhou University, Zhengzhou 450003, China

2 Department of Radiology, Henan Provincial People's Hopspital, Zhengzhou 450003, China

3 Department of Radiology, General Hospital of Pingmei Shenma Medical Group, Pingdingshan 467000, China

Corresponding author: WANG M Y, E-mail: mywang@zzu.edu.cn

Conflicts of interest   None.

Received  2026-03-12
Accepted  2026-08-18
DOI: 10.12015/issn.1674-8034.2026.09.008
Cite this article as: TAN J S, HAN C, SI Y N, et al. Abnormalities in static and dynamic amplitude of low-frequency fluctuations and their spatial correlations with the dopamine / 5-hydroxytryptamine systems in patients with autism spectrum disorder[J]. Chin J Magn Reson Imaging, 2026, 17(9): 55-61, 68. DOI:10.12015/issn.1674-8034.2026.09.008.

[1]
HIROTA T, KING B H. Autism Spectrum Disorder: A Review[J]. JAMA, 2023, 329(2): 157-168. DOI: 10.1001/jama.2022.23661.
[2]
SHEN Y Y, ZHAO X, QIN C, et al. Application of arterial spin labeling in autism spectrum disorder with or without global developmental delay[J]. Journal of Practical Radiology, 2024, 40(3): 443-446. DOI: 10.3969/j.issn.1002-1671.2024.03.023.
[3]
SHAW K A, WILLIAMS S, PATRICK M E, et al. Prevalence and Early Identification of Autism Spectrum Disorder Among Children Aged 4 and 8 Years-Autism and Developmental Disabilities Monitoring Network, 16 Sites, United States, 2022[J]. MMWR Surveill Summ, 2025, 74(2): 1-22. DOI: 10.15585/mmwr.ss7402a1.
[4]
ZHUANG H, LIANG Z, MA G, et al. Autism spectrum disorder: pathogenesis, biomarker, and intervention therapy[J/OL]. MedComm (2020), 2024, 5(3): e497 [2026-03-12]. https://doi.org/10.1002/mco2.497. DOI: 10.1002/mco2.497.
[5]
RAJABI P, NOORI A S, SARGOLZAEI J. Autism spectrum disorder and various mechanisms behind it[J/OL]. Pharmacol Biochem Behav, 2024, 245: 173887 [2026-03-12]. https://doi.org/10.1016/j.pbb.2024.173887. DOI: 10.1016/j.pbb.2024.173887.
[6]
ZANG Y F, HE Y, ZHU C Z, et al. Altered baseline brain activity in children with ADHD revealed by resting-state functional MRI[J]. Brain & Development, 2007, 29(2): 83-91. DOI: 10.1016/j.braindev.2006.07.002.
[7]
DI MARTINO A, YAN C G, LI Q, et al. The autism brain imaging data exchange: towards a large-scale evaluation of the intrinsic brain architecture in autism[J]. Mol Psychiatry, 2014, 19(6): 659-667. DOI: 10.1038/mp.2013.78.
[8]
UDDIN L Q, SUPEKAR K, LYNCH C J, et al. Salience network-based classification and prediction of symptom severity in children with autism[J]. JAMA Psychiatry, 2013, 70(8): 869-879. DOI: 10.1001/jamapsychiatry.2013.104.
[9]
FAGHIRI A, STEPHEN J M, WANG Y P, et al. Changing brain connectivity dynamics: From early childhood to adulthood[J]. Hum Brain Mapp, 2018, 39(3): 1108-1117. DOI: 10.1002/hbm.23896.
[10]
ZOU Q H, ZHU C Z, YANG Y, et al. An improved approach to detection of amplitude of low-frequency fluctuation (ALFF) for resting-state fMRI: fractional ALFF[J]. J Neurosci Methods, 2008, 172(1): 137-141. DOI: 10.1016/j.jneumeth.2008.04.012.
[11]
ZHAO L, ZENG W, SHI Y, et al. Dynamic visual cortical connectivity analysis based on functional magnetic resonance imaging[J/OL]. Brain Behav, 2020, 10(7): e01698 [2026-03-12]. https://doi.org/10.1002/brb3.1698. DOI: 10.1002/brb3.1698.
