Although dopaminergic disturbances are well-known in schizophrenia, the understanding of dopamine-related brain dynamics remains limited. This study investigates the dynamic coactivation patterns (CAPs) associated with the substantia nigra (SN), a key dopaminergic nucleus, in first-episode treatment-naïve patients with schizophrenia (FES).

Resting-state fMRI data were collected from 84 FES and 94 healthy controls (HCs). Frame-wise clustering was implemented to generate CAPs related to SN activation or deactivation. Connectome features of each CAP were derived using an edge-centric method. The occurrence for each CAP and the balance ratio for antagonistic CAPs were calculated and compared between two groups, and correlations between temporal dynamic metrics and symptom burdens were explored.

Functional reconfigurations in CAPs exhibited significant differences between the activation and deactivation states of SN. During SN activation, FES more frequently recruited a CAP characterized by activated default network, language network, control network, and the caudate, compared to HCs (F = 8.54, FDR-p = 0.030). Moreover, FES displayed a tilted balance towards a CAP featuring SN-coactivation with the control network, caudate, and thalamus, as opposed to its antagonistic CAP (F = 7.48, FDR-p = 0.030). During SN deactivation, FES exhibited increased recruitment of a CAP with activated visual and dorsal attention networks but decreased recruitment of its opposing CAP (F = 6.58, FDR-p = 0.034).

Our results suggest that neuroregulatory dysfunction in dopaminergic pathways involving SN potentially mediates aberrant time-varying functional reorganizations in schizophrenia. This finding enriches the dopamine hypothesis of schizophrenia from the perspective of brain dynamics.

Previous research on the changes in resting-state functional connectivity (rsFC) in anorexia nervosa (AN) has been limited by an insufficient sample size, which reduced the reliability of the results and made it difficult to set the whole brain as regions of interest (ROIs).

We analyzed functional magnetic resonance imaging data from 114 female AN patients and 135 healthy controls (HC) and obtained self-reported psychological scales, including eating disorder examination questionnaire 6.0. One hundred sixty-four cortical, subcortical, cerebellar, and network parcellation regions were considered as ROIs. We calculated the ROI-to-ROI rsFCs and performed group comparisons.

Compared to HC, AN patients showed 12 stronger rsFCs mainly in regions containing dorsolateral prefrontal cortex (DLPFC), and 33 weaker rsFCs primarily in regions containing cerebellum, within temporal lobe, between posterior fusiform cortex and lateral part of visual network, and between anterior cingulate cortex (ACC) and thalamus (p < 0.01, false discovery rate [FDR] correction). Comparisons between AN subtypes showed that there were stronger rsFCs between right lingual gyrus and right supracalcarine cortex and between left temporal occipital fusiform cortex and medial part of visual network in the restricting type compared to the binge/purging type (p < 0.01, FDR correction).

Stronger rsFCs in regions containing mainly DLPFC, and weaker rsFCs in regions containing primarily cerebellum, within temporal lobe, between posterior fusiform cortex and lateral part of visual network, and between ACC and thalamus, may represent categorical diagnostic markers discriminating AN patients from HC.

Major depressive disorder (MDD) is associated not only with disorders in multiple brain networks but also with frequency-specific brain activities. The abnormality of spatiotemporal networks in patients with MDD remains largely unclear.

We investigated the alterations of the global spatiotemporal network in MDD patients using a large-sample multicenter resting-state functional magnetic resonance imaging dataset. The spatiotemporal characteristics were measured by the variability of global signal (GS) and its correlation with local signals (GSCORR) at multiple frequency bands. The association between these indicators and clinical scores was further assessed.

The GS fluctuations were reduced in patients with MDD across the full frequency range (0–0.1852 Hz). The GSCORR was also reduced in the MDD group, especially in the relatively higher frequency range (0.0728–0.1852 Hz). Interestingly, these indicators showed positive correlations with depressive scores in the MDD group and relative negative correlations in the control group.

The GS and its spatiotemporal effects on local signals were weakened in patients with MDD, which may impair inter-regional synchronization and related functions. Patients with severe depression may use the compensatory mechanism to make up for the functional impairments.

Late-life suicide is the most serious consequences of late-life depression (LLD). Nevertheless, suicidal behavior is complex and hard to predict. With the help of MRI scans and machine learning algorithm, we aim to examine the neural signatures of suicidality in patients of LLD.

