Table 1.
Demographic and phenomenological information.
Table 2.
Overview of brain regions with significant Ketamine-induced increase in gamma-band power and aperiodic slope change.
Fig 1.
Topography of gamma-band power and aperiodic slope effects.
(A) Depicted are grand-averaged (n = 12) topographies of averaged power estimates (30-90 Hz) for each condition (left panels), topographies of power difference values (post-condition, i.e., during continuous infusion, minus pre-condition, i.e., before administration; middle panels), and t-values of the statistical comparison (contrast of power difference values; right panels). Positive t-values indicate increased gamma-band power in the Ketamine compared to the placebo condition. White dots indicate sensors belonging to the cluster with significant effect. (B) Same as in (A) for the aperiodic slope effect. Negative t-values indicate a flatter slope in the Ketamine compared to the placebo condition. PLA = Placebo, KET = Ketamine.
Fig 2.
Gamma-band power and aperiodic slope change at virtual channel level.
(A) Grand-averaged (n = 12) power spectrum in gamma range (30-90 Hz) per condition (black: Placebo, red: Ketamine, dotted line: pre infusion onset, straight line: post infusion onset), averaged across regions with significant gamma-band power change and across participants. Shaded envelope indicates standard error of the mean. (B) Centroids of cortical (red) and subcortical (blue) brain regions with significant gamma-band power change. Perspective from the left (upper figure) and above (lower figure) on a semi-transparent brain. Labels of these regions can be found in Table 2. (C) Gamma-band power difference values (post minus pre administration) for each participant (dark grey dots) averaged across regions with significant gamma power change, and averaged across participants (black dot) with standard deviation indication (black error bars). (D) Grand-averaged aperiodic fit (n = 12) per condition (black: Placebo, red: Ketamine, dotted line: pre infusion onset, straight line: post infusion onset), averaged across regions with significant slope change and across participants. The more transparent lines in the background show the aperiodic power spectrum in the respective conditions, averaged across regions with significant gamma-band power change and across participants, with the standard error of the mean as shaded envelope. (E, F) Same as (B, C) for the aperiodic slope.
Fig 3.
Results of the partial correlations of different gene expressions with Ketamine-induced differences in gamma-band power and aperiodic slope.
(A) Partial correlations with standard error. * indicate significant partial correlations. Negative correlations with slope change indicate a correlation with a flatter slope after Ketamine administration. Positive correlations with gamma change indicate a correlation with elevated gamma-band power levels after Ketamine administration. (B) Spatial distributions of the gamma-band power and aperiodic slope difference estimates (Ketamine minus placebo) and the expressions of parvalbumin and GRIN2D genes. Dots depict centroids of the examined left-hemisphere regions according to the AAL atlas. Brighter dots indicate higher difference/gene expression values. Perspective from the left on a semi-transparent brain. KET = Ketamine, PLA = placebo, PVALB = parvalbumin gene, SST = somatostatin gene, VIP = vasoactive intestinal peptide gene, GRIN2A = gene for GluN2A NMDA receptor subunit, GRIN2B = gene for GluN2B NMDA receptor subunit, GRIN2C = gene for GluN2C NMDA receptor subunit, GRIN2D = gene for GluN2D NMDA receptor subunit.
Fig 4.
Human cortical layer-2/3 model.
(A) Representation of the model with 1000 neurons, the neural morphologies of each modeled neuron type, and pie chart with the proportion of neuron types in the model (Pyramidal [Pyr] neurons 80%; somatostatin [SST] interneurons 5%; parvalbumin [PV] interneurons 7%; vasoactivate intestinal peptide [VIP] interneurons 8%). (B) Connectivity diagram of the microcircuit with main connections between neuron types. Blue circles indicate the site at which NMDA-R conductance was reduced (NMDA to [1] pyramidal cells, [2] PV interneurons, [3] SST interneurons, and [4] VIP interneurons). (A, B) Reprinted and adapted with permission from [45].
Table 3.
Gamma-band power increase in modeled NMDA-R dysfunction.
Fig 5.
Gamma-band power and aperiodic components of simulated data with NMDA-R reductions.
Panels (A-C) depict the averaged power spectrum of the fast-Fourier transformed data in the gamma-power range. Panels (D-F) show the aperiodic component of the power spectrum in log-log space. Shaded envelopes indicate standard error. Control condition (black, dotted line) without any manipulations. In the test conditions (straight, colored lines), NMDA receptors of (A, D) parvalbumin neurons, PV, (B, E) somatostatin neurons, SST, (C, F) vasoactive-intestinal peptide neurons, VIP, and pyramidal neurons, Pyr, and in all aforementioned neuron types simultaneously, were reduced by the indicated amount.
Fig 6.
Mean spike rates of different modeled neuron types with NMDA receptor reductions.
In different modeling conditions, NMDA receptors of (A) parvalbumin interneurons, PV, (B) somatostatin neurons, SST, (C) vasoactive-intestinal peptide neurons, VIP, or pyramidal neurons, Pyr, and in all aforementioned neuron types simultaneously, were reduced by the indicated amount. Control condition without any manipulations. Mean spike rate is given in Hz. Error bars indicate standard error of the mean.