Ketamine Alters Electrophysiological Responses to Emotional Faces in Major Depressive Disorder

Lundin, Nancy B.; Sepe-Forrest, Linnea; Gilbert, Jessica R.; Carver, Frederick W.; Furey, Maura L.; Zarate, Carlos A.; Nugent, Allison C.

doi:10.1016/j.jad.2020.10.007

Cited by 7 publications

(8 citation statements)

References 60 publications

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“…Lundin et al used an emotional evaluation task to assess event-related electrical changes in the calcarine sulcus, occipital, and fusiform cortices to assess early visual responses to emotional stimuli and their potential relationship with ketamine's antidepressant response. 54 In this report, there were no associations between MADRS change and event-related field amplitudes in the calcarine sulcus nor with latency in the left middle occipital cortex. In the fusiform cortex, however, higher baseline M170 amplitudes that normalized to levels similar to healthy controls post-ketamine corresponded with greater antidepressant response.…”

Section: Magnetoencephalography (Meg)contrasting

confidence: 58%

Biomarkers of ketamine’s antidepressant effect: a clinical review of genetics, functional connectivity, and neurophysiology

Alario

Niciu

2021

Chronic Stress

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Major depressive disorder (MDD) is one of the leading causes of morbidity and all-cause mortality (including suicide) worldwide, and, unfortunately, first-line monoaminergic antidepressants and evidence-based psychotherapies are not effective for all patients. Subanesthetic doses of the N-methyl-D-aspartate receptor antagonists and glutamate modulators ketamine and S-ketamine have rapid and robust antidepressant efficacy in such treatment-resistant depressed patients (TRD). Yet, as with all antidepressant treatments including electroconvulsive therapy (ECT), not all TRD patients adequately respond, and we are presently unable to a priori predict who will respond or not respond to ketamine. Therefore, antidepressant treatment response biomarkers to ketamine have been a major focus of research for over a decade. In this article, we review the evidence in support of treatment response biomarkers, with a particular focus on genetics, functional magnetic resonance imaging, and neurophysiological studies, i.e. electroencephalography and magnetoencephalography. The studies outlined here lay the groundwork for replication and dissemination.

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Section: Magnetoencephalography (Meg)contrasting

confidence: 58%

Biomarkers of ketamine’s antidepressant effect: a clinical review of genetics, functional connectivity, and neurophysiology

Alario

Niciu

2021

Chronic Stress

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“…Ketamine has revolutionized the treatment of major depressive disorder (MDD) by displaying an antidepressant effect within 24 h after a single application in subanesthetic doses 1 , while traditional antidepressants, serotonin reuptake inhibitors, show their effects within 3 to 4 weeks. Besides its general effect on depressive symptoms, ketamine also modulates neural affective processing 2 – 4 , which has been suggested to play a major role in pathophysiology and the treatment of MDD 5 . The affect-modulated startle reflex (AMSR) paradigm is a well-established translational paradigm to examine the behavioral aspect of affective reactivity.…”

Section: Introductionmentioning

confidence: 99%

The effect of ketamine on affective modulation of the startle reflex and its resting-state brain correlates

Sen,

Chand,

Danyeli

et al. 2023

Sci Rep

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Ketamine is a rapid-acting antidepressant that also influences neural reactivity to affective stimuli. However, the effect of ketamine on behavioral affective reactivity is yet to be elucidated. The affect-modulated startle reflex paradigm (AMSR) allows examining the valence-specific aspects of behavioral affective reactivity. We hypothesized that ketamine alters the modulation of the startle reflex during processing of unpleasant and pleasant stimuli and weakens the resting-state functional connectivity (rsFC) within the modulatory pathway, namely between the centromedial nucleus of the amygdala and nucleus reticularis pontis caudalis. In a randomized, double-blind, placebo-controlled, cross-over study, thirty-two healthy male participants underwent ultra-high field resting-state functional magnetic resonance imaging at 7 T before and 24 h after placebo and S-ketamine infusions. Participants completed the AMSR task at baseline and one day after each infusion. In contrast to our hypothesis, ketamine infusion did not impact startle potentiation during processing of unpleasant stimuli but resulted in diminished startle attenuation during processing of pleasant stimuli. This diminishment significantly correlated with end-of-infusion plasma levels of ketamine and norketamine. Furthermore, ketamine induced a decrease in rsFC within the modulatory startle reflex pathway. The results of this first study on the effect of ketamine on the AMSR suggest that ketamine might attenuate the motivational significance of pleasant stimuli in healthy participants one day after infusion.

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“…Bortolon et al, 2015). In addition to general impairments in face processing, ketamine-induced impairments in facial emotion processing have been demonstrated using behavioural (Malhotra et al, 1997) and electrophysiological (Lundin et al, 2020) approaches. Such impairments have also been observed in patients with schizophrenia (Chan et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

“…Unlike dopaminergic agents, which primarily model the positive symptoms of schizophrenia (e.g., hallucinations, delusions), the ketamine model additionally produces negative symptoms including flat affect, emotional withdrawal, and cognitive symptoms (see for review Beck et al, 2020). These cognitive symptoms include impairments of configural and emotional face processing (Lundin et al, 2020; Neill et al, 2015; Reed et al, 2019; Schmidt et al, 2013), suggesting that investigations of face processing using the ketamine model may provide a gateway to further understanding of cognitive and face-processing impairments in schizophrenia.…”

Section: Introductionmentioning

confidence: 99%

Ketamine disrupts gaze patterns during face viewing in the common marmoset

Schaeffer

Selvanayagam

Wong

et al. 2021

Preprint

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Faces are stimuli of critical importance for primates. The common marmoset (Callithrix jacchus) is a promising model for investigations of face processing, as this species possesses oculomotor and face processing networks resembling those of macaques and humans. Face processing is often disrupted in neuropsychiatric conditions such as schizophrenia (SZ) and thus it is important to recapitulate underlying circuitry dysfunction preclinically. The N-Methyl-D-aspartate (NMDA) non-competitive antagonist ketamine has been used extensively to model the cognitive symptoms of SZ. Here, we investigated the effects of a subanesthetic dose of ketamine on oculomotor behaviour in marmosets during face viewing. Four marmosets received systemic ketamine or saline injections while viewing phase-scrambled or intact videos of conspecifics' faces. To evaluate effects of ketamine on scan paths during face viewing, we identified regions of interest in each face video, and classified locations of saccade onsets and landing positions within these areas. A preference for the snout over eye regions was observed following ketamine administration. In addition, regions in which saccades landed could be significantly predicted by saccade onset region in the saline but not the ketamine condition. No significant drug effects were observed for phase-scrambled videos. Effects on saccade control were limited to a reduction in saccade amplitudes during viewing of scrambled videos. Thus, ketamine induced a significant disruption of scan paths during viewing of conspecific faces but limited effects on saccade motor control. These findings support the use of ketamine in marmosets for investigating changes in neural circuits underlying social cognition in neuropsychiatric disorders.

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Ketamine Alters Electrophysiological Responses to Emotional Faces in Major Depressive Disorder

Cited by 7 publications

References 60 publications

Biomarkers of ketamine’s antidepressant effect: a clinical review of genetics, functional connectivity, and neurophysiology

Biomarkers of ketamine’s antidepressant effect: a clinical review of genetics, functional connectivity, and neurophysiology

The effect of ketamine on affective modulation of the startle reflex and its resting-state brain correlates

Ketamine disrupts gaze patterns during face viewing in the common marmoset

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