The overall goal of this study is to examine the effects of acute alcohol intoxication on spatio-temporal changes in the brain oscillatory dynamics and long-range functional integration during cognitive control. The employed multimodal imaging approach combines magnetoencephalography (MEG) and structural magnetic resonance imaging (MRI) to provide insight into the neural basis of decision making with high temporal precision and at the level of an interactive system.

Flexible behavior makes it possible to adapt to changing contextual demands and to switch strategically between different tasks and requirements in agreement with one's intents and goals. The capacity to suppress automatic responses in favor of goal-relevant but non-habitual actions is an essential aspect of cognitive control. Extensive evidence suggests that it is subserved by a predominantly frontal cortical network, with the anterior cingulate cortex (ACC) as a central node in this interactive network¹^,²^,³^,⁴. While the abundant anatomical connectivity between the ACC and lateral frontal cortices is well-described⁵^,⁶, the functional characteristics of communication between these regions during cognitive control, response selection and execution, are poorly understood.

The highly influential conflict monitoring theory⁷^,⁸ proposes that cognitive control arises from a dynamic interaction between the medial and lateral prefrontal cortices. This account purports that the ACC monitors conflict between competing representations and engages the lateral prefrontal cortex (latPFC) to implement response control and optimize performance. However, this account is primarily based on the functional MRI (fMRI) studies using the blood oxygenation level dependent (BOLD) signal. The fMRI-BOLD signal is an excellent spatial mapping tool, but its temporal resolution is limited because it reflects regional hemodynamic changes mediated by neurovascular coupling. As a result, the BOLD signal changes unfold on a much slower time scale (in seconds) than the underlying neural events (in milliseconds)⁹. Moreover, the BOLD signal is sensitive to alcohol's vasoactive effects¹⁰ and may not accurately represent the magnitude of neural changes, which makes it less suitable for studies of acute alcohol intoxication. Therefore, the presumed interplay between the medial and lateral prefrontal cortices and its sensitivity to alcohol intoxication need to be examined by methods that record neural events in a temporally precise manner. MEG has an excellent temporal resolution since it directly reflects postsynaptic currents. The anatomically-constrained MEG (aMEG) methodology employed here is a multimodal approach that combines distributed source modeling of the MEG signal with structural MRI. It allows for the estimation of where the conflict- and beverage-related brain oscillatory changes are occurring and to understand the temporal sequence ("when") of the involved neural components.

Decision making relies on the interactions of distributed brain regions that are dynamically engaged to deal with increased demands on cognitive control. One way to estimate event-related changes in long-range synchrony between two cortical regions is to calculate their phase coupling as an index of their co-oscillations¹¹^,¹². The present study applied a phase-locking analysis to test the basic tenet of the conflict monitoring theory by examining the co-oscillatory interactions between the ACC and latPFC. Neural oscillations in theta range (4 - 7 Hz) are associated with cognitive control and have been proposed as a fundamental mechanism supporting the long-range synchronization needed for top-down cognitive processing¹³^,¹⁴^,¹⁵^,¹⁶. They are generated in prefrontal areas as a function of task difficulty and are significantly attenuated by acute alcohol intoxication¹⁷^,¹⁸^,¹⁹^,²⁰.

Long-term excessive alcohol intake is associated with a range of cognitive deficits with prefrontal circuitry being especially affected²¹^,²². Acute alcohol intoxication is detrimental to cognitive control under conditions of increased difficulty, ambiguity, or those that induce response incompatibility¹⁷^,²³^,²⁴. By affecting decision making, alcohol may interfere with goal-directed behavior, may result in poor self-control and increased drinking, and may also contribute to traffic- or work-related hazards²⁵^,²⁶^,²⁷. The present study uses an aMEG approach to measure the oscillatory activity in theta band and synchrony between the principal executive areas with excellent temporal resolution. The effects of alcohol on theta activity and co-oscillations between the ACC and the latPFC are examined as a function of conflict elicited by the Stroop interference task. We hypothesize that increased cognitive demands are associated with greater functional synchrony and that alcohol-induced dysregulation of synchronous activity of the medial and lateral prefrontal cortices underlies impairments in cognitive control.

Disruption of Frontal Lobe Neural Synchrony During Cognitive Control by Alcohol Intoxication