Altered Functional Connectivity Research Articles

Associations between brain network, puberty, and behaviors in boys with Klinefelter syndrome.

Klinefelter syndrome (KS), also referred to as XXY syndrome, is a significant but inadequately studied risk factor for neuropsychiatric disability. Whether alterations in functional brain connectivity or pubertal delays are associated with aberrant cognitive-behavioral outcomes in individuals with KS is largely unknown. In this observational study, we investigated KS-related alterations in the resting-state brain network, testosterone level, and cognitive-behavioral impairment in adolescents with Klinefelter syndrome. We recruited 46 boys with KS, ages 8 to 17 years, and 51 age-matched typically developing (TD) boys. All participants underwent resting-state functional magnetic resonance imaging scans, pubertal, and cognitive-behavioral assessments. Resting-state functional connectivity and regional brain activity of the participants were assessed. We found widespread alterations in global functional connectivity among the inferior frontal gyrus, temporal-parietal area, and hippocampus in boys with KS. Aberrant regional activities, including enhanced fALFF in the motor area and reduced ReHo in the caudate, were also found in the KS group compared to the TD children. Further, using machine learning methods, brain network alterations in these regions accurately differentiated boys with KS from TD controls. Finally, we showed that the alterations of brain network properties not only effectively predict cognitive-behavioral impairment in boys with KS, but also appear to mediate the association between total testosterone level and language ability, a cognitive domain at particular risk for dysfunction in this condition. Our results offer an informatic neurobiological foundation for understanding cognitive-behavioral impairments in individuals with KS and contribute to our understanding of the interplay between pubertal status, brain function, and cognitive-behavioral outcome in this population.

Anterior–temporal hippocampal network mechanisms of left angular gyrus-navigated rTMS for memory improvement in aMCI: A sham-controlled study

IntroductionNeuro-navigated repetitive transcranial magnetic stimulation (rTMS) of the left angular gyrus has been broadly investigated for the treatment of amnestic mild cognitive impairment (aMCI). Although abnormalities in two hippocampal networks, the anterior–temporal (AT) and posterior–medial (PM) networks, are consistent with aMCI and are potential therapeutic targets for rTMS, the underlying mechanisms of the therapeutic effects of rTMS on hippocampal network connections remain unknown. Here, we assessed the impact of left angular gyrus rTMS on activity in these networks and explored whether the treatment response was due to the distance between the clinically applied target (the group average optimal site) and the personalized target in patients with aMCI. MethodsSixty subjects clinically diagnosed with aMCI participated in this study after 20 sessions of sham-controlled rTMS targeting the left angular gyrus. Resting-state functional magnetic resonance imaging and neuropsychological assessments were performed before and after rTMS. Functional connectivity alterations in the PM and AT networks were assessed using seed-based functional connectivity analysis and two-factor repeated measures analysis of variance (ANOVA). We then computed the correlations between the functional connectivity changes and clinical rating scales. Finally, we examined whether the Euclidean distance between the clinically applied and personalized targets predicted the subsequent treatment response. ResultsCompared with the sham group, the active rTMS group showed rTMS-induced deactivation of functional connectivity within the medial temporal lobe-AT network, with a negative correlation with episodic memory score changes. Moreover, the active rTMS lowers the interdependency of changes in the PM and AT networks. Finally, the Euclidean distance between the clinically applied and personalized target distances could predict subsequent network lever responses in the active rTMS group. ConclusionsNeuro-navigated rTMS selectively modulates widespread functional connectivity abnormalities in the PM and AT hippocampal networks in aMCI patients, and the modulation of hippocampal-AT network connectivity can efficiently reverse memory deficits. The results also highlight the necessity of personalized targets for fMRI.

Inhibition abilities and functional brain connectivity in school-aged term-born and preterm-born children.

