RPS 1311 - Imaging the psychiatric brain: new frontiers and insights

Author Block: Q. Guo, H. Yang; Hangzhou/CN
Purpose: To examine connectome gradient dysfunction associated with major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SCZ), and to identify transdiagnostic variation patterns.
Methods or Background: Using a large cohort of resting-state fMRI data from 3266 participants recruited at 23 sites, including 1275 healthy controls (HC), 1531 MDD, 187 BD and 273 SCZ patients, we applied diffusion map embedding to estimate connectome gradient. Statistical analyses were conducted on range, variance, and gradient values of principal gradient, and correlations were examined with clinical scales.
Results or Findings: The principal gradient extends from primary visual (VIS) and somatosensory/motor networks (SMN) to default mode network (DMN). MDD showed less variance than HC. BD and SCZ exhibited narrower range and less variance than HC and MDD. Regionally, gradient values in DMN regions exhibited a pattern of SCZ < BD < MDD < HC. MDD, BD, and SCZ groups had lower gradient scores in VIS regions and higher in SMN compared to HC, indicating opposite changes within primary systems. The mean gradient value in SMN regions of MDD showed significant positive correlations with anxious mood and tension scores (FDR-corrected). MDD and SCZ in VIS exhibited positive correlation trends with scores on several items of their respective scales (p < 0.05 before FDR correction).
Conclusion: This study demonstrated that principal gradient compression was both shared and spectrally distributed across MDD, BD, and SCZ. The non-uniform compression was characterized by heterogeneous alterations within primary systems. These findings not only provide a unified neurobiological account for sensory-cognitive integration deficits in these disorders but also propose a new perspective: mental disorder patients may maintain a relatively stable baseline of sensory reality through VIS's protective compensation.
Limitations: The sample sizes for BD and SCZ groups are relatively small.
Funding for this study: No funding was received for this study.
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: The study was approved by the ethical committee of the First Affiliated Hospital of Zhejiang University School of Medicine (Approval No. IIT20220463B-R1).

Author Block: C. Dalmasso, F. Andersson, I. Maldonado, M. A. Siragusa, V. Lefevre, C. Destrieux, W. El-Hage, T. Desmidt, J-P. Cottier; Tours/FR
Purpose: While numerous studies have examined the effects of musical styles on pleasure and fear, few have investigated the overall brain activity underlying these emotional responses, particularly across different styles and periods of classical music.
The present study aimed to use fMRI to explore functional connectivity during listening to four excerpts from different periods of Classical music, and to identify musical parameters associated with the engagement of clinically relevant networks.
Methods or Background: This prospective, single-centre study included 25 healthy subjects with musician status and psychometric assessment using validated scales. A 3T MRI scanner acquired BOLD fMRI data during a task involving watching emotionally neutral images and listening to four 1-minute excerpts presented in random order (Rossini Guillaume Tell, Minkus La Bayadère, Satie Gymnopédie No. 1, Stravinsky The Rite of Spring). Data were processed using the Conn Toolbox and MatLab®, highlighting significant co-activations for each stimulus (atlas MNI AAL3).
Results or Findings: Each contrast (opposing stimuli) revealed significant co-activations (t-tests, p < 0.05) between distinct brain areas, recruiting different network profiles: audio–visuo–fronto-linguistic coupling with orbitofrontal involvement (valence/reward) for Rossini; limbic–cerebellar and occipital circuits (contextual encoding, motor imagery) for Minkus; salience/interoception pole (insula) and thalamic-striatal-cerebellar loops compatible with calm attentional state for Satie; orbitofrontal axis–temporal poles (structural complexity, semantic combinatorics, emotional coloring) for Stravinsky. Slow tempi and regular meters favored insula–thalamus/limbic and cerebellar networks, whereas fast tempi and/or irregular meters engaged orbitofrontal and temporal poles.
Conclusion: Our results highlight a diversity of cerebral co-activation during listening to different classical styles. Tempo and metrical regularity appeared as modulators of network architecture. This network-centered mapping may pave the way for personalized “musical prescriptions” in music therapy (interoceptive calming, language/rhythm training, cognitive flexibility...).
Limitations: Not applicable
Funding for this study: Kahler Communication France
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: The study protocol was approved by the human ethical committee of Toulouse (France).