We recruited 83 patients of LLD with a mean age of 68.8 years, where 48 were suicidal (26 with suicidal ideation and 22 with past suicide attempts). Cross-sample entropy (CSE) analysis was employed to analyze the resting-state function MRI data. Three-dimensional CSE volume in 90 region-of-interest of the brain in each participant was input into convolutional neural networks (CNN) to test the classification accuracy of suicidality.

After six-fold cross-validation, we found several regions in the default mode, fronto-parietal, and cingulo-opercular resting-state networks to have a mean accuracy above 75% to predict suicidality. Moreover, the models with right amygdala and left caudate provided the most reliable accuracy in all cross-validation folds, signifying their unique roles in late-life suicide.

Our results provide potential targets for intervention or biomarkers in late-life suicide. More research must be conducted to consolidate our results with scalable implementation in clinical setting.

Fatigue is a central feature of myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS), but many ME/CFS patients also report comorbid pain symptoms. It remains unclear whether these symptoms are related to similar or dissociable brain networks. This study used resting-state fMRI to disentangle networks associated with fatigue and pain symptoms in ME/CFS patients, and to link changes in those networks to clinical improvements following cognitive behavioral therapy (CBT).

Relationships between pain and fatigue symptoms and cortico-cortical connectivity were assessed within ME/CFS patients at baseline (N = 72) and after CBT (N = 33) and waiting list (WL, N = 18) and compared to healthy controls (HC, N = 29). The analyses focused on four networks previously associated with pain and/or fatigue, i.e. the fronto-parietal network (FPN), premotor network (PMN), somatomotor network (SMN), and default mode network (DMN).

At baseline, variation in pain and fatigue symptoms related to partially dissociable brain networks. Fatigue was associated with higher SMN-PMN connectivity and lower SMN-DMN connectivity. Pain was associated with lower PMN-DMN connectivity. CBT improved SMN-DMN connectivity, compared to WL. Larger clinical improvements were associated with larger increases in frontal SMN-DMN connectivity. No CBT effects were observed for PMN-DMN or SMN-PMN connectivity.

These results provide insight into the dissociable neural mechanisms underlying fatigue and pain symptoms in ME/CFS and how they are affected by CBT in successfully treated patients. Further investigation of how and in whom behavioral and biomedical treatments affect these networks is warranted to improve and individualize existing or new treatments for ME/CFS.

Understanding the neural mechanism underlying the transition from suicidal ideation to action is crucial but remains unclear. To explore this mechanism, we combined resting-state functional connectivity (rsFC) and computational modeling to investigate differences between those who attempted suicide(SA) and those who hold only high levels of suicidal ideation(HSI).

A total of 120 MDD patients were categorized into SA group (n=47) and HSI group (n=73). All participants completed a resting-state functional MRI scan, with three subregions of the insula and the dorsal anterior cingulate cortex (dACC) being chosen as the region of interest (ROI) in seed-to-voxel analyses. Additionally, 86 participants completed the balloon analogue risk task (BART), and a five-parameter Bayesian modeling of BART was estimated.

In the SA group, the FC between the ventral anterior insula (vAI) and the superior/middle frontal gyrus (vAI-SFG, vAI-MFG), as well as the FC between posterior insula (pI) and MFG (pI-MFG), were lower than those in HSI group. The correlation analysis showed a negative correlation between the FC of vAI-SFG and psychological pain avoidance in SA group, whereas a positive correlation in HSI group. Furthermore, the FC of vAI-MFG displayed a negative correlation with loss aversion in SA group, while a positive correlation was found with psychological pain avoidance in HSI group.

In current study, two distinct neural mechanisms were identified in the insula which involving in the progression from suicidal ideation to action. Dysfunction in vAI FCs may gradually stabilize as individuals experience heightened psychological pain, and a shift from positive to negative correlation patterns of vAI-MFC may indicate a transition from state to trait impairment. Additionally, the dysfunction in PI FC may lead to a lowered threshold for suicide by blunting the perception of physical harm.

Schizotypy is associated with increased vulnerability to schizophrenia spectrum disorders. Therefore, investigation of its brain correlates seems prominent for better understanding of schizophrenia-spectrum continuum as well as for development of biological treatments for schizotypal personality disorder. Functional alterations of prefrontal cortex (PFC) and their associations with clinical symptoms are well-known to exist in schizophrenia. However, their relevance to schizotypy remains unclear.