Inhibition abilities are known to have impact on self-regulation, behavior, and academic success, and they are frequently impaired in children born preterm. We investigated the possible contributions of resting-state functional brain connectivity to inhibition following preterm birth. Forty-four preterm and 59 term-born participants aged 8-13 years were administered two inhibition tasks and resting-state functional MRI was performed. Functional connectivity (FC) networks were compared between groups using network-based statistics. Associations of FCNs and inhibition abilities were investigated through multivariate linear regression models accounting for the interaction between birth status and inhibition. NBS revealed weaker FC in children born preterm compared to term-born peers in connections between motor and supplementary motor regions, frontal lobe, precuneus, and insula. Irrespective of birth status, connections between the cerebellum, frontal, and occipital lobes and inter-lobar, subcortical, intra-hemispheric long-range connections were positively correlated with one of the two inhibition tasks. Preterm birth results in long-term alterations of FC at network level but these FCN alterations do not specifically account for inhibition problems in children born very preterm. Irrespective of birth status, significant associations were found between the subdomain of response inhibition and functional connectivity in some subnetworks. A group comparisons of functional brain connectivity measured by rsfMRI in school-aged children born very preterm and at term. The investigation of network-level functional connectivity at rest does not appear adequate to explain differences in inhibition abilities between children born very preterm and at term, hence other imaging techniques might be more suited to explore the underlying neural mechanisms of inhibition abilities in school-aged children born very preterm.

Functional connectivity of the default mode network in first-episode drug-naïve patients with major depressive disorder

BackgroundAlterations in the default mode network (DMN) have been reported in major depressive disorder (MDD), well-replicated robust alterations of functional connectivity (FC) of DMN remain to be established. Investigating the functional connections of DMN at the overall and subsystem level in early MDD patients has the potential to advance our understanding of the physiopathology of this disorder. MethodsWe recruited 115 first-episode drug-naïve patients with MDD and 137 demographic-matched healthy controls (HCs). We first compared FC within the DMN, within/between the DMN subsystems, and from DMN subsystems to the whole brain between groups. Subsequently, we explored correlations between clinical features and identified alterations in FC. ResultsFirst-episode drug-naïve patients with MDD showed significantly increased FC within the DMN, dorsal DMN and medial DMN. Each subsystem showed a distinct FC pattern with other brain networks. Increased FC between the subsystems (core DMN, dorsal DMN) and other networks was associated with more severe depressive symptoms, while medial DMN-related connectivity correlated with memory performance. LimitationsThe relatively large “pure” MDD sample could only be generalized to a limited population. And, atypical asymmetric FCs in the DMN related to MDD might be missed for only left-lateralized ROIs were used to avoid strong correlations between mirrored (right/left) seed regions. ConclusionThese findings suggest patients with early MDD showed distinct patterns of FC alterations throughout DMN and its subsystems, which were related to illness severity and illness-associated cognitive impairment, highlighting their clinical significance.

Racial Discrimination, Neural Connectivity, and Epigenetic Aging Among Black Women

Racial discrimination increases the risk of adverse brain health outcomes, potentially via neuroplastic changes in emotion processing networks. The involvement of deep brain regions (brainstem and midbrain) in these responses is unknown. Potential associations of racial discrimination with alterations in deep brain functional connectivity and accelerated epigenetic aging, a process that substantially increases vulnerability to health problems, are also unknown. To examine associations of racial discrimination with brainstem and midbrain resting-state functional connectivity (RSFC) and DNA methylation age acceleration (DMAA) among Black women in the US. This cohort study was conducted between January 1, 2012, and February 28, 2015, and included a community-based sample of Black women (aged ≥18 years) recruited as part of the Grady Trauma Project. Self-reported racial discrimination was examined in association with seed-to-voxel brain connectivity, including the locus coeruleus (LC), periaqueductal gray (PAG), and superior colliculus (SC); an index of DMAA (Horvath clock) was also evaluated. Posttraumatic stress disorder (PTSD), trauma exposure, and age were used as covariates in statistical models to isolate racial discrimination-related variance. Data analysis was conducted between January 10 and October 30, 2023. Varying levels of racial discrimination exposure, other trauma exposure, and posttraumatic stress disorder (PTSD). Racial discrimination frequency was assessed with the Experiences of Discrimination Scale, other trauma exposure was evaluated with the Traumatic Events Inventory, and current PTSD was evaluated with the PTSD Symptom Scale. Seed-to-voxel functional connectivity analyses were conducted with LC, PAG, and SC seeds. To assess DMAA, the Methylation EPIC BeadChip assay (Illumina) was conducted with whole-blood samples from a subset of 49 participants. This study included 90 Black women, with a mean (SD) age of 38.5 (11.3) years. Greater racial discrimination was associated with greater left LC RSFC to the bilateral precuneus (a region within the default mode network implicated in rumination and reliving of past events; cluster size k = 228; t85 = 4.78; P < .001, false discovery rate-corrected). Significant indirect effects were observed for the left LC-precuneus RSFC on the association between racial discrimination and DMAA (β [SE] = 0.45 [0.16]; 95% CI, 0.12-0.77). In this study, more frequent racial discrimination was associated with proportionately greater RSFC of the LC to the precuneus, and these connectivity alterations were associated with DMAA. These findings suggest that racial discrimination contributes to accelerated biological aging via altered connectivity between the LC and default mode network, increasing vulnerability for brain health problems.

