Ketamine administration reduces amygdalo-hippocampal reactivity to emotional stimulation - PubMed (original) (raw)

. 2016 May;37(5):1941-52.

doi: 10.1002/hbm.23148. Epub 2016 Feb 25.

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Ketamine administration reduces amygdalo-hippocampal reactivity to emotional stimulation

Milan Scheidegger et al. Hum Brain Mapp. 2016 May.

Abstract

Increased amygdala reactivity might lead to negative bias during emotional processing that can be reversed by antidepressant drug treatment. However, little is known on how N-methyl-d-aspartate (NMDA) receptor antagonism with ketamine as a novel antidepressant drug target might modulate amygdala reactivity to emotional stimulation. Using functional magnetic resonance imaging (fMRI) and resting-state fMRI (rsfMRI), we assessed amygdalo-hippocampal reactivity at baseline and during pharmacological stimulation with ketamine (intravenous bolus of 0.12 mg/kg, followed by a continuous infusion of 0.25 mg/kg/h) in 23 healthy subjects that were presented with stimuli from the International Affective Picture System (IAPS). We found that ketamine reduced neural reactivity in the bilateral amygdalo-hippocampal complex during emotional stimulation. Reduced amygdala reactivity to negative pictures was correlated to resting-state connectivity to the pregenual anterior cingulate cortex. Interestingly, subjects experienced intensity of psychedelic alterations of consciousness during ketamine infusion predicted the reduction in neural responsivity to negative but not to positive or neutral stimuli. Our findings suggest that the pharmacological modulation of glutamate-responsive cerebral circuits, which is associated with a shift in emotional bias and a reduction of amygdalo-hippocampal reactivity to emotional stimuli, represents an early biomechanism to restore parts of the disrupted neurobehavioral homeostasis in MDD patients. Hum Brain Mapp 37:1941-1952, 2016. © 2016 Wiley Periodicals, Inc.

Keywords: antidepressants; depression; emotional processing; fMRI; glutamate; ketamine.

© 2016 Wiley Periodicals, Inc.

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Figures

Figure 1

Figure 1

Significant negative correlation between reaction times and increased scores in the scales of oceanic boundlessness in the ketamine condition (n = 20, r = −0.637, p = 0.003).

Figure 2

Figure 2

Reduced BOLD reactivity in the amygdalo‐hippocampal complex during processing of positive, negative, and neutral stimuli after ketamine administration compared to baseline (whole brain paired t test, n = 23, FDR‐corrected, k > 25).

Figure 3

Figure 3

Reduced BOLD reactivity to positive, negative, and neutral stimuli in the bilateral amygdala and hippocampus (extracted using AAL MNI ROI library and Marsbar SPM8 ROI toolbox). Bars indicate task‐specific %‐BOLD signal changes (positive, negative, and neutral) for the baseline (green) and ketamine (blue) session (paired t test, n = 23, error bars: ±SEM). [Color figure can be viewed in the online issue, which is available at

http://wileyonlinelibrary.com

.]

Figure 4

Figure 4

Significant positive correlations between %BOLD signal reductions to negative stimuli and psychedelic alterations of consciousness for the left amygdala and the left hippocampus.

Figure 5

Figure 5

Significant positive correlation between %BOLD signal changes to negative pictures in both amygdalae with functional connectivities to the pgACC during the ketamine condition (AMG left: n = 23, r = 0.530, p = 0.009; AMG right: n = 23, r = 0.501, p = 0.015).

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