Brain functional specialization and cooperation in Alzheimer's disease.

BACKGROUND: Cerebral specialization and interhemispheric cooperation are two vital features of the human brain. Their dysfunction may be associated with disease progression in patients with Alzheimer's disease (AD), which is featured as progressive cognitive degeneration and asymmetric neuropathology. OBJECTIVE: This study aimed to examine and define two inherent properties of hemispheric function in patients with AD by utilizing resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: Sixty-four clinically diagnosed AD patients and 52 age- and sex-matched cognitively normal subjects were recruited and underwent MRI and clinical evaluation. We calculated and compared brain specialization (autonomy index, AI) and interhemispheric cooperation (connectivity between functionally homotopic voxels, CFH). RESULTS: In comparison to healthy controls, patients with AD exhibited enhanced AI in the left middle occipital gyrus. This increase in specialization can be attributed to reduced functional connectivity in the contralateral region, such as the right temporal lobe. The CFH of the bilateral precuneus and prefrontal areas was significantly decreased in AD patients compared to controls. Imaging-cognitive correlation analysis indicated that the CFH of the right prefrontal cortex was marginally positively related to the Montreal Cognitive Assessment score in patients and the Auditory Verbal Learning Test score. Moreover, taking abnormal AI and CFH values as features, support vector machine-based classification achieved good accuracy, sensitivity, specificity, and area under the curve by leave-one-out cross-validation. CONCLUSION: This study suggests that individuals with AD have abnormal cerebral specialization and interhemispheric cooperation. This provides new insights for further elucidation of the pathological mechanisms of AD.

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.

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.

Heterogeneous Brain Abnormalities in Schizophrenia Converge on a Common Network Associated With Symptom Remission.

BACKGROUND AND HYPOTHESIS: There is a huge heterogeneity of magnetic resonance imaging findings in schizophrenia studies. Here, we hypothesized that brain regions identified by structural and functional imaging studies of schizophrenia could be reconciled in a common network. STUDY DESIGN: We systematically reviewed the case-control studies that estimated the brain morphology or resting-state local function for schizophrenia patients in the literature. Using the healthy human connectome (n = 652) and a validated technique "coordinate network mapping" to identify a common brain network affected in schizophrenia. Then, the specificity of this schizophrenia network was examined by independent data collected from 13 meta-analyses. The clinical relevance of this schizophrenia network was tested on independent data of medication, neuromodulation, and brain lesions. STUDY RESULTS: We identified 83 morphological and 60 functional studies comprising 7389 patients with schizophrenia and 7408 control subjects. The "coordinate network mapping" showed that the atrophy and dysfunction coordinates were functionally connected to a common network although they were spatially distant from each other. Taking all 143 studies together, we identified the schizophrenia network with hub regions in the bilateral anterior cingulate cortex, insula, temporal lobe, and subcortical structures. Based on independent data from 13 meta-analyses, we showed that these hub regions were specifically connected with regions of cortical thickness changes in schizophrenia. More importantly, this schizophrenia network was remarkably aligned with regions involving psychotic symptom remission. CONCLUSIONS: Neuroimaging abnormalities in cross-sectional schizophrenia studies converged into a common brain network that provided testable targets for developing precise therapies.

Effects of a periodic intermittent theta burst stimulation in Alzheimer's disease.

Background: Previous studies have demonstrated that excitatory repetitive transcranial magnetic stimulation (rTMS) can improve the cognitive function of patients with Alzheimer's disease (AD). Intermittent theta burst stimulation (iTBS) is a novel excitatory rTMS protocol for brain activity stimulation with the ability to induce long-term potentiation-like plasticity and represents a promising treatment for AD. However, the long-term effects of iTBS on cognitive decline and brain structure in patients with AD are unknown. Aims: We aimed to explore whether repeating accelerated iTBS every three months could slow down the cognitive decline in patients with AD. Methods: In this randomised, assessor-blinded, controlled trial, iTBS was administered to the left dorsolateral prefrontal cortex (DLPFC) of 42 patients with AD for 14 days every 13 weeks. Measurements included the Montreal Cognitive Assessment (MoCA), a comprehensive neuropsychological battery, and the grey matter volume (GMV) of the hippocampus. Patients were evaluated at baseline and after follow-up. The longitudinal pipeline of the Computational Anatomy Toolbox for SPM was used to detect significant treatment-related changes over time. Results: The iTBS group maintained MoCA scores relative to the control group (t=3.26, p=0.013) and reduced hippocampal atrophy, which was significantly correlated with global degeneration scale changes. The baseline Mini-Mental State Examination (MMSE) score, apolipoprotein E genotype and Clinical Dementia Rating were indicative of MoCA scores at follow-up. Moreover, the GMV of the left (t=0.08, p=0.996) and right (t=0.19, p=0.977) hippocampus were maintained in the active group but significantly declined in the control group (left: t=4.13, p<0.001; right: t=5.31, p<0.001). GMV change in the left (r=0.35, p=0.023) and right (r=0.36, p=0.021) hippocampus across the intervention positively correlated with MoCA changes; left hippocampal GMV change was negatively correlated with global degeneration scale (r=-0.32, p=0.041) changes. Conclusions: DLPFC-iTBS may be a feasible and easy-to-implement non-pharmacological intervention to slow down the progressive decline of overall cognition and quality of life in patients with AD, providing a new AD treatment option. Trial registration number: NCT04754152.