[12]
CARRASCO-GÓMEZ M, GARCÍA-COLOMO A, NEBREDA A, et al. Dynamic functional connectivity is modulated by the amount of p-Tau231 in blood in cognitively intact participants[J/OL]. Clin Neurophysiol, 2025, 175: 2110751 [2026-03-12]. https://doi.org/10.1016/j.clinph.2025.2110751. DOI: 10.1016/j.clinph.2025.2110751.
[13]
LORENZINI L, INGALA S, COLLIJ L E, et al. Eigenvector centrality dynamics are related to Alzheimer's disease pathological changes in non-demented individuals[J/OL]. Brain Commun, 2023, 5(3): fcad088 [2026-03-12]. https://doi.org/10.1093/braincomms/fcad088. DOI: 10.1093/braincomms/fcad088.
[14]
JIANG W H, LIU J, ZHOU J, et al. Altered dynamic brain activity and functional connectivity in thyroid-associated ophthalmopathy[J]. Hum Brain Mapp, 2023, 44(16): 5346-5356. DOI: 10.1002/hbm.26437.
[15]
LIAO W, LI J, JI G J, et al. Endless Fluctuations: Temporal Dynamics of the Amplitude of Low Frequency Fluctuations[J]. IEEE Trans Med Imaging, 2019, 38(11): 2523-2532. DOI: 10.1109/tmi.2019.2904555.
[16]
HU R, DU W, TAN F, et al. Dynamic alterations in spontaneous neural activity in patients with attention-deficit/hyperactivity disorder: A resting-state fMRI study[J/OL]. Brain Res Bull, 2025, 222: 111230 [2026-03-12]. https://doi.org/10.1016/j.brainresbull.2025.111230. DOI: 10.1016/j.brainresbull.2025.111230.
[17]
ZHONG M, HOU W, LIU Z, et al. Temporal dynamic changes of intrinsic brain regional activity in depression with smoking[J]. J Affect Disord, 2025, 377: 175-183. DOI: 10.1016/j.jad.2025.02.061.
[18]
ZHANG C, ZHANG L, LIANG J, et al. Dynamic ALFF and dynamic Reho in bipolar disorder: Genetic links and predictive value for diagnosis and therapy[J/OL]. Asian J Psychiatr, 2025, 114: 104764 [2026-03-12]. https://doi.org/10.1016/j.ajp.2025.104764. DOI: 10.1016/j.ajp.2025.104764.
[19]
CHEN J, WEI Y, XUE K, et al. Static and temporal dynamic changes of intrinsic brain activity in early-onset and adult-onset schizophrenia: a fMRI study of interaction effects[J/OL]. Front Neurol, 2024, 15: 1445599 [2026-03-12]. https://doi.org/10.3389/fneur.2024.1445599. DOI: 10.3389/fneur.2024.1445599.
[20]
ZHANG S T, HAN C, XU J Y, et al. Research progress in neuroimaging of autism[J]. Chin J Magn Reson Imaging, 2025, 16(7): 91-96, 128. DOI: 10.12015/issn.1674-8034.2025.07.015.
[21]
COVEY D P, FRANKLIN K B J. Editorial: Brain reward and aversion circuits: progress review on current and future breakthroughs[J/OL]. Front Behav Neurosci, 2025, 19: 1632916 [2026-03-12]. https://doi.org/10.3389/fnbeh.2025.1632916. DOI: 10.3389/fnbeh.2025.1632916.
[22]
SCHULTZ W. A dopamine mechanism for reward maximization[J/OL]. Proc Natl Acad Sci U S A, 2024, 121(20): e2316658121 [2026-03-12]. https://doi.org/10.1073/pnas.2316658121. DOI: 10.1073/pnas.2316658121.
