Abstracts

Rationale: Patients with epilepsy frequently have comorbid attention deficit hyperactivity disorder (ADHD). However, screening for ADHD is difficult given a lack of an objective biomarker. Prior studies have evaluated biomarkers within the EEG including the theta-beta ratio; however, these biomarkers have not been widely accepted. Another plausible biomarker for sustained attention could be theta-gamma phase-amplitude coupling in the posterior parietal cortex, which has been described as a critical node for integrating top-down and bottom-up attention processes. Methods: Adult wild type mice on a C57/Bl6 background, at least 8 weeks (2 months) old, are food-deprived to achieve 85-90% of their free-feeding, baseline body weight prior to being trained on the 5-Choice Serial Reaction Time Task (5-CRSTT, Bari et al., 2008). Mice are trained with increasing difficulty from a stimulus duration (SD) of 30 seconds to 1 second, prior to being implanted with bilateral frontal and posterior parietal electrodes. The ‘attentive period’ is defined as the fixed 5 second intertrial interval prior to stimulus onset. Task difficulty is then further increased with a stimulus duration of 1 second down to 0.6 seconds with the addition of variable intertrial intervals. EEG recordings are processed using EEGLAB in MATLAB. Then, power and phase-amplitude coupling (PAC) analyses of the EEG recordings are conducted using Brainstorm in MATLAB. Results: Between the bilateral frontal and posterior parietal regions of cortex, only the right posterior parietal region showed a significant increase in theta-gamma coupling (TGC) during the intertrial interval compared to the mean TGC over the entire procedure at a stimulus duration of 1 second (n=6, paired t-test, p=0.0055). In mice that were able to progress down to a stimulus duration of 0.6 seconds, theta-gamma coupling was consistently higher in the right posterior parietal region compared to the left posterior parietal region (2-way ANOVA, n=4 mice, p=0.0001). Accuracy had an inverted-U relationship with relative time-resolved PAC, with greatest accuracy between 5-45% above average PAC. Relative gamma power also significantly increased in the intertrial interval before a correct response, with accuracy steadily increasing before plateauing at a level of 45% above average PAC. Interestingly, there was no significant relationship between time-resolved gamma and time-resolved PAC (p=0.68), suggesting that the modulation of PAC was independent of changes in gamma power. Conclusions: Here we show that posterior parietal theta-gamma coupling may be a potential biomarker for sustained attention in mice, but further work is necessary in order to determine whether these findings can be translated to patients with or without epilepsy. Funding: NIH NINDS K08 NS096029Brain and Behavior NARSAD Young Investigator Grant