Decreases in energy and increases in phase locking of event-related oscillations to auditory stimuli occur during adolescence in human and rodent brain

Abstract

Synchrony of phase (phase locking) of event-related oscillations (EROs) within and between different brain areas has been suggested to reflect communication exchange between neural networks and as such may be a sensitive and translational measure of changes in brain remodeling that occur during adolescence. This study sought to investigate developmental changes in EROs using a similar auditory event-related potential (ERP) paradigm in both rats and humans. Energy and phase variability of EROs collected from 38 young adult men (aged 18-25 years), 33 periadolescent boys (aged 10-14 years), 15 male periadolescent rats [at postnatal day (PD) 36] and 19 male adult rats (at PD103) were investigated. Three channels of ERP data (frontal cortex, central cortex and parietal cortex) were collected from the humans using an 'oddball plus noise' paradigm that was presented under passive (no behavioral response required) conditions in the periadolescents and under active conditions (where each subject was instructed to depress a counter each time he detected an infrequent target tone) in adults and adolescents. ERPs were recorded in rats using only the passive paradigm. In order to compare the tasks used in rats to those used in humans, we first studied whether three ERO measures [energy, phase locking index (PLI) within an electrode site and phase difference locking index (PDLI) between different electrode sites] differentiated the 'active' from 'passive' ERP tasks. Secondly, we explored our main question of whether the three ERO measures differentiated adults from periadolescents in a similar manner in both humans and rats. No significant changes were found in measures of ERO energy between the active and passive tasks in the periadolescent human participants. There was a smaller but significant increase in PLI but not PDLI as a function of active task requirements. Developmental differences were found in energy, PLI and PDLI values between the periadolescents and adults in both the rats and the human participants. Neuronal synchrony as indexed by PLI and PDLI was significantly higher to the infrequent (target) tone compared to the frequent (nontarget) tone in all brain sites in all of the regions of interest time-frequency intervals. Significantly higher ERO energy and significantly lower synchrony was seen in the periadolescent humans and rats compared to their adult counterparts. Taken together these findings are consistent with the hypothesis that adolescent remodeling of the brain includes decreases in energy and increases in synchrony over a wide frequency range both within and between neuronal networks and that these effects are conserved over evolution.

Figure 1

Grand mean values for energy, phase locking index (PLI) and phase difference lock index (PDLI) of event-related oscillations for the passive and active task in periadolescents. (a) MANOVA revealed that the infrequent (target) tone (white bars), as compared to the frequent (non-target) tone (black bars), produced no significant differences in energy by tone or between passive and active task. (b) PLI was significantly increased following the infrequent tone compared to the frequent tone [** indicates p<0.001] and was decreased in the active task [+ indicates p<0.007]. (c) PDLI was also significantly increased following the infrequent tone but not different between the tasks. Error Bars = S.E.M

Figure 2

Significant mean values for energy of event-related oscillations (EROs) following the infrequent (target) tone for periadolescents (white bars) and adults (black bars) in the delta (1-4 Hz, 200-500 ms), theta (4-7 Hz 10-400 ms), alpha (7-13 Hz, 0-300 ms), and beta (13-30 Hz, 0-300 ms) time-frequency ranges for the three electrode locations in the humans (a) (periadolescent n=19, adult n=38) (FZ=midline frontal cortex, CZ=midline central cortex, PZ=midline parietal cortex) and in the rats (b) (periadolescent n=15, adult n=19) (FCTX= frontal cortex, PCTX= parietal cortex). Energy in periadolescents, as compared to adults, is significantly higher across most frequency bands and electrode sites in humans and in rats. * indicates p<0.01, ** p<0.001. Error Bars = S.E.M

Figure 3

Grand averages of energy for event–related oscillations (EROs) in humans given the active task (periadolescent n=19, adult n=38). Each graph depicts a time-frequency representation of energy values in periadolescents and adults following the infrequent (target) tone in the three electrode locations (FZ=midline frontal cortex, CZ=midline central cortex, PZ=midline parietal cortex). In each graph, frequency (Hz) is presented on the Y-axis, time regions of interest on the X-axis (msec). Energy is presented as color equivalents as indicated on the bar at the bottom of each graph. Periadolescents compared to adults show overall higher energy across the time-frequencies and in all electrode sites compared to adults.

Figure 4

Significant mean values for the phase lock index (PLI) of event-related oscillations (EROs) following the infrequent (target) tone for periadolescents (white bars) and adults (black bars) for delta (1-4 Hz, 200-500 ms), theta (4-7 Hz 10-400 ms) and alpha (7-13 Hz, 0-300 ms) time-frequency ranges. (a) Human adults (periadolescents n=19, adults n=38) showed significantly higher phase lock index in the delta and theta time-frequencies across all three electrode locations compared to periadolescents. (b) Adult rats (periadolescent n=15, adult n=19) showed a significant decrease in the delta time-frequency in the frontal cortex and an increase in alpha time-frequencies at parietal cortex when compared to periadolescents. * indicates p<0.01, ** p<0.001. Error Bars = S.E.M.

Figure 5

Grand averages of PLI (phase lock index) for event–related oscillations (EROs) in humans given the active task (periadolescent n=19, adult n=38). Each graph depicts a time-frequency representation of phase angle synchrony values in periadolescents and adults following the infrequent (target) tone in the three electrode locations (FZ=midline frontal cortex, CZ=midline central cortex, PZ=midline parietal cortex). In each graph frequency (Hz) is presented on the Y-axis, time regions of interest on the X-axis (msec). PLI is presented as color equivalents as indicated on the bar at the bottom of each graph.

Figure 6

Significant mean values for the phase difference lock index (PDLI) of event-related oscillations (EROs) following the infrequent (target) tone for periadolescent (white bars) and adults (black bars) in the delta (1-4 Hz, 200-500 ms), theta (4-7 Hz 10-400 ms), alpha (7-13 Hz, 0-300 ms), and beta (13-30 Hz, 0-300 ms) time-frequency ranges. Phase differences were calculated between midline frontal cortex (FZ) and midline parietal cortex (PZ) for the human study and between frontal cortex (FCTX) and parietal cortex (PCTX) in the rats. (a) Human adults showed significantly increased PDLI across all frequency bands when compared to periadolescents. (b) Adult rats (periadolescent n=14, adult n=18) also had significant increases in PDLI in the theta, alpha and beta time-frequencies. * indicates p<0.01, ** p<0.001. Error Bars = S.E.M.

Figure 7

Grand averages of energy for event–related oscillations (EROs) in rats (periadolescents n=13, adults n=18). Each graph depicts a time-frequency representation of energy values in periadolescent and adult rats following the infrequent (target) tone in two electrode locations (FCTX=frontal cortex, PCTX=parietal cortex). In each graph frequency (Hz) is presented on the Y-axis, time regions of interest on the X-axis (msec) and energy is presented as color equivalents as indicated on the bar at the bottom of each graph. Periadolescent rats show greater energy across the time-frequencies and in both electrode sites when compared to adult rats.

Figure 8

Grand averages of PLI (phase lock index) for event–related oscillations (EROs) in rats (periadolescents n=13, adults n=18). Each graph depicts a time-frequency representation of phase angle synchrony in adolescent and adult rats following the infrequent (target) tone in two electrode locations (FCTX=frontal cortex, PCTX=parietal cortex). In each graph frequency (Hz) is presented on the Y-axis, time regions of interest on the X-axis (msec) and PLI is presented as color equivalents as indicated on the bar at the bottom of each graph.