Large-Scale Persistent Network Reconfiguration Induced by Ketamine in Anesthetized Monkeys: Relevance to Mood Disorders

Lv, Qian; Yang, Li; Li, Guoliang; Wang, Zhiwei; Shen, Zhuangming; Yu, Wenwen; Jiang, Qinying; Hou, Baoyu; Pu, Jian; Hu, Hailan; Wang, Zheng

doi:10.1016/j.biopsych.2015.02.028

Cited by 61 publications

(49 citation statements)

References 67 publications

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“…This is the most common type of functional connectivity analysis used for determining brain networks. Changes to seed-based functional connectivity observed during acute ketamine administration (Dandash et al, 2015; Gopinath et al, 2016) may be related to psychotomimetic effects, while persistent changes observed 24-hours post-infusion (Abdallah et al, 2016; Lv et al, 2016) may be more closely related to antidepressant effects.…”

Section: Pharmacological Imaging Methodsmentioning

confidence: 99%

“…Independent component analysis and graph network analysis (Joules et al, 2015; Lv et al, 2016) have also been used to investigate the effects of sub-anesthetic ketamine. These analysis methods use algorithms to automatically segment the brain into intrinsic, functionally connected networks (Braga and Buckner, 2017).…”

Section: Pharmacological Imaging Methodsmentioning

confidence: 99%

“…While nonhuman primate models have been underutilized in studies of depression (Shively and Willard, 2012), the use of phMRI in conscious animals could be particularly important for investigating the mechanisms underlying the rapid antidepressant effects of ketamine. The only study to investigate the sustained effects of ketamine in nonhuman primates (Lv et al, 2016) reported significant changes in functional connectivity 24 hours post-infusion. However, very different analysis methods were used than in Abdallah et al (2016) and the use of anesthesia represents a potential confound (Hodkinson et al, 2012; Hudetz, 2012).…”

Section: Future Directionsmentioning

confidence: 99%

See 2 more Smart Citations

Ketamine and pharmacological imaging: use of functional magnetic resonance imaging to evaluate mechanisms of action

Maltbie¹,

Kaundinya²,

Howell

2017

Behavioural Pharmacology

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Ketamine has been used as a pharmacological model for schizophrenia, as sub-anesthetic infusions have been shown to produce temporary schizophrenia-like symptoms in healthy humans. More recently, ketamine has emerged as a potential treatment for multiple psychiatric disorders, including treatment-resistant depression and suicidal ideation. However, the mechanisms underlying both the psychotomimetic and therapeutic effects of ketamine remain poorly understood. This review provides an overview of what is known of the neural mechanisms underlying the effects of ketamine and details what functional magnetic resonance imaging studies have revealed at a systems level focused on brain circuitry. Multiple analytic approaches show that ketamine produces robust and consistent effects at the whole-brain level. These effects are highly conserved across human and nonhuman primates, validating the use of nonhuman primate models for further investigations with ketamine. Regional analysis of brain functional connectivity suggests that the therapeutic potential of ketamine may be derived from a strengthening of executive control circuitry, making it an intriguing candidate for the treatment of drug abuse. There are still important questions about the mechanism of action and therapeutic potential of ketamine that can be addressed using appropriate functional neuroimaging techniques.

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Section: Pharmacological Imaging Methodsmentioning

confidence: 99%

Section: Pharmacological Imaging Methodsmentioning

confidence: 99%

Section: Future Directionsmentioning

confidence: 99%

See 1 more Smart Citation

Ketamine and pharmacological imaging: use of functional magnetic resonance imaging to evaluate mechanisms of action

Maltbie¹,

Kaundinya²,

Howell

2017

Behavioural Pharmacology

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“…It is likely that brain imaging and cognitive studies using genetically-engineered monkeys will be available soon, and will provide causal links between genes and brain structure in the non-human primate. An elegant example is the work by Wang and colleagues, who investigated the effects of ketamine on the functional brain network using magnetic resonance imaging [17]. …”

Section: Connectomic View Of the Psychiatric Brainmentioning

confidence: 99%

Non-human Primate Models for Brain Disorders – Towards Genetic Manipulations via Innovative Technology

Qiu

Xiao

2017

Neurosci. Bull.

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Modeling brain disorders has always been one of the key tasks in neurobiological studies. A wide range of organisms including worms, fruit flies, zebrafish, and rodents have been used for modeling brain disorders. However, whether complicated neurological and psychiatric symptoms can be faithfully mimicked in animals is still debatable. In this review, we discuss key findings using non-human primates to address the neural mechanisms underlying stress and anxiety behaviors, as well as technical advances for establishing genetically-engineered non-human primate models of autism spectrum disorders and other disorders. Considering the close evolutionary connections and similarity of brain structures between non-human primates and humans, together with the rapid progress in genome-editing technology, non-human primates will be indispensable for pathophysiological studies and exploring potential therapeutic methods for treating brain disorders.

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“…Many studies examined the effects of acute ketamine administration on rsFC in healthy volunteers and clinical populations (Abdallah et al, 2016; Li and Vlisides, 2016; Wong et al, 2016) as well as in non-human primates (Gopinath et al, 2016; Lv et al, 2016). In healthy humans, ketamine increased cortical/subcortical-hippocampal connectivity (Grimm et al, 2015; Khalili-Mahani et al, 2015) and thalamic connectivity to the somatosensory and temporal cortex (Hoflich et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Depression in chronic ketamine users: Sex differences and neural bases

Zhang

Hung³

et al. 2017

Psychiatry Research: Neuroimaging

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Chronic ketamine use leads to cognitive and affective deficits including depression. Here, we examined sex differences and neural bases of depression in chronic ketamine users. Compared to non-drug using healthy controls (HC), ketamine-using females but not males showed increased depression score as assessed by the Center of Epidemiological Studies Depression Scale (CES-D). We evaluated resting state functional connectivity (rsFC) of the subgenual anterior cingulate cortex (sgACC), a prefrontal structure consistently implicated in the pathogenesis of depression. Compared to HC, ketamine users (KU) did not demonstrate significant changes in sgACC connectivities at a corrected threshold. However, in KU, a linear regression against CES-D score showed less sgACC connectivity to the orbitofrontal cortex (OFC) with increasing depression severity. Examined separately, male and female KU showed higher sgACC connectivity to bilateral superior temporal gyrus and dorsomedial prefrontal cortex (dmPFC), respectively, in correlation with depression. The linear correlation of sgACC-OFC and sgACC-dmPFC connectivity with depression was significantly different in slope between KU and HC. These findings highlighted changes in rsFC of the sgACC as associated with depression and sex differences in these changes in chronic ketamine users.

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Large-Scale Persistent Network Reconfiguration Induced by Ketamine in Anesthetized Monkeys: Relevance to Mood Disorders

Cited by 61 publications

References 67 publications

Ketamine and pharmacological imaging: use of functional magnetic resonance imaging to evaluate mechanisms of action

Ketamine and pharmacological imaging: use of functional magnetic resonance imaging to evaluate mechanisms of action

Non-human Primate Models for Brain Disorders – Towards Genetic Manipulations via Innovative Technology

Depression in chronic ketamine users: Sex differences and neural bases

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