Discussion
neurobiological disorder, behavioral deficits, impairment of behavior
Inhibitory control is a complex cognitive function, involving many coordinated brain regions, and neurobiology that is not yet fully understood. Likewise, the mechanisms underlying disruptions of the inhibitory control system, either due to a neurobiological disorder, such as ADHDWe found that inhibitory behavior, as measured by the Go/No-go task, was only affected at moderate doses of alcohol, such that performance was significantly worse after alcohol consumption compared to before. Correspondingly, we found that post-moderate performance was significantly worse than post-placebo performance, but not post-low performance. These results indicate that moderate levels of acute alcohol intoxication significantly change subjects’ ability to discriminate and respond accurately to go and no-go stimuli. In this version of the task, we found that at low levels of intoxication subjects performed comparably to pre-dose and post-placebo sessions. Furthermore, we only observed a significant decrease in reaction times in the placebo sessions (post-ingestion compared to pre-ingestion) suggesting that the unimpaired individual can execute the task faster without compromising performance. While we did not replicate prior findings of change in reaction times across different intoxication levelsWe examined whether brain activity during the inhibitory control task could provide more reliable measures of intoxication. As a first step, we confirmed the importance of prefrontal regions during the Go/No-go taskBecause we observed a reliable change in performance at moderate levels of intoxication, we expected to see complementary disruptive changes in prefrontal brain activation. Indeed, it was only in the moderate dose that the expected activations patterns (both in terms of right activity and lateralization) disappeared in the GLM results. Furthermore, the moderate dose—when compared directly to the low dose of alcohol—showed significantly less GLM-based lateralization. At low levels of intoxication, task performance was unaffected, which could manifest as: (1) unaltered activity (intoxication not strong enough), or (2) changes in brain activity (possibly compensatory) that precede behavioral deficits. Qualitatively, we observed different patterns of significant prefrontal brain activity between low- and placebo-doses, yet, both showed GLM-based right lateralization—pointing towards a potential compensatory mechanism. To further assess differences between placebo and alcohol doses, we investigated metrics computed over the epoched time courses. While the direction metric distinguished between placebo and low-dose, our novel time-locked angle metric provided statistical discernibility between the placebo dose and both alcohol dosing sessions. To our knowledge, this is the most comprehensive comparison of dose-dependent changes in brain activity to date.It is well-known that alcohol impairs inhibitory control, but the underlying contributing factors, neural and otherwise, remain unclear. In fact, our society uses BAC as the legal standard for impairment, even though subjective feelings of intoxication and behavioral performance across individuals can vary greatly when BAC is similar, a phenomenon often referred to as tolerance. In our data, pairwise correlations revealed a significant relationship between the change in behavioral performance and BAC (direct measure of intoxication), as well as both the direction and angle lateralization metrics (brain measures of intoxication). The correlation between the direction metric and performance is in agreement with Tsujii et al.It is worth noting that the current study has multiple limitations. First, dosing in both our low and moderate sessions were below desired targets, which may lead to only seeing effects in the moderate dose. Indeed, we observed significant impairment of behavior only in the moderate dose. However, we not only observed neural changes in each dose, but also revealed differential brain activity between the two doses. Second, there was an overlap in BAC values across dosing sessions. As a result, our group-level statistics included individuals with similar levels of BAC across low and moderate dosing sessions. In addition, half of our participants experienced a placebo-effect with corresponding changes in brain activity. Together, these confounds likely had a negative impact on our repeated measure statistics, some of which would not survive corrections for multiple comparisons. Third, it is difficult to administer a believable placebo dose of alcoholThere are multiple advantages of using a TD-fNIRS system for such investigations. Importantly, TD-fNIRS enhances depth sensitivity beyond the more commonly used continuous-wave (CW)-fNIRS, as it captures the arrival times of photons. Late arriving photons are more likely to have reached the brain than photons with earlier arrival times, which likely have only interacted with superficial tissues. The change in light absorption in the tissue at different depths can thereby be captured in the moments of DToFs (e.g. mean, variance). In fact, others have demonstrated the feasibility of using moments from a single wavelength in a TD-fNIRS system to detect brain activityIn short, this study provides critical evidence that dose-dependent changes in prefrontal brain activity can be measured with TD-fNIRS. We introduced novel metrics for measuring brain asymmetry that retain information about time-sensitive cross-hemispheric variability and absolute changes in brain activity. A highlight of this study is that we fully explored the extent to which changes in prefrontal lateralization can explain changes in task performance, by considering other potentially impactful features. The culmination of our study highlights the powerfulness and robustness of brain activity in explaining behaviorally relevant measures of intoxicated individuals. This underscores the importance of recording neural signals not just in academic laboratories seeking to understand neural mechanisms, but also in clinics, and pharmacological research.