[23]
PAQUELET G E, CARRION K, LACEFIELD C O, et al. Single-cell activity and network properties of dorsal raphe nucleus serotonin neurons during emotionally salient behaviors[J/OL]. Neuron, 2022, 110(16): 2664-2679.e8 [2026-03-12]. https://doi.org/10.1016/j.neuron.2022.05.015. DOI: 10.1016/j.neuron.2022.05.015.
[24]
SONG Z, HUANG C X, ZHANG H, et al. Integrated single-cell atlases unveil the operation principles of whole-brain 5-HT neuronal subsystems[J/OL]. Sci Adv, 2025, 11(50): eadv8128 [2026-03-12]. https://doi.org/10.1126/sciadv.adv8128. DOI: 10.1126/sciadv.adv8128.
[25]
HIGA G S V, VIANA F J C, FRANCIS-OLIVEIRA J, et al. Serotonergic neuromodulation of synaptic plasticity[J/OL]. Neuropharmacology, 2024, 257: 110036 [2026-03-12]. https://doi.org/10.1016/j.neuropharm.2024.110036. DOI: 10.1016/j.neuropharm.2024.110036.
[26]
MULLER C L, ANACKER A M J, VEENSTRA-VANDERWEELE J. The serotonin system in autism spectrum disorder: From biomarker to animal models[J]. Neuroscience, 2016, 321: 24-41. DOI: 10.1016/j.neuroscience.2015.11.010.
[27]
LOVE C, SOMINSKY L, O'HELY M, et al. Prenatal environmental risk factors for autism spectrum disorder and their potential mechanisms[J/OL]. BMC Med, 2024, 22(1): 393 [2026-03-12]. https://doi.org/10.1186/s12916-024-03617-3. DOI: 10.1186/s12916-024-03617-3.
[28]
MANTER M A, BIRTWELL K B, BATH J, et al. Pharmacological treatment in autism: a proposal for guidelines on common co-occurring psychiatric symptoms[J/OL]. BMC Med, 2025, 23(1): 11 [2026-03-12]. https://doi.org/10.1186/s12916-024-03814-0. DOI: 10.1186/s12916-024-03814-0.
[29]
DUKART J, HOLIGA S, RULLMANN M, et al. JuSpace: A tool for spatial correlation analyses of magnetic resonance imaging data with nuclear imaging derived neurotransmitter maps[J]. Hum Brain Mapp, 2021, 42(3): 555-566. DOI: 10.1002/hbm.25244.
[30]
CHEN D, LIU C, WANG F, et al. Structure-function interrelationships and associated neurotransmitter profiles in drug-naïve benign childhood epilepsy with central-temporal spikes patients[J]. Eur Radiol, 2025, 35(1): 417-426. DOI: 10.1007/s00330-024-10954-7.
[31]
YANG C, ZHANG L, LIU J, et al. More Severe Brain Network Hierarchy Disorganization in Treatment-Naive Deficit Compared to Non-deficit Schizophrenia and Underlying Neurotransmitter Associations[J/OL]. Schizophr Bull, 2026, 52(1): sbae231 [2026-03-12]. https://doi.org/10.1093/schbul/sbae231. DOI: 10.1093/schbul/sbae231.
[32]
KIPKEMOI P, SAVAGE J E, GONA J, et al. Evaluation of the Psychometric Properties of the Social Communication Questionnaire in Rural Kenya[J]. J Autism Dev Disord, 2025, 55(8): 2919-2937. DOI: 10.1007/s10803-024-06380-9.
[33]
YAN C G, WANG X D, ZUO X N, et al. DPABI: Data Processing & Analysis for (Resting-State) Brain Imaging[J]. Neuroinformatics, 2016, 14(3): 339-351. DOI: 10.1007/s12021-016-9299-4.
[34]
ORLHAC F, EERTINK J J, COTTEREAU A S, et al. A Guide to ComBat Harmonization of Imaging Biomarkers in Multicenter Studies[J]. J Nucl Med, 2022, 63(2): 172-179. DOI: 10.2967/jnumed.121.262464.
[35]
LIU F, WANG Y, LI M, et al. Dynamic functional network connectivity in idiopathic generalized epilepsy with generalized tonic-clonic seizure[J]. Hum Brain Mapp, 2017, 38(2): 957-973. DOI: 10.1002/hbm.23430.