Author Block: N. Dichko; Kyiv/UA
Purpose: Hypoxic–ischaemic (HI) events during early brain development can lead to structural and functional alterations that may predispose children to neurodevelopmental disorders (NDDs).
Methods or Background: Perinatal and early childhood HI events can disrupt the maturation of neural networks. Increasing evidence suggests that such early-life brain insults may contribute to the development of neurodevelopmental disorders (NDDs). Despite emerging interest in the link between HI injury and NDDs, there is still limited large-scale clinical research exploring this association across diverse pediatric age groups.
This study aims to fill this gap by evaluating structural brain alterations following HI injury and examining their potential association with subsequent diagnoses of ASD and/or speech delay in a well-characterized pediatric cohort.

This retrospective observational study included 331 pediatric patients, inclusion criteria required evidence of hypoxic–ischaemic brain injury confirmed through neuroimaging (MRI) and availability of clinical neurodevelopmental assessments.
Patients with genetic syndromes or major congenital brain malformations unrelated to HI injury were excluded.
Results or Findings: Hypoxic–ischaemic brain alterations were predominantly observed in the periventricular white matter (63%), basal ganglia and thalami (41%), temporal lobes (38%), and frontal lobes (26%). Diffuse white matter abnormalities and cortical atrophy were more common in patients diagnosed with ASD or combined ASD and speech delay.
• Periventricular leukomalacia (PVL), basal ganglia and thalamic involvement, temporal lobe abnormalities and diffuse cortical atrophy showed a strong correlation of combined ASD and speech delay.
Conclusion: Our findings support the growing evidence that early-life HI injury disrupts critical neural pathways involved in language acquisition, social communication, and cognitive functioning. Early neuroimaging, particularly MRI, plays a vital role in identifying at-risk children and may provide predictive value for long-term neurodevelopmental outcomes.
Limitations: Retrospective design, heterogeneity of age and timing of injury, imaging modalities and quality.
Funding for this study: This study did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.Future research expansion and longitudinal follow-up will require external funding support.
Has your study been approved by an ethics committee? Not applicable
Ethics committee - additional information:

Author Block: S. Reddy Kankara, D. Jayanna, S. R. Kankara, U. Nayak, A. Josephine, V. M. Tellis; Bangalore/IN
Purpose: To assess glymphatic system alterations in children with autism spectrum disorder (ASD) using diffusion tensor imaging along the perivascular space (DTI-ALPS) and to compare findings with age- and sex-matched healthy controls.
Methods or Background: The glymphatic system facilitates metabolic waste clearance via perivascular pathways, and dysfunction may contribute to neurodevelopmental disorders. In this retrospective case–control study, 30 children with DSM-5–confirmed ASD (mean age 7.4 ± 2.0 years; 22 males) and 30 matched controls (7.1 ± 2.3 years; 21 males) were included. Eligibility required age 3–12 years and diagnostic-quality 3T MRI with DTI; exclusions were prior CNS infection/trauma, structural brain abnormalities, or motion-degraded scans. ALPS indices were derived at the lateral ventricular body using standardized ROIs in projection and association fibers, placed independently by two blinded raters. Group comparisons were performed with independent-samples t-tests, and age–ALPS relationships were assessed with Pearson correlation.
Results or Findings: Children with ASD showed significantly lower ALPS indices than controls (Left: 1.10 ± 0.13 vs 1.32 ± 0.16, p < 0.001; Right: 1.12 ± 0.14 vs 1.30 ± 0.15, p = 0.002), remaining significant after bilateral correction. Age correlated positively with ALPS in both ASD (r = 0.38, p = 0.04) and controls (r = 0.31, p = 0.04), indicating maturational improvement; however, values in ASD remained consistently lower across the age spectrum.
Conclusion: Pediatric ASD is associated with reduced DTI-ALPS indices, consistent with impaired glymphatic function. Despite age-related gains, glymphatic activity remains attenuated in ASD. DTI-ALPS provides a feasible, non-contrast imaging biomarker of neurofluid dynamics, with potential relevance for studying neurodevelopmental disorders.
Limitations: The study is limited by its retrospective, single-center nature, small cohort, and reliance on manual ROI selection. Future work could include longitudinal evaluations and explore associations with clinical severity.
Funding for this study: Not applicable
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: The study was approved by the Institutional Ethics Committee

