Abnormal dynamic functional connectivity of hippocampal subregions associated with working memory impairment in melancholic depression

2021 ◽  
pp. 1-13
Author(s):  
Lai Shunkai ◽  
Ting Su ◽  
Shuming Zhong ◽  
Guangmao Chen ◽  
Yiliang Zhang ◽  
...  

Abstract Background Previous studies have demonstrated structural and functional changes of the hippocampus in patients with major depressive disorder (MDD). However, no studies have analyzed the dynamic functional connectivity (dFC) of hippocampal subregions in melancholic MDD. We aimed to reveal the patterns for dFC variability in hippocampus subregions – including the bilateral rostral and caudal areas and its associations with cognitive impairment in melancholic MDD. Methods Forty-two treatment-naive MDD patients with melancholic features and 55 demographically matched healthy controls were included. The sliding-window analysis was used to evaluate whole-brain dFC for each hippocampal subregions seed. We assessed between-group differences in the dFC variability values of each hippocampal subregion in the whole brain and cognitive performance on the MATRICS Consensus Cognitive Battery (MCCB). Finally, association analysis was conducted to investigate their relationships. Results Patients with melancholic MDD showed decreased dFC variability between the left rostral hippocampus and left anterior lobe of cerebellum compared with healthy controls (voxel p < 0.005, cluster p < 0.0125, GRF corrected), and poorer cognitive scores in working memory, verbal learning, visual learning, and social cognition (all p < 0.05). Association analysis showed that working memory was positively correlated with the dFC variability values of the left rostral hippocampus-left anterior lobe of the cerebellum (r = 0.338, p = 0.029) in melancholic MDD. Conclusions These findings confirmed the distinct dynamic functional pathway of hippocampal subregions in patients with melancholic MDD, and suggested that the dysfunction of hippocampus-cerebellum connectivity may be underlying the neural substrate of working memory impairment in melancholic MDD.

2017 ◽  
Author(s):  
Masahiro Yamashita ◽  
Yujiro Yoshihara ◽  
Ryuichiro Hashimoto ◽  
Noriaki Yahata ◽  
Naho Ichikawa ◽  
...  

AbstractIndividual differences in cognitive function have been shown to correlate with brain-wide functional connectivity, suggesting a common foundation relating connectivity to cognitive function across healthy populations. However, it remains unknown whether this relationship is preserved in cognitive deficits seen in a range of psychiatric disorders. Using machine learning methods, we built a prediction model of working memory function from whole-brain functional connectivity among a healthy population (N = 17, age 19-24 years). We applied this normative model to a series of independently collected resting state functional connectivity datasets (N = 968), involving multiple psychiatric diagnoses, sites, ages (18-65 years), and ethnicities. We found that predicted working memory ability was correlated with actually measured working memory performance in both schizophrenia patients (partial correlation, ρ = 0.25, P = 0.033, N = 58) and a healthy population (partial correlation, ρ = 0.11, P = 0.0072, N = 474). Moreover, the model predicted diagnosis-specific severity of working memory impairments in schizophrenia (N = 58, with 60 controls), major depressive disorder (N = 77, with 63 controls), obsessive-compulsive disorder (N = 46, with 50 controls), and autism spectrum disorder (N = 69, with 71 controls) with effect sizes g = −0.68, −0.29, −0.19, and 0.09, respectively. According to the model, each diagnosis’s working memory impairment resulted from the accumulation of distinct functional connectivity differences that characterizes each diagnosis, including both diagnosis-specific and diagnosis-invariant functional connectivity differences. Severe working memory impairment in schizophrenia was related not only with fronto-parietal, but also widespread network changes. Autism spectrum disorder showed greater negative connectivity that related to improved working memory function, suggesting that some non-normative functional connections can be behaviorally advantageous. Our results suggest that the relationship between brain connectivity and working memory function in healthy populations can be generalized across multiple psychiatric diagnoses. This approach may shed new light on behavioral variances in psychiatric disease and suggests that whole-brain functional connectivity can provide an individual quantitative behavioral profile in a range of psychiatric disorders.


2017 ◽  
Vol 41 (S1) ◽  
pp. S212-S212
Author(s):  
E. Stella ◽  
M. La Montagna ◽  
L. Borraccino ◽  
F. Ricci ◽  
A.I. Triggiani ◽  
...  

IntroductionCognitive dysfunctions concerning working memory, attention, psychomotor speed, and verbal memory are a disabling feature of the bipolar disorder (BD). According to scientific literature, cognitive disturbances are present not only in depressive and manic phases of BD, but also during the euthymic period, without regard to whether or not drugs are assumed.ObjectiveTo determine the presence of one or more dysfunctions in cognitive domains in a sample of subjects suffering from BD, in euthymic phase, compared with healthy controls.AimsEvaluation of the following cognitive performances in subjects affected by BD: speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition.MethodsForty-six patients affected by BD in the euthymic phase (mean age: 43.17 years old; 39.13% male), and 58 healthy controls (mean age: 39.21 years old; 51.72% male) were enrolled in the psychiatric unit of Azienda Sanitaria Locale, Foggia. The neuropsychological battery MATRICS Consensus Cognitive Battery (MCCB) was administered by trained psychiatrists.ResultsWe found the presence of cognitive impairment, affecting six out of seven of cognitive functions assessed (P < 0.001): speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving.ConclusionsThese preliminary results from our case-control study show that cognitive deficits are clearly present also during the euthymic phases of subjects with bipolar disorder (mainly pertaining attention/vigilance domain). These cognitive abnormalities may represent a biomarker of bipolar disorder.Disclosure of interestThe authors have not supplied their declaration of competing interest.


2020 ◽  
Vol 17 (4) ◽  
pp. 373-381
Author(s):  
Wuhai Tao ◽  
Jinping Sun ◽  
Xin Li ◽  
Wen Shao ◽  
Jing Pei ◽  
...  

Background: Subjective Memory Impairment (SMI) may tremendously increase the risk of Alzheimer’s Disease (AD). The full understanding of the neuromechanism of SMI will shed light on the early intervention of AD. Methods: In the current study, 23 Healthy Controls (HC), 22 SMI subjects and 24 amnestic Mild Cognitive Impairment (aMCI) subjects underwent the comprehensive neuropsychological assessment and the resting-state functional magnetic resonance imaging scan. The difference in the connectivity of the Default Mode Network (DMN) and Functional Connectivity (FC) from the Region of Interest (ROI) to the whole brain were compared, respectively. Results: The results showed that HC and SMI subjects had significantly higher connectivity in the region of the precuneus area compared to aMCI subjects. However, from this region to the whole brain, SMI and aMCI subjects had significant FC decrease in the right anterior cingulum, left superior frontal and left medial superior frontal gyrus compared to HC. In addition, this FC change was significantly correlated with the cognitive function decline in participants. Conclusion: Our study indicated that SMI subjects had relatively intact DMN connectivity but impaired FC between the anterior and posterior brain. The findings suggest that long-distance FC is more vulnerable than the short ones in the people with SMI.


2015 ◽  
Vol 45 (12) ◽  
pp. 2657-2666 ◽  
Author(s):  
A. McCleery ◽  
M. F. Green ◽  
G. S. Hellemann ◽  
L. E. Baade ◽  
J. M. Gold ◽  
...  

BackgroundThe number of separable cognitive dimensions in schizophrenia has been debated. Guided by the extant factor analytic literature, the NIMH Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative selected seven cognitive domains relevant to treatment studies in schizophrenia: speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition. These domains are assessed in the MATRICS Consensus Cognitive Battery (MCCB). The aim of this study was to conduct a confirmatory factor analysis (CFA) of the beta battery of the MCCB to compare the fit of the MATRICS consensus seven-domain model to other models in the current literature on cognition in schizophrenia.MethodUsing data from 281 schizophrenia outpatients, we compared the seven correlated factors model with alternative models. Specifically, we compared the 7-factor model to (a) a single-factor model, (b) a three correlated factors model including speed of processing, working memory, and general cognition, and (c) a hierarchical model in which seven first-order factors loaded onto a second-order general cognitive factor.ResultsMultiple fit indices indicated the seven correlated factors model was the best fit for the data and provided significant improvement in model fit beyond the comparison models.ConclusionsThese results support the assessment of these seven cognitive dimensions in clinical trials of interventions to improve cognition in schizophrenia. Because these cognitive factors are separable to some degree, it is plausible that specific interventions may have differential effects on the domains.


PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e10208
Author(s):  
Wei Zheng ◽  
Yan-Ling Zhou ◽  
Cheng-Yu Wang ◽  
Xiao-Feng Lan ◽  
Bin Zhang ◽  
...  

Objective The N-methyl-D-aspartate subtype glutamate receptor antagonist ketamine has rapid antidepressant and antisuicidal effects in treating treatment-resistant bipolar depression (TRBD). The neurocognitive effects of repeated ketamine infusions in TRBD are not known. Methods Six intravenous infusions of ketamine (0.5 mg/kg over 40 min) were administered on a Monday–Wednesday–Friday schedule during a 12-day period on 16 patients with TRBD followed by a 2-week observational period. The assessment of neurocognitive function was conducted using the MATRICS Consensus Cognitive Battery at baseline, 13 and 26 days. Tasks were designed to test speed of processing, working memory, visual learning and verbal learning. Results A significant improvement was found only in scores of speed of processing (F = 9.9, p = 0.001) after a 2-week observational period, which was accounted for by the improvement of depression symptoms. There were no significant changes over time in terms of working memory, visual learning and verbal learning. Pearson correlation analysis showed that the improvement of depression symptoms through six ketamine infusions was greater among TRBD patients with lower working memory at baseline (r = 0.54, p = 0.03). In multiple regression analysis, the significant correlation was still maintained (beta = 0.67, t = 2.2, p = 0.04). Conclusion This preliminary study indicated that six ketamine infusions were not harmful but were slightly beneficial for speed of processing in TRBD. However, this change was mainly accounted for the improvement of depression symptoms over time. Lower baseline working memory appears to be associated with greater antidepressant response after completion of six ketamine infusions in patients with TRBD.


2021 ◽  
Author(s):  
Lili Wei ◽  
Jintao Wang ◽  
Yingchun Zhang ◽  
Luoyi Xu ◽  
Kehua Yang ◽  
...  

Abstract Background Repetitive transcranial magnetic stimulation (rTMS) is thought to be a promising therapeutic approach for Alzheimer's disease patients. Methods In the present report, a double-blind, randomized, sham-controlled rTMS trial was conducted in mild-to-moderate Alzheimer's disease patients. High-frequency rTMS was delivered to a subject-specific left lateral parietal region that demonstrated highest functional connectivity with the hippocampus using resting-state fMRI. The Mini Mental State Examination (MMSE) and Philadelphia Verbal Learning Test (PVLT) were used to evaluate patients’ cognitive functions. Results Patients receiving active rTMS treatment (n = 31) showed a significant increase in the MMSE, PVLT-Immediate recall, and PVLT-Short Delay recall scores after two weeks of rTMS treatment, whereas patients who received sham rTMS (n = 27) did not show significant changes in these measures. Dynamic functional connectivity (dFC) magnitude of the default mode network (DMN) in the active-rTMS group showed a significant increase after two weeks of rTMS treatment, and no significant changes were found in the sham-rTMS group. There was a significantly positive correlation between changes of the MMSE and changes of the dFC magnitude of DMN in the active-rTMS group, but not the sham-rTMS group. Conclusions Our findings are novel in demonstrating the feasibility and effectiveness of the fMRI-guided rTMS treatment in Alzheimer's disease patients, and DMN might play a vital role in therapeutic effectiveness of rTMS in Alzheimer’s disease. Trial registration: China National Medical Research Platform (http://114.255.48.20/login, No:MR-33-20-004217), retrospectively registered 2020-12-23.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sumiao Zhou ◽  
Yuanyuan Huang ◽  
Yangdong Feng ◽  
Hehua Li ◽  
Kai Wu ◽  
...  

AbstractIt was still unclear how homocysteine (Hcy) levels and cognitive deficits change in patients with schizophrenia of various ages. The present article attempts to assess the relationship between Hcy levels and cognitive deficits in patients with schizophrenia across age groups, especially in young people. Totals of 103 patients and 122 healthy controls were included. All participants were stratified into four groups according to their age: 18–29 years, 30–39 years, 40–49 years, and 50–59 years. Clinical data, plasma Hcy levels, and cognitive function score were collected. Cognitive function was evaluated using the MATRICS Consensus Cognitive Battery of tests assessing speed of processing, verbal learning and memory, visual learning and memory, working memory, and attention/vigilance. Compared with the healthy group, Hcy levels increased significantly, and all the measured cognitive function score were significantly lower in all age groups of patients with schizophrenia (p < 0.001). Hcy levels were negatively associated with speed of processing (SoP), working memory (WM), and visual learning and memory (Vis Lrng) score in 18–29 years. Further multiple regression analysis showed that SoP were independently associated with Hcy levels in patients with schizophrenia aged 18–29 years (B = 0.74, t = 3.12, p = 0.008). Based on our results, patients with schizophrenia performed worse on cognitive assessments and Hcy levels were more closely related to cognition in young patients.


2020 ◽  
Vol 66 (3) ◽  
pp. 240-248 ◽  
Author(s):  
Afaf Hamed Khalil ◽  
Marwa Abd el-Meguid ◽  
Mostafa Bastawy ◽  
Samah Rabei ◽  
Ramy Ali ◽  
...  

Introduction: Cognitive impairment is one of the fundamental features among patients with schizophrenia. The relationship between schizophrenia symptoms, insight and cognitive domains remains controversial. We aimed to study these relations in a sample of Egyptian patients with schizophrenia. Methods: A total of 109 patients with schizophrenia were assessed using Structured Clinical Interview for DSM-IV ( Diagnostic and Statistical Manual of Mental Disorders (4th ed.)) Axis I diagnosis (SCID-I), Positive and Negative Syndrome Scale (PANSS) and Scale to Assess Unawareness of Medical Disorder (SUMD). Cognitive functions were assessed using the Wechsler Adult Intelligence Scale (WAIS), the Wisconsin Card Sorting Test (WCST) and the Wechsler Memory Scale (WMS). The cognitive functions would be distributed to cover six cognitive domains: attention/vigilance speed of processing, verbal learning, visual learning, working memory and reasoning/problem solving. Results: There was a significant correlation between all cognitive domains (except attention) and PANSS subscales. PANSS negative and general psychopathology subscales were significantly correlated with five cognitive domains: speed of processing, verbal learning, visual learning, working memory and reasoning/problem solving. PANSS negative subscale was significantly correlated with verbal learning (verbal paired association 1) and visual learning (visual paired association 1). There was a significant correlation between all cognitive domains and SUMD, except verbal and visual learning domains assessed by verbal and visual paired association 1 subtests, as well as attention assessed by failure to maintain set subtest. Only visual learning (trials administered), working memory (percentage error), and processing speed (perseverative responses, and trials to complete first category) were significantly negatively correlated to SUMD. Conclusion: Cognitive impairment in patients with schizophrenia is most likely to underlie negative symptoms, general psychopathology symptoms and poor insight, suggesting that treatment strategies minimizing these symptoms would improve cognitive impairment.


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