[36]
LI J, DUAN X, CUI Q, et al. More than just statics: temporal dynamics of intrinsic brain activity predicts the suicidal ideation in depressed patients[J]. Psychol Med, 2019, 49(5): 852-860. DOI: 10.1017/s0033291718001502.
[37]
LIAO X, YUAN L, ZHAO T, et al. Spontaneous functional network dynamics and associated structural substrates in the human brain[J/OL]. Front Hum Neurosci, 2015, 9: 478 [2026-03-12]. https://doi.org/10.3389/fnhum.2015.00478. DOI: 10.3389/fnhum.2015.00478.
[38]
LEONARDI N, VAN DE VILLE D. On spurious and real fluctuations of dynamic functional connectivity during rest[J]. NeuroImage, 2015, 104: 430-436. DOI: 10.1016/j.neuroimage.2014.09.007.
[39]
HE C, CHEN Y, JIAN T, et al. Dynamic functional connectivity analysis reveals decreased variability of the default-mode network in developing autistic brain[J]. Autism Res, 2018, 11(11): 1479-1493. DOI: 10.1002/aur.2020.
[40]
GUO X, DUAN X, CHEN H, et al. Altered inter- and intrahemispheric functional connectivity dynamics in autistic children[J]. Hum Brain Mapp, 2020, 41(2): 419-428. DOI: 10.1002/hbm.24812.
[41]
LI R, LIAO W, YU Y, et al. Differential patterns of dynamic functional connectivity variability of striato–cortical circuitry in children with benign epilepsy with centrotemporal spikes[J]. Hum Brain Mapp, 2018, 39(3): 1207-1217. DOI: 10.1002/hbm.23910.
[42]
QIN X, CHEN X, YAO L, et al. Differential brain activity in patients with disorders of consciousness: a 3-month rs-fMRI study using amplitude of low-frequency fluctuation[J/OL]. Front Neurol, 2024, 15: 1477596 [2026-03-12]. https://doi.org/10.3389/fneur.2024.1477596. DOI: 10.3389/fneur.2024.1477596.
[43]
ROLLS E T. Emotion, motivation, decision-making, the orbitofrontal cortex, anterior cingulate cortex, and the amygdala[J]. Brain Struct Funct, 2023, 228(5): 1201-1257. DOI: 10.1007/s00429-023-02644-9.
[44]
ARNSTEN A F T, JOYCE M K P, ROBERTS A C. The Aversive Lens: Stress effects on the prefrontal-cingulate cortical pathways that regulate emotion[J/OL]. Neurosci Biobehav Rev, 2023, 145: 105000 [2026-03-12]. https://doi.org/10.1016/j.neubiorev.2022.105000. DOI: 10.1016/j.neubiorev.2022.105000.
[45]
RASHID B, DAMARAJU E, PEARLSON G D, et al. Dynamic connectivity states estimated from resting fMRI Identify differences among Schizophrenia, bipolar disorder, and healthy control subjects[J/OL]. Front Hum Neurosci, 2014, 8: 897 [2026-03-12]. https://doi.org/10.3389/fnhum.2014.00897. DOI: 10.3389/fnhum.2014.00897.
[46]
YUE X, SHEN Y, LI Y, et al. Regional Dynamic Neuroimaging Changes of Adults with Autism Spectrum Disorder[J]. Neuroscience, 2023, 523: 132-139. DOI: 10.1016/j.neuroscience.2023.04.016.
[47]
LORD C, ELSABBAGH M, BAIRD G, et al. Autism spectrum disorder[J]. Lancet, 2018, 392(10146): 508-520. DOI: 10.1016/s0140-6736(18)31129-2.
[48]
GIEDD J N, BLUMENTHAL J, JEFFRIES N O, et al. Brain development during childhood and adolescence: a longitudinal MRI study[J]. Nat Neurosci, 1999, 2(10): 861-863. DOI: 10.1038/13158.
