RPS 211 - Normal brain development and psychiatric disorders

Author Block: A. Istomina¹, A. Faber¹, M. Ublinskiy¹, A. Manzhurtsev¹, M. Arsalidou²; ¹Moscow/RU, ²Toronto, ON/CA
Purpose: Addition is a basic mathematical operation that is taught first in school, and it is the most popular math operation in functional magnetic resonance imaging (fMRI) studies. fMRI studies consistently show that solving addition problems elicit fronto-parietal and cingulo-opercular areas in adults. Results in children is less consistent and no study to our knowledge examines addition problem-solving with 2-digit and 3-digit problems in children, adolescents, and adults. This current fMRI study highlights developmental effect in complex addition problem-solving.
Methods or Background: Structural (TR=8.4 ms, matrix=240×222, voxel size=1.0×1.0×1.0 mm; FOV=240×240×170 mm; TE=3.9 ms; flip angle=8°) and functional (TR=2500 ms; TE=35 ms; FOV=230×230×150; 260 measurements per run; voxel size=3.0×3.0×3.0 mm) brain data of 20 children (9 female, 11-13 years), 20 adolescents (9 female, 14-16 years) and 20 adults (12 females; 18–29 years) were acquired using a magnetic resonance Philips Achieva dStream 3.0T scanner. Participants performed 2-digit and 3-digit addition tasks in a block design that lasted 32 seconds each. Participants were instructed to provide as many correct answers as possible. Data processing and analysis were carried out using AFNI software.
Results or Findings: Solving difficult addition problems elicits activity in common and distinct regions across age groups. Common areas include middle and superior frontal gyri, inferior parietal lobule, insular cortex. Adults also engaged the bilateral cerebellar and supplementary motor areas, whereas in children and adolescents, cerebellar activation was in the right hemisphere.
Conclusion: Results suggest that cognitive strategies may not be fully developed in children and adolescents. The agreement in brain areas among adults, contrasted with their absence in children and adolescents, offers insights into neural processing during math tasks. This highlights developmental distinctions in brain function and cognitive capacities across these groups.
Limitations: Motion is the most prevalent artifact, especially in pediatric samples.
Funding for this study: The study was funded by the Brain Program of the IDEAS Research Center.
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: The local ethics committee approved all materials and procedures.

Author Block: J. Sun, H. Lv, Z. Wang; Beijing/CN
Purpose: This study aimed to examine the associations of long-term variability in body mass index (BMI) and waist-to-hip ratio (WHR) with neuroimaging metrics that approximate brain structural health.
Methods or Background: This cohort study recruited 1,114 participants aged 25-83 years from the subset of brain MRI acquisition within Kailuan study from 2020 onward. BMI and WHR variability during 2006-2018 were calculated as the average slope incorporating seven biennial measurements separately. We investigated the associations of BMI and WHR variability with MRI markers of brain tissue volumes, white matter microstructural integrity, white matter hyperintensity, and cerebral small vessel diseases.
Results or Findings: Progressive weight gain during follow-up was associated with decreased global fractional anisotropy (beta = -0.19, 95% CI -0.35 to -0.02) and increased mean diffusivity (beta = 0.16, 95% CI 0.01 to 0.31) and radial diffusivity (beta = 0.18, 95% CI 0.03 to 0.33). Weight loss was associated with lower periventricular white matter hyperintensity load (beta = -0.24, 95% CI -0.47 to -0.02) and lower risk of moderate-to-severe basal ganglia enlarged perivascular spaces (OR = 0.41, 95% CI 0.21 to 0.83). In adults with central obesity, WHR loss was associated with larger volumes of gray matter (beta = 0.50, 95% CI 0.11 to 0.89), hippocampus (beta = 0.62, 95% CI 0.15 to 1.09), and parahippocampal gyrus (beta = 0.85, 95% CI 0.34 to 1.37).
Conclusion: Progressive weight gain is associated with impaired white matter integrity. Weight and WHR losses are associated with improved general brain structural health. The present study contributes to a better understanding of the integrated associations between variations in general and central adiposity and brain structural health, especially in the early stages of the prevention of adiposity-related Alzheimer’s disease and dementia.
Limitations: None
Funding for this study: This study was supported by grants 62171297 and 61931013 from the National Natural Science Foundation of China (No. [2015] 160 from the Beijing Scholars Program, No. ZYLX202101 from Beijing Hospitals Authority Clinical Medicine Development of Special Funding Support, No. 2021-135 from Beijing Municipal Health Commission-Beijing Key Clinical Discipline Funding.
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: The Medical Ethics Committee of Kailuan General Hospital approved the META-KLS study (IRB number: 2021002). Written informed consent was obtained from all the participants.

