scholarly journals Replicating Global Brain Connectivity as an Imaging Marker for Depression – Influence of Preprocessing Strategies and Randomized Placebo-Controlled Ketamine Treatment

2019 ◽  
Author(s):  
Christoph Kraus ◽  
Anahit Mkrtchian ◽  
Bashkim Kadriu ◽  
Allison C. Nugent ◽  
Carlos A. Zarate ◽  
...  
Keyword(s):  
Antidepressant Treatment ◽  
Brain Connectivity ◽  
Physiological Parameter ◽  
Functional Magnetic Resonance ◽  
Major Depressive ◽  
Global Signal ◽  
Z Scores ◽  
Independent Replication ◽  
Global Brain ◽  
Large Clusters

AbstractMajor depressive disorder (MDD) is associated with altered global brain connectivity (GBC), as assessed via resting state functional magnetic resonance imaging (rsfMRI). Previous studies found that antidepressant treatment with ketamine normalized aberrant GBC changes in the prefrontal and cingulate cortices, warranting further investigations of GBC as a putative imaging marker. However, the results were only obtained via global signal regression (GSR). This study is an independent replication of that analysis using a separate dataset. GBC was analyzed in 28 individuals with MDD and 22 healthy controls (HCs) at baseline, post-placebo, and post-ketamine. To investigate the effects of preprocessing, three distinct pipelines were used: 1) regression of white matter (WM)/cerebrospinal fluid (CSF) signals only (BASE); 2) WM/CSF+GSR (GSR); and 3) WM/CSF+physiological parameter regression (PHYSIO). Compared to PHYSIO and BASE regression, GSR reduced Fisher Z-scores (Fz-scores) in large clusters. PHYSIO did not resemble GBC preprocessed with GSR (GBCr). Reduced GBCr was observed in individuals with MDD at baseline in the anterior and medial cingulate cortices, as well as in the prefrontal cortex. Significant results were only found with GSR. Ketamine had no effect compared to baseline or placebo in either group. These results concur with several studies that used GSR to study GBC. Altered GBCr was observed in the cingulate and prefrontal cortices, but ketamine treatment had no effect. Further investigations are warranted into disease-specific components of global fMRI signals that may drive these results and of GBCr as a potential imaging marker in MDD.

scholarly journals Ketamine, but Not the NMDAR Antagonist Lanicemine, Increases Prefrontal Global Connectivity in Depressed Patients

2018 ◽  
Vol 2 ◽  
pp. 247054701879610 ◽  
Author(s):  
Chadi G. Abdallah ◽  
Arpan Dutta ◽  
Christopher L. Averill ◽  
Shane McKie ◽  
Teddy J. Akiki ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Brain Connectivity ◽  
Acute Effects ◽  
Major Depressive ◽  
Aspartate Receptor ◽  
Global Signal ◽  
Global Brain ◽  
The Relationship

Background Identifying the neural correlates of ketamine treatment may facilitate and expedite the development of novel, robust, and safe rapid-acting antidepressants. Prefrontal cortex (PFC) global brain connectivity with global signal regression (GBCr) was recently identified as a putative biomarker of major depressive disorder. Accumulating evidence have repeatedly shown reduced PFC GBCr in major depressive disorder, an abnormality that appears to normalize following ketamine treatment. Methods Fifty-six unmedicated participants with major depressive disorder were randomized to intravenous placebo (normal saline; n = 18), ketamine (0.5 mg/kg; n = 19), or lanicemine (100 mg; n = 19). PFC GBCr was computed using time series from functional magnetic resonance imaging scans that were completed at baseline, during infusion, and at 24-h posttreatment. Results Compared to placebo, ketamine significantly increased average PFC GBCr during infusion ( p = 0.01) and at 24-h posttreatment ( p = 0.02). Lanicemine had no significant effects on GBCr during infusion ( p = 0.45) and at 24-h posttreatment ( p = 0.23) compared to placebo. Average delta PFC GBCr (during minus baseline) showed a pattern of positively predicting depression improvement in participants receiving ketamine ( r = 0.44; p = 0.06; d = 1.0) or lanicemine ( r = 0.55; p = 0.01; d = 1.3) but not those receiving placebo ( r = −0.1; p = 0.69; d = 0.02). Follow-up vertex-wise analyses showed ketamine-induced GBCr increases in the dorsolateral, dorsomedial, and frontomedial PFC during infusion and in the dorsolateral and dorsomedial PFC at 24-h posttreatment ( corrected p < 0.05). Exploratory vertex-wise analyses examining the relationship with depression improvement showed positive correlation with GBCr in the dorsal PFC during infusion and at 24-h posttreatment but negative correlation with GBCr in the ventral PFC during infusion ( uncorrected p < 0.01). Conclusions In a randomized placebo-controlled approach, the results provide the first evidence in major depressive disorder of ketamine-induced increases in PFC GBCr during infusion and suggest that ketamine’s rapid-acting antidepressant properties are related to its acute effects on prefrontal connectivity. Overall, the study findings underscore the similarity and differences between ketamine and another N-methyl-D-aspartate receptor antagonist while proposing a pharmacoimaging paradigm for the optimization of novel rapid-acting antidepressants prior to testing in costly clinical trials.

scholarly journals The Temporal Dedifferentiation of Global Brain Signal Fluctuations During Human Brain Aging

2021 ◽  
Author(s):  
Yifeng Wang ◽  
Yujia Ao ◽  
Chengxiao Yang ◽  
Juan Kou ◽  
Lihui Huang ◽  
...  
Keyword(s):  
Healthy Aging ◽  
Brain Aging ◽  
Power Spectra ◽  
Head Motion ◽  
Aging Brain ◽  
Functional Magnetic Resonance ◽  
Hemodynamic Response Function ◽  
Brain Organization ◽  
Global Signal ◽  
Global Brain

Abstract The variation of brain organization as healthy aging has been discussed widely using resting-state functional magnetic resonance imaging. Previous conclusions may be misinterpreted without considering the effects of global signal (GS) on local activities and the variation of GS as age is still unknown. To fill this gap, we systematically examined the correlation between GS fluctuations and age. Correlations were evaluated between age and parameters of GS fluctuations including power at each frequency point, spectral centroids, and trends of power spectra. Data with hemodynamic response function (HRF) de-convolution and head motion parameter were further analyzed to test whether the age effect of GS fluctuations has neural origins. GS fluctuations varied as age in three ways. First, general GS power reductions were found in both time and frequency dimensions. Second, the GS power at lower frequencies transferring to higher frequencies was observed. Third, more evenly distributed power across frequencies was showed in aging brain. These trends were partly impacted by HRF de-convolution, but not by head motion. These results suggest that GS fluctuations are weaker and more evenly distributed across frequencies in elderly brain. It may indicate the temporal dedifferentiation hypothesis of brain aging from the global signal level.

Resting-state brain alteration after a single dose of SSRI administration predicts 8-week remission of patients with major depressive disorder

2016 ◽  
Vol 47 (3) ◽  
pp. 438-450 ◽  
Author(s):  
Y. Cheng ◽  
J. Xu ◽  
D. Arnone ◽  
B. Nie ◽  
H. Yu ◽  
...  
Keyword(s):  
Resting State ◽  
Pharmacological Treatment ◽  
Early Stage ◽  
Antidepressant Treatment ◽  
Occipital Cortex ◽  
First Episode ◽  
Acute Administration ◽  
Functional Magnetic Resonance ◽  
Major Depressive ◽  
State Activity

BackgroundThe present study investigated alteration of brain resting-state activity induced by antidepressant treatment and attempted to investigate whether treatment efficacy can be predicted at an early stage of pharmacological treatment.MethodForty-eight first-episode medication-free patients diagnosed with major depression received treatment with escitalopram. Resting-state functional magnetic resonance imaging was administered prior to treatment, 5 h after the first dose, during the course of pharmacological treatment (week 4) and at endpoint (week 8). Resting-state activity was evaluated in the course of the 8-week treatment and in relation to clinical improvement.ResultsEscitalopram dynamically modified resting-state activity in depression during the treatment. After 5 h the antidepressant induced a significant decrease in the signal in the occipital cortex and an increase in the dorsolateral and dorsomedial prefrontal cortices and middle cingulate cortex. Furthermore, while remitters demonstrated more obvious changes following treatment, these were more modest in non-responders suggesting possible tonic and dynamic differences in the serotonergic system. Changes after 5 h in the caudate, occipital and temporal cortices were the best predictor of clinical remission at endpoint.ConclusionsThis study revealed the possibility of using the measurement of resting-state neural changes a few hours after acute administration of antidepressant to identify individuals likely to remit after a few weeks of treatment.

scholarly journals Altered Global Brain Signal during Physiologic, Pharmacologic, and Pathologic States of Unconsciousness in Humans and Rats

2020 ◽  
Vol 132 (6) ◽  
pp. 1392-1406 ◽  
Author(s):  
Sean Tanabe ◽  
Zirui Huang ◽  
Jun Zhang ◽  
Yali Chen ◽  
Stuart Fogel ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Signal Amplitude ◽  
Global Network ◽  
Unresponsive Wakefulness Syndrome ◽  
Functional Magnetic Resonance ◽  
Resonance Imaging ◽  
Temporal Coordination ◽  
Global Signal ◽  
Global Brain

Abstract Background Consciousness is supported by integrated brain activity across widespread functionally segregated networks. The functional magnetic resonance imaging–derived global brain signal is a candidate marker for a conscious state, and thus the authors hypothesized that unconsciousness would be accompanied by a loss of global temporal coordination, with specific patterns of decoupling between local regions and global activity differentiating among various unconscious states. Methods Functional magnetic resonance imaging global signals were studied in physiologic, pharmacologic, and pathologic states of unconsciousness in human natural sleep (n = 9), propofol anesthesia (humans, n = 14; male rats, n = 12), and neuropathological patients (n = 21). The global signal amplitude as well as the correlation between global signal and signals of local voxels were quantified. The former reflects the net strength of global temporal coordination, and the latter yields global signal topography. Results A profound reduction of global signal amplitude was seen consistently across the various unconscious states: wakefulness (median [1st, 3rd quartile], 0.46 [0.21, 0.50]) versus non-rapid eye movement stage 3 of sleep (0.30 [0.24, 0.32]; P = 0.035), wakefulness (0.36 [0.31, 0.42]) versus general anesthesia (0.25 [0.21, 0.28]; P = 0.001), healthy controls (0.30 [0.27, 0.37]) versus unresponsive wakefulness syndrome (0.22 [0.15, 0.24]; P &lt; 0.001), and low dose (0.07 [0.06, 0.08]) versus high dose of propofol (0.04 [0.03, 0.05]; P = 0.028) in rats. Furthermore, non-rapid eye movement stage 3 of sleep was characterized by a decoupling of sensory and attention networks from the global network. General anesthesia and unresponsive wakefulness syndrome were characterized by a dissociation of the majority of functional networks from the global network. This decoupling, however, was dominated by distinct neuroanatomic foci (e.g., precuneus and anterior cingulate cortices). Conclusions The global temporal coordination of various modules across the brain may distinguish the coarse-grained state of consciousness versus unconsciousness, while the relationship between the global and local signals may define the particular qualities of a particular unconscious state. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

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