[49]
BARNES S J K, THOMAS M, MCCLINTOCK P V E, et al. Theta and alpha connectivity in children with autism spectrum disorder[J/OL]. Brain Commun, 2025, 7(2): fcaf084 [2026-03-12]. https://doi.org/10.1093/braincomms/fcaf084. DOI: 10.1093/braincomms/fcaf084.
[50]
FALAHPOUR M, THOMPSON W K, ABBOTT A E, et al. Underconnected, But Not Broken? Dynamic Functional Connectivity MRI Shows Underconnectivity in Autism Is Linked to Increased Intra-Individual Variability Across Time[J]. Brain Connect, 2016, 6(5): 403-414. DOI: 10.1089/brain.2015.0389.
[51]
DUAN Y, MA Z, TSAI P J, et al. Frontostriatal regulation of brain circuits contributes to flexible decision making[J]. Neuropsychopharmacology, 2025, 50(7): 1156-1166. DOI: 10.1038/s41386-025-02065-8.
[52]
SUPEKAR K, RYALI S, MISTRY P, et al. Aberrant dynamics of cognitive control and motor circuits predict distinct restricted and repetitive behaviors in children with autism[J/OL]. Nat Commun, 2021, 12(1): 3537 [2026-03-12]. https://doi.org/10.1038/s41467-021-23822-5. DOI: 10.1038/s41467-021-23822-5.
[53]
SRINIVASAN C, PHAN B N, LAWLER A J, et al. Addiction-associated genetic variants implicate brain cell type- And region-specific cis-regulatory elements in addiction neurobiology[J]. J Neurosci, 2021, 41(43): 9008-9030. DOI: 10.1523/JNEUROSCI.2534-20.2021.
[54]
PAVĂL D. A Dopamine Hypothesis of Autism Spectrum Disorder[J]. Dev Neurosci, 2017, 39(5): 355-360. DOI: 10.1159/000478725.
[55]
NOPPARI T, TUISKU J, LUKKARINEN L, et al. Aberrant type 2 dopamine and mu-opioid receptor availability in autism spectrum disorder[J]. Eur J Nucl Med Mol Imaging, 2026, 53(3): 2069-2082. DOI: 10.1007/s00259-025-07620-5.
[56]
MOU Q H, ZHANG Q, CHEN L, et al. Gender specific influence of serotonin on core symptoms and neurodevelopment of autism spectrum disorders: A multicenter study in China[J/OL]. Child Adolesc Psychiatry Ment Health, 2025, 19(1): 35 [2026-03-12]. https://doi.org/10.1186/s13034-025-00892-7. DOI: 10.1186/s13034-025-00892-7.
[57]
XIN Y, YANG Y, QIAN Q, et al. A pilot study of the plasma and urinary neurotransmitters in Chinese children with autism spectrum disorder[J/OL]. BMC Psychiatry, 2025, 26(1): 59 [2026-03-12]. https://doi.org/10.1186/s12888-025-07682-7. DOI: 10.1186/s12888-025-07682-7.
[58]
TANG S, QIN B, ZHANG Y, et al. Spontaneous neural activity changes in minimal hepatic encephalopathy before and 1 month after liver transplantation[J/OL]. Front Hum Neurosci, 2025, 19: 1682584 [2026-03-12]. https://doi.org/10.3389/fnhum.2025.1682584. DOI: 10.3389/fnhum.2025.1682584.
[59]
WU G, SONG L, ZHANG G, et al. Sex Differences in Functional Gradients and Dynamic Functional Connectivity in Preschool-Aged Children With ASD[J/OL]. CNS Neurosci Ther, 2025, 31(8): e70562 [2026-03-12]. https://doi.org/10.1111/cns.70562. DOI: 10.1111/cns.70562.
[60]
VAN'T WESTEINDE A, CAUVET É, TORO R, et al. Sex differences in brain structure: a twin study on restricted and repetitive behaviors in twin pairs with and without autism[J/OL]. Mol Autism, 2020, 11(1): 1 [2026-03-12]. https://doi.org/10.1186/s13229-019-0309-x. DOI: 10.1186/s13229-019-0309-x.

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