Author Block: L. Chen¹, N. Pan¹, L. Li², G. J. Kemp³, S. Wang¹, Q. Gong¹, X. Suo¹; ¹Chengdu/CN, ²Changsha/CN, ³Liverpool/UK
Purpose: The heterogeneity of post-traumatic stress disorder (PTSD) is an obstacle to both understanding and therapy, and this has prompted a search for internally-homogeneous biological subgroups within the broad clinical diagnosis. Our goal was to do this using the individual differential structural covariance network (IDSCN).
Methods or Background: We constructed cortical thickness-based IDSCN using T1-weighted images of 89 individuals with PTSD (mean age 42.8 years, 60 female) and 89 demographically-matched trauma-exposed non-PTSD (TENP) controls (mean age 43.1 years, 63 female). The IDSCN metric quantifies how the structural covariance edges in a patient differ from those in the controls. We examined the structural diversity of PTSD and variation among subtypes using a hierarchical clustering analysis, the correlation between IDSCN and individually clinical symptoms, and sex-by-subtype interactions.
Results or Findings: PTSD patients exhibited notable diversity in distinct structural covariance edges, but mainly affecting three networks: default mode, ventral attention and sensorimotor. These changes predicted individual PTSD symptom severity. We identified two neuroanatomical subtypes: the one with greater PTSD symptom severity showed lower structural covariance edges in the frontal cortex and between frontal, parietal, and occipital cortex regions which are functionally implicated in selective attention, response selection and learning tasks. And there was no significant PTSD subtype x sex interaction.
Conclusion: Deviations in structural covariance in large-scale networks are common in PTSD, but fall into two subtypes. This work sheds light on the neurobiological mechanisms underlying the clinical heterogeneity, and may aid in personalised diagnosis and therapeutic interventions.
Limitations: First, this was one dataset and a single modality; future studies could use multimodal imaging and validation in an independent dataset. Second, it was a cross-sectional design; longitudinal research would be needed to establish whether these two PTSD subtypes showed different responses to treatment.
Funding for this study: This work was supported by the National Natural Science Foundation of China (Grant Nos. 82001800, 81761128023, 81820108018, and 82027808), and the Young Elite Scientists Sponsorship Program by CAST (Grant No. 2022QNRC001).
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: The study protocol was reviewed and approved by the Sichuan University Research Ethics Committee. Each participant provided full-informed written consent. This study conforms to the provisions of the Declaration of Helsinki.

Author Block: O. Zakomornyi, L. Myroniak, I. Kobzar, O. Omelchenko, I. Dykan; Kyiv/UA
Purpose: The purpose of this study was to detect functional connectivity of the mirror-neuron system and the overlap with the default-mode network as a potential marker of PTSD in trauma-exposed veterans.
Methods or Background: Fifteen trauma-exposed veterans (mean PCL5 value = 24) were studied with the fMRI using the event-related paradigm of different right-hand motion types observation with subsequent execution. A 3T scanner was used with the 16ch head-neck coil. Invivo fMRI stimulation hardware with mirror goggles and a display screen was used. EPI pulse sequence with TR/TE=3000/100. FSL software library was used for the analysis.
Results or Findings: Mirror neuron system fMRI activation was detected during the hand motion observation periods. In particular, activation of the posterior inferior frontal gyrus of the right and left hemispheres and extensive activation of inferior parietal lobules bilaterally were observed. In addition to the described activation of the precuneus, the inferior parietal lobules region was detected during the described motion observation phases. Default-mode network deactivation was not detected in its typical regions.
Conclusion: "Social-brain" networks like default-mode network and mirror-neuron system were detected to function coherently, while the deactivation of the default-mode network was decreased, which might be the imaging signature of PTSD in veterans and might be used for the detection of the PTSD severity markers.
Limitations: The study applies to the patient population with subacute trauma exposure period.
Funding for this study: No additional funding was received.
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: Local ethics committee approval was received before the study.

