Electrophysiological biomarkers of antidepressant response to ketamine in treatment-resistant depression: Gamma power and long-term potentiation

Abstract

Over the last two decades, the discovery of ketamine's antidepressant properties has galvanized research into the neurobiology of treatment-resistant depression. Nevertheless, the mechanism of action underlying antidepressant response to ketamine remains unclear. This study reviews electrophysiological studies of ketamine's effects in individuals with depression as well as healthy controls, with a focus on two putative markers of synaptic potentiation: gamma oscillations and long-term potentiation. The review focuses on: 1) measures of gamma oscillations and power and their relationship to both acute, psychotomimetic drug effects as well as delayed antidepressant response in mood disorders; 2) changes in long-term potentiation as a promising measure of synaptic potentiation following ketamine administration; and 3) recent efforts to model antidepressant response to ketamine using novel computational modeling techniques, in particular the application of dynamic causal modeling to electrophysiological data. The latter promises to better characterize the mechanisms underlying ketamine's antidepressant effects.

Ketamine and attentional bias to threat: dynamic causal modeling of magnetoencephalographic connectivity in treatment-resistant depression

“…Because the study focused on measuring parameters that were significantly altered following ketamine administration, the post-ketamine scan was directly compared with both the baseline and placebo saline scans. It was predicted that ketamine would increase gamma power in our defined network—particularly in the amygdala—in line with previous findings of gamma power as a putative marker of ketamine-mediated synaptic potentiation (Gilbert and Zarate, 2020) and a normalizer of activation in the amygdala post-ketamine administration (Reed et al, 2018). The study also sought to examine group (MDD participants versus healthy volunteers) by session (ketamine versus baseline/placebo) interaction effects on modeled parameter estimates governing receptor time constants and connectivity within the amygdala, a key region involved in the emotional processing of face stimuli.…”

“…The multiple sparse priors routine implemented in SPM12 was used to identify gamma frequency (30-58 Hz) sources of activity from each participant’s sensor-level data over a peristimulus event time window from −100 to 1000 msec. Gamma frequency was targeted, as recent findings in both animals and humans have demonstrated robust, ketamine-mediated cortical responses in that band (Cornwell et al, 2012; Hong et al, 2010; Lazarewicz et al, 2010; Muthukumaraswamy et al, 2015; Shaw et al, 2015), in keeping with ketamine’s ability to alter excitation-inhibition balance (Gilbert and Zarate, 2020). Induced responses to face pairs were localized to 512 potential mesh points using a variational Bayesian approach following co-registration of sensor positions to a canonical template brain.…”

From Mechanisms to Functions: The Role of Synchronization in the Intrahippocampal Circuits

“…Nevertheless, both mechanisms do not contradict each other and most likely function simultaneously, which makes gammas one of the most common rhythms in the brain. Gammas oscillations have been observed in many brain regions, in a wide variety of physiological states and in the experiments in vitro (Traub et al, 1996;Schneider et al, 2015;Lundqvist et al, 2016;de la Prida and Huberfeld, 2019;Gilbert and Zarate, 2020). A high tendency of neuronal networks to generate gammas leads to the possibility of resonance between two connected brain structures, and as a result, to high coherence.…”

Advances in neurochemical measurements: A review of biomarkers and devices for the development of closed-loop deep brain stimulation systems

“…Such technology will prove beneficial for exploring brain structure and function as well as for integrating multimodal feedback for enhanced calibration of neurostimulation parameters. A more thorough discussion of the electrophysiological fundamentals can be found in recent reviews [60,[63][64][65].…”