Author Block: S. Guo, Q. Gong, Y. Zhao, S. Lui, L. Li, R. Xie, X. Zhang; Chengdu/CN
Purpose: Dysregulation of excitation–inhibition balance in specific neural circuits is believed to underlie the diverse positive and negative symptoms of schizophrenia (SCZ). This study aimed to identify neurobiological subtypes of drug-naïve first-episode SCZ (FES) using cortical excitability (CE) mapping to advance precision-medicine approaches for SCZ.
Methods or Background: Resting-state fMRI data from 77 drug-naïve FES patients and 76 matched healthy controls were analyzed using a novel CE-mapping approach. After deriving individual CE profiles, support vector machines (SVM) assessed diagnostic accuracy, and hierarchical clustering delineated neurobiological subtypes. Twelve-month follow-up data evaluated treatment-related changes. Molecular analyses integrated transcriptomic data via partial least squares regression with functional enrichment and JuSpace-based neuroreceptor mapping to identify subtype-specific molecular correlates.
Results or Findings: FES patients exhibited significantly reduced CE compared with controls, predominantly in the bilateral frontal lobes, sensorimotor cortex, and right cuneus. SVM achieved 86.7% diagnostic accuracy. Hierarchical clustering identified two subtypes: FES1, showing widespread CE reductions with more severe depressive, negative, and cognitive symptoms; and FES2, showing milder alterations. Longitudinal analysis revealed partial CE recovery in FES1 but persistent reductions in FES2. Molecular profiling suggested that FES1 was characterized by synaptic dysfunction and neurodevelopmental disruption, whereas FES2 reflected multisystem impairments accompanied by compensatory processes.
Conclusion: This study delineates two neurobiological subtypes of FES with distinct CE profiles and molecular underpinnings. CE-based subtyping offers a promising framework for linking clinical heterogeneity with underlying neurobiology and may inform precision treatment strategies in SCZ.
Limitations: The modest sample size and one-year follow-up may limit generalizability, and clinical assessments were restricted, constraining exploration of CE–FES heterogeneity. Transcriptomic analyses were confined to the left hemisphere, precluding bilateral evaluation of gene–CE associations.
Funding for this study: This study was supported by grants from the National Key R&D Program of China (2022YFC2009900), National Natural Science Foundation of China (82027808), and National Natural Science Foundation of China (82302167).
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: The study was approved by the Research Ethics Committee of West China Hospital of Sichuan University (Approval No. 2022-886).

Author Block: X. Yi¹, B. T. Chen²; ¹Chongqing/CN, ²Duarte, CA/US
Purpose: Adolescents with bipolar disorder (BD) exhibit heightened emotional reactivity and deficits in cognitive control, yet the neural mechanism underlying attentional control under emotional interference remains poorly understood.
Methods or Background: Using brain functional magnetic resonance imaging (fMRI), we examined brain activation during an emotional Go/No-Go task in 43 adolescents with BD and 18 age- and gender-matched healthy control (HC) participants. Emotional (happy/sad) versus neutral facial expressions were contrasted to isolate emotion-specific neural responses. Behavioral performance data, clinical symptoms, and cognitive functions were also assessed.
Results or Findings: Compared to the HC participants, the adolescents with BD exhibited significantly increased activation in the cognitive control network, particularly in the inferior frontal gyrus, caudate nucleus and cingulate cortex, during emotional versus neutral conditions. Aberrant activation in the right inferior frontal gyrus was significantly correlated with response inhibition errors, executive function scores on the Stroop Color and Word Test, and depressive symptom severity.
Conclusion: The adolescents with BD showed increased activation in the brain regions for attentional and inhibitory control, which may reflect compensatory mechanism to allocate more resource to maintain cognitive control when processing emotional stimuli. These findings implicated dysfunctional emotion-attention interactions in adolescents with BD and suggested potential neural targets for early intervention.
Limitations: The sample size was relatively small, and this was a cross-sectional study.
Funding for this study: None
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: The present study was approved by the ethics committee of our institute

