Decreased inter-hemispheric cooperation in major depressive disorder and its association with neurotransmitter profiles.

BACKGROUND: Inter-hemispheric cooperation is a prominent feature of the human brain, and previous neuroimaging studies have revealed aberrant inter-hemispheric cooperation patterns in patients with major depressive disorder (MDD). Typically, inter-hemispheric cooperation is examined by calculating the functional connectivity (FC) between each voxel in one hemisphere and its anatomical (structurally homotopic) counterpart in the opposite hemisphere. However, bilateral hemispheres are actually asymmetric in anatomy. METHODS: In the present study, we utilized connectivity between functionally homotopic voxels (CFH) to investigate abnormal inter-hemispheric cooperation in 96 MDD patients compared to 173 age- and sex-matched healthy controls (HCs). In addition, we analyzed the spatial correlations between abnormal CFH and the density maps of 13 neurotransmitter receptors and transporters. RESULTS: The CFH values in bilateral orbital frontal gyri and bilateral postcentral gyri were abnormally decreased in patients with MDD. Furthermore, these CFH abnormalities were correlated with clinical symptoms. In addition, the abnormal CFH pattern in MDD patients was spatially correlated with the distribution pattern of 5-HT1AR. LIMITATIONS: drug effect; the cross-sectional research design precludes causal inferences; the neurotransmitter atlases selected were constructed from healthy individuals rather than MDD patients. CONCLUSION: These findings characterized the abnormal inter-hemispheric cooperation in MDD using a novel method and the underlying neurotransmitter mechanism, which promotes our understanding of the pathophysiology of depression.

Individual large-scale functional network mapping for major depressive disorder with electroconvulsive therapy.

Personalized functional connectivity mapping has been demonstrated to be promising in identifying underlying neurophysiological basis for brain disorders and treatment effects. Electroconvulsive therapy (ECT) has been proved to be an effective treatment for major depressive disorder (MDD) while its active mechanisms remain unclear. Here, 46 MDD patients before and after ECT as well as 46 demographically matched healthy controls (HC) underwent resting-state functional magnetic resonance imaging (rs-fMRI) scans. A spatially regularized form of non-negative matrix factorization (NMF) was used to accurately identify functional networks (FNs) in individuals to map individual-level static and dynamic functional network connectivity (FNC) to reveal the underlying neurophysiological basis of therepetical effects of ECT for MDD. Moreover, these static and dynamic FNCs were used as features to predict the clinical treatment outcomes for MDD patients. We found that ECT could modulate both static and dynamic large-scale FNCs at individual level in MDD patients, and dynamic FNCs were closely associated with depression and anxiety symptoms. Importantly, we found that individual FNCs, particularly the individual dynamic FNCs could better predict the treatment outcomes of ECT suggesting that dynamic functional connectivity analysis may be better to link brain functional characteristics with clinical symptoms and treatment outcomes. Taken together, our findings provide new evidence for the active mechanisms and biomarkers for ECT to improve diagnostic accuracy and to guide individual treatment selection for MDD patients.

Molecular mechanisms underlying structural plasticity of electroconvulsive therapy in major depressive disorder.

Although previous studies reported structural changes associated with electroconvulsive therapy (ECT) in major depressive disorder (MDD), the underlying molecular basis of ECT remains largely unknown. Here, we combined two independent structural MRI datasets of MDD patients receiving ECT and transcriptomic gene expression data from Allen Human Brain Atlas to reveal the molecular basis of ECT for MDD. We performed partial least square regression to explore whether/how gray matter volume (GMV) alterations were associated with gene expression level. Functional enrichment analysis was conducted using Metascape to explore ontological pathways of the associated genes. Finally, these genes were further assigned to seven cell types to determine which cell types contribute most to the structural changes in MDD patients after ECT. We found significantly increased GMV in bilateral hippocampus in MDD patients after ECT. Transcriptome-neuroimaging association analyses showed that expression levels of 726 genes were positively correlated with the increased GMV in MDD after ECT. These genes were mainly involved in synaptic signaling, calcium ion binding and cell-cell signaling, and mostly belonged to excitatory and inhibitory neurons. Moreover, we found that the MDD risk genes of CNR1, HTR1A, MAOA, PDE1A, and SST as well as ECT related genes of BDNF, DRD2, APOE, P2RX7, and TBC1D14 showed significantly positive associations with increased GMV. Overall, our findings provide biological and molecular mechanisms underlying structural plasticity induced by ECT in MDD and the identified genes may facilitate future therapy for MDD.

Electroconvulsive Therapy Regulates Brain Connectome Dynamics in Patients With Major Depressive Disorder.

BACKGROUND: Electroconvulsive therapy (ECT) is an effective treatment for patients with major depressive disorder (MDD), but its underlying neural mechanisms remain largely unknown. The aim of this study was to identify changes in brain connectome dynamics after ECT in MDD and to explore their associations with treatment outcome. METHODS: We collected longitudinal resting-state functional magnetic resonance imaging data from 80 patients with MDD (50 with suicidal ideation [MDD-SI] and 30 without [MDD-NSI]) before and after ECT and 37 age- and sex-matched healthy control participants. A multilayer network model was used to assess modular switching over time in functional connectomes. Support vector regression was used to assess whether pre-ECT network dynamics could predict treatment response in terms of symptom severity. RESULTS: At baseline, patients with MDD had lower global modularity and higher modular variability in functional connectomes than control participants. Network modularity increased and network variability decreased after ECT in patients with MDD, predominantly in the default mode and somatomotor networks. Moreover, ECT was associated with decreased modular variability in the left dorsal anterior cingulate cortex of MDD-SI but not MDD-NSI patients, and pre-ECT modular variability significantly predicted symptom improvement in the MDD-SI group but not in the MDD-NSI group. CONCLUSIONS: We highlight ECT-induced changes in MDD brain network dynamics and their predictive value for treatment outcome, particularly in patients with SI. This study advances our understanding of the neural mechanisms of ECT from a dynamic brain network perspective and suggests potential prognostic biomarkers for predicting ECT efficacy in patients with MDD.

Molecular basis underlying changes of brain entropy and functional connectivity in major depressive disorders after electroconvulsive therapy.

INTRODUCTION: Electroconvulsive therapy (ECT) is widely used for treatment-resistant depression. However, it is unclear whether/how ECT can be targeted to affect brain regions and circuits in the brain to dynamically regulate mood and cognition. METHODS: This study used brain entropy (BEN) to measure the irregular levels of brain systems in 46 major depressive disorder (MDD) patients before and after ECT treatment. Functional connectivity (FC) was further adopted to reveal changes of functional couplings. Moreover, transcriptomic and neurotransmitter receptor data were used to reveal genetic and molecular basis of the changes of BEN and functional connectivities. RESULTS: Compared to pretreatment, the BEN in the posterior cerebellar lobe (PCL) significantly decreased and FC between the PCL and the right temporal pole (TP) significantly increased in MDD patients after treatment. Moreover, we found that these changes of BEN and FC were closely associated with genes' expression profiles involved in MAPK signaling pathway, GABAergic synapse, and dopaminergic synapse and were significantly correlated with the receptor/transporter density of 5-HT, norepinephrine, glutamate, etc. CONCLUSION: These findings suggest that loops in the cerebellum and TP are crucial for ECT regulation of mood and cognition, which provides new evidence for the antidepressant effects of ECT and the potential molecular mechanism leading to cognitive impairment.

Abnormal hemispheric specialization and inter-hemispheric functional cooperation in generalized anxiety disorder.

Abnormal hemispheric specialization and inter-hemispheric interactions may contribute to the pathogenesis of general anxiety disorder (GAD). The current study investigated these abnormalities in GAD patients based on the two analytic approaches and examined whether such abnormalities are correlated with anxiety symptom severity. Seventy-three patients with GAD and 60 matched healthy controls were recruited. All participants completed anxiety symptoms assessment and resting-state functional magnetic resonance imaging (rs-fMRI). The autonomy index (AI) and Connectivity between Functionally Homotopic voxels (CFH) were applied to measure and compared between groups. Compared to controls, patients showed stronger AI in the right middle temporal gyrus (MTG). Seed-based analysis revealed stronger functional connectivity (FC) of the right MTG with both right precuneus and right dorsolateral prefrontal cortex (dlPFC) in patients. Patients also exhibited greater CFH in right anterior cingulate cortex (ACC) but decreased CFH in bilateral postcentral gyrus (PCG) and superior occipital gyrus (SOG). Further there were significant correlations between these regional CFH and anxiety symptoms severity. GAD patients demonstrate right hemispheric specialization and aberrant inter-hemispheric functional cooperation, and abnormal inter-hemispheric coordination is associated with anxiety symptom severity. These findings provide a clue to understanding the neuropathological mechanisms of GAD.

Apathy in melancholic depression and abnormal neural activity within the reward-related circuit.

Major depressive disorder is a heterogeneous syndrome, of which the most common subtype is melancholic depression (MEL). Previous studies have indicated that anhedonia is frequently a cardinal feature in MEL. As a common syndrome of motivational deficit, anhedonia is closely associated with dysfunction in reward-related networks. However, little is currently known about apathy, another syndrome of motivational deficits, and the underlying neural mechanisms in MEL and non-melancholic depression (NMEL). Herein, the Apathy Evaluation Scale (AES) was used to compare apathy between MEL and NMEL. On the basis of resting-state functional magnetic resonance imaging, functional connectivity strength (FCS) and seed-based functional connectivity (FC) were calculated within reward-related networks and compared among 43 patients with MEL, 30 patients with NMEL, and 35 healthy controls. Patients with MEL had higher AES scores than those with NMEL (t = -2.20, P = 0.03). Relative to NMEL, MEL was associated with greater FCS (t = 4.27, P < 0.001) in the left ventral striatum (VS), and greater FC of the VS with the ventral medial prefrontal cortex (t = 5.03, P < 0.001) and dorsolateral prefrontal cortex (t = 3.18, P = 0.005). Taken together the results indicate that reward-related networks may play diverse pathophysiological roles in MEL and NMEL, thus providing potential directions for future interventions in the treatment of various depression subtypes.

Abnormal resting-state function within language network and its improvement among post-stroke aphasia.

Several studies with resting-state magnetic resonance imaging (rs-fMRI) have examined functional impairments and plasticity within language network in patients with post-stroke aphasia (PSA). However, there is still ubiquitous inconsistency across these studies, partly due to restricted to very small sample size and the absence of validation with follow-up data. In the current study, we aimed at providing relatively strong evidence to support functional impairments and its reorganization in PSA. Here, the amplitude of low frequency fluctuations (ALFF) and functional connectivity were used to assess functional alterations of PSA with moderate sample size at baseline (thirty-five PSA patients and thirty-five healthy controls). Functional abnormalities at baseline were observed whether improved among sixteen follow-up patients. Compared with controls, PSA at baseline presented decreased ALFF in the left inferior frontal gyrus (IFG) and decreased functional connectivity of the left IFG with the bilateral supplementary motor area (SMA) and right superior temporal gyrus (STG). The decreased ALFF in IFG, decreased IFG-SMA and IFG-STG connectivity were enhanced among follow-up patients and was synchronized with language-performance improvement. Our results revealed reduced intrinsic neural activity and inter-connections within language network in PSA, which would be normalized synchronously as the improvement of language performance.

Oxytocin-Receptor Gene Modulates Reward-Network Connection and Relationship with Empathy Performance.

Introduction: Empathy traits are highly heritable and linked with reward processing. It is implicated that common variations of the oxytocin-receptor gene (OXTR) play a modulatory effect on empathic performance. However, it is unclear about the neural substrates underlying the modulatory effect of the OXTR genotype on empathic performance. This study aimed to characterize the modulatory effect of common OXTR variations on reward-circuitry function and its relationship with empathy. Methods: Based on the seed of the nucleus accumbens (NAcc; a key hub of reward circuitry), we examined differences in spontaneous local activity and functional connectivity between OXTR rs2268493 genotype groups and their relationship with empathic performance among 402 high-homogeneity participants. Results: Comparing with C carriers (CC/CT) group, the individuals with the rs2268493 TT genotype exhibited lower functional connectivity of the right NAcc with the medial prefrontal cortex (mPFC) and inferior frontal gyrus. Similarly lower functional connectivity was found between the left NAcc and mPFC. Consequently, no significant difference was found in the spontaneous local activity of NAcc. Discussion: Our findings suggested that common OXTR variations have a modulatory effect on the connection of the NAcc with the hub of empathic networks (mPFC and IFG), which may provide insight on the neural substrate underlying the modulatory effect of OXTR on empathic behavior.

Volume of hippocampus-amygdala transition area predicts outcomes of electroconvulsive therapy in major depressive disorder: high accuracy validated in two independent cohorts.

BACKGROUND: Although many previous studies reported structural plasticity of the hippocampus and amygdala induced by electroconvulsive therapy (ECT) in major depressive disorder (MDD), yet the exact roles of both areas for antidepressant effects are still controversial. METHODS: In the current study, segmentation of amygdala and hippocampal sub-regions was used to investigate the longitudinal changes of volume, the relationship between volume and antidepressant effects, and prediction performances for ECT in MDD patients before and after ECT using two independent datasets. RESULTS: As a result, MDD patients showed selectively and consistently increased volume in the left lateral nucleus, right accessory basal nucleus, bilateral basal nucleus, bilateral corticoamygdaloid transition (CAT), bilateral paralaminar nucleus of the amygdala, and bilateral hippocampus-amygdala transition area (HATA) after ECT in both datasets, whereas marginally significant increase of volume in bilateral granule cell molecular layer of the head of dentate gyrus, the bilateral head of cornu ammonis (CA) 4, and left head of CA 3. Correlation analyses revealed that increased volume of left HATA was significantly associated with antidepressant effects after ECT. Moreover, volumes of HATA in the MDD patients before ECT could be served as potential biomarkers to predict ECT remission with the highest accuracy of 86.95% and 82.92% in two datasets (The predictive models were trained on Dataset 2 and the sensitivity, specificity and accuracy of Dataset 2 were obtained from leave-one-out-cross-validation. Thus, they were not independent and very likely to be inflated). CONCLUSIONS: These results not only suggested that ECT could selectively induce structural plasticity of the amygdala and hippocampal sub-regions associated with antidepressant effects of ECT in MDD patients, but also provided potential biomarkers (especially HATA) for effectively and timely interventions for ECT in clinical applications.

Linking Personalized Brain Atrophy to Schizophrenia Network and Treatment Response.

BACKGROUND AND HYPOTHESIS: Schizophrenia manifests with marked heterogeneity in both clinical presentation and underlying biology. Modeling individual differences within clinical cohorts is critical to translate knowledge reliably into clinical practice. We hypothesized that individualized brain atrophy in patients with schizophrenia may explain the heterogeneous outcomes of repetitive transcranial magnetic stimulation (rTMS). STUDY DESIGN: The magnetic resonance imaging (MRI) data of 797 healthy subjects and 91 schizophrenia patients (between January 1, 2015, and December 31, 2020) were retrospectively selected from our hospital database. The healthy subjects were used to establish normative reference ranges for cortical thickness as a function of age and sex. Then, a schizophrenia patient's personalized atrophy map was computed as vertex-wise deviations from the normative model. Each patient's atrophy network was mapped using resting-state functional connectivity MRI from a subgroup of healthy subjects (n = 652). In total 52 of the 91 schizophrenia patients received rTMS in a randomized clinical trial (RCT). Their longitudinal symptom changes were adopted to test the clinical utility of the personalized atrophy map. RESULTS: The personalized atrophy maps were highly heterogeneous across patients, but functionally converged to a putative schizophrenia network that comprised regions implicated by previous group-level findings. More importantly, retrospective analysis of rTMS-RCT data indicated that functional connectivity of the personalized atrophy maps with rTMS targets was significantly associated with the symptom outcomes of schizophrenia patients. CONCLUSIONS: Normative modeling can aid in mapping the personalized atrophy network associated with treatment outcomes of patients with schizophrenia.

Effect of high-definition transcranial direct current stimulation on improving depression and modulating functional activity in emotion-related cortical-subcortical regions in bipolar depression.

Preliminary studies have suggested that transcranial direct current stimulation (tDCS) is effective for bipolar depression, However, brain correlates of the depression alleviating are unclear. To determine the efficacy and safety of tDCS as an add-on treatment for patients with bipolar depression and further to identify the effect of tDCS on the resting-state brain activities, we recruited fifty patients with bipolar depression to complete the double-blind, sham-controlled and randomized clinical trial. Fourteen sessions of tDCS were performed once a day for 14 days. The anode was placed over F3 with return electrodes placed at FP1, FZ, C3 and F7. Regional homogeneity (ReHo) was examined on 50 patients with bipolar depression before and after 14-day active or sham tDCS. Patients in the active group showed significantly superior alleviating the depression symptoms compared with those receiving sham. The active group after 14-day active tDCS showed increased ReHo values in the orbitofrontal cortex and middle frontal gyrus and decreased ReHo values in subcortical structures including hippocampus, parahippocampa gyrus, amygdala, putamen and lentiform nucleus. The reduction of depression severity showed positive correlation of increased ReHo values in the orbitofrontal cortex and middle frontal gyrus and negative correlation of altered ReHo values in the putamen and lentiform. TDCS was an effective and safe add-on intervention for this small bipolar depression sample. The reduction of depression induced by tDCS is associated with a modulation of neural synchronization in the cortical and subcortical structures (ReHo values) within an emotion-related brain network.

Neuroplasticity-Related Genes and Dopamine Receptors Associated with Regional Cortical Thickness Increase Following Electroconvulsive Therapy for Major Depressive Disorder.

Electroconvulsive therapy (ECT) is an effective neuromodulatory therapy for major depressive disorder (MDD). Treatment is associated with regional changes in brain structure and function, indicating activation of neuroplastic processes. To investigate the underlying neurobiological mechanism of macroscopic reorganization following ECT, we longitudinally (before and after ECT in two centers) collected magnetic resonance images for 96 MDD patients. Similar patterns of cortical thickness (CT) changes following ECT were observed in two centers. These CT changes were spatially colocalized with a weighted combination of genes enriched for neuroplasticity-related ontology terms and pathways (e.g., synaptic pruning) as well as with a higher density of D2/3 dopamine receptors. A multiple linear regression model indicated that the region-specific gene expression and receptor density patterns explained 40% of the variance in CT changes after ECT. In conclusion, these findings suggested that dopamine signaling and neuroplasticity-related genes are associated with the ECT-induced morphological reorganization.

The Common Neural Mechanism of Somatic Symptoms of Depression and Anxiety Disorders: A Resting-State Functional Magnetic Resonance Imaging Study.

INTRODUCTION: Somatic symptoms often occur as a manifestation of depression and anxiety. The subgenual anterior cingulate cortex (sgACC) has been shown to be closely related to both depression and anxiety and plays an important role in somatic symptoms. However, little is known regarding whether the abnormal function of the sgACC contributes to the common somatic symptoms of depression and anxiety. METHODS: Resting-state functional connectivity (RSFC) analysis based on the seed of the sgACC was investigated in 23 major depressive disorder (MDD) patients with somatic symptoms, 20 generalized anxiety disorder (GAD) patients with somatic symptoms, and 22 demographically matched healthy controls (HCs). The severity of depression, anxiety, and somatic symptoms was assessed using the Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA), and the 15-item somatic symptom severity scale from the Patient Health Questionnaire (PHQ-15), respectively. An analysis of covariance analysis (ANCOVA) was conducted to determine RSFC alterations among GAD, MDD, and HC groups with age, gender, and head motion as covariates. Correlation analyses were conducted between the RSFC of the sgACC and PHQ-15. RESULTS: The significantly different RSFC of right sgACC among the three groups was found in right STG, left cerebellum, and right postcentral. Post hoc analysis indicated that both MDD and GAD patients showed a decreased RSFC between the right sgACC and right STG than HCs, and both were negatively correlated with the PHQ-15 scores. CONCLUSION: The abnormally decreased RSFC of the sgACC and STG may be the underlying common mechanisms of depression and anxiety combined with somatic symptoms.

Neural signatures of default mode network in major depression disorder after electroconvulsive therapy.

Functional abnormalities of default mode network (DMN) have been well documented in major depressive disorder (MDD). However, the association of DMN functional reorganization with antidepressant treatment and gene expression is unclear. Moreover, whether the functional interactions of DMN could predict treatment efficacy is also unknown. Here, we investigated the link of treatment response with functional alterations of DMN and gene expression with a comparably large sample including 46 individuals with MDD before and after electroconvulsive therapy (ECT) and 46 age- and sex-matched healthy controls. Static and dynamic functional connectivity (dFC) analyses showed increased intrinsic/static but decreased dynamic functional couplings of inter- and intra-subsystems and between nodes of DMN. The changes of static functional connections of DMN were spatially correlated with brain gene expression profiles. Moreover, static and dFC of the DMN before treatment as features could predict depressive symptom improvement following ECT. Taken together, these results shed light on the underlying neural and genetic basis of antidepressant effect of ECT and the intrinsic functional connectivity of DMN have the potential to serve as prognostic biomarkers to guide accurate personalized treatment.

Electroconvulsive therapy changes temporal dynamics of intrinsic brain activity in depressed patients.

Electroconvulsive therapy (ECT) has been demonstrated to be effective in treating depressed patients. Previous neuroimaging studies have focused mainly on alterations in static brain activity and connectivity to study the effects of ECT in depressed patients. However, it remains unclear whether the temporal dynamics of brain activity are associated with mechanisms of ECT in depressed patients. We measured the dynamics of spontaneous brain activity using dynamic amplitude of low-frequency fluctuation (dALFF) in healthy controls (n = 40) and patients diagnosed with unipolar depression (UD, n = 36) or bipolar disorder (BD, n = 9) before and after ECT. Furthermore, the temporal variability of intrinsic brain activity (iBA) was quantified as the variance of dALFF across sliding window. In addition, correlation analysis was performed to investigate the relationships among dALFF, depressive symptoms, and cognitive function in depressed patients. We lack second resting-state functional magnetic resonance imaging (rs-fMRI) data for healthy controls. After ECT, patients showed decreased brain dynamics (less temporal variability) in the right dorsal anterior cingulate cortex (dACC) and the right precuneus, whereas they showed increased brain dynamics in the bilateral superior medial frontal cortex (mSFC). No significant correlation was found between the dALFF and clinical variables in depressed patients. Our findings suggest that right dACC, right precuneus, and bilateral mSFC play an important role in response to ECT depressed patients from the perspective of dynamic local brain activity, indicating that the dALFF variability may be useful in further understanding the mechanisms of ECT's antidepressant effects.

Reduced nucleus accumbens functional connectivity in reward network and default mode network in patients with recurrent major depressive disorder.

The nucleus accumbens (NAc) is considered a hub of reward processing and a growing body of evidence has suggested its crucial role in the pathophysiology of major depressive disorder (MDD). However, inconsistent results have been reported by studies on reward network-focused resting-state functional MRI (rs-fMRI). In this study, we examined functional alterations of the NAc-based reward circuits in patients with MDD via meta- and mega-analysis. First, we performed a coordinated-based meta-analysis with a new SDM-PSI method for all up-to-date rs-fMRI studies that focused on the reward circuits of patients with MDD. Then, we tested the meta-analysis results in the REST-meta-MDD database which provided anonymous rs-fMRI data from 186 recurrent MDDs and 465 healthy controls. Decreased functional connectivity (FC) within the reward system in patients with recurrent MDD was the most robust finding in this study. We also found disrupted NAc FCs in the DMN in patients with recurrent MDD compared with healthy controls. Specifically, the combination of disrupted NAc FCs within the reward network could discriminate patients with recurrent MDD from healthy controls with an optimal accuracy of 74.7%. This study confirmed the critical role of decreased FC in the reward network in the neuropathology of MDD. Disrupted inter-network connectivity between the reward network and DMN may also have contributed to the neural mechanisms of MDD. These abnormalities have potential to serve as brain-based biomarkers for individual diagnosis to differentiate patients with recurrent MDD from healthy controls.

Resting-State Neural-Activity Alterations in Subacute Aphasia after Stroke.

Linguistic deficits are frequent symptoms among stroke survivors. The neural mechanism of post-stroke aphasia (PSA) was incompletely understood. Recently, resting-state functional magnetic resonance imaging (rs-fMRI) was widely used among several neuropsychological disorders. However, previous rs-fMRI studies of PSA were limited to very small sample size and the absence of reproducibility with different neuroimaging indexes. The present study performed comparisons with static and dynamic amplitude of low-frequency fluctuations (ALFF) and functional connectivity (FC) based on modest sample size (40 PSA and 37 healthy controls). Compared with controls, PSA showed significantly increased static ALFF predominantly in the bilateral supplementary motor area (SMA) and right hippocampus-parahippocampus (R HIP-ParaHip) and decreased static ALFF in right cerebellum. The increased dynamic ALFF in SMA and decreased dynamic ALFF in right cerebellum were also found in PSA. The static and dynamic ALFF in right cerebellum was positively correlated with spontaneous speech. The FC between the SMA and R HIP-ParaHip was significantly stronger in patients than controls and positively correlated with ALFF in bilateral SMA. In addition, the FC between the R HIP-ParaHip and the right temporal was also enhanced in patients and negatively correlated with repetition, naming, and comprehension score. These findings revealed consistently abnormal intrinsic neural activity in SMA and cerebellum, which may underlie linguistic deficits in PSA.