Table 2. Relationship of low frequency peak in OFF zolpidem baseline and time interval between doses.
| SUBJECT 2 center frequency for low frequency peak in hour prior to dose across channels and transitions | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline 1 | Significant | Baseline 2 | Significant | Baseline 3 | Significant | Baseline 4 | Significant | Baseline 5 | Significant | ||
| (20 hr off drug) | On vs off | (16 hr off drug) | On vs off | (6 hr off drug) | On vs off | (5 hr off drug) | On vs off | (4 hr off drug) | On vs off | ||
| Channel | Pairs | 4:30PM, 1st | suppression | 8:30AM, 1st | suppression | 4:30PM, 2nd | suppression | 5:00PM, 3rd | suppression | 12:15PM, 2nd | suppression |
| Fp1 | F3 | 7 | * | – | n.s. | 7.3 | * | 7.7 | n.s. | 8 | n.s. |
| Fp2 | F4 | 7 | * | 8.5 | * | 7.3 | * | 7 | * | 7.7 | n.s. |
| F3 | C3 | 7.7 | * | 8.5 | * | 7.7 | * | 7.7 | * | 7.7 | * |
| F4 | C4 | 7.7 | * | 8 | * | 7.7 | * | 7.7 | * | 7.3 | * |
| F7 | T3 | 7.7 | n.s | – | * | 7.7 | n.s | 7.7 | n.s. | 6 | n.s. |
| F8 | T4 | (No data) | 8 | n.s. | 7.3 | * | 7 | n.s. | 7.3 | n.s. | |
| Fp1 | F7 | 7 | n.s | – | * | 7.7 | * | 7.7 | n.s. | 7 | n.s. |
| Fp2 | F8 | 7.7 | * | – | n.s. | 7 | * | 6.7 | n.s. | 7.3 | n.s. |
| Fz | Cz | 7.7 | * | 8.5 | * | 7 | * | 7.7 | * | 7 | n.s. |
| Anterior Channels | |||||||||||
| Average Center Freq | 7.4 | 8.3 | 7.4 | 7.4 | 7.3 | ||||||
| Standard Deviation | 0.4 | 0.3 | 0.3 | 0.4 | 0.6 | ||||||
| C3 | P3 | 8.3 | * | 8.5 | * | 7.7 | * | 8.3 | * | 8.7 | n.s. |
| C4 | P4 | 8 | * | 9 | * | 9.3 | * | 8.3 | * | 7.7 | n.s. |
| P3 | O1 | 7.7 | * | 9 | * | 11.3 | * | 8.7 | * | 8 | n.s. |
| P4 | O2 | 8.3 | * | 9 | * | 10 | * | 8.7 | * | 8.3 | n.s. |
| T3 | T5 | 7 | * | 8.5 | * | 7.7 | * | 11.7 | n.s. | 11.7 | n.s. |
| T4 | T6 | (No data) | 9 | * | 9.3 | n.s | 10 | * | 10 | n.s. | |
| T5 | O1 | 8 | * | 9 | * | 10 | * | 8.3 | * | 11.3 | n.s. |
| T6 | O2 | 8 | * | 9.5 | * | 10 | * | 9.7 | * | 11 | n.s. |
| Cz | Pz | 8.3 | * | 8.5 | * | 9 | * | 8.7 | * | 7.7 | n.s. |
| Posterior Channels | |||||||||||
| Average Center Freq | 8.0 | 8.9 | 9.4 | 9.2 | 9.4 | ||||||
| Standard Deviation | 0.4 | 0.3 | 1.2 | 1.1 | 1.6 | ||||||
| Average Center Freq | 7.7 | 8.7 | 8.4 | 8.3 | 8.3 | ||||||
| Standard Deviation | 0.5 | 0.4 | 1.3 | 1.2 | 1.6 | ||||||
Table 2 shows average center frequency of low frequency peak at∼6–10 Hz, if present, across all channels for Subjects 2 in relation to time off zolpidem prior to 1 hr baseline EEG measurements and clock time of each dose. In both patients, shorter zolpidem dosing intervals are associated with higher center frequencies across posterior but not anterior EEG channels. Similarly, an increased standard deviation of the measurement is observed as interval between doses is shorten for the posterior EEG channel measurements. Of note, for both subjects, anterior EEG channel pre-zolpidem dose baselines revealed a consistent∼7.4 Hz average center frequency with a small standard deviation. The consistency of these findings despite the wide difference in their underlying etiologies of injury support the proposed common cellular and circuit mechanism; the correspondence of the∼7.4 Hz peak and intrinsic oscillation frequency of neocortical Layer V cells (Silva et al., 1991) also support this model. Of note as an outlier is the second baseline for this subject which is the only measurement early in the morning (8:30) suggesting a possible interaction with diurnal activity of the brain arousal system, however, insufficient data is available to establish this linkage.