Ketamine modulates hippocampal neurochemistry and functional connectivity: a combined magnetic resonance spectroscopy and resting-state fMRI study in healthy volunteers

Kraguljac, Nina; Frölich, Michael A.; Tran, Steve; White, David M.; Nichols, Nona; Barton-McArdle, Alexander; Reid, Meredith A.; Bolding, Mark; Lahti, Adrienne C.

doi:10.1038/mp.2016.122

Cited by 92 publications

(89 citation statements)

References 73 publications

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“…A number of fMRI studies have examined modifications of connectivity at sub-anesthetic doses of ketamine. However, a confusing pattern emerges in these papers, with some showing increases in connectivity (Driesen et al, 2013;Anticevic et al, 2015;Dandash et al, 2015), whereas others show decreases (Kraguljac et al, 2017;Wong et al, 2016). This pattern may be related to the many different analytical techniques to both preprocess and quantify FC in the BOLD data.…”

Section: Functional Connectivity and Signal Variabilitymentioning

confidence: 99%

Decreased Directed Functional Connectivity in the Psychedelic State

Barnett

Muthukumaraswamy

Carhart‐Harris

et al. 2019

Preprint

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Neuroimaging studies of the psychedelic state offer a unique window onto the neural basis of conscious perception and selfhood. Despite well understood pharmacological mechanisms of action, the largescale changes in neural dynamics induced by psychedelic compounds remain poorly understood. Using source-localised, steady-state MEG recordings, we describe changes in functional connectivity following the controlled administration of LSD, psilocybin and low-dose ketamine, as well as, for comparison, the (non-psychedelic) anticonvulsant drug tiagabine. We compare both undirected and directed measures of functional connectivity between placebo and drug conditions. We observe a general decrease in directed functional connectivity for all three psychedelics, as measured by Granger causality, throughout the brain. These data support the view that the psychedelic state involves a breakdown in patterns of functional organisation or information flow in the brain. In the case of LSD, the decrease in directed functional connectivity is coupled with an increase in undirected functional connectivity, which we measure using correlation and coherence. This surprising opposite movement of directed and undirected measures is of more general interest for functional connectivity analyses, which we interpret using analytical modelling. Overall, our results uncover the neural dynamics of information flow in the psychedelic state, and highlight the importance of comparing multiple measures of functional connectivity when analysing time-resolved neuroimaging data.

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Section: Functional Connectivity and Signal Variabilitymentioning

confidence: 99%

Decreased Directed Functional Connectivity in the Psychedelic State

Barnett

Muthukumaraswamy

Carhart‐Harris

et al. 2019

Preprint

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“…Subchronic PCP treatment also results in decreased thalamic, hippocampal and PFC connectivity and induces a decrease in the functional integration between the hippocampus and PFC (Dawson et al, ), which could contribute to the cognitive deficits seen as a result of prolonged NMDA receptor hypofunction. Decreased hippocampal‐PFC resting‐state FC is also seen in patients with SZ (Kraguljac et al, ) and genetic rodent models relevant to the disorder (Dawson et al, ; Sigurdsson et al, ). Again, a central role for altered neuromodulatory system connectivity is indicated as a result of prolonged NMDA receptor hypofunction, with decreased PFC – LC connectivity supported (Dawson et al, ).…”

Section: Insights From Rodent Studies Characterizing the Impact Of Nmmentioning

confidence: 99%

Glutamatergic regulation of cognition and functional brain connectivity: insights from pharmacological, genetic and translational schizophrenia research

Dauvermann

Lee

Dawson

2017

British J Pharmacology

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The pharmacological modulation of glutamatergic neurotransmission to improve cognitive function has been a focus of intensive research, particularly in relation to the cognitive deficits seen in schizophrenia. Despite this effort, there has been little success in the clinical use of glutamatergic compounds as procognitive drugs. Here, we review a selection of the drugs used to modulate glutamatergic signalling and how they impact on cognitive function in rodents and humans. We highlight how glutamatergic dysfunction, and NMDA receptor hypofunction in particular, is a key mechanism contributing to the cognitive deficits observed in schizophrenia and outline some of the glutamatergic targets that have been tested as putative procognitive targets for this disorder. Using translational research in this area as a leading exemplar, namely, models of NMDA receptor hypofunction, we discuss how the study of functional brain network connectivity can provide new insight into how the glutamatergic system impacts on cognitive function. Future studies characterizing functional brain network connectivity will increase our understanding of how glutamatergic compounds regulate cognition and could contribute to the future success of glutamatergic drug validation.

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“…Notably, Grimm observed increased FC of the dlPFC bilaterally to only the left HPC, a finding consistent with hypermetabolism of the left CA1 hippocampal region present in clinical high risk individuals that precedes hippocampal atrophy . However, Kraguljac and colleagues reported a decrease in HPC FC with the frontal cluster. Thus, HPC‐prefrontal FC seems to be altered by acute ketamine infusion in humans, but the direction of change is unclear and more studies using comparable experimental settings and methods of analysis are needed to elucidate under which conditions ketamine increases or decreases hippocampal FC.…”

Section: Discoordination In Large‐scale Networkmentioning

confidence: 71%

Neural and neuronal discoordination in schizophrenia: From ensembles through networks to symptoms

et al. 2019

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Despite the substantial knowledge accumulated by past research, the exact mechanisms of the pathogenesis of schizophrenia and causal treatments still remain unclear. Deficits of cognition and information processing in schizophrenia are today often viewed as the primary and core symptoms of this devastating disorder. These deficits likely result from disruptions in the coordination of neuronal and neural activity. The aim of this review is to bring together convergent evidence of discoordinated brain circuits in schizophrenia at multiple levels of resolution, ranging from principal cells and interneurons, neuronal ensembles and local circuits, to large-scale brain networks. We show how these aberrations could underlie deficits in cognitive control and other higher order cognitive-behavioural functions. Converging evidence from both animal models and patients with schizophrenia is presented in an effort to gain insight into common features of deficits in the brain information processing in this disorder, marked by disruption of several neurotransmitter and signalling systems and severe behavioural outcomes. K E Y W O R D SfMRI, GABA interneurons, humans, oscillations, psychosis, rats

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Ketamine modulates hippocampal neurochemistry and functional connectivity: a combined magnetic resonance spectroscopy and resting-state fMRI study in healthy volunteers

Cited by 92 publications

References 73 publications

Decreased Directed Functional Connectivity in the Psychedelic State

Decreased Directed Functional Connectivity in the Psychedelic State

Glutamatergic regulation of cognition and functional brain connectivity: insights from pharmacological, genetic and translational schizophrenia research

Neural and neuronal discoordination in schizophrenia: From ensembles through networks to symptoms

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