Name: disruption of frontal lobe neural synchrony during cognitive control by alcohol intoxication
Uploaded: 2019-02-06T15:00:00
Description: Watch this Scientific Journal Video about Disruption of Frontal Lobe Neural Synchrony During Cognitive Control by Alcohol Intoxication at JoVE.com

This work has been supported by the National Institutes of Health (R01-AA016624). We are grateful to Dr. Sanja Kovacevic for her important contributions.

This experimental protocol has been approved by the Human Subjects Protection Committee at the University of California, San Diego.
1. Human Subjects
<ol>
	<li>Recruit healthy right-handed adult volunteers, obtain their consent, and screen them on the inclusion/exclusion criteria. 
	NOTE: In this study, twenty young, healthy individuals (mean &#177; standard deviation [SD] age = 25.3 &#177; 4.4 years) including 8 women were recruited who drink in moderation, who have ne...

The multimodal imaging method used in this study comprises distributed source modeling of the temporally precise MEG signal along with spatial constraints of inverse estimates derived from each participant&#39;s structural MRI. The aMEG approach combines the strengths of these techniques to provide insight into the spatio-temporal stages of oscillatory dynamics and the long-range integration subserving cognitive control. This method provides greater temporal precision than other neuroimaging techniques such as fMRI-BOLD ...

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&#39;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&#39;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 (&#34;when&#34;) 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.

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	<tbody>
		<tr height="40">
			<td height="40" style="height:40px;width:222px;">Elekta Neuromag</td>
			<td style="width:125px;">Elekta</td>
			<td style="width:354px;"></td>
			<td style="width:171px;">Magnetoencephalography system</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">1.5 T GE EXCITE HG</td>
			<td>General Electric</td>
			<td></td>
			<td>Magnetic Resonance Imaging scanner</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">Gold Cup Electrodes</td>
			<td>OpenBCI</td>
			<td></td>
			<td>Electroencephalography electrodes for optional simultaneous EEG recording</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">Prep Check Impedance Meter</td>
			<td>General Devices</td>
			<td></td>
			<td>Check electrode impedances</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">HPI Coils</td>
			<td>Elekta</td>
			<td></td>
			<td>Head position indicator coils for co-registration</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">Alcotest</td>
			<td>Draeger</td>
			<td></td>
			<td>Breathalyzer</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">Fiber Optic Response Pad</td>
			<td>Current Designs, Inc</td>
			<td></td>
			<td>MEG-compatible response pad</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">Grey Goose Vodka</td>
			<td>Bacardi</td>
			<td></td>
			<td>Vodka is used during the alcohol session</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">Orange Juice</td>
			<td>Naked</td>
			<td></td>
			<td>Orange juice is used as the beverage during the placebo session as well as mixed with vodka during the alcohol session</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">Discover Drug Test Card</td>
			<td colspan="2">American Screening Corp</td>
			<td>Multi-screen drug test</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">QED Saliva Alcohol Test</td>
			<td colspan="2">OraSure Technologies</td>
			<td>Saliva alcohol test</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">Urine Hcg Test Strips</td>
			<td>Joylive</td>
			<td></td>
			<td>Pregnancy test</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">Short Michigan Alcohol Screening Test</td>
			<td>Selzer et al., 1975</td>
			<td></td>
			<td>Alcoholism screening questionnaire</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">Zuckerman Sensation Seeking Scale</td>
			<td>Zuckerman, 1971</td>
			<td></td>
			<td>Questionnaire: disinhibitory, novelty-seeking, and socialization traits</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">Eysenck Impulsivity Inventory</td>
			<td colspan="2">Eysenck &#38; Eysenck, 1978</td>
			<td>Questionnaire: impulsivity traits</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">Eysenck Personality Questionnaire</td>
			<td colspan="2">Eysenck &#38; Eysenck, 1975</td>
			<td>Questionnaire: personality traits</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">Biphasic Alcohol Effects Scale&#160;</td>
			<td>Martin et al., 1993</td>
			<td></td>
			<td>Questionnaire: subjective experience of the effects of alcohol</td>
		</tr>
	</tbody>
</table>

disruption of frontal lobe neural synchrony during cognitive control by alcohol intoxication

Decision making relies on dynamic interactions of distributed, primarily frontal brain regions. Extensive evidence from functional magnetic resonance imaging (fMRI) studies indicates that the anterior cingulate (ACC) and the lateral prefrontal cortices (latPFC) are essential nodes subserving cognitive control. However, because of its limited temporal resolution, fMRI cannot accurately reflect the timing and nature of their presumed interplay. The present study combines distributed source modeling of the temporally precise magnetoencephalography (MEG) signal with structural MRI in the form of &#34;brain movies&#34; to: (1) estimate the cortical areas involved in cognitive control (&#34;where&#34;), (2) characterize their temporal sequence (&#34;when&#34;), and (3) quantify the oscillatory dynamics of their neural interactions in real time. Stroop interference was associated with greater event-related theta (4 - 7 Hz) power in the ACC during conflict detection followed by sustained sensitivity to cognitive demands in the ACC and latPFC during integration and response preparation. A phase-locking analysis revealed co-oscillatory interactions between these areas indicating their increased neural synchrony in theta band during conflict-inducing incongruous trials. These results confirm that theta oscillations are fundamental to long-range synchronization needed for integrating top-down influences during cognitive control. MEG reflects neural activity directly, which makes it suitable for pharmacological manipulations in contrast to fMRI that is sensitive to vasoactive confounds. In the present study, healthy social drinkers were given a moderate alcohol dose and placebo in a within-subject design. Acute intoxication attenuated theta power to Stroop conflict and dysregulated co-oscillations between the ACC and latPFC, confirming that alcohol is detrimental to neural synchrony subserving cognitive control. It interferes with goal-directed behavior that may result in deficient self-control, contributing to compulsive drinking. In sum, this method can provide insight into real-time interactions during cognitive processing and can characterize the selective sensitivity to pharmacological challenge across relevant neural networks.

Behavioral results indicate that the Stroop task successfully manipulated response interference because the accuracy was the lowest and the response times the longest on incongruous trials (Figure 6). Alcohol intoxication lowered accuracy but did not affect reaction times18.
The spatio-temporal sequence of activity in theta frequency band revealed with the aMEG approach is ov...

Watch this Scientific Journal Video about Disruption of Frontal Lobe Neural Synchrony During Cognitive Control by Alcohol Intoxication at JoVE.com

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

This experiment uses an anatomically-constrained magnetoencephalography (aMEG) method to examine brain oscillatory dynamics and long-range functional synchrony during engagement of cognitive control as a function of acute alcohol intoxication.

Decision making relies on dynamic interactions of distributed, primarily frontal brain regions. Extensive evidence from functional magnetic resonance ...

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