scholarly journals Ketamine Treatment and Global Brain Connectivity in Major Depression

2016 ◽  
Vol 42 (6) ◽  
pp. 1210-1219 ◽  
Author(s):  
Chadi G Abdallah ◽  
Lynnette A Averill ◽  
Katherine A Collins ◽  
Paul Geha ◽  
Jaclyn Schwartz ◽  
...  
2019 ◽  
Author(s):  
Christoph Kraus ◽  
Anahit Mkrtchian ◽  
Bashkim Kadriu ◽  
Allison C. Nugent ◽  
Carlos A. Zarate Jr. ◽  
...  

2014 ◽  
Vol 21 (8) ◽  
pp. 1003-1012 ◽  
Author(s):  
Salvatore Nigro ◽  
Luca Passamonti ◽  
Roberta Riccelli ◽  
Nicola Toschi ◽  
Federico Rocca ◽  
...  

Background: Major depression (MD) is a common psychiatric disorder in multiple sclerosis (MS). Despite the negative impact of MD on the quality of life of MS patients, little is known about its underlying brain mechanisms. Objective: We studied the whole-brain connectivity patterns that were associated with MD in MS. Alterations were mainly expected within limbic circuits. Methods: Diffusion tensor imaging data were collected in 20 MS patients with MD, 22 non-depressed MS patients and 16 healthy controls. We used deterministic tractography and graph analysis to study the white-matter connectivity patterns that characterized MS patients with MD. Results: We found that MD in MS was associated with increased local path length in the right hippocampus and right amygdala. Further analyses revealed that these effects were driven by an increased shortest distance between both the right hippocampus and right amygdala and a series of regions including the dorsolateral and ventrolateral prefrontal cortex, orbitofrontal cortex, sensory-motor cortices and supplementary motor area. Conclusion: Our data provide strong support for neurobiological accounts positing that MD in MS is mediated by abnormal ‘communications’ within limbic circuits. We also found evidence that MD in MS may be linked with connectivity alterations at the limbic-motor interface, a group of regions that translates emotions into survival-oriented behaviors.


eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Nicholas L Balderston ◽  
Elizabeth Hale ◽  
Abigail Hsiung ◽  
Salvatore Torrisi ◽  
Tom Holroyd ◽  
...  

Anxiety disorders affect approximately 1 in 5 (18%) Americans within a given 1 year period, placing a substantial burden on the national health care system. Therefore, there is a critical need to understand the neural mechanisms mediating anxiety symptoms. We used unbiased, multimodal, data-driven, whole-brain measures of neural activity (magnetoencephalography) and connectivity (fMRI) to identify the regions of the brain that contribute most prominently to sustained anxiety. We report that a single brain region, the intraparietal sulcus (IPS), shows both elevated neural activity and global brain connectivity during threat. The IPS plays a key role in attention orienting and may contribute to the hypervigilance that is a common symptom of pathological anxiety. Hyperactivation of this region during elevated state anxiety may account for the paradoxical facilitation of performance on tasks that require an external focus of attention, and impairment of performance on tasks that require an internal focus of attention.


2020 ◽  
Vol 45 (6) ◽  
pp. 982-989 ◽  
Author(s):  
Christoph Kraus ◽  
Anahit Mkrtchian ◽  
Bashkim Kadriu ◽  
Allison C. Nugent ◽  
Carlos A. Zarate ◽  
...  

2016 ◽  
Vol 63 (12) ◽  
pp. 2540-2549 ◽  
Author(s):  
Dustin Scheinost ◽  
Fuyuze Tokoglu ◽  
Xilin Shen ◽  
Emily S. Finn ◽  
Stephanie Noble ◽  
...  

2018 ◽  
Vol 2 ◽  
pp. 247054701879610 ◽  
Author(s):  
Chadi G. Abdallah ◽  
Arpan Dutta ◽  
Christopher L. Averill ◽  
Shane McKie ◽  
Teddy J. Akiki ◽  
...  

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.


2021 ◽  
Author(s):  
Seda Sacu ◽  
Carolin Wackerhagen ◽  
Susanne Erk ◽  
Nina Romanczuk-Seiferth ◽  
Kristina Schwarz ◽  
...  

Abstract Background: Aberrant brain connectivity during emotional processing, especially within the fronto-limbic pathway, is one of the hallmarks of major depressive disorder (MDD). However, a lack of systematic approaches in previous studies made it difficult to determine whether a specific alteration in brain connectivity reflects a cause, correlate, or effect of the disorder. The current study aimed to investigate neural mechanisms that correspond to disease, risk and resilience in major depression during implicit processing of emotion cues. Methods: Forty-eight patients with MDD, 49 first-degree relatives of patients with MDD and 103 healthy controls performed a face-matching task during functional magnetic resonance imaging. We used dynamic causal modelling to estimate task-dependent effective connectivity at the subject level. Parametric empirical Bayes was then performed to quantify group differences in effective connectivity. Results: Depressive pathology was associated with decreased effective connectivity from the left amygdala and left dorsolateral prefrontal cortex to the right fusiform gyrus, whereas familial risk for depression corresponded to decreased connectivity from the right orbitofrontal cortex to the left insula and from the left orbitofrontal cortex to the right fusiform gyrus. Resilience for depression was related to increased connectivity from the anterior cingulate cortex to the left dorsolateral prefrontal cortex. Conclusions: Our results suggest that the depressive state alters top-down control of higher visual regions during the processing of emotional faces, whereas increased connectivity within the cognitive control network promotes resilience to depression.


2019 ◽  
Author(s):  
Christoph Kraus ◽  
Anahit Mkrtchian ◽  
Bashkim Kadriu ◽  
Allison C. Nugent ◽  
Carlos A. Zarate ◽  
...  

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.


2020 ◽  
Author(s):  
Qian Zhuang ◽  
Lei Xu ◽  
Feng Zhou ◽  
Shuxia Yao ◽  
Xiaoxiao Zheng ◽  
...  

AbstractInhibitory control hierarchically regulates cognitive and emotional systems in the service of adaptive goal-directed behavior across changing task demands and environments. While previous studies convergently determined the contribution of prefrontal-striatal systems to general inhibitory control, findings on the specific circuits that mediate the context-specific impact of inhibitory control remained inconclusive. Against this background we employed an evaluated emotional Go/No Go task with fMRI in a large cohort of subjects (N = 250) to segregate brain systems and circuits that mediate domain-general from emotion-specific inhibition control. Particularly during a positive emotional context, behavioral results showed a lower accuracy for No Go trials and a faster response time for Go trials. While the dorsal striatum and lateral frontal regions were involved in inhibitory control irrespective of emotional context, activity in the ventral striatum (VS) and medial orbitofrontal cortex (mOFC) varied as a function of emotional context. On the voxel-wise network level, limbic and striatal systems generally exhibited highest changes in global brain connectivity during inhibitory control, while global brain connectivity of the left mOFC was less suppressed during emotional contexts. Functional connectivity analyses moreover revealed that negative coupling between the VS with inferior frontal gyrus (IFG)/insula and mOFC varied as a function of emotional context. Together these findings indicated separable domain general systems as well emotional context-specific inhibitory brain systems which specifically encompass the VS and its connections with frontal regions.


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