The aim of the study was to check for associations between schizotypal traits in a non-clinical sample and whole-brain functional connectivity (FC) of lateral as well as medial PFC (lPFC and mPFC, respectively).

Eighty-two healthy individuals (52 females, mean age 24.8±5.48) filled out the Schizotypal Personality Questionnaire (SPQ-74) and underwent resting-state fMRI (3T). Seeds in lPFC and mPFC were taken from frontoparietal and default mode networks (atlas by Yeo et al., 2011). We analyzed correlations between four schizotypal factors (cognitive/perceptual, paranoid, negative, and disorganization; Stefanis et al., 2004) and whole-brain FC of the seeds (statistical threshold: p<.001 voxelwise; p[FDR]<.05 clusterwise).

Cognitive/perceptual factor (‘Odd beliefs/magical thinking’ and ‘Unusual perceptual experiences’ SPQ-74 subscales) is negatively correlated to FC of bilateral mPFC with a cluster in the right cerebellum (Crus 1, 2).

Prefrontal-cerebellar dysconnectivity may be one of the neurobiological factors underlying positive-symptoms-like schizotypal traits in non-clinical subjects. To some extent, it coincides with the data on associations between functional features of these brain structures and positive symptoms in schizophrenia (Pinheiro et al., 2021; Goghari et al., 2010).

The study was supported by RFBR Grant 20-013-00748.

Schizophrenia is heterogeneous in terms of symptoms and outcome, but neurobiology of this heterogeneity is not well-studied. Local correlation analysis of fMRI data provides a measure of local coherence, i.e., average correlation between BOLD-signal in a voxel and its neighbours. Local correlation is a promising approach, and it seems important to find links between local brain coherence and schizophrenia outcome.

We aimed to compare brain local coherence between schizophrenia patients with varied long-term outcomes and healthy controls (HC).

Patients with chronic schizophrenia spectrum disorders (37 males, mean age 41.5±5.5) and HC (17 males, mean age 38±7.7) underwent resting-state fMRI (3T). Cluster analysis based on PANSS and PSP allowed us to allocate patients into two subgroups (N = 13/24). The second subgroup had significantly more marked negative and general psychopathology symptoms and worse functioning than the first subgroup. Local coherence in the brain was compared between clinical subgroups and HC (ANOVA, p<.001 voxelwise, p[FDR]<.05 clusterwise).

Local coherence in the paracingulate gyri bilaterally ({-2; 58; 14}; 2712 mm3) differentiated the groups. Post hoc analysis revealed decreased local coherence in the subgroup with poorer outcome compared to HC, along with the absence of differences between the subgroup with better outcome and HC. There were no differences between clinical subgroups.

Hypoactivity of the cingulate cortex is related to negative symptoms (Bersani et al., 2014). Their severity, in turn, is strongly associated with outcome. Thus, local coherence in the cingulate cortex may be one of the factors which underlie outcome heterogeneity.

No significant relationships.

Patients with schizophrenia spectrum disorders (SP) demonstrate heterogeneity in executive functions (EF) associated with the quality of outcome. However, neurobiological mechanisms of this heterogeneity are understudied.

We aimed to identify features of resting-state functional connectivity (FC) within the frontoparietal network (FPN) that discriminate between SP and healthy individuals (HI) with better and worse EF.

Twenty-five SP (mean age 20.8±3.23, illness duration 1.3±2.1 years, all males) and twenty-six HI (mean age 25.17±3.46, all males) underwent EF assessment (4 verbal fluency tests and a modified Stroop task) as well as resting-state fMRI (3T).

We used k-means clustering based on EF scores to divide all participants into groups with worse (15 SP, 6 HI) and better EF (10 SP, 20 HI). These groups differed in productivity of all verbal fluency tasks and performance time of the Stroop task. Differences between four subgroups (HI/SP with worse/better EF) were revealed in FC between the cingulate and lateral prefrontal cortex in the left hemisphere (ANCOVA, p-uncorrected<.005, p[FDR]<.05; Fig. 1). SP and HI within each group demonstrated a similar FC pattern. SP with poorer EF had increased FC, compared to HI with higher EF. HI with poorer EF demonstrated increased FC, compared to HI and SP with better EF.

