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 never been in treatment or arrested for drug or alcohol related offenses, who report no alcoholism-related symptoms on the Short Michigan Alcoholism Screening Test28, who do not smoke nor use illegal substances, who do not have a history of neuropsychiatric disorders or any current health problems, and who are medication free and have no internal ferromagnetic objects or implants.</li>
</ol>
2. Experimental Design
<ol>
	<li>Scan each participant four times, including three MEG sessions (a no-beverage introductory session and two experimental beverage sessions in which alcohol and placebo are administered in a counterbalanced manner), and one structural MRI scan. 
	NOTE: In this within-subject design, participants serve as their own controls by participating in both alcohol and placebo sessions. This design reduces error variance and increases statistical power by minimizing influence of individual variability in brain anatomy, activity patterns, and alcohol metabolism.</li>
</ol>
3. Collecting MEG Scans
<ol>
	<li>Perform familiarization session.
	<ol>
		<li>During the initial introductory session, administer questionnaires to obtain more information about the participants&#39; medical history, their drinking patterns and severity of alcoholism-related symptoms28,29, family history of alcoholism30, and personality traits including impulsivity31,32.</li>
		<li>Carry out an initial recording in the MEG scanner following the protocol described below in steps 3.2, 3.3, and 3.5. Do not provide any beverage. Explain the task and run the practice version allowing participants to get familiarized with it beforehand. 
		NOTE: The acclimation to the experimental situation serves the purpose of minimizing potential effects of situation-induced arousal33, thereby equating subsequent alcohol and placebo sessions on that dimension.</li>
	</ol>
	</li>
	<li>Perform the alcohol/placebo experimental sessions. 
	NOTE: Follow the same experimental procedures during both alcohol and placebo sessions with the exception of the administered beverage. Counterbalance beverage order by administering alcohol beverage first to one half of participants and placebo to the other half in a random order.
	<ol>
		<li>Upon their arrival to the MEG lab, run a brief test scan by putting the participant in the scanner and checking the channels for possible magnetization. Measure their weight. Screen them with an electronic breathalyzer. Query them about compliance with the requirements to abstain from alcohol for 48 h and from food for 3 h prior to the experiment.</li>
		<li>Collect urine samples for a multi-drug test panel from all participants and exclude those who test positive for any drug. In addition, check female participants for pregnancy with a urine test and exclude those who test positive or if they suspect that they might be pregnant.</li>
		<li>Assess dynamic changes in the subjective effects of alcohol by asking participants to rate their momentary feelings and states on a standardized scale34 prior to drinking and on two additional occasions during the experiment - on the ascending limb (~15 min after consuming beverage) and descending limb of the breath alcohol concentration curve (BrAC), after the MEG recording.</li>
		<li>Administer a practice run of the Stroop task on a laptop with stimulus presentation software to ensure that the participants understand the task before recording. 
		NOTE: This version of the Stroop task combines reading and color naming (Figure 1). The congruent condition consists of color words (i.e., red, green, blue, yellow) that are printed in the matching font color (i.e., the word &#34;green&#34; is printed in green). In the incongruous condition, color words are printed in color that does not match their meaning (i.e., the word &#34;green&#34; is printed in yellow). Ask the participants to press one of four buttons corresponding to the font color whenever a word is written in color, or, when a word is written in gray, to press a button corresponding to the meaning of the word18,23.</li>
	</ol>
	</li>
	<li>Prepare the MEG/EEG recording. 
	NOTE: Details of MEG data acquisition have been described in previous publications35,36,37.
	<ol>
		<li>Position the EEG cap or individual EEG electrodes on the head of the participant and check that all impedances are below 5 k&#937;.</li>
		<li>Attach the head position indicator (HPI) coils on either side of the forehead and behind each ear. 
		NOTE: This step is specific to Neuromag systems.</li>
		<li>Digitize positions of the fiducial points including the nasion and two preauricular points, positions of HPI coils, EEG electrodes, and obtain a large number of additional points (~200) delineating the head shape. Use this information for the co-registration with anatomical MRI images (Figure 2).</li>
	</ol>
	</li>
	<li>Administer beverage.
	<ol>
		<li>Prepare alcohol beverage by mixing premium quality vodka with chilled orange juice (25% v/v), based on each participant&#39;s gender and weight (0.60 g/kg alcohol for men, 0.55 g/kg alcohol for women), targeting a BrAC of 0.06%38. Serve the same volume of orange juice in glasses with rims swabbed with vodka as a placebo beverage. Ask the participant to consume the beverage in approximately 10 min.</li>
		<li>Check the participants&#39; BrAC with the breathalyzer starting at ~15 min after drinking and then every 5 min until they enter the recording chamber. Since electronic devices cannot be used in the shielded room, use a saliva alcohol test, which consists of a cotton swab that is saturated in saliva and is inserted into a receptacle that provides a readout.</li>
	</ol>
	</li>
	<li>Acquire MEG/EEG data.
	<ol>
		<li>Position the participant comfortably in the scanner. Since the prefrontal activity is of particular interest, ensure that the participant is positioned so that his/her head is touching the top of the helmet and is aligned along the front. 