Disrupted dynamic brain functional connectivity in male cocaine use disorder: Hyperconnectivity, strongly-connected state tendency, and links to impulsivity and borderline traits

Cocaine use is a major public health problem with serious negative consequences at both the individual and societal levels. Cocaine use disorder (CUD) is associated with cognitive and emotional impairments, often manifesting as alterations in brain functional connectivity (FC). This study employed resting-state functional magnetic resonance imaging (rs-fMRI) to examine dynamic FC in 38 male participants with CUD and 31 matched healthy controls. Using group spatial independent component analysis (group ICA) combined with sliding window approach, we identified two recurring distinct connectivity states: the strongly-connected state (state 1) and weakly-connected state (state 2). CUD patients exhibited significant increased mean dwell and fraction time in state 1, and increased transitions from state 2 to state 1, demonstrated significant strongly-connected state tendency. Our analysis revealed abnormal FC patterns that are state-dependent and state-shared in CUD patients. This study observed hyperconnectivity within the default mode network (DMN) and between DMN and other networks, which varied depending on the state. Furthermore, after adjustment for multiple comparisons, we found significant correlations between these altered dynamic FCs and clinical measures of impulsivity and borderline personality disorder. The disrupted FC and repetitive effects of precuneus and angular gyrus across correlations suggested that they might be the important hub of neural circuits related behaviorally and mentally in CUD. In summary, our study highlighted the potential of these disrupted FC as neuroimaging biomarkers and therapeutic targets, and provided new insights into the understanding of the neurophysiologic mechanisms of CUD.

Altered dynamic functional connectivity of motor cerebellum with sensorimotor network and default mode network in juvenile myoclonic epilepsy.

To investigate whether changes occur in the dynamic functional connectivity (dFC) of motor cerebellum with cerebral cortex in juvenile myoclonic epilepsy (JME). We adopted resting-state electroencephalography-functional magnetic resonance imaging (EEG-fMRI) and a sliding-window approach to explore the dFC of motor cerebellum with cortex in 36 JME patients compared with 30 and age-matched health controls (HCs). The motor cerebellum was divided into five lobules (I-V, VI, VIIb, VIIIa, and VIIIb). Additionally, correlation analyses were conducted between the variability of dFC and clinical variables in the Juvenile Myoclonic Epilepsy (JME) group, such as disease duration, age at disease onset, and frequency score of myoclonic seizures. Compared to HCs, the JME group presented increased dFC between the motor cerebellum with SMN and DMN. Specifically, connectivity between lobule VIIb and left precentral gyrus and right inferior parietal lobule (IPL); between lobule VIIIa and right inferior frontal gyrus (IFG) and left IPL; and between lobule VIIIb and left middle frontal gyrus (MFG), bilateral superior parietal gyrus (SPG), and left precuneus. In addition, within the JME group, the strength of dFC between lobule VIIIb and left precuneus was negatively (r = -0.424, p = 0.025, Bonferroni correction) related with the frequency score of myoclonic seizures. In patients with JME, there is a functional dysregulation between the motor cerebellum with DMN and SMN, and the variability of dynamic functional connectivity may be closely associated with the occurrence of motor symptoms in JME.

Sex differences in aberrant functional connectivity of three core networks and subcortical networks in medication-free adolescent-onset major depressive disorder.

Major depressive disorder demonstrated sex differences in prevalence and symptoms, which were more pronounced during adolescence. Yet, research on sex-specific brain network characteristics in adolescent-onset major depressive disorder remains limited. This study investigated sex-specific and nonspecific alterations in resting-state functional connectivity of three core networks (frontoparietal network, salience network, and default mode network) and subcortical networks in adolescent-onset major depressive disorder, using seed-based resting-state functional connectivity in 50 medication-free patients with adolescent-onset major depressive disorder and 56 healthy controls. Irrespective of sex, compared with healthy controls, adolescent-onset major depressive disorder patients showed hypoconnectivity between bilateral hippocampus and right superior temporal gyrus (default mode network). More importantly, we further found that females with adolescent-onset major depressive disorder exhibited hypoconnectivity within the default mode network (medial prefrontal cortex), and between the subcortical regions (i.e. amygdala, striatum, and thalamus) with the default mode network (angular gyrus and posterior cingulate cortex) and the frontoparietal network (dorsal prefrontal cortex), while the opposite patterns of resting-state functional connectivity alterations were observed in males with adolescent-onset major depressive disorder, relative to their sex-matched healthy controls. Moreover, several sex-specific resting-state functional connectivity changes were correlated with age of onset, sleep disturbance, and anxiety in adolescent-onset major depressive disorder with different sex. These findings suggested that these sex-specific resting-state functional connectivity alterations may reflect the differences in brain development or processes related to early illness onset, underscoring the necessity for sex-tailored diagnostic and therapeutic approaches in adolescent-onset major depressive disorder.

Functional connectivity changes in the brain of adolescents with internet addiction: A systematic literature review of imaging studies

Internet usage has seen a stark global rise over the last few decades, particularly among adolescents and young people, who have also been diagnosed increasingly with internet addiction (IA). IA impacts several neural networks that influence an adolescent’s behaviour and development. This article issued a literature review on the resting-state and task-based functional magnetic resonance imaging (fMRI) studies to inspect the consequences of IA on the functional connectivity (FC) in the adolescent brain and its subsequent effects on their behaviour and development. A systematic search was conducted from two databases, PubMed and PsycINFO, to select eligible articles according to the inclusion and exclusion criteria. Eligibility criteria was especially stringent regarding the adolescent age range (10–19) and formal diagnosis of IA. Bias and quality of individual studies were evaluated. The fMRI results from 12 articles demonstrated that the effects of IA were seen throughout multiple neural networks: a mix of increases/decreases in FC in the default mode network; an overall decrease in FC in the executive control network; and no clear increase or decrease in FC within the salience network and reward pathway. The FC changes led to addictive behaviour and tendencies in adolescents. The subsequent behavioural changes are associated with the mechanisms relating to the areas of cognitive control, reward valuation, motor coordination, and the developing adolescent brain. Our results presented the FC alterations in numerous brain regions of adolescents with IA leading to the behavioural and developmental changes. Research on this topic had a low frequency with adolescent samples and were primarily produced in Asian countries. Future research studies of comparing results from Western adolescent samples provide more insight on therapeutic intervention.

Unraveling Alzheimer's Disease: Investigating Dynamic Functional Connectivity in the Default Mode Network through DCC-GARCH Modeling.

Alzheimer's disease (AD) has a prolonged latent phase. Sensitive biomarkers of amyloid beta ( ), in the absence of clinical symptoms, offer opportunities for early detection and identification of patients at risk. Current biomarkers, such as CSF and PET biomarkers, are effective but face practical limitations due to high cost and limited availability. Recent blood plasma biomarkers, though accessible, still incur high costs and lack physiological significance in the Alzheimer's process. This study explores the potential of brain functional connectivity (FC) alterations associated with AD pathology as a non-invasive avenue for detection. While current stationary FC measurements lack sensitivity at the single-subject level, our investigation focuses on dynamic FC using resting-state functional MRI (rs-fMRI) and introduces the Generalized Auto-Regressive Conditional Heteroscedastic Dynamic Conditional Correlation (DCC-GARCH) model. Our findings demonstrate the superior sensitivity of DCC-GARCH to CSF status, and offer key insights into dynamic functional connectivity analysis in AD.

Epilepsy alters brain networks in patients with insular glioma.

We intend to elucidate the alterations of cerebral networks in patients with insular glioma-related epilepsy (GRE) based on resting-state functional magnetic resonance images. We collected 62 insular glioma patients, who were subsequently categorized into glioma-related epilepsy (GRE) and glioma with no epilepsy (GnE) groups, and recruited 16 healthy individuals matched to the patient's age and gender to form the healthy control (HC) group. Graph theoretical analysis was applied to reveal differences in sensorimotor, default mode, visual, and executive networks among different subgroups. No significant alterations in functional connectivity were found in either hemisphere insular glioma. Using graph theoretical analysis, differences were found in visual, sensorimotor, and default mode networks (p < 0.05). When the glioma located in the left hemisphere, the degree centrality was reduced in the GE group compared to the GnE group. When the glioma located in the right insula, the degree centrality, nodal efficiency, nodal local efficiency, and nodal clustering coefficient of the GE group were lower than those of the GnE group. The impact of insular glioma itself and GRE on the brain network is widespread. The networks altered by insular GRE differ depending on the hemisphere location. GRE reduces the nodal properties of brain networks than that in insular glioma.

Reduced functional connectivity induced by longitudinal alterations of structure and perfusion may be associated with cognitive impairment in patients on maintenance hemodialysis.

Hemodialysis (HD) leads to cognitive impairment; however, the pathophysiology of maintenance HD remains unclear. This study aimed to investigate the longitudinal alterations in gray matter volume (GMV) and cerebral blood flow (CBF) in patients on HD at follow-up compared with baseline, examine the alterations in functional connectivity (FC) by defining co-changed brain regions as seed points, and investigate the correlation between the co-changed brain regions and neuropsychological test scores. Twenty-seven patients with HD and 30 healthy controls were enrolled in this study. All participants underwent high-resolution T1-weighted imaging, arterial spin labeling, and functional MR imaging to measure GMV, CBF, and FC. The patients on HD were assessed at baseline and 3years subsequently. The right and left medial superior frontal gyrus (SFGmed.L) exhibited significantly lower GMV and CBF in patients on HD at follow-up compared with baseline and lower FC between the SFGmed.L and left middle temporal gyrus (MTG.L). FC between the SFGmed.L and MTG.L was positively correlated with neuropsychological test scores in the HD group at follow-up. Reduced GMV and CBF may result in decreased FC between the SFGmed.L and MTG.L, which may be associated with cognitive impairment in patients on maintenance HD. Our findings provide unique insights into the pathological mechanisms of patients on maintenance HD with cognitive impairment.

The altered functional status in vestibular migraine: A meta‐analysis

AbstractPurposeVestibular migraine (VM) is a disorder with prominent vestibular symptoms that are causally correlated with migraine and is the most prevalent neurological cause of episodic vertigo. Nevertheless, the functional underpinnings of VM remain largely unclear. This study aimed to reveal concordant alteration patterns of functional connectivity (FC) in VM patients.MethodsWe searched literature measuring resting‐state FC abnormalities of VM patients in PubMed, Embase, Cochrane, and Scopus databases before May 2023. Furthermore, we applied the anisotropic effect size‐signed differential mapping (AES‐SDM) to conduct a whole‐brain voxel‐wise meta‐analysis to identify the convergence of FC alterations in VM patients.ResultsNine studies containing 251 VM patients and 257 healthy controls (HCs) were included. Relative to HCs, VM patients showed reduced activity in the left superior temporal gyrus and left midcingulate/paracingulate gyri, and increased activity in the precuneus, right superior parietal gyrus, and right middle frontal gyrus. Jackknife's analysis and subgroup analysis further supported the generalization and robustness of the main results. Furthermore, meta‐regression analyses indicated that the Dizziness Handicap Inventory (DHI) ratings were positively correlated with the activity in the precuneus, while higher Headache Impact Test‐6 and DHI scores were associated with lower activity within the left midcingulate/paracingulate gyri.ConclusionsThe study indicates that VM is associated with specific functional deficits of VM patients in crucial regions involved in the vestibular and pain networks and provides further information on the pathophysiological mechanisms of VM.

Structural and functional disruption of subcortical limbic structures related with executive function in pediatric bipolar disorder

BackgroundImpaired cognition has been demonstrated in pediatric bipolar disorder (PBD). The subcortical limbic structures play a key role in PBD. However, alternations of anatomical and functional characteristics of subcortical limbic structures and their relationship with neurocognition of PBD remain unclear. MethodsThirty-six PBD type I (PBD-I) (15.36 ± 0.32 years old), twenty PBD type II (PBD-II) (14.80 ± 0.32 years old) and nineteen age-gender matched healthy controls (HCs) (14.16 ± 0.36 years old) were enlisted. Primarily, the volumes of the subcortical limbic structures were obtained and differences in the volumes were evaluated. Then, these structures served as seeds of regions of interest to calculate the voxel-wised functional connectivity (FC). After that, correlation analysis was completed between volumes and FC of brain regions showing significant differences and neuropsychological tests. ResultsCompared to HCs, both PBD-I and PBD-II patients showed a decrease in the Stroop color word test (SCWT) and digit span backward test scores. Compared with HCs, PBD-II patients exhibited a significantly increased volume of right septal nuclei, and PBD-I patients presented increased FC of right nucleus accumbens and bilateral pallidum, of right basal forebrain with right putamen and left pallidum. Both the significantly altered volumes and FC were negatively correlated with SCWT scores. SignificanceThe study revealed the role of subcortical limbic structural and functional abnormalities on cognitive impairments in PBD patients. These may have far-reaching significance for the etiology of PBD and provide neuroimaging clues for the differential diagnosis of PBD subtypes. ConclusionsDistinctive features of neural structure and function in PBD subtypes may contribute to better comprehending the potential mechanisms of PBD.

Amygdala structural and functional reorganization as an indicator of affective dysfunction in patients with tinnitus.

The aim of this study was to systematically investigate structural and functional alterations in amygdala subregions using multimodal magnetic resonance imaging (MRI) in patients with tinnitus with or without affective dysfunction. Sixty patients with persistent tinnitus and 40 healthy controls (HCs) were recruited. Based on a questionnaire assessment, 26 and 34 patients were categorized into the tinnitus patients with affective dysfunction (TPAD) and tinnitus patients without affective dysfunction (TPWAD) groups, respectively. MRI-based measurements of gray matter volume, fractional anisotropy (FA), fractional amplitude of low-frequency fluctuations (fALFF), regional homogeneity (ReHo), degree centrality (DC), and functional connectivity (FC) were conducted within 14 amygdala subregions for intergroup comparisons. Associations between the MRI properties and clinical characteristics were estimated via partial correlation analyses. Compared with that of the HCs, the TPAD and TPWAD groups exhibited significant structural and functional changes, including white matter integrity (WMI), fALFF, ReHo, DC, and FC alterations, with more pronounced WMI changes in the TPAD group, predominantly within the left auxiliary basal or basomedial nucleus (AB/BM), right central nucleus, right lateral nuclei (dorsal portion), and left lateral nuclei (ventral portion containing basolateral portions). Moreover, the TPAD group exhibited decreased FC between the left AB/BM and left middle occipital gyrus and right superior frontal gyrus (SFG), left basal nucleus and right SFG, and right lateral nuclei (intermediate portion) and right SFG. In combination, these amygdalar alterations exhibited a sensitivity of 65.4% and specificity of 96.9% in predicting affective dysfunction in patients with tinnitus. Although similar structural and functional amygdala remodeling were observed in the TPAD and TPWAD groups, the changes were more pronounced in the TPAD group. These changes mainly involved alterations in functionality and white matter microstructure in various amygdala subregions; in combination, these changes could serve as an imaging-based predictor of emotional disorders in patients with tinnitus.