A Controlled Clinical Study of Accelerated High-Dose Theta Burst Stimulation in Patients with Obsessive-Compulsive Disorder.

Background: Obsessive-compulsive disorder (OCD) is frequently treated using a combination of counseling, drugs, and, more recently various transcranial stimulation protocols, but all require several weeks to months for clinically significant improvement, so there is a need for treatments with faster onset. This study investigated whether an accelerated high-dose theta burst stimulation (ahTBS) protocol significantly improves the efficacy of OCD compared to traditional 1-Hz repetitive transcranial magnetic stimulation (rTMS) in the routine clinical setting. Method: Forty-five patients with OCD were randomized into two groups and treated with ahTBS or 1-Hz rTMS for 5 days. Patients were assessed at baseline at the end of treatment using the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Results: After 5 days of treatment, there was a significant decrease in Y-BOCS scores in both groups (p < 0.001), and the difference between the two groups was not statistically significant (group × time interaction, F = 1.90, p=0.18). There was also no statistically significant difference in other secondary outcome indicators, including depression, anxiety symptoms, and response rate. However, the ahTBS group had a greater trend in response rate. Neuropsychological testing showed no negative cognitive side effects of either treatment. Conclusion: Accelerated high-dose TBS is as safe and has comparable short-term efficacy to traditional 1-Hz rTMS for the clinical treatment of OCD. Further research is needed to explore optimal ahTBS parameters, validate the utility of this treatment modality, and identify factors predictive of rapid clinical response to guide clinical decision-making. This trial is registered with NCT05221632.

Abnormal interhemispheric functional cooperation in schizophrenia follows the neurotransmitter profiles.

BACKGROUND: Interhemispheric cooperation is one of the most prominent functional architectures of the human brain. In patients with schizophrenia, interhemispheric cooperation deficits have been reported using increasingly powerful neurobehavioural and neuroimaging measures. However, these methods rely in part on the assumption of anatomic symmetry between hemispheres. In the present study, we explored interhemispheric cooperation deficits in schizophrenia using a newly developed index, connectivity between functionally homotopic voxels (CFH), which is unbiased by hemispheric asymmetry. METHODS: Patients with schizophrenia and age- and sexmatched healthy controls underwent multimodal MRI, and whole-brain CFH maps were constructed for comparison between groups. We examined the correlations of differing CFH values between the schizophrenia and control groups using various neurotransmitter receptor and transporter densities. RESULTS: We included 86 patients with schizophrenia and 86 matched controls in our analysis. Patients with schizophrenia showed significantly lower CFH values in the frontal lobes, left postcentral gyrus and right inferior temporal gyrus, and significantly greater CFH values in the right caudate nucleus than healthy controls. Moreover, the differing CFH values in patients with schizophrenia were significantly correlated with positive symptom score and illness duration. Functional connectivity within frontal lobes was significantly reduced at the voxel cluster level compared with healthy controls. Finally, the abnormal CFH map of patients with schizophrenia was spatially associated with the densities of the dopamine D1 and D2 receptors, fluorodopa, dopamine transporter, serotonin transporter and acetylcholine transporter. CONCLUSION: Regional abnormalities in interhemispheric cooperation may contribute to the clinical symptoms of schizophrenia. These CFH abnormalities may be associated with dysfunction in neurotransmitter systems strongly implicated in schizophrenia.

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.

Effects of high-definition transcranial direct current stimulation on implicit emotion regulation of social pain in healthy individuals.

BACKGROUND: Implicit emotion regulation (ER), a form of ER, is essential for protecting mental health in the process of social interaction. Both the ventrolateral prefrontal cortex (VLPFC) and the dorsolateral prefrontal cortex (DLPFC) have been shown to be involved in ER processes, including explicit ER of social pain, but whether they play a role in implicit ER is unclear. METHODS: We investigated whether anodal high-definition transcranial direct current stimulation (HD-tDCS) of the right VLPFC (rVLPFC) or the right DLPFC (rDLPFC) influences implicit ER. In total, 63 healthy participants completed an emotion priming task, which measures the implicit ER of social pain, before and after receiving active or sham HD-tDCS (2 mA for 20 min, 10 consecutive days). Event-related potentials (ERPs) were recorded during task performance. RESULTS: Combined with the results of the behavioral and electrophysiological indices indicated that stimulation of both the rVLPFC and the rDLPFC by anodic HD-tDCS could significantly reduce the affective responses caused by social exclusion. The further results also suggested that rDLPFC activation may contribute to promoting the involvement of early cognitive resources in the implicit ER process of social pain, thus helping to reduce the subjective negative experience of individuals. LIMITATIONS: There were no dynamic interactive emotional stimuli to induce social pain, and only static images of social exclusion were used. CONCLUSION: Our study provides cognitive and neurological evidence that expands our knowledge of the role of the rDLPFC and the rVLPFC in social ER. It can also serve as a reference for targeted intervention of implicit ER in social pain.

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.

Longitudinal changes in mental health among medical students in China during the COVID-19 epidemic: depression, anxiety and stress at 1-year follow -up.

This study aimed to evaluate the influence of COVID-19 on the mental health of Chinese medical students at 1-year of follow-up. From 2 February 2020 to 23 February 2021, we conducted three waves of research online (T1 = during outbreak, T2 = controlling period, T3 = 1 year after outbreak). The survey collected demographic data and several self reporting questionnaires to measure the depressive, anxiety and stress symptoms. A total of 4002 participants complete the whole research phases. The study major, grade level and gender were the main factors related to psychological distress caused by the COVID-19 crisis. Importantly, medical knowledge has a protective effect on medical students' psychological distress during the COVID-19 period.

Different Dynamic Nodal Properties Contribute to Cognitive Impairment in Patients with White Matter Hyperintensities.

White matter hyperintensities (WMHs) are commonly observed in older adults and are associated with cognitive impairment. Although previous studies have found abnormal functional connectivities in patients with WMHs based on static functional magnetic resonance imaging (fMRI), the topological properties in the context of brain dynamics remain relatively unexplored. Herein, we explored disrupted dynamic topological properties of functional network connectivity in patients with WMHs and its relationship with cognitive impairment. We included 36 healthy controls (HC) and 104 patients with mild WMHs (n = 39), moderate WMHs (n = 37), and severe (n = 28) WMHs. The fMRI data of all participants were analyzed using Anatomical Automatic Labeling (AAL) and a sliding-window approach to generate dynamic functional connectivity matrics. Then, graph theory methods were applied to calculate the topological properties. Comprehensive neuropsychological scales were used to assess cognitive functions. Relationships between cognitive functions and abnormal dynamic topological properties were evaluated by Pearson's correlation. We found that the patients with WMHs had higher temporal variability in regional properties, including betweenness centrality, nodal efficiencies, and nodal clustering coefficient. Furthermore, we found that the degree of centrality was related to executive function and memory, and the local coefficient correlated to executive function. Our results indicate that patients with WMHs have higher temporal variabilities in regional properties and are associated with executive and memory function.

Frontothalamic Circuit Abnormalities in Patients With Bipolar Depression and Suicide Attempts.

Objective: Suicide is the leading cause of premature death among patients with bipolar disorder (BD), so it is imperative to identify biological or psychometric markers for suicide risk. Previous functional neuroimaging studies of the general BD population have focused on abnormalities within cortical-subcortical circuits. The aim of the current study was to examine potential cortico-subcortical circuit abnormalities predictive of suicide attempt in patients with BD.Methods: We examined functional connectivity (FC) based on 5 regions of interest: bilateral anterior cingulate cortex (ACC), medial frontal cortex, inferior frontal cortex, amygdala, and thalamus, by resting-state functional magnetic resonance imaging (rs-fMRI) in 65 participants, including patients with BD and suicide attempts (SA group; n = 24), patients with BD and no suicide attempts (NSA group; n = 15), and healthy control subjects (HC group; n = 26). Patients met DSM-5 criteria for bipolar I disorder with current major depressive episode.Results: The total patient group (SA+NSA) exhibited significantly lower FC between bilateral thalamus and frontal cortex (F = 35.11, P < .01), and this deficit was most severe in the SA group. In addition, patients demonstrated significantly reduced FC values between bilateral inferior frontal gyrus and both inferior temporal gyrus (F = 20.68, P < .01) and fusiform gyrus (F = 20.98, P < .01), but FC was stronger in the SA group than the NSA group. Both patient groups also exhibited reduced FC based on these seeds including bilateral amygdala, medial frontal cortex, and ACC, but without significant differences between the SA and NSA groups.Conclusions: The results suggest that reduced FC within specific frontothalamic circuits may increase the vulnerability for suicidal behavior in patients with BD. These FC abnormalities might provide potential predictors of suicide attempt in BD.

Minimal scanning duration for producing individualized repetitive transcranial magnetic stimulation targets.

This study aimed to determine the minimal scanning duration of functional magnetic resonance imaging (fMRI) for producing individualized repetitive transcranial magnetic stimulation (rTMS) targets that are superior to the group-level targets. This study included 30 healthy subjects and 20 depressive patients with high-sampled fMRI data (> 69 min). We computed suboptimal targets by gradually increasing the scanning duration beginning at 6 min. The suboptimal target connectivity and spatial distance to the optimal target (based on the full-duration scanning data) were compared to an anatomically fixed target from a group analysis (termed as the group target). These analyses were repeated for healthy subjects and depressive patients, as well as for target masks in the dorsolateral prefrontal cortex (DLPFC) and inferior parietal lobule (IPL). As the scanning duration increased, the suboptimal targets gradually approached the optimal targets in the healthy subjects. Compared with the group targets, the suboptimal targets in the DLPFC showed higher connectivity strength after 10 min of data collection and shorter spatial distance after 40 min. Similar results were found in major depressive patients. In the IPL, the minimal scanning duration decreased to 6 and 8 min for connectivity strength and distance, respectively. These findings provide an important reference for individualized target definition in terms of scanning duration, which may standardize connectivity-based personalized studies. Future research is needed to further validate the therapeutic effects of the approach.

Efficacy of twice-daily high-frequency repetitive transcranial magnetic stimulation on associative memory.

Objectives: Several studies have examined the effects of repetitive transcranial magnetic stimulation (rTMS) on associative memory (AM) but findings were inconsistent. Here, we aimed to test whether twice-daily rTMS could significantly improve AM. Methods: In this single-blind, sham-controlled experiment, 40 participants were randomized to receive twice-daily sham or real rTMS sessions for five consecutive days (a total of 16,000 pulses). The stimulation target in left inferior parietal lobule (IPL) exhibiting peak functional connectivity to the left hippocampus was individually defined for each participant. Participants completed both a picture-cued word association task and Stroop test at baseline and 1 day after the final real or sham rTMS session. Effects of twice-daily rTMS on AM and Stroop test performance were compared using two-way repeated measures analysis of variance with main factors Group (real vs. sham) and Time (baseline vs. post-rTMS). Results: There was a significant Group × Time interaction effect. AM score was significantly enhanced in the twice-daily real group after rTMS, but this difference could not survive the post hoc analysis after multiple comparison correction. Further, AM improvement in the twice-daily real group was not superior to a previously reported once-daily rTMS group receiving 8,000 pulses. Then, we combined the twice- and once-daily real groups, and found a significant Group × Time interaction effect. Post hoc analysis indicated that the AM score was significantly enhanced in the real group after multiple comparisons correction. Conclusion: Our prospective experiment did not show significant rTMS effect on AM, but this effect may become significant if more participants could be recruited as revealed by our retrospective analysis.

A landmark-based approach to locate symptom-specific transcranial magnetic stimulation targets of depression.

Objective: Two subregions of the dorsolateral prefrontal cortex have been identified as effective repetitive transcranial magnetic stimulation (rTMS) targets for the "anxiosomatic" and "dysphoric" symptoms, respectively. We aimed to develop a convenient approach to locate these targets on the scalp. Materials and methods: In a discovery experiment, the two personalized targets were precisely identified on 24 subjects using a neuronavigation system. Then, a localized approach was developed based on individual scalp landmarks. This "landmark-based approach" was replicated and validated in an independent cohort (N = 25). Reliability of the approach was tested by calculating the correlation of both the inter-rater and intra-rater results. Validity was tested by comparing the mean distance between the personalized and landmark-based targets to the TMS spatial resolution (i.e., 5 mm). We further conducted a total of 24 sham rTMS sessions to estimate the misplacement between the coil center and target during a 10-min stimulation without neuronavigation. Results: The parameters of the "landmark-based approach" in the discovery experiment were replicated well in an independent cohort. Using discovery parameters, we successfully identified the symptom-specific targets in the independent cohort. Specifically, the mean distance between the personalized and landmark-based targets on the cortex was not significantly larger than 5 mm. However, the personalized and landmark-based targets distance exceeded 5 mm in more than 50% of subjects. During the 10-min sham rTMS session, the average coil misplacement was significantly larger than 5 mm. Conclusion: The "landmark-based approach" can conveniently and reliably locate the two symptom-specific targets at group level. However, the accuracy was highly varied at individual level and further improvement is needed.

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.