Author Block: R. Yu, N. Liu; Nanchong/CN
Purpose: This study aims to investigate the structural characteristics of the reward circuit in adolescents with non-suicidal self-injury (NSSI) in the absence of comorbidities using subcortical volume and lateralisation index(LI). The objective is to elucidate the pathophysiological mechanisms of NSSI and provide structural evidence for NSSI.
Methods or Background: This study prospectively enrolled 30 primary NSSI patients and 29 healthy controls (HC). Clinical characteristics included the self-rating anxiety scale (SAS), Beck Scale for Suicidal Ideation (BSI), Brief Assessment of Cognition in Schizophrenia (BACS), and Ottawa Self-Injury Inventory (OSI). Subcortical volume segmentation was conducted using Freesurfer software. LI quantified differences in left and right subcortical volume. Statistical analysis of clinical features, subcortical volume, and LI were performed using wilcoxon rank-sum and independent sample t-tests. Pearson or Spearman correlation was used to explore relationships between subcortical volume or LI and clinical characteristics.
Results or Findings: The NSSI group had higher SAS scores compared to the HC group (P<0.05). BACS scores in the NSSI group were lower than in the HC group (P<0.05). Compared to the HC group, the NSSI group exhibited reduced volume in the left accumbens and putamen, along with an increased LI of the accumbens (p<0.05). In the NSSI group, left putamen volume was negatively correlated with OSI scores (p=0.045), left accumbens volume was positively correlated with BACS scores (p=0.033), and LI of the accumbens was negatively correlated with OSI scores (p=0.044).
Conclusion: Our study reveals that in primary NSSI adolescents, subcortical volume of the left putamen and left accumbens are diminished, with LI indicating potential left-sided vulnerability. These findings provide a new sight and structural evidence for the reward circuits mechanism of NSSI.
Limitations: This is a cross-sectional study, so the exploration of the efficacy is limited.
Funding for this study: The Bureau of Science & Technology and Intellectual Property Nanchong City (NO. 22SXQT0305). The Opening Project of Functional and Molecular Imaging Key Laboratory of Sichuan Province (NO. SCU-HM-202307001).
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: Ethical approval was obtained from the ethics board of the Affiliated Hospital of North Sichuan Medical College(2022ER406-1).

Author Block: S. Li, W. Zhang, S. Lui; Chengdu/CN
Purpose: Schizophrenia typically manifests during late adolescence and early adulthood. Studying early-stage patients is vital for understanding brain function without the influence of antipsychotic medications. While previous research has identified brain region and network deficits, little attention has been given to network controllability. Controllability is a predictor of the brain's capacity to transition between different states, with modal controllability being a phenotype associated with substantial changes in brain states. This study aims to investigate network controllability deficits in the early stages of schizophrenia while controlling for the influence of antipsychotic medication.
Methods or Background: The study included 135 drug-naïve first-episode schizophrenia patients aged 16-30 and 119 matched healthy controls. Resting-state fMRI data were acquired using a 3-Tesla GE scanner. DPASF software processed data and computed voxel-wise functional connectivity. Linear Mixed-Effects Models incorporated regional modal controllability and factors including controllability, category (schizophrenia or healthy), gender, age, education level, and category interactions. Inter-group comparisons assessed regional modal controllability and age-related changes.
Results or Findings: Schizophrenia patients exhibited significantly lower regional modal controllability in the left inferior parietal gyrus compared to healthy controls (p=0.02, corrected). As schizophrenia patients aged, their regional modal controllability decreased, whereas healthy controls showed increased modal controllability with age. A significant difference in age-related changes in regional modal controllability emerged between diagnostic groups (p=0.009, corrected).
Conclusion: This study uncovers abnormal network development patterns in early-stage schizophrenia marked by reduced regional modal controllability, notably in the left inferior parietal gyrus. Understanding network controllability in schizophrenia's early stages is crucial and may inform treatment and intervention strategies.
Limitations: The study did not include long-term follow-up data to track how network controllability deficits evolve over time in early-stage schizophrenia. Longitudinal data could provide a more comprehensive understanding of disease progression.
Funding for this study: This study was funded by the Miaozi Project in Science and Technology Innovation Program of Sichuan Province: Grant No. 2021028.
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: This study was approved by the Ethics Committee of West China Hospital, Sichuan University.