FC within FPN may be one of the neurophysiological underpinnings of EF heterogeneity in SP as well as in HI. Further machine learning fMRI studies are needed to clarify whether FC within FPN is a prognostic marker in schizophrenia.

The study was supported by RFBR Grant 20-013-00748.

Repetitive negative thinking (RNT), a cognitive process that encompasses past (rumination) and future (worry) directed thoughts focusing on negative experiences and the self, is a transdiagnostic construct that is especially relevant for major depressive disorder (MDD). Severe RNT often occurs in individuals with severe levels of MDD, which makes it challenging to disambiguate the neural circuitry underlying RNT from depression severity.

We used a propensity score, i.e., a conditional probability of having high RNT given observed covariates to match high and low RNT individuals who are similar in the severity of depression, anxiety, and demographic characteristics. Of 148 MDD individuals, we matched high and low RNT groups (n = 50/group) and used a data-driven whole-brain voxel-to-voxel connectivity pattern analysis to investigate the resting-state functional connectivity differences between the groups.

There was an association between RNT and connectivity in the bilateral superior temporal sulcus (STS), an important region for speech processing including inner speech. High relative to low RNT individuals showed greater connectivity between right STS and bilateral anterior insular cortex (AI), and between bilateral STS and left dorsolateral prefrontal cortex (DLPFC). Greater connectivity in those regions was specifically related to RNT but not to depression severity.

RNT intensity is directly related to connectivity between STS and AI/DLPFC. This might be a mechanism underlying the role of RNT in perceptive, cognitive, speech, and emotional processing. Future investigations will need to determine whether modifying these connectivities could be a treatment target to reduce RNT.

To determine whether depressive symptoms in traumatic brain injury (TBI) patients were associated with altered resting-state functional connectivity (rs-fc) or voxel-based morphology in brain regions involved in emotional regulation and associated with depression.

In the present study, we examined 79 patients (57 males; age range = 17–70 years, M ± s.d. = 38 ± 16.13; BDI-II, M ± s.d. = 9.84 ± 8.67) with TBI. We used structural MRI and resting-state fMRI to examine whether there was a relationship between depression, as measured with the Beck Depression Inventory (BDI-II), and the voxel-based morphology or functional connectivity in regions previously identified as involved in emotional regulation in patients following TBI. Patients were at least 4 months post-TBI (M ± s.d. = 15.13 ± 11.67 months) and the severity of the injury included mild to severe cases [Glasgow Coma Scale (GCS), M ± s.d. = 6.87 ± 3.31].

Our results showed that BDI-II scores were unrelated to voxel-based morphology in the examined regions. We found a positive association between depression scores and rs-fc between limbic regions and cognitive control regions. Conversely, there was a negative association between depression scores and rs-fc between limbic and frontal regions involved in emotion regulation.

These findings lead to a better understanding of the exact mechanisms that contribute to depression following TBI and better inform treatment decisions.

Schizophrenia patients with auditory verbal hallucinations (AVH) demonstrate impaired functional connectivity (FC) between brain regions, involved in executive functions and language. However, as most studies compare patients to healthy controls, the specificity of these findings either for schizophrenia in general or for AVH is unclear.

We aimed to compare whole-brain resting-state FC of main language brain regions between schizophrenia patients with and without history of AVH and healthy controls.

Schizophrenia male patients with (n=31; mean age 29,8±11,6) or without history of AVH (n=16; 29±12,4) and 39 healthy male controls (30±8,9) underwent resting-state fMRI on 3T Philips scanner. No between-group differences in age, illness duration, and severity of clinical symptoms except AVH were revealed. Regions of interest (ROIs) were taken from the independent fMRI study with conventional language localizer and included left inferior frontal gyrus (l_IFG) and superior temporal gyri (STG) bilaterally. Whole-brain FC of each ROI was compared between groups (ANCOVA; p<.005 voxelwise; p(FDR)<.017 clusterwise, corrected for number of ROIs) with post hoc tests.

Decreased FC between each STG (left and right) and anterior cingulate cortex (ACC) was revealed in all patients, compared to healthy controls. Patients with history of AVH, compared to other groups, showed decreased FC between l_IFG and ACC.

Disrupted fronto-temporal FC is non-specific for AVH and characterizes all schizophrenia patients. Patients with history of AVH have impaired FC between the l_IFG, underlying language production, and ACC, involved in differentiation between language production and comprehension. The study was supported by RFBR grant 18-013-01214.

The study was supported by RFBR grant 18-013-01214.

Schizophrenia patients with auditory verbal hallucinations (AVH) demonstrate impaired functional connectivity (FC) between brain regions, involved in executive functions and language. However, as most studies compare patients to healthy controls, the specificity of these findings either for schizophrenia in general or for AVH is unclear.

We aimed to compare whole-brain resting-state FC of main language brain regions between schizophrenia patients with and without history of AVH and healthy controls.

Schizophrenia male patients with (n=31; mean age 29,8±11,6) or without history of AVH (n=16; 29±12,4) and 39 healthy male controls (30±8,9) underwent resting-state fMRI on 3T Philips scanner. No between-group differences in age, illness duration, and severity of clinical symptoms except AVH were revealed. Regions of interest (ROIs) were taken from the independent fMRI study with conventional language localizer and included left inferior frontal gyrus (l_IFG) and superior temporal gyri (STG) bilaterally. Whole-brain FC of each ROI was compared between groups (ANCOVA; p<.005 voxelwise; p(FDR)<.017 clusterwise, corrected for number of ROIs) with post hoc tests.

Decreased FC between each STG (left and right) and anterior cingulate cortex (ACC) was revealed in all patients, compared to healthy controls. Patients with history of AVH, compared to other groups, showed decreased FC between l_IFG and ACC.

Disrupted fronto-temporal FC is non-specific for AVH and characterizes all schizophrenia patients. Patients with history of AVH have impaired FC between the l_IFG, underlying language production, and ACC, involved in differentiation between language production and comprehension. The study was supported by RFBR grant 18-013-01214.

Recently proposed alternative dimensional models of personality disorder (PD) place the severity of impairments in self and interpersonal functioning at the core of personality pathology. However, associations of these impairments with disturbances in social, cognitive, and affective brain networks remain uninvestigated.

The present study examined patterns of resting-state functional connectivity (rsFC) in a sample of 74 age- and sex-matched participants (45 inpatients with PD and 29 healthy controls). At a minimum, PD patients carried a diagnosis of borderline PD, although the majority of the sample had one or more additional PDs. rsFC patterns in the following networks were compared between groups and in association with dimensional personality impairments: default mode network (DMN)/core mentalization, frontolimbic, salience, and central executive. Further, the extent to which variation in rsFC was explained by levels of personality impairment as compared to typology-specific borderline PD symptom severity was explored.

Relative to controls, the PD group showed disruptions in rsFC within the DMN/core mentalization and frontolimbic networks. Among PD patients, greater severity of dimensional self-interpersonal impairment was associated with stronger intralimbic rsFC. In contrast, severity of borderline PD-specific typology was not associated with any rsFC patterns.

Disruptions in core mentalization and affective networks are present in PD. Higher intralimbic functional connectivity may underlie self-interpersonal personality impairment in PD regardless of diagnostic typology-specific PD symptoms, providing initial neurobiological evidence supporting alternative dimensional conceptualizations of personality pathology.

Refugees commonly experience difficulties with emotional processing, such as alexithymia, due to stressful or traumatic experiences. However, the functional connectivity of the amygdala, which is central to emotional processing, has yet to be assessed in refugees. Thus, the present study investigated the resting-state functional connectivity of the amygdala and its association with emotional processing in North Korean (NK) refugees.

This study included 45 NK refugees and 40 native South Koreans (SK). All participants were administered the Toronto Alexithymia Scale (TAS), Beck Depression Inventory (BDI), and Clinician-administered PTSD Scale (CAPS), and differences between NK refugees and native SK in terms of resting-state functional connectivity of the amygdala were assessed. Additionally, the association between the strength of amygdala connectivity and the TAS score was examined.

Resting-state connectivity values from the left amygdala to the bilateral dorsolateral prefrontal cortex (dlPFC) and dorsal anterior cingulate cortex (dACC) were higher in NK refugees than in native SK. Additionally, the strength of connectivity between the left amygdala and right dlPFC was positively associated with TAS score after controlling for the number of traumatic experiences and BDI and CAPS scores.

The present study found that NK refugees exhibited heightened frontal–amygdala connectivity, and that this connectivity was correlated with alexithymia. The present results suggest that increased frontal–amygdala connectivity in refugees may represent frontal down-regulation of the amygdala, which in turn may produce alexithymia.