		NOTE: Head position can affect activity estimates in significant ways because the magnetic field gradients decrease with the cube of the distance between the sensors and the brain sources39.</li>
		<li>Connect HPI coils and all of the electrodes to their respective inputs on the scanner. Position response pads so that the buttons can be pressed comfortably. Ascertain that the font is clearly legible on the projection screen in front of the participant.</li>
		<li>Back in the console room, check that the intercom is functioning properly. Remind the participant to minimize blinking and to avoid movements including head motion caused by talking. Instruct the participant to reply to questions by pressing response buttons instead.</li>
		<li>Check that all response and stimulus triggers are recorded correctly. Examine all channels for artifacts and measure the head position in the scanner.</li>
		<li>Start data acquisition and begin the task. Give breaks every ~2.5 min to rest the eyes. Save the data upon task completion and escort the participant out of the recording chamber.</li>
		<li>When the participant has exited the scanner, acquire approximately two minutes of data from the empty room as a measure of instrumental noise.</li>
		<li>Ask the participant to rate perceived task difficulty, content of the imbibed beverage, how intoxicated they felt, as well as their momentary moods and feelings34.</li>
	</ol>
	</li>
</ol>
4. Image Acquisition and Cortical Reconstruction of Structural MRI
<ol>
	<li>Obtain a high-resolution anatomical MRI scan for each participant, and reconstruct each participant&#39;s cortical surface with FreeSurfer software40,41,42.</li>
	<li>Use the inner skull surface derived from the segmented structural MRI images to generate a boundary element model of the volume conductor, which is used to provide a model for the forward solution that is consistent with each individual&#39;s brain anatomy43,44.</li>
</ol>
5. MEG Data Analysis
NOTE: Analyze the data with the anatomically-constrained MEG approach which uses each participant&#39;s reconstructed cortical surface to constrain source estimates to the cortical ribbon40,45,46. The analysis stream relies on custom functions with dependencies on publicly available packages including FieldTrip47, EEGLab48, and MNE49.
<ol>
	<li>During data preprocessing, use a permissive band-pass filter (e.g., 0.1 - 100 Hz) and epoch data with respect to stimulus onset into segments that include padding intervals on each end (e.g., -600 to 1100 ms for an interval of interest spanning -300 to 800 ms after the removal of padding).</li>
	<li>Remove noisy and flat channels, as well as trials containing artifacts by visual inspection and using threshold-based rejection. Use independent component analysis48 to remove eyeblink and heartbeat artifacts. Eliminate trials with incorrect responses.</li>
	<li>Apply Morlet wavelets (Figure 3)47 to calculate complex power spectrum for each trial in 1 Hz increments for theta frequency band (4 - 7 Hz). Remove any additional artifacts. Compute the noise covariance from empty room data.</li>
	<li>Co-register the MEG data with MRI images using the three-dimensional (3D) head digitization information (Figure 2).
	<ol>
		<li>Open the MRIlab module.</li>
		<li>Select File| Open| Select subject&#39;s structural MRI.</li>
		<li>Select File| Import| Isotrak data| select raw data.fif file| Make Points.</li>
		<li>Select Windows| Landmarks| Adjust fiducial landmarks until co-registration of MEG data and MRI are acceptable.</li>
		<li>Select File| Save.</li>
	</ol>
	</li>
	<li>Calculate noise-sensitivity normalized estimates of theta source power and phase with a spectral dynamic statistical mapping approach18,50. Express event-related theta source power as percent signal change relative to baseline.</li>
	<li>Create group averages of event-related theta source power by morphing each participant&#39;s estimates onto an average cortical representation51.</li>
	<li>Visualize the source estimates on an inflated average surface to enhance visibility of sulcal estimates (Figure 4).
	<ol>
		<li>Open the MNE software.</li>
		<li>Select File| Load Surface| Load inflated group-average FreeSurfer cortical surface.</li>
		<li>Select File| Manage overlays| Load stc| Load group-averaged data| Select loaded file from available overlays.</li>
		<li>Select overlay type as Other.</li>
		<li>Adjust Color Scale thresholding| Show.</li>
		<li>View brain movies and examine spatio-temporal stages of processing by identifying areas and time windows characterized by highest activation.</li>
	</ol>
	</li>
	<li>Create unbiased regions of interest (ROIs) based on overall group-averaged estimates to incorporate cortical locations with most notable source power. Calculate time courses for each subject, condition, and ROI (Figure 5).</li>
	<li>Submit the obtained theta source power estimates to the statistical analysis.
	<ol>
		<li>Extract time windows of interest from each ROI time course and perform analysis of variance (ANOVA) with beverage (alcohol, placebo) and trial type (congruous, incongruous) as within subject factors. Use a nonparametric cluster-based permutation test52 to examine beverage and condition comparisons of event-related theta power as well as phase-locking values (PLV).</li>
	</ol>
	</li>
	<li>Estimate task-related changes in the long-range synchronization between the main activation foci in the ACC and the latPFC by computing the PLV12. Express PLV as percent change relative to baseline. 
	NOTE: The PLV is an indicator of consistency of the phase angle between the two ROIs across trials as it measures the extent to which they co-oscillate at a particular frequency and in real time (Movie 1).</li>
	<li>Calculate correlations between ROI MEG activity estimates, indices of behavioral performance, and questionnaire scores to inform interpretation of the observed results.</li>
</ol>

