Functional neural substrates of Parkinson's disease and potential underpinnings of acute responses to acupuncture stimulation.

Parkinson's disease is a heterogenous neurodegenerative disorder with a wide variety of motor and non-motor symptoms. This study used resting-state fMRI to identify the neural substrates of PD and explore the acute neural response to acupuncture stimulation in 74 participants (50 patients with PD and 24 healthy controls). All participants with PD were evaluated for the severity of symptoms using the Unified Parkinson's Disease Rating Scale and Balance Master. The z-transformed fractional amplitude of low-frequency fluctuation analysis showed significant differences between the PD and healthy controls in the cerebellar regions, which are thought to play a crucial role in PD pathology. Subsequently, seed-based functional connectivity of the cerebellum with the frontal, parietal, and limbic regions was identified as a potential diagnostic marker for PD. In addition, spontaneous neural activity in the precentral gyrus and thalamus was significantly associated with the severity of PD symptoms. Neural activity in the precentral gyrus, precuneus, and superior temporal gyrus showed a significant correlation with Balance Master indicators. Finally, acupuncture stimulation at GB34 significantly reduced the activity of the occipital regions in patients with PD, but this effect was not observed in healthy controls. The mixed-effects analysis revealed an interaction effects between group and acupuncture stimulation, suggesting that the modulatory effects of acupuncture could differ depending on disease status. Therefore, this study suggests the neural substrates of PD and potential underpinnings of acute neural response to acupuncture stimulation.

Exploring spontaneous brain activity changes in high-altitude smokers: Insights from ALFF/fALFF analysis.

INTRODUCTION: This study aims to explore the impact of smoking on intrinsic brain activity among high-altitude (HA) populations. Smoking is associated with various neural alterations, but it remains unclear whether smokers in HA environments exhibit specific neural characteristics. METHODS: We employed ALFF and fALFF methods across different frequency bands to investigate differences in brain functional activity between high-altitude smokers and non-smokers. 31 smokers and 31 non-smokers from HA regions participated, undergoing resting-state functional magnetic resonance imaging (rs-fMRI) scans. ALFF/fALFF values were compared between the two groups. Correlation analyses explored relationships between brain activity and clinical data. RESULTS: Smokers showed increased ALFF values in the right superior frontal gyrus (R-SFG), right middle frontal gyrus (R-MFG), right anterior cingulate cortex (R-ACC), right inferior frontal gyrus (R-IFG), right superior/medial frontal gyrus (R-MSFG), and left SFG compared to non-smokers in HA. In sub-frequency bands (0.01-0.027 Hz and 0.027-0.073 Hz), smokers showed increased ALFF values in R-SFG, R-MFG, right middle cingulate cortex (R-MCC), R-MSFG, Right precentral gyrus and L-SFG while decreased fALFF values were noted in the right postcentral and precentral gyrus in the 0.01-0.027 Hz band. Negative correlations were found between ALFF values in the R-SFG and smoking years. CONCLUSION: Our study reveals the neural characteristics of smokers in high-altitude environments, highlighting the potential impact of smoking on brain function. These results provide new insights into the neural mechanisms of high-altitude smoking addiction and may inform the development of relevant intervention measures.

Spontaneous neural activity underlying neutral and happy speech recognition in noise and its association with psychiatric symptoms in patients with schizophrenia.

BACKGROUND: Deficits in speech and emotion perception are intertwined with psychiatric symptoms. How the happy prosody embedded in speech affects target speech-in-noise recognition (TSR) and relates to psychiatric symptoms in patients with schizophrenia (SCHs) remains unclear. This study examined spontaneous brain activity underlying happy TSR and its association with psychiatric symptom dimensions in SCHs. METHODS: Fifty-four SCHs and 59 healthy control participants (HCs) underwent the TSR task, Positive and Negative Syndrome Scale (PANSS) assessment, and magnetic resonance imaging scanning. Multivariate analyses of partial least squares (PLS) regression were used to explore the associations between whole-brain fractional amplitude of low-frequency fluctuations (fALFF), happy-neutral TSR (target pseudo-sentences were uttered in happy and neutral prosodies), and five PANSS factor scores (excitement/hostility, depression/anxiety, cognition, positive, and negative). RESULTS: The happy prosody did not alter TSR or TSR changing rates in either SCHs or HCs. SCHs exhibited lower happy and neutral TSR than HCs. A fALFF PLS component (including precentral/postcentral gyrus, Subcallosal Cortex, several temporal regions, and cerebellum) was associated with happy and neutral TSR. SCHs demonstrated higher PLS fALFF scores and PLS TSR scores than HCs. In SCHs, PLS fALFF scores were correlated with the PANSS positive factor score, and PLS TSR scores were correlated with the PANSS cognition factor score. CONCLUSIONS: The positive-psychiatric-symptoms-related spontaneous activity profile was associated with happy and neutral TSR, contributing to the cognition psychiatric symptoms dimension. The findings suggest the potential to improve positive and cognitive symptoms by enhancing happy and neutral TSR in schizophrenia based on neuroplasticity.

Impact of high-frequency rTMS combined with pharmacotherapy on the left dorsolateral prefrontal cortex in treating major depressive disorder: A real-world study.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) combined with pharmacotherapy is a promising treatment method for depression. However, its treatment mechanism needs further research. METHODS: This study recruited 38 healthy individuals (HC) and 52 patients with severe depression (MDD) and divided patients into two treatment groups: the rTMS combined antidepressant (rTMS+ADP) group and the single antidepressant (ADP) group. We used functional magnetic resonance imaging to calculate the fractional amplitude of low-frequency fluctuations (fALFF) in the left dorsolateral prefrontal cortex (DLPFC) to investigate the functional change after treatment. RESULT: The fALFF in the left DLPFC was significantly lower in the MDD group than that in the HC group (p < 0.05). In addition, fALFF values of the left DLPFC negatively correlated with HAMD-24 scores (r = -0.294, p = 0.005). After treatment, both MDD groups showed a significant decrease in HAMD-24 scores, with a response rate of 88.89 % and a remission rate of 62.96 % in the rTMS+ADP group, compared to 64 % response and 56 % remission rates in the ADP group. The fALFF values in patients' left DLPFC significantly reduced in the rTMS+ADP group (p < 0.05), but not in the ADP group. LIMITATIONS: Our study only focused on the treatment effect in the left DLPFC, without exploring the other brain regions or networks. CONCLUSIONS: This study emphasizes the significance of the left DLPFC in MDD treatment. However, combined left DLPFC rTMS with ADP causes deviation from the normal resting brain function of the left DLPFC, indicating that future research should explore targeted treatment methods to normalize the left DLPFC.

Aberrant activity at rest of the associative striatum in schizophrenia: Meta-analyses of the amplitude of low frequency fluctuations.

Schizophrenia is a severe psychiatric disorder associated with brain alterations at rest. Amplitude of low-frequency fluctuations (ALFF) and its fractional version (fALFF) have been widely used to investigate alterations in spontaneous brain activity in schizophrenia. However, results are still inconsistent. Furthermore, while these measurements are similar, they showed some differences, and no meta-analysis has been yet performed to compare them in schizophrenia. Thus, we conducted systematic research in five databases and in the grey literature to find articles investigating fALFF and/or ALFF alterations in schizophrenia. Two separate meta-analyses were performed using the SDM-PSI software to identify fALFF and ALFF alterations separately. Then, a conjunction analysis was conducted to determine congruent results between the two approaches. We found that patients with schizophrenia showed altered fALFF activity in the left insula/putamen, the right paracentral lobule and the left middle occipital gyrus compared to healthy individuals. Patients with schizophrenia exhibited ALFF alterations in the bilateral putamen, the bilateral caudate nucleus, the bilateral inferior frontal gyrus, the right precuneus, the right precentral gyrus, the left postcentral gyrus, the right posterior cingulate gyrus, compared to healthy controls. ALFF increased activity in the left putamen was higher in drug-naïve patients and was correlated with positive symptoms. The conjunction analysis revealed a spatial convergence between fALFF and ALFF studies in the left putamen. This left putamen cluster is part of the associative striatum. Its alteration in schizophrenia provides additional support to the influential aberrant salience hypothesis of psychosis.

Predicting tremor improvement after MRgFUS thalamotomy in essential tremor from preoperative spontaneous brain activity: A machine learning approach.

Magnetic resonance-guided focused ultrasound surgery (MRgFUS) thalamotomy is an emerging technique for medication-refractory essential tremor (ET), but with variable outcomes. This study used pattern regression analysis to identify brain signatures predictive of tremor improvements. Fifty-four ET patients (mean age = 63.06 years, standard deviation (SD) = 10.55 years, 38 males) underwent unilateral MRgFUS thalamotomy and were scanned for resting-state functional magnetic resonance imaging (rs-fMRI). Seventy-four healthy controls (mean age = 58.09 years, SD = 10.30 years, 38 males) were recruited for comparison. Tremor responses at 12 months posttreatment were evaluated by the Clinical Rating Scale for Tremor. The fractional amplitude of low-frequency fluctuations (fALFF) was calculated from rs-fMRI data. Two-sample t-test was used to generate a disease-specific mask, within which Multivariate Kernel Ridge Regression analyses were conducted. Predicted and actual clinical scores were compared using Pearson's correlation coefficient (r) and normalized mean squared error (Norm. MSE). Permutation test and leave-one-out strategy were applied for results validation. KRR identified fALFF patterns that significantly predicted the hand tremor improvement (r = 0.23, P = 0.025; Norm. MSE = 0.05, P = 0.026) and the postural tremor improvement (r = 0.28, P = 0.025; Norm. MSE = 0.06, P = 0.023), but not action tremor improvement. Lobule VI of right cerebellum (Cerebelum_6_R), right superior occipital gyrus (Occipital_Sup_R) and lobule X of vermis (Vermis_10) contributed most for hand tremor prediction (normalized weights (NW): 2.77%, 2.40%, 2.34%) while Vermis_10, left supplementary motor area (Supp_Motor_Area_L) and right hippocampus (Hippocampus_R) for postural tremor prediction (NW: 2.69%, 2.12%, 2.05%). The low contributing NW of the individual brain regions suggested that the fALFF pattern as a whole is an overall predicting feature. Preoperative fALFF pattern predicts tremor benefits induced by MRgFUS thalamotomy. ClinicalTrials.gov number: NCT04570046.

Resting-state functional magnetic resonance imaging alterations in first-degree relatives of individuals with bipolar disorder: A systematic review.

BACKGROUND: Relatives of individuals with bipolar disorder (BD) are at higher risk of developing the disorder. Identifying brain alterations associated with familial vulnerability in BD can help discover endophenotypes, which are quantifiable biological traits more prevalent in unaffected relatives of BD (BD-RELs) than the general population. This review aimed at expanding our knowledge on endophenotypes of BD by providing an overview of resting-state functional magnetic resonance imaging (rs-fMRI) alterations in BD-RELs. METHODS: A systematic search of PubMed, Scopus, and Web of Science was performed to identify all available rs-fMRI studies conducted in BD-RELs up to January 2024. A total of 18 studies were selected. Six included BD-RELs with no history of psychiatric disorders and 10 included BD-RELs that presented psychiatric disorders. Two investigations examined rs-fMRI alterations in BD-RELs with and without subthreshold symptoms for BD. RESULTS: BD-RELs presented rs-fMRI alterations in the cortico-limbic network, fronto-thalamic-striatal circuit, fronto-occipital network, and, to a lesser extent, in the default mode network. This was true both for BD-RELs with no history of psychopathology and for BD-RELs that presented psychiatric disorders. The direct comparison of rs-fMRI alterations in BD-RELs with and without psychiatric symptoms displayed largely non-overlapping patterns of rs-fMRI abnormalities. LIMITATIONS: Small sample sizes and the clinical heterogeneity of BD-RELs limit the generalizability of our findings. CONCLUSIONS: The current literature suggests that first-degree BD-RELs exhibit rs-fMRI alterations in brain circuits involved in emotion regulation, cognition, reward processing, and psychosis susceptibility. Future studies are needed to validate these findings and to explore their potential as biomarkers for early detection and intervention.

Transdiagnostic markers across the psychosis continuum: a systematic review and meta-analysis of resting state fMRI studies.

Psychotic symptoms are among the most debilitating and challenging presentations of severe psychiatric diseases, such as schizophrenia, schizoaffective, and bipolar disorder. A pathophysiological understanding of intrinsic brain activity underlying psychosis is crucial to improve diagnosis and treatment. While a potential continuum along the psychotic spectrum has been recently described in neuroimaging studies, especially for what concerns absolute and relative amplitude of low-frequency fluctuations (ALFF and fALFF), these efforts have given heterogeneous results. A transdiagnostic meta-analysis of ALFF/fALFF in patients with psychosis compared to healthy controls is currently lacking. Therefore, in this pre-registered systematic review and meta-analysis PubMed, Scopus, and Embase were searched for articles comparing ALFF/fALFF between psychotic patients and healthy controls. A quantitative synthesis of differences in (f)ALFF between patients along the psychotic spectrum and healthy controls was performed with Seed-based d Mapping, adjusting for age, sex, duration of illness, clinical severity. All results were corrected for multiple comparisons by Family-Wise Error rates. While lower ALFF and fALFF were detected in patients with psychosis in comparison to controls, no specific finding survived correction for multiple comparisons. Lack of this correction might explain the discordant findings highlighted in previous literature. Other potential explanations include methodological issues, such as the lack of standardization in pre-processing or analytical procedures among studies. Future research on ALFF/fALFF differences for patients with psychosis should prioritize the replicability of individual studies. Systematic review registration: https://osf.io/, identifier (ycqpz).

Impaired effective functional connectivity in the social preference of children with autism spectrum disorder.

Background: The medial prefrontal cortex (mPFC), amygdala (Amyg), and nucleus accumbens (NAc) have been identified as critical players in the social preference of individuals with ASD. However, the specific pathophysiological mechanisms underlying this role requires further clarification. In the current study, we applied Granger Causality Analysis (GCA) to investigate the neural connectivity of these three brain regions of interest (ROIs) in patients with ASD, aiming to elucidate their associations with clinical features of the disorder. Methods: Resting-state functional magnetic resonance imaging (rs-fMRI) data were acquired from the ABIDE II database, which included 37 patients with ASD and 50 typically developing (TD) controls. The mPFC, Amyg, and NAc were defined as ROIs, and the differences in fractional amplitude of low-frequency fluctuations (fALFF) within the ROIs between the ASD and TD groups were computed. Subsequently, we employed GCA to investigate the bidirectional effective connectivity between the ROIs and the rest of the brain. Finally, we explored whether this effective connectivity was associated with the social responsiveness scale (SRS) scores of children with ASD. Results: The fALFF values in the ROIs were reduced in children with ASD when compared to the TD group. In terms of the efferent connectivity from the ROIs to the whole brain, the ASD group exhibited increased connectivity in the right cingulate gyrus and decreased connectivity in the right superior temporal gyrus. Regarding the afferent connectivity from the whole brain to the ROIs, the ASD group displayed increased connectivity in the right globus pallidus and decreased connectivity in the right cerebellar Crus 1 area and left cingulate gyrus. Additionally, we demonstrated a positive correlation between effective connectivity derived from GCA and SRS scores. Conclusion: Impairments in social preference ASD children is linked to impaired effective connectivity in brain regions associated with social cognition, emotional responses, social rewards, and social decision-making. This finding further reveals the potential neuropathological mechanisms underlying ASD.

Abnormalities of regional brain activity and executive function in patients with temporal lobe epilepsy: A cross-sectional and longitudinal resting-state functional MRI study.

PURPOSE: We decided to track changes in regional brain activity and executive function in temporal lobe epilepsy (TLE) patients based on cross-sectional and longitudinal designs and sought potential imaging features for follow-up observation. METHODS: Thirty-two TLE patients and thirty-three healthy controls (HCs) were recruited to detect changes in fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo) and to evaluate executive function both at baseline and at two-year (23.3 ± 8.3 months) follow-up. Moreover, multivariate pattern analysis (MVPA) was used for follow-up observation. RESULTS: TLE patients displayed lower fALFF values in the right superior frontal gyrus (SFG) and higher ReHo values in the left putamen (PUT) relative to the HCs. Longitudinal analysis revealed that TLE patients at follow-up exhibited higher fALFF values in the left postcentral gyrus (PoCG), higher ReHo values in the left PoCG and the right middle frontal gyrus (MFG), lower ReHo values in the bilateral PUT and the right fusiform gyrus (FFG) compared with these patients at baseline. The executive function was impaired in TLE patients but didn't deteriorate over time. No correlations were discovered between regional brain activity and executive function. The MVPA based on ReHo performed well in differentiating the follow-up group from the baseline group. CONCLUSION: We revealed the abnormalities in regional brain activity and executive function as well as their longitudinal trends in TLE patients. The ReHo might be a good imaging feature for follow-up observation.

Fractional amplitude of low-frequency fluctuations associated with µ-opioid and dopamine receptor distributions in the central nervous system after high-intensity exercise bouts.

Introduction: Dopaminergic, opiod and endocannabinoid neurotransmission are thought to play an important role in the neurobiology of acute exercise and, in particular, in mediating positive affective responses and reward processes. Recent evidence indicates that changes in fractional amplitude of low-frequency fluctuations (zfALFF) in resting-state functional MRI (rs-fMRI) may reflect changes in specific neurotransmitter systems as tested by means of spatial correlation analyses. Methods: Here, we investigated this relationship at different exercise intensities in twenty young healthy trained athletes performing low-intensity (LIIE), high-intensity (HIIE) interval exercises, and a control condition on three separate days. Positive And Negative Affect Schedule (PANAS) scores and rs-fMRI were acquired before and after each of the three experimental conditions. Respective zfALFF changes were analyzed using repeated measures ANOVAs. We examined the spatial correspondence of changes in zfALFF before and after training with the available neurotransmitter maps across all voxels and additionally, hypothesis-driven, for neurotransmitter maps implicated in the neurobiology of exercise (dopaminergic, opiodic and endocannabinoid) in specific brain networks associated with "reward" and "emotion." Results: Elevated PANAS Positive Affect was observed after LIIE and HIIE but not after the control condition. HIIE compared to the control condition resulted in differential zfALFF decreases in precuneus, temporo-occipital, midcingulate and frontal regions, thalamus, and cerebellum, whereas differential zfALFF increases were identified in hypothalamus, pituitary, and periaqueductal gray. The spatial alteration patterns in zfALFF during HIIE were positively associated with dopaminergic and µ-opioidergic receptor distributions within the 'reward' network. Discussion: These findings provide new insight into the neurobiology of exercise supporting the importance of reward-related neurotransmission at least during high-intensity physical activity.

Investigating the impact of rumination and adverse childhood experiences on resting-state neural activity and connectivity in depression.

BACKGROUND: Both ruminative thought processes and adverse childhood experiences (ACEs) are well-established risk factors for the emergence and maintenance of depression. However, the neurobiological mechanisms underlying these associations remain poorly understood. METHODS: We examined resting-state functional magnetic resonance imaging data (3 T Tim Trio MR scanner; Siemens, Erlangen) of 44 individuals diagnosed with an acute depressive episode. Specifically, we focused on investigating functional brain activity and connectivity within and between three large-scale neural networks associated with processes affected in depression: the default mode network (DMN), the salience network (SN), and the central executive network (CEN). Correlational and regression-based analyses were performed. RESULTS: Our regions of interest analyses revealed that region-specific spontaneous neural activity in the anterior DMN was associated with self-reported trait rumination, specifically, the pregenual anterior cingulate cortex (pgACC). Furthermore, using a liberal statistical threshold, we found that spontaneous neural activity of the ventromedial prefrontal cortex and the pgACC were associated with depression symptom severity. Neither spontaneous neural activity in the SN and CEN nor functional connectivity within and across the investigated networks was associated with depression severity or rumination. Furthermore, there was no association between ACEs and brain activity and connectivity. LIMITATIONS: Lack of a formal control group or low-risk group for comparison. CONCLUSIONS: Overall, our results indicate network-specific changes in spontaneous brain activity, that are linked to both depression severity and rumination. Findings underscore the crucial role of the pgACC in depression and contribute to a dimensional and symptom-based understanding of depression-related network imbalances.

Dynamic Changes in Local Brain Connectivity and Activity: A Longitudinal Study in Adolescent Anorexia Nervosa.

BACKGROUND: Resting-state functional connectivity analysis has been used to study disruptions in neural circuitries underlying eating disorder symptoms. Research has shown resting-state functional connectivity to be altered during the acute phase of anorexia nervosa (AN), but little is known about the biological mechanisms underlying neural changes associated with weight restoration. The goal of the current study was to investigate longitudinal changes in regional homogeneity (ReHo) among neighboring voxels, degree centrality (DC) (a voxelwise whole brain correlation coefficient), voxel-mirrored homotopic connectivity (VMHC) (measuring the synchronization between hemispheres), and the fractional amplitude of low-frequency fluctuations associated with weight gain during AN treatment. METHODS: Resting-state functional connectivity data were acquired and analyzed from a sample of 174 female volunteers: 87 underweight patients with AN that were scanned before treatment and again after at least 12% body mass index increase, as well as 87 age-matched healthy control participants. RESULTS: Longitudinal changes in ReHo, DC, VMHC, and the fractional amplitude of low-frequency fluctuations were observed in most regions identified to differ between patients with AN before treatment and healthy control participants. However, the degree of normalization varied for each parameter, ranging from 9% of all clusters in DC to 66% in VMHC. Longitudinal changes in ReHo and VMHC showed a linear association weight gain. CONCLUSIONS: Resting-state functional magnetic resonance imaging measures, including ReHo, DC, VMHC, and the fractional amplitude of low-frequency fluctuations, show varying degrees of recovery after short-term weight restoration. Although only some of these changes were related to weight gain, our results provide an overall positive message, suggesting that weight restoration is associated with changes in functional brain measures that point toward normalization.

Altered regional brain activity moderating the relationship between childhood trauma and depression severity.

OBJECTIVE: Childhood trauma (CT) is a major environmental risk factor for an adverse course and treatment outcome of major depressive disorder (MDD). Evidence suggests that an altered regional brain activity may play a crucial role in the relationship between CT and MDD. This study aimed to clarify the relationship between CT, regional brain activity, and depression severity. METHODS: In this study, 96 patients with MDD and 82 healthy controls (HCs) participated. Regional brain activity was measured using the fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo). These measures were compared between the MDD and HC groups, and the values of different brain regions were extracted as moderators. RESULTS: Increased fALFF and ReHo values were observed in the left middle temporal gyrus in the MDD group compared with the HC group (p < 0.001). Furthermore, the fALFF and ReHo values moderated the positive correlation between the Childhood Trauma Questionnaire (CTQ) score, 17-item Hamilton Depression Rating Scale (HAMD-17) total score, and retardation factor score in the MDD group (all, p < 0.05). Finally, as the fALFF and ReHo values increased, the positive correlations between CTQ, HAMD-17 total, and retardation dimension scores became stronger. CONCLUSION: Our study highlighted the crucial role of altered brain function in connecting childhood maltreatment with depressive symptoms. Our findings indicate that an altered regional brain activity could explain the potential neurobiological mechanisms of MDD symptoms, offering the opportunity to function as a powerful diagnostic biomarker.

Neural correlates of social interaction anxiety and their relation to emotional intelligence: A resting-state fMRI study.

Social interaction anxiety refers to a state of anxiety resulting from the prospect or presence of interpersonal evaluation in real or imagined social settings. Previous neuroimaging studies have revealed neural basis of social anxiety disorder. However, little is known about the neural correlates of individual differences in social interaction anxiety in nonclinical population. In the present study, we used resting-state functional magnetic resonance imaging to explore the relationship between individual's spontaneous neural activity and social interaction anxiety, and the role that emotional intelligence played in the relationship. To this end, the correlation between the regional fractional amplitude of low-frequency fluctuations (fALFF) of the brain and individuals' social interaction anxiety scores was examined. We found that social interaction anxiety was correlated with the fALFF in the insula, parahippocampal gyrus, bilateral superior temporal gyrus, and superior parietal lobule. Furthermore, we also found that emotional intelligence partially mediated the association between the fALFF in these regions and social interaction anxiety. Taken together, our study provided the first evidence for the spontaneous neural basis of social interaction anxiety in normal population, and highlighted the neural substrates through which emotional intelligence might play an important role in social interaction anxiety.

Altered fractional amplitude of low-frequency fluctuations in the superior temporal gyrus: a resting-state fMRI study in anxious depression.

BACKGROUND: Anxious depression, which is a common subtype of major depressive disorder, has distinct clinical features from nonanxious depression. However, little is known about the neurobiological characteristics of anxious depression. In this study, we explored resting-state regional brain activity changes between anxious depression and nonanxious depression. METHOD: Resting-state functional magnetic resonance (rs-fMRI) imaging data were collected from 60 patients with anxious depression, 38 patients with nonanxious depression, and 60 matched healthy controls (HCs). One-way analysis of variance was performed to compare the whole-brain fractional amplitude of low-frequency fluctuation (fALFF) in the three groups. The correlation between the fALFF values and the clinical measures was examined. RESULTS: Compared with those of HCs, the fALFF values in the left superior temporal gyrus (STG) in patients with anxious depression were significantly increased, while the fALFF values in the left middle temporal gyrus (MTG), left STG, and right STG in patients with nonanxious depression were significantly increased. Patients with anxious depression showed reduced fALFF values in the right STG compared with patients with nonanxious depression (p < 0.001, corrected). Within the anxious depression group, fALFF value in the right STG was positively correlated with the cognitive disturbance score (r = 0.36, p = 0.005 corrected). CONCLUSION: The bilateral STG and left MTG, which are related to the default mode network, appear to be key brain regions in nonanxious depression, while the right STG plays an essential role in the neuropathological mechanism of anxious depression.

Altered neural intrinsic oscillations in patients with multiple sclerosis: effects of cortical thickness.

Objective: To investigate the effects of cortical thickness on the identification accuracy of fractional amplitude of low-frequency fluctuation (fALFF) in patients with multiple sclerosis (MS). Methods: Resting-state functional magnetic resonance imaging data were collected from 31 remitting MS, 20 acute MS, and 42 healthy controls (HCs). After preprocessing, we first calculated two-dimensional fALFF (2d-fALFF) maps using the DPABISurf toolkit, and 2d-fALFF per unit thickness was obtained by dividing 2d-fALFF by cortical thickness. Then, between-group comparison, clinical correlation, and classification analyses were performed in 2d-fALFF and 2d-fALFF per unit thickness maps. Finally, we also examined whether the effect of cortical thickness on 2d-fALFF maps was affected by the subfrequency band. Results: In contrast with 2d-fALFF, more changed regions in 2d-fALFF per unit thickness maps were detected in MS patients, such as increased region of the right inferior frontal cortex and faded regions of the right paracentral lobule, middle cingulate cortex, and right medial temporal cortex. There was a significant positive correlation between the disease duration and the 2d-fALFF values in the left early visual cortex in remitting MS patients (r = 0.517, Bonferroni-corrected, p = 0.008 × 4 < 0.05). In contrast with 2d-fALFF, we detected a positive correlation between the 2d-fALFF per unit thickness of the right ventral stream visual cortex and the modified Fatigue Impact Scale (MFIS) scores (r = 0.555, Bonferroni-corrected, p = 0.017 × 4 > 0.05). For detecting MS patients, 2d-fALFF and 2d- fALFF per unit thickness both performed remarkably well in support vector machine (SVM) analysis, especially in the remitting phase (AUC = 86, 83%). Compared with 2d-fALFF, the SVM model of 2d-fALFF per unit thickness had significantly higher classification performance in distinguishing between remitting and acute MS. More changed regions and more clinically relevant 2d-fALFF per unit thickness maps in the subfrequency band were also detected in MS patients. Conclusion: By dividing the functional value by the cortical thickness, the identification accuracy of fALFF in MS patients was detected to be potentially influenced by cortical thickness. Additionally, 2d-fALFF per unit thickness is a potential diagnostic marker that can be utilized to distinguish between acute and remitting MS patients. Notably, we observed similar variations in the subfrequency band.

Basal forebrain activity predicts functional degeneration in the entorhinal cortex in Alzheimer's disease.

Recent models of Alzheimer's disease suggest the nucleus basalis of Meynert (NbM) as an early origin of structural degeneration followed by the entorhinal cortex (EC). However, the functional properties of NbM and EC regarding amyloid-ß and hyperphosphorylated tau remain unclear. We analysed resting-state functional fMRI data with CSF assays from the Alzheimer's Disease Neuroimaging Initiative (n = 71) at baseline and 2 years later. At baseline, local activity, as quantified by fractional amplitude of low-frequency fluctuations, differentiated between normal and abnormal CSF groups in the NbM but not EC. Further, NbM activity linearly decreased as a function of CSF ratio, resembling the disease status. Finally, NbM activity predicted the annual percentage signal change in EC, but not the reverse, independent from CSF ratio. Our findings give novel insights into the pathogenesis of Alzheimer's disease by showing that local activity in NbM is affected by proteinopathology and predicts functional degeneration within the EC.

Resting-state functional magnetic resonance imaging alterations in borderline personality disorder: A systematic review.

BACKGROUND: Borderline personality disorder (BPD) is a severe psychiatric disorder characterized by emotion dysregulation, impulsivity, and interpersonal disturbances. Several structural and functional neuroimaging abnormalities have been described in BPD. In particular, resting-state functional magnetic resonance imaging (rs-fMRI) studies have recently suggested various connectivity alterations within and between large-scale brain networks in BPD. This review aimed at providing an updated summary of the evidence reported by the available rs-fMRI studies in BPD individuals. METHODS: A search on PubMed, Scopus, and Web of Science was performed to identify rs-fMRI alterations in BPD. A total of 15 studies met our inclusion criteria. RESULTS: Overall, aberrant resting-state functional connectivity (rs-FC) within and between default mode network (DMN), salience network (SN), and central executive network (CEN) were observed in BPD compared to healthy controls, as well as selective functional impairments in bilateral amygdala, anterior and posterior cingulate cortex, hippocampus, and prefrontal cortex. LIMITATIONS: The observational design, small sample size, prevalence of females, high rates of concurrent comorbidities and medications, and heterogeneity across imaging methodologies limit the generalizability of the results. CONCLUSIONS: The identification of altered patterns of rs-FC within and between selective brain networks, including DMN, SN, and CEN, could further our knowledge of the clinical symptoms of BPD, and therefore, future studies with multimodal methodologies and longitudinal designs are warranted to further explore the neural correlates of this disorder.

Investigation of functional connectivity in Bell's palsy using functional magnetic resonance imaging: prospective cross-sectional study.

Background: The most common cause of lower motor neuron facial palsy is Bell's palsy (BP). BP results in partial or complete inability to automatically move the facial muscles on the affected side and, in some cases, to close the eyelids, which can cause permanent eye damage. This study investigated changes in brain function and connectivity abnormalities in patients with BP. Methods: This study included 46 patients with unilateral BP and 34 healthy controls (HCs). Resting-state brain functional magnetic resonance imaging (fMRI) images were acquired, and Toronto Facial Grading System (TFGS) scores were obtained for all participants. The fractional amplitude of low-frequency fluctuation (fALFF) was estimated, and the relationship between the TFGS and fALFF was determined using correlation analysis for brain regions with changes in fALFF in those with BP versus HCs. Brain regions associated with TFGS were used as seeds for further functional connectivity (FC) analysis; relationships between FC values of abnormal areas and TFGS scores were also analyzed. Results: Activation of the right precuneus, right angular gyrus, left supramarginal gyrus, and left middle occipital gyrus was significantly decreased in the BP group. fALFF was significantly higher in the right thalamus, vermis, and cerebellum of the BP group compared with that in the HC group (P<0.05). The FC between the left middle occipital gyrus and right angular gyrus, left precuneus, and right middle frontal gyrus increased sharply, but decreased in the left angular gyrus, left posterior cingulate gyrus, left middle frontal gyrus, inferior cerebellum, and left middle temporal gyrus. Furthermore, the fALFF in the left middle occipital gyrus was negatively correlated with TFGS score (R=0.144; P=0.008). Conclusions: The pathogenesis of BP is closely related to functional reorganization of the cerebral cortex. Patients with BP have altered fALFF activity in cortical regions associated with facial motion feedback monitoring.