Author Block: X. Wei¹, H. Cao², C. Luo¹, Q. Zhao¹, C. Xia¹, Z. Li¹, Z. Liu¹, Q. Gong¹, S. Lui¹; ¹Chengdu/CN, ²Manhasset, NY/US
Purpose: We aimed to the find the detailed directional connectivity disruption of cerebellar cortex.
Methods or Background: Cerebellar functional dysconnectivity plays a key role in schizophrenia (SZ) pathology. One hundred and eighty drug naïve first-episode patients with SZ (54 were reassessed after one-year treatment) and 166 healthy controls (HCs) were included. Their resting-state functional magnetic resonance images were used to perform Granger causal analysis, in which nine functional systems of the cerebellum were defined as seeds. The observed directional connectivity alterations at baseline were further assessed at follow-up and associated with psychotic symptom changes.
Results or Findings: We observed increased information projections in the first episode SZ from cerebellum to cerebrum (i.e., from the cerebellar attention and cingulo-opercular systems to the bilateral angular gyri, and from the cerebellar cingulo-opercular system to the right inferior frontal gyrus). In contrast, decreased information projections in the first episode SZ were mainly from cerebrum to cerebellum (i.e., from the right inferior temporal gyrus, the left middle temporal gyrus, the left putamen, and the right angular gyrus to the cerebellar language system) and inside the cerebellum (i.e., from the cerebellar cingulo-opercular system to the right cerebellum Crus II). With symptom remission after one-year antipsychotic treatment, the information projections from cerebrum to cerebellum were partly restored. The normalization extent of the information projection from the left middle temporal gyrus to the cerebellar language system was positively correlated with the change in general psychopathological symptoms.
Conclusion: These findings suggest that the decreased information projections from the cerebrum into the cerebellum during the acute phase of schizophrenia may be a state-dependent alteration that is related to symptoms and medication. While the increased information projections from the cerebellum may reflect a persistent pathologic trait.
Limitations: Not applicable.
Funding for this study: This study was supported by the National Natural Science Foundation of China (Project Nos. 82120108014, 82071908), National Key R&D Program of China (Project Nos.2022YFC2009901,2022YFC2009900/2022YFC209903), China Postdoctoral Science Foundation (Project No. 2022M722270), the Youth Science Fund of the Natural Science Foundation of Sichuan Province, China (Project No. 2022NSFSC1435), CAMS Innovation Fund for Medical Sciences (CIFMS) (Project No. 2021-I2M-C&T-A-022), Chengdu Science and Technology Office, major technology application demonstration project (Project Nos. 2022-YF09-00062-SN, 2022-GH03-00017-HZ), Sichuan Science and Technology Program (Project No. 2021JDTD0002), Sichuan University Postdoctoral Interdisciplinary Innovation Fund (Project No. JCXK2209), the Fund of the Beijing Medical Award Foundation (Project No. YXJL-2022-0665-0189), Dr. Su Lui acknowledges the support from Humboldt Foundation Friedrich Wilhelm Bessel Research Award and Chang Jiang Scholars (Program No. T2019069).
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: This study was approved by the Ethics Committee on Biomedical Research, West China Hospital of Sichuan University

Author Block: R. Rastogi, D. Goel; Moradabad/IN
Purpose: Psychosis is a complex group of disease showing significant alterations in corpus callosum affecting the cognitive behavior of the patient. Diffuse tensor imaging (DTI) is an advanced MR imaging tool that depicts the microstructural changes in the white matter of the brain. Since DTI can predict callosal changes before visible thinning, hence it can be used to determine the prognosis of patients and manage patients accordingly.
Methods or Background: Twenty patients with proven psychosis for more than one year underwent noncontrast MRI brain and DTI on 1.5T scanner followed by evaluation of callosal MD, FA & ADC measurement as well as changes in its thickness. This data was compared to 20 age & sex matched subjects who were normal healthy volunteers.
Results or Findings: Fourteen out of 20 patients revealed alterations in MD, ADC and FA of the corpus callosum with only 3 out of 14 revealed thinning of corpus callosum with ventriculomegaly.
Conclusion: Callosal DTI MR imaging in psychotic patients may be a novel screening tool of disease progression and prognostication allowing early identification of patients who may require adjuvant psychotherapy or more aggressive management. It may also serve as an objective tool for evaluating the effects of various drug in the management of retarding or cessation of the progression of psychosis.
Limitations: Small sample volume, single centre study
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: This study was ethically approved.

Author Block: A. N. Parimalai, A. Chellathurai, M. K. Logudoss, D. Lakshmi; Chennai/IN
Purpose: The aim of the study is to analyse the various functionally connected networks in obsessive-compulsive disorder using Rs-fMRI (resting state functional MRI) and to compare the same with normal individuals, thereby defining the pathophysiology of obsessive-compulsive disorder.
Methods or Background: All the patients who were diagnosed under DSM-5 criteria and were registered and undergoing treatment in the psychiatry Department in Government Stanley Medical College, Chennai. All our images were acquired using a 1.5 T MRI system and the resting state functional images were acquired using an echo-planar imaging (EPI) sequence.
Results or Findings: OCD patients showed significant decrease/absence of functional connectivity in executive control network and significant increase/presence of functional connectivity in orbito-fronto-striatal thalamic network
Conclusion: The altered functional connectivity in executive control network and orbito-fronto -striatal thalamic network forms the root cause for the obsessions & compulsions in OCD
Limitations: Not applicable
Funding for this study: No funding was received for this study
Has your study been approved by an ethics committee? Not applicable
Ethics committee - additional information: It is an educational study and no ethical approval was sought.

Author Block: F. Aldhafeeri, K. Al Enazi; Hafar al-Batin/SA
Purpose: Auditory verbal hallucinations (AVH) refer to the perception of voices by subjects in the absence of external auditory stimulation. The objective of this study was to investigate the underlying neural mechanisms associated with experiencing AVH while excluding any presence of psychological or neurological condition.
Methods or Background: This study was approved by the local research ethics committee. A total of 14 subjects suffering from AVH and 15 age and sex matched healthy controls were recruited in this study. All participants underwent structural magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), and resting-state functional MRI (rs-fMRI). The findings acquired from each modality were utilised for statistical comparison between the control group and AVH group
Results or Findings: Structural MRI revealed a remarkable cortical thickness reductions in the frontal and temporal lobes and cingulate cortex in the AVH group compared to the controls. Rs-fMRI exhibited reduced functional connectivity (FC) in the AVH group compared to the controls in the following regions: inferior frontal gyrus, anterior cingulate, and temporal cortex bilaterally. AVH subjects have demonstrated increased FC in the right thalamus, left hippocampal region and amygdala. Compared to the healthy control group, AVH demonstrated reduced mean fractional anisotropy (FA) in the right fronto-occipital fasciculus and the corpus callosum and higher mean diffusivity (MD) in the left inferior fronto-occipital fasciculus and anterior thalamic radiation
Conclusion: Using a multimodel MRI techniques, current findings shed the light on the brain mechanisms of AVH by revealing the causal involvement of key brain areas involving the auditory, language, and memory networks.
Limitations: This study is limited by a small sample size; therefore, we recommend further studies with larger sample sizes to better understand the neural correlates of AVH.
Funding for this study: This study did not receive any funding.
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: This study was approved by the Local Research Ethics Committee at University of Hafr Albatin, SA.