Attenuation of the BOLD fMRI Signal and Changes in Functional Connectivity Affecting the Whole Brain in Presence of Brain Metastasis.

To date, there are almost no investigations addressing functional connectivity (FC) in patients with brain metastases (BM). In this retrospective study, we investigate the influence of BM on hemodynamic brain signals derived from functional magnetic resonance imaging (fMRI) and FC. Motor-fMRI data of 29 patients with BM and 29 matched healthy controls were analyzed to assess percent signal changes (PSC) in the ROIs motor cortex, premotor cortex, and supplementary motor cortex and FC in the sensorimotor, default mode, and salience networks using Statistical Parametric Mapping (SPM12) and marsbar and CONN toolboxes. In the PSC analysis, an attenuation of the BOLD signal in the metastases-affected hemisphere compared to the contralateral hemisphere was significant only in the supplementary motor cortex during hand movement. In the FC analysis, we found alterations in patients' FC compared to controls in all examined networks, also in the hemisphere contralateral to the metastasis. This indicates a qualitative attenuation of the BOLD signal in the affected hemisphere and also that FC is altered by the presence of BM, similarly to what is known for primary brain tumors. This transformation is not only visible in the infiltrated hemisphere, but also in the contralateral one, suggesting an influence of BM beyond local damage.

Dynamical and individualised approach of transcranial ultrasound neuromodulation effects in non-human primates

Low-frequency transcranial ultrasound stimulation (TUS) allows to alter brain functioning with a high spatial resolution and to reach deep targets. However, the time-course of TUS effects remains largely unknown. We applied TUS on three brain targets for three different monkeys: the anterior medial prefrontal cortex, the supplementary motor area and the perigenual anterior cingulate cortex. For each, one resting-state fMRI was acquired between 30 and 150 min after TUS as well as one without stimulation (control). We captured seed-based brain connectivity changes dynamically and on an individual basis. We also assessed between individuals and between targets homogeneity and brain features that predicted TUS changes. We found that TUS prompts heterogenous functional connectivity alterations yet retain certain consistent changes; we identified 6 time-courses of changes including transient and long duration alterations; with a notable degree of accuracy we found that brain alterations could partially be predicted. Altogether, our results highlight that TUS induces heterogeneous functional connectivity alterations. On a more technical point, we also emphasize the need to consider brain changes over-time rather than just observed during a snapshot; to consider inter-individual variability since changes could be highly different from one individual to another.

#659 Analysis of functional brain connectivity in patient with end-stage kidney disease undergoing peritoneal dialysis

Abstract Background and Aims Neurological complications are common in patients with end-stage kidney disease (ESKD). However, the mechanisms underlying neurological complications of ESKD are poorly understood. Research on brain connectivity in patients undergoing peritoneal dialysis (PD) is limited. In this study, we aimed to examine alterations in functional brain connectivity in patients with ESKD undergoing PD compared to the control group using functional near infrared spectroscopy (fNIRS). Method We prospectively enrolled 20 patients with ESKD who had been receiving PD for more than 6 months and had no prior history of psychiatric or neurological diseases, along with 20 healthy controls. The fNIRS data were obtained using an NIRSIT Lite instrument. After processing all the data, we used Pearson correlation analysis to create a weighted connectivity matrix. Functional connectivity measures were derived from the connectivity matrix using graph theory. Functional connectivity measures were compared between the controls and patients with ESKD undergoing PD. Results The average degree, average strength, and small-worldness were significantly lower in patients with ESKD undergoing PD than in the controls (9.333 [8.000∼11.433] vs. 12.733 [9.600∼13.400], p = 0.030; 6.865 [4.768∼7.560] vs. 8.432 [6.593∼9.432], p = 0.036; 0.836 [0.724∼0.900] vs. 0.949 [0.882∼0.972], p = 0.025, respectively). Conclusion This study demonstrated significant alterations in functional brain connectivity in patients with ESKD undergoing PD, suggesting that functional brain connectivity is significantly reduced in patients with ESKD undergoing PD when compared with that in healthy controls.

Abnormal intrinsic functional hubs and connectivity in patients with post-stroke depression.

The present study aimed to investigate the specific alterations of brain networks in patients with post-stroke depression (PSD), and further assist in elucidating the brain mechanisms underlying the PSD which would provide supporting evidence for early diagnosis and interventions for the disease. Resting-state functional magnetic resonace imaging data were acquired from 82 nondepressed stroke patients (Stroke), 39 PSD patients, and 74 healthy controls (HC). Voxel-wise degree centrality (DC) conjoined with seed-based functional connectivity (FC) analyses were performed to investigate the PSD-related connectivity alterations. The relationship between these alterations and depression severity was further examined in PSD patients. Relative to both Stroke and HC groups, (1) PSD showed increased centrality in regions within the default mode network (DMN), including contralesional angular gyrus (ANG), posterior cingulate cortex (PCC), and hippocampus (HIP). DC values in contralesional ANG positively correlated with the Patient Health Questionnaire-9 (PHQ-9) scores in PSD group. (2) PSD exhibited increased connectivity between these three seeds showing altered DC and regions within the DMN: bilateral medial prefrontal cortex and middle temporal gyrus and ipsilesional superior parietal gyrus, and regions outside the DMN: bilateral calcarine, ipsilesional inferior occipital gyrus and contralesional lingual gyrus, while decreased connectivity between contralesional ANG and contralesional supramarginal gyrus. Moreover, these FC alterations could predict PHQ-9 scores in PSD group. These findings highlight that PSD was related with increased functional connectivity strength in some areas within the DMN, which might be attribute to the specific alterations of connectivity between within DMN and outside DMN regions in PSD.

Analysis of functional connectivity changes in attention networks and default mode networks in patients with depression and insomnia.

Major Depressive Disorder (MDD) and Insomnia Disorder (ID) are prevalent psychiatric conditions often occurring concurrently, leading to substantial impairment in daily functioning. Understanding the neurobiological underpinnings of these disorders and their comorbidity is crucial for developing effective interventions. This study aims to analyze changes in functional connectivity within attention networks and default mode networks in patients with depression and insomnia. The functional connectivity alterations in individuals with MDD, ID, comorbid MDD and insomnia (iMDD), and healthy controls (HC) were assessed from a cohort of 174 participants. They underwent rs-fMRI scans, demographic assessments, and scale evaluations for depression and sleep quality. Functional connectivity analysis was conducted using region-of-interest (ROI) and whole-brain methods. The MDD and iMDD groups exhibited higher Hamilton Depression Scale (HAMD) scores compared to HC and ID groups (P < 0.001). Both ID and MDD groups displayed enhanced connectivity between the left and right orbital frontal cortex compared to HC (P < 0.05), while the iMDD group showed reduced connectivity compared to HC and ID groups (P < 0.05). In the left insula, reduced connectivity with the right medial superior frontal gyrus was observed across patient groups compared to HC (P < 0.05), with the iMDD group showing increased connectivity compared to MDD (P < 0.05). Moreover, alterations in functional connectivity between the left thalamus and left temporal pole were found in iMDD compared to HC and MDD (P < 0.05). Correlation analyses revealed associations between abnormal connectivity and symptom severity in MDD and ID groups. Our findings demonstrate distinct patterns of altered functional connectivity in individuals with MDD, ID, and iMDD compared to healthy controls. These findings contribute to a better understanding of the pathophysiology of depression and insomnia, which could be used as a reference for the diagnosis and treatments of these patients.