The authors have nothing to disclose.

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.

<table><tbody><tr><td>Elekta Neuromag</td><td>Elekta</td><td></td><td>Magnetoencephalography system</td></tr><tr><td>1.5 T GE EXCITE HG</td><td>General Electric</td><td></td><td>Magnetic Resonance Imaging scanner</td></tr><tr><td>Gold Cup Electrodes</td><td>OpenBCI</td><td></td><td>Electroencephalography electrodes for optional simultaneous EEG recording</td></tr><tr><td>Prep Check Impedance Meter</td><td>General Devices</td><td></td><td>Check electrode impedances</td></tr><tr><td>HPI Coils</td><td>Elekta</td><td></td><td>Head position indicator coils for co-registration</td></tr><tr><td>Alcotest</td><td>Draeger</td><td></td><td>Breathalyzer</td></tr><tr><td>Fiber Optic Response Pad</td><td>Current Designs, Inc</td><td></td><td>MEG-compatible response pad</td></tr><tr><td>Grey Goose Vodka</td><td>Bacardi</td><td></td><td>Vodka is used during the alcohol session</td></tr><tr><td>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><td>Discover Drug Test Card</td><td>American Screening Corp</td><td>Multi-screen drug test</td><td></td></tr><tr><td>QED Saliva Alcohol Test</td><td>OraSure Technologies</td><td>Saliva alcohol test</td><td></td></tr><tr><td>Urine Hcg Test Strips</td><td>Joylive</td><td></td><td>Pregnancy test</td></tr><tr><td>Short Michigan Alcohol Screening Test</td><td>Selzer et al., 1975</td><td></td><td>Alcoholism screening questionnaire</td></tr><tr><td>Zuckerman Sensation Seeking Scale</td><td>Zuckerman, 1971</td><td></td><td>Questionnaire: disinhibitory, novelty-seeking, and socialization traits</td></tr><tr><td>Eysenck Impulsivity Inventory</td><td>Eysenck &amp;amp; Eysenck, 1978</td><td>Questionnaire: impulsivity traits</td><td></td></tr><tr><td>Eysenck Personality Questionnaire</td><td>Eysenck &amp;amp; Eysenck, 1975</td><td>Questionnaire: personality traits</td><td></td></tr><tr><td>Biphasic Alcohol Effects Scale&amp;nbsp;</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 ...

disruption-frontal-lobe-neural-synchrony-during-cognitive-control

Research

JoVE Journal

Neuroscience

18.7K Views.  San Diego State University. Besluitvorming is een dynamisch, interactief proces dat uitgebreid is bestudeerd met functionele magnetische resonantie beeldvorming, of FMRI. Neuroimaging bewijs geeft aan dat de voorste cingulate en de laterale prefrontale cortices zijn essentiële knooppunten in dat neurale netwerk. Vanwege de beperkte temporele resolutie kan FMRI echter niet nauwkeurig de timing en aard van hun samenspel in realtime weergeven.De huidige studie maakt gebruik van een anatomisch beperkte magneto-en el...