Author Block: S. Capelli¹, A. Arrigoni¹, S. Saluzzi², P. Patani², S. Martinelli², A. Caroli¹, A. Di Giorgio², S. Gerevini²; ¹Ranica/IT, ²Bergamo/IT
Purpose: Diffusion-weighted MRI (DW-MRI) tractography enables non-invasive mapping of brain connectivity and may reveal biomarkers of structural network alterations in psychiatric disorders. This study investigated connectome changes across clinical stages of Bipolar Disorder (BD), including individuals at familial risk, using advanced DW-MRI processing and graph analysis.
Methods or Background: Forty-five participants were recruited from two Italian centers and classified according to the Kupka–Hillegers staging model: Stage 0–1 (n = 13, familial risk and subthreshold symptoms), Stage 2 (n = 8, first hypo/manic episode), Stage 3 (n = 13, recurrent episodes), and Stage 4 (n = 11, chronic non-remissive course). DW-MRI data were acquired using a 3T scanner and processed with a custom pipeline integrating single-shell 3-tissue constrained spherical deconvolution (SS3T-CSD), anatomically constrained probabilistic tractography (iFOD2-ACT), and graph-based connectome analysis. Tractograms were optimized with the COMMIT2 method, and connectivity metrics were derived using Python’s bctpy package. T1-weighted imaging was coregistered to the DW-MRI scan using ANT and parcellated with FreeSurfer. Group differences were assessed with Kruskal-Wallis tests and Wilcoxon pairwise comparisons (p < 0.05), with Bonferroni correction applied.
Results or Findings: Mean nodal strength showed a significant group effect (p = 0.024), with post hoc analysis indicating reduced strength in Stage 4 compared to Stage 2 (p = 0.002) and a trend compared to Stage 3 (p = 0.072). Among node-wise metrics, the betweenness of the left posterior cingulate cortex (PCC) had the most significant effect (p < 0.001), which remained significant after Bonferroni correction.
Conclusion: Findings indicate progressive disruption of structural connectivity with advancing BD stage, particularly affecting PCC centrality. DW-MRI tractography and connectome metrics hold promise as biomarkers for disease progression and stratification in BD.
Limitations: Single-center image acquisition, modest sample size, and lack of external validation.
Funding for this study: NextGeneration EU - PNRR: M6/C2_CALL 2022
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: Protocol title: BipOlAR Disorder Integrative stagiNG: incorporating the role of biomarkers into Progression AcrosS Stages (BOARDING-PASS)

Author Block: L. Ma, M. Zhang, B. Mei, Y. Wei, S. Han, Y. Zhang; Zhengzhou/CN
Purpose: Previous studies have demonstrated that nicotine addiction and alcohol dependence are frequently comorbid. However, the underlying neurobiological mechanisms remain unclear. Therefore, we will investigate the impacts of two factors on spontaneous neural activity and specific neurotransmitter system.
Methods or Background: This study used a two-way factorial design, including the following four groups: 1) Alcohol dependence smokers (n = 32); 2) Non-alcohol dependence smokers (n = 30); 3) Alcohol dependence non-smokers (n = 21); 4) Healthy control (n = 27). Functional magnetic resonance imaging (fMRI) was used to compare the differences in fractional amplitude of low-frequency fluctuation (fALFF) among the four groups to detect the interaction effect of nicotine addiction and alcohol dependence on spontaneous neural activity. Furthermore, correlations between fALFF values and PET- and SPECT-driven maps to examine specific neurotransmitter system alternations underlying two factors.
Results or Findings: Our study revealed a significant antagonistic interaction between two factors in the right cerebellum. The main effect of nicotine addiction is in the bilateral occipital lobes. The main effects of alcohol dependence are in the bilateral precentral gyrus. Cross-modal correlations revealed alternations in spontaneous neural activity in interactive brain regions associated with the serotonin system (5-HT1b).
Conclusion: This study identified an antagonistic interaction of the cerebellum between nicotine addiction and alcohol dependence. Besides, our study further correlates the serotonin system with the intrinsic neural activity associated with this comorbidity. This may be a potential neurobiological mechanism of smoking and alcohol, offering new directions for the treatment of this comorbidity.
Limitations: The Juspace toolbox achieves indirect coupling of functional imaging with neurotransmitter systems. However, these neurotransmitters are limited in types and information. Future studies should use PET and MRI to provide more direct evidence.
Funding for this study: This study was supported by the Natural Science Foundation of China [grant numbers 81601467, 81871327, and 62106229] and the Funding for Scientific Research and Innovation Team of The First Affiliated Hospital of Zhengzhou University [grant numbers QNCXTD2023007].
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: The First Affiliated Hospital of Zhengzhou University

Author Block: S. S. Bhoyar, P. Shah, P. NAIK, A. G. Sasane; Pune/IN
Purpose: Alcohol dependence is associated with selective brain atrophy, yet conventional magnetic resonance imaging remains largely qualitative and observer-dependent. Artificial intelligence–assisted voxel-based morphometry enables automated, reproducible volumetric quantification. This study evaluated its ability to objectively identify region-specific atrophy in alcohol dependence and explored its potential role as a clinically translatable imaging biomarker.
Methods or Background: Sixty consecutive adult patients diagnosed with alcohol dependence syndrome (ICD-10 criteria) were prospectively enrolled over 18 months. Magnetic resonance imaging was performed on a 1.5T system using a three-dimensional T1-weighted spoiled gradient recalled acquisition sequence. Automated segmentation and volumetric analysis were conducted using a validated artificial intelligence–based morphometry pipeline, normalised to intracranial volume. Quantitative volumes of cortical and subcortical regions were compared with established normative references.
Results or Findings: Frontal lobe atrophy was universal (100 per cent), with high prevalence also observed in the temporal lobes (93 per cent), cerebellum (90 per cent), basal ganglia (putamen 90 per cent, caudate 88 per cent), and hippocampus (81.7 per cent). The amygdala (68 per cent) and thalamus (65 per cent) were variably affected, while the occipital lobes (40 per cent) and brainstem (23 per cent) were relatively preserved. This pattern highlights selective vulnerability of fronto-limbic and cerebellar circuits, correlating with executive dysfunction, impaired memory, and motor incoordination. The artificial intelligence–assisted pipeline consistently generated robust, reproducible volumetric outputs with reduced observer bias and faster processing compared with conventional approaches.
Conclusion: Artificial intelligence–assisted voxel-based morphometry provides objective, reproducible imaging biomarkers of alcohol-related brain atrophy. It paves the way for early diagnosis, personalised risk stratification, and treatment monitoring, positioning artificial intelligence as a transformative tool in neuropsychiatric care.
Limitations: Absence of a matched control group and lack of direct neuropsychological correlation.
Funding for this study: No funding was received for this study.
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: Approved by the Institutional Ethics Committee of SKNMC,Pune, approval number [SKNMC/2023/103]

Author Block: L. Ma, M. Zhang, B. Mei, Y. Wei, S. Han, Y. Zhang; Zhengzhou/CN
Purpose: Sleep disorders can impair the glymphatic system and may exacerbate cognitive deficits in internet gaming disorder (IGD). Therefore, this study aimed to investigate whether the glymphatic system and the human brain network are impaired in IGD patients with sleep disorder (IGDSD) compared to IGD patients without sleep disorders (IGDNSD), which is crucial for elucidating the neuropathological mechanisms of IGD.
Methods or Background: This study recruited 36 IGDSD, 30 IGDNSD, and 30 healthy controls, who performed magnetic resonance imaging (MRI) scanning and clinical symptom assessment. The glymphatic function and network efficiency were calculated based on diffusion images along the perivascular space (DTI-ALPS) index and resting-state functional MRI, respectively. Differences between groups, neural/clinical correlations, mediation analyses, and diagnostic performance were further explored.
Results or Findings: Compared to IGDNSD, IGDSD had a significantly lower ALPS index. The correlation analysis showed that the ALPS index in IGDSD was significantly correlated with the local brain efficiency and the sleep quality. The mediation analysis showed that sleep quality partially mediated the effect of local brain efficiency on glymphatic system function. In addition, the area under the ROC curve of ALPS in distinguishing IGDSD from IGDNSD was 0.93, with a cut-off value of 1.32.
Conclusion: These results indicated the severely impaired glymphatic function and network efficiency in IGDSD. And this study also adds important evidence that the brain network efficiency disrupts the glymphatic system function by affecting sleep quality, which may reveal the neuropathological mechanisms of IGDSD.
Limitations: The DTI-ALPS method is a deductive measure of glymphatic system function. The ALPS index does not comprehensively reflect the clearance function of the glymphatic system.
Funding for this study: This study was supported by the Natural Science Foundation of China [grant numbers 81601467, 81871327, and 62106229] and the Funding for Scientific Research and Innovation Team of The First Affiliated Hospital of Zhengzhou University [grant numbers QNCXTD2023007].
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: The First Affiliated Hospital of Zhengzhou University

Author Block: B. Cheng; Chengdu/CN
Purpose: Postpartum women (PW) undergo profound brain functional and structural reorganization to support maternal adaptation. However, the specific neural adaptation mechanisms keep unclear. This study used multimodal MRI and clinical assessments to investigate brain changes in PW. We analyzed functional gradients, network topology, and brain volumes using advanced computational tools. The study aimed to: identify postpartum-specific brain changes; test if GMV mediates functional gradient shifts via network integration/segregation; link neural measures to clinical symptoms; and track longitudinal recovery of brain, hormonal, and clinical changes.
Methods or Background: The current study employed a multimodal MRI approach integrating functional gradient analysis, graph-theoretical network metrics, and morphometry to explore the brain connectome reorganization across the postpartum period and its clinical correlates in 206 participants (134 PW and 72 healthy nulliparous women (HNW)).
Results or Findings: Compared to HNW, PW exhibited a significant contraction of the first two principal functional gradients, reduced network modularity and local efficiency, and widespread gray matter volume (GMV) reductions. Mediation analysis revealed that GMV alterations modulate functional gradient reorganization by influencing network integration and segregation. These neural changes were closely linked to clinical symptoms including sleep disturbance, stress, and grit. Longitudinal modeling captured dynamic trajectories of brain plasticity, prolactin levels, and clinical symptom recovery.
Conclusion: Our findings unveil a transient, disorder-like network reconfiguration supporting maternal behavior, simultaneously elucidating neurobiological mechanisms of adaptive plasticity and vulnerability to postpartum mood disorders.
Limitations: First, while our study examined neuroplastic changes in PW, it did not address the distinct neural signatures associated with postpartum depression or anxiety. Future research should investigate disorder-specific neuropathological profiles to better understand their underlying mechanisms. Second, while we demonstrate macroscale hierarchical network alterations, their underlying biological mechanisms require further validation.
Funding for this study: Nono
Has your study been approved by an ethics committee? Not applicable
Ethics committee - additional information: