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. 2020 Apr 8:14:315.
doi: 10.3389/fnins.2020.00315. eCollection 2020.

Constitutive and Stress-Induced Psychomotor Cortical Responses to Compound K Supplementation

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Constitutive and Stress-Induced Psychomotor Cortical Responses to Compound K Supplementation

Shawn D Flanagan et al. Front Neurosci. .

Abstract

Isolated ginsenoside metabolites such as Compound K (CK) are of increasing interest to consumer and clinical populations as safe and non-pharmacological means to enhance psychomotor performance constitutively and in response to physical or cognitive stress. Nevertheless, the influence of CK on behavioral performance and EEG measures of cortical activity in humans is undetermined. In this double-blinded, placebo-controlled, counterbalanced within-group study, dose-dependent responses to CK (placebo, 160 and 960 mg) were assessed after 2 weeks of supplementation in nineteen healthy men and women (age: 39.9 ± 7.9 year, height 170.2 ± 8.6 cm, weight 79.7 ± 11.9 kg). Performance on upper- and lower-body choice reaction tests (CRTs) was tested before and after intense lower-body anaerobic exercise. Treatment- and stress-related changes in brain activity were measured with high-density EEG based on event-related potentials, oscillations, and source activity. Upper- (-12.3 ± 3.5 ms, p = 0.002) and lower-body (-12.3 ± 4.9 ms, p = 0.021) response times improved after exercise, with no difference between treatments (upper: p = 0.354; lower: p = 0.926). Analysis of cortical activity in sensor and source space revealed global increases in cortical arousal after exercise. CK increased activity in cortical regions responsible for sustained attention and mitigated exercise-induced increases in arousal. Responses to exercise varied depending on task, but CK appeared to reduce sensory interference from lower-body exercise during an upper-body CRT and improve the general maintenance of task-relevant sensory processes.

Keywords: EEG; cortical activity; event-related potentials; exercise; ginsenoside; psychomotor performance; source localization; stress.

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Figures

FIGURE 1
FIGURE 1
Choice Reaction Test Setup. Participants responded to the random illumination of one of five equidistantly spaced circles by touching the corresponding point on the presentation screen (upper-body CRT) or foot pad (lower-body CRT) as quickly and accurately as possible. Each test was comprised of 120 stimuli divided into three blocks of 40 with 30s rest between and a 500 ± 30 ms post-response stimulus onset delay. Stimulus onset and offset (response) timing were detected with photodiodes and marked at the corresponding timepoints in continuous EEG recordings with minimal delay or jitter (≤2 ms). Comparison of analog event markers and computer-generated response times confirmed the accuracy of stimulus and response co-registration. CRT, choice reaction test.
FIGURE 2
FIGURE 2
Event-Related Potential Waveforms, Response Times, and Interpolated Scalp Maps. (A) Grand-averaged 64-channel ERP tracings for each segment and timepoint plus the pre- minus post-exercise difference waveform (expanded 10–20 montage, common average reference). Waveforms are time-locked to stimulus presentation (solid gray line at 0 ms). For each trace, histograms of all qualifying response times are provided on the X-axis, with median response time indicted above the gray dashed lines. Black lines Triangles correspond to spherical spline interpolated 2D scalp voltage topography maps at the indicated time points with colors matched to identified ERP components and post-exercise map intensity scaled in relation to the corresponding pre-exercise condition. (B) Grand-averaged lower body P1/N1 latencies were reduced after exercise with 960mg, while a (C) dose-dependent increase in P3b latency after exercise was evident for the upper body. (D) As indicated by ICs for each respective ERP, amplitudes were generally lower after exercise. ERP, event-related potential; IC, independent component.
FIGURE 3
FIGURE 3
IC Waveforms and CDRs for Upper-Body Stimuli. Three ICs were identified from grand-averaged 64-channel ERP waveforms. For each treatment and timepoint, IC waveforms are depicted in the upper axis and matched by color and ERP correspondence, with the IC-filtered grand average waveform depicted on the lower axis. Spherical spline interpolated 2D scalp load distribution maps for each component are depicted to the right of the waveforms. IC-based sLORETA CDR localizations are provided at the bottom of each panel (common average reference). The displayed perspectives emphasize areas of maximal activation common to each treatment and timepoint. Intensities of 2D maps and source plots are scaled in relation to pre-exercise placebo values for each component (maps) or timepoint (sources). For source plots, activation was clipped at 50% to emphasize the most prominent sources. Source activity is displayed in pseudo-F scale units, with a regularization factor of λ = 351. ERP, event-related potential; IC, independent component; sLORETA, standardized low-resolution brain electromagnetic tomography; CDR, current density reconstruction.
FIGURE 4
FIGURE 4
IC Waveforms and CDRs for Lower-Body Stimuli. Two ICs were identified from the grand-averaged 64-channel ERP waveforms. For each treatment and timepoint, IC waveforms are depicted in the upper axis and matched by color and ERP correspondence, with the IC-filtered grand average waveform depicted on the lower axis. Spherical spline interpolated 2D scalp load distribution maps for each component are depicted to the right of the waveforms. IC-based sLORETA CDR localizations are provided at the bottom of each panel (common average reference). The displayed perspectives emphasize areas of maximal activation common to each treatment and timepoint. Intensities of 2D maps and source plots are scaled in relation to pre-exercise Placebo values for each component (maps) or timepoint (sources). For source plots, activation was clipped at 50% to emphasize the most prominent sources. Source activity is displayed in pseudo-F scale units, with a regularization factor of λ = 221. ERP, event-related potential; IC, independent component; sLORETA: standardized low-resolution brain electromagnetic tomography; CDR, current density reconstruction.
FIGURE 5
FIGURE 5
Event-Related Oscillatory Activity for Upper-Body Stimuli. (A–F) FFTs were applied to ERPs from –500 to 1000 ms with a Hann Filter (10% width). Spectral activity was binned from 0.5 to 4.0 Hz (delta), 4.0 to 8.0 Hz (theta), 8.0 to 14.0 Hz (alpha), 14.0 to 30.0 Hz (beta), and 30.0 to 40 Hz (gamma). Each plot depicts grand-averaged spectral activity (mean ± SE) for regions with statistical interactions between treatment and timepoint ( = p ≤ 0.05). Black and open bars indicate pre- and post-exercise values, respectively. (G–H) Time-varying and overall phase-locked spectral activity was examined with spectrograms and spectrum plots of grand-averaged ERPs using wavelet analysis (Mexican Hat, resolution = 1.0Hz, Teager-Kaiser, 0.5–62.5 Hz activity, and –200 to 700 ms) and FFTs for midline (Fz, Cz, Pz, and Oz) and lateral electrode averages (C5–C6 and T7–T8) based on the results of quantitative ERP and FFT analyses. Spectrogram activity is interpolated and scaled against pre-exercise placebo values specific to each sensor. For sensors that displayed qualitative dose-dependent responses (Fz and T7–T8), spectrograms are difference plots (pre- minus post-exercise activity) while the spectrum plots display 0–15 Hz activity with pre- and post-exercise activity overlaid. FFT, fast Fourier transform; ERP, event-related potential.
FIGURE 6
FIGURE 6
Event-Related Oscillatory Activity for Lower-Body Stimuli. (A–C) FFTs were applied to ERPs from –500 to 1000 ms with a Hann Filter (10% width). Spectral activity was binned from 0.5–4.0 Hz (delta), 4.0–8.0 Hz (theta), 8.0–14.0 Hz (alpha), 14.0–30.0 Hz (beta), and 30.0–40 Hz (gamma). Each plot depicts grand-averaged spectral activity (mean ± SE) for regions with statistical interactions between treatment and timepoint ( = p ≤ 0.05). Black and open bars indicate pre- and post-exercise values, respectively. (D–E) Time-varying and overall phase-locked spectral activity was examined with spectrograms and spectrum plots of grand-averaged ERPs using wavelet analysis (Mexican Hat, resolution = 1.0Hz, Teager-Kaiser, 0.5–62.5Hz activity, –200 to 1000 ms) and FFTs for midline (Fz, Cz, Pz, and Oz) and lateral electrode averages (C5-C6 and T7-T8) based on the results of quantitative ERP and FFT analyses. Spectrogram activity is interpolated and scaled against pre-exercise placebo values specific to each sensor. For sensors that displayed qualitative dose-dependent responses (Fz and T7-T8), spectrograms are difference plots (pre- minus post-exercise activity) while the spectrum plots display 0–15 Hz activity with pre- and post-exercise activity overlaid. FFT, fast Fourier transform; ERP, event-related potential.

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