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

A Cognitive Paradigm to Investigate Interference in Working Memory by Distractions and Interruptions

Goal-directed behavior is often impaired by interference from the external environment, either in the form of distraction by irrelevant information that one attempts to ignore, or by interrupting information that demands attention as part of another (secondary) task goal. Both forms of external interference have been shown to detrimentally impact the ability to maintain information in working memory (WM). Emerging evidence suggests that these different types of external interference exert different effects on behavior and may be mediated by distinct neural mechanisms. Better characterizing the distinct neuro-behavioral impact of irrelevant distractions versus attended interruptions is essential for advancing an understanding of top-down attention, resolution of external interference, and how these abilities become degraded in healthy aging and in neuropsychiatric conditions. This manuscript describes a novel cognitive paradigm developed the Gazzaley lab that has now been modified into several distinct versions used to elucidate behavioral and neural correlates of interference, by to-be-ignored distractors versus to-be-attended interruptors. Details are provided on variants of this paradigm for investigating interference in visual and auditory modalities, at multiple levels of stimulus complexity, and with experimental timing optimized for electroencephalography (EEG) or functional magnetic resonance imaging (fMRI) studies. In addition, data from younger and older adult participants obtained using this paradigm is reviewed and discussed in the context of its relationship with the broader literatures on external interference and age-related neuro-behavioral changes in resolving interference in working memory.

A novel cognitive paradigm is developed to elucidate behavioral and neural correlates of interference by to-be-ignored distractors versus interference by to-be-attended interruptors during a working memory task. In this manuscript, several variants of this paradigm are detailed, and data obtained with this paradigm in younger/older adult participants is reviewed.

Goal-directed behavior is often impaired by interference from the external environment, either in the form of distraction by irrelevant information that ...

Behavior

Moderate Prenatal Alcohol Exposure and Quantification of Social Behavior in Adult Rats

Alterations in social behavior are among the major negative consequences observed in children with Fetal Alcohol Spectrum Disorders (FASDs). Several independent laboratories have demonstrated robust alterations in the social behavior of rodents exposed to alcohol during brain development across a wide range of exposure durations, timing, doses, and ages at the time of behavioral quantification. Prior work from this laboratory has identified reliable alterations in specific forms of social interaction following moderate prenatal alcohol exposure (PAE) in the rat that persist well into adulthood, including increased wrestling and decreased investigation. These behavioral alterations have been useful in identifying neural circuits altered by moderate PAE1, and may hold importance for progressing toward a more complete understanding of the neural bases of PAE-related alterations in social behavior. This paper describes procedures for performing moderate PAE in which rat dams voluntarily consume ethanol or saccharin (control) throughout gestation, and measurement of social behaviors in adult offspring.

The goal of the protocol presented here is to describe procedures to expose rats to moderate levels of alcohol during prenatal brain development and to quantify resulting alterations in social behavior during adulthood.

Alterations in social behavior are among the major negative consequences observed in children with Fetal Alcohol Spectrum Disorders (FASDs). Several ...

Brain Imaging Investigation of the Impairing Effect of Emotion on Cognition

Emotions can impact cognition by exerting both enhancing (e.g., better memory for emotional events) and impairing (e.g., increased emotional distractibility) effects (reviewed in 1). Complementing our recent protocol 2 describing a method that allows investigation of the neural correlates of the memory-enhancing effect of emotion (see also 1, 3-5), here we present a protocol that allows investigation of the neural correlates of the detrimental impact of emotion on cognition. The main feature of this method is that it allows identification of reciprocal modulations between activity in a ventral neural system, involved in 'hot' emotion processing (HotEmo system), and a dorsal system, involved in higher-level 'cold' cognitive/executive processing (ColdEx system), which are linked to cognitive performance and to individual variations in behavior (reviewed in 1). Since its initial introduction 6, this design has proven particularly versatile and influential in the elucidation of various aspects concerning the neural correlates of the detrimental impact of emotional distraction on cognition, with a focus on working memory (WM), and of coping with such distraction 7,11, in both healthy 8-11 and clinical participants 12-14.

We present a protocol that allows investigation of the neural mechanisms mediating the detrimental impact of emotion on cognition, using functional magnetic resonance imaging. This protocol can be used with both healthy and clinical participants.

Emotions can impact cognition by exerting both enhancing (e.g., better memory for emotional events) and impairing (e.g., increased emotional ...

Wheel Running and Environmental Complexity as a Therapeutic Intervention in an Animal Model of FASD

Aerobic exercise (e.g., wheel running (WR) extensively used in animal research) positively impacts many measures of neuroplastic potential in the brain, such as rates of adult neurogenesis, angiogenesis, and expression of neurotrophic factors in rodents. This intervention has also been shown to mitigate behavioral and neuroanatomical aspects of the negative impacts of teratogens (i.e., developmental exposure to alcohol) and age-related neurodegeneration in rodents. Environmental complexity (EC) has been shown to produce numerous neuroplastic benefits in cortical and subcortical structures and can be coupled with wheel running to increase the proliferation and survival of new cells in the adult hippocampus. The combination of these two interventions provides a robust &#34;superintervention&#34; (WR-EC) that can be implemented in a range of rodent models of neurological disorders. We will discuss the implementation of WR/EC and its constituent interventions for use as a more powerful therapeutic intervention in rats using the animal model of prenatal exposure to alcohol in humans. We will also discuss which elements of the procedures are absolutely necessary for the interventions and which ones may be altered depending on the experimenter&#39;s question or facilities.

Cardiovascular exercise and stimulating experiences in a complex environment have positive benefits on multiple measures of neuroplasticity within the rodent brain. This article will discuss the implementation of these interventions as a &#34;superintervention&#34; which combines wheel running and environmental complexity and will address the limitations of these interventions.

Aerobic exercise (e.g., wheel running (WR) extensively used in animal research) positively impacts many measures of neuroplastic potential in the brain, ...

Flypub To Study Ethanol Induced Behavioral Disinhibition and Sensitization

Alcohol use disorder (AUD) remains a serious problem in our society. To develop effective interventions for addiction, it is important to understand the underlying neurobiological mechanisms, for which diverse experimental approaches and model systems are needed. The main ingredient of alcoholic beverages is ethanol, which causes adaptive changes in the central nervous system and behavior upon chronic intake. Behavioral sensitization (i.e., escalated responses) in particular represents a key adaptive change underlying addiction. Most ethanol-induced behavioral sensitization studies in animal models have been conducted on the locomotor activating effect of ethanol. A prominent effect of ethanol is behavioral disinhibition. Behavioral sensitization to the disinhibition effect of ethanol, however, is underrepresented. To address this issue, we developed the Flypub assay that allows measuring the escalated increase in disinhibited courtship activities upon recurring ethanol exposure in Drosophila melanogaster.&#160;Here, we report the step-by-step Flypub assay including assembly of ethanol exposure chambers, setup of the assay station, criteria for fly care and collection, ethanol delivery, quantification of disinhibited courtship activities, data processing and statistical analysis. Also provided are how to troubleshoot critical steps, overcome limitations and expand its utility to assess additional ethanol-induced behaviors. The Flypub assay in combination with powerful genetic tools in Drosophila melanogaster will facilitate the task of discovering the mechanism underlying ethanol-induced behavioral sensitization.

The Flypub assay measures the behaviors that the fruit fly Drosophila melanogaster displays under the influence of ethanol. The assay can be readily mastered by experimenters at all levels and applied to various vaporized stimuli, facilitating substance abuse and addiction studies.

Alcohol use disorder (AUD) remains a serious problem in our society. To develop effective interventions for addiction, it is important to understand the ...

The Use of Trace Eyeblink Classical Conditioning to Assess Hippocampal Dysfunction in a Rat Model of Fetal Alcohol Spectrum Disorders

Neonatal rats were administered a relatively high concentration of ethyl alcohol (11.9% v/v) during postnatal days 4-9, a time when the fetal brain undergoes rapid organizational change and is similar to accelerated brain changes that occur during the third trimester in humans. This model of fetal alcohol spectrum disorders (FASDs) produces severe brain damage, mimicking the amount and pattern of binge-drinking that occurs in some pregnant alcoholic mothers. We describe the use of trace eyeblink classical conditioning (ECC), a higher-order variant of associative learning, to assess long-term hippocampal dysfunction that is typically seen in alcohol-exposed adult offspring. At 90 days of age, rodents were surgically prepared with recording and stimulating electrodes, which measured electromyographic (EMG) blink activity from the left eyelid muscle and delivered mild shock posterior to the left eye, respectively. After a 5 day recovery period, they underwent 6 sessions of trace ECC to determine associative learning differences between alcohol-exposed and control rats. Trace ECC is one of many possible ECC procedures that can be easily modified using the same equipment and software, so that different neural systems can be assessed. ECC procedures in general, can be used as diagnostic tools for detecting neural pathology in different brain systems and different conditions that insult the brain.

Trace eyeblink classical conditioning (ECC) was used to assess hippocampal-dependent associative learning in adult rats that were administered a high concentration (11.9% v/v) of alcohol during early neonatal brain development. In general, ECC procedures are sound diagnostic tools for detecting brain dysfunction across many psychological and biomedical settings.

Neonatal rats were administered a relatively high concentration of ethyl alcohol (11.9% v/v) during postnatal days 4-9, a time when the fetal brain ...

A Prediction Error-driven Retrieval Procedure for Destabilizing and Rewriting Maladaptive Reward Memories in Hazardous Drinkers

Maladaptive reward memories (MRMs) can become unstable following retrieval under certain conditions, allowing their modification by subsequent new learning. However, robust (well-rehearsed) and chronologically old MRMs, such as those underlying substance use disorders, do not destabilize easily when retrieved. A key determinate of memory destabilization during retrieval is prediction error (PE). We describe a retrieval procedure for alcohol MRMs in hazardous drinkers that specifically aims to maximize the generation of PE and therefore the likelihood of MRM destabilization. The procedure requires explicitly generating the expectancy of alcohol consumption and then violating this expectancy (withholding alcohol) following the presentation of a brief set of prototypical alcohol cue images (retrieval + PE). Control procedures involve presenting the same cue images, but allow alcohol to be consumed, generating minimal PE (retrieval-no PE) or generate PE without retrieval of alcohol MRMs, by presenting orange juice cues (no retrieval + PE). Subsequently, we describe a multisensory disgust-based counterconditioning procedure to probe MRM destabilization by re-writing alcohol cue-reward associations prior to reconsolidation. This procedure pairs alcohol cues with images invoking pathogen disgust and an extremely bitter-tasting solution (denatonium benzoate), generating gustatory disgust. Following retrieval + PE, but not no retrieval + PE or retrieval-no PE, counterconditioning produces evidence of MRM rewriting as indexed by lasting reductions in alcohol cue valuation, attentional capture, and alcohol craving.

This manuscript describes a memory retrieval procedure for destabilizing robust reward memories and rewriting them with counterconditioning prior to their reconsolidation.

Maladaptive reward memories (MRMs) can become unstable following retrieval under certain conditions, allowing their modification by subsequent new ...

How to Calculate and Validate Inter-brain Synchronization in a fNIRS Hyperscanning Study

The dynamics between coupled brains of individuals have been increasingly represented by inter-brain synchronization (IBS) when they coordinate with each other, mostly using simultaneous-recording signals of brains (namely hyperscanning) with fNIRS. In fNIRS hyperscanning studies, IBS has been commonly assessed through the wavelet transform coherence (WTC) method because of its advantage on expanding time series into time-frequency space where oscillations can be seen in a highly intuitive way. The observed IBS can be further validated via the permutation-based random pairing of the trial, partner, and condition. Here, a protocol is presented to describe how to obtain brain signals via fNIRS technology, calculate IBS through the WTC method, and validate IBS by permutation in a hyperscanning study. Further, we discuss the critical issues when using the above methods, including the choice of fNIRS signals, methods of data preprocessing, and optional parameters of computations.&#160;In summary, using the WTC method and permutation is a potentially standard pipeline for analyzing IBS in fNIRS hyperscanning studies, contributing to both the reproducibility and reliability of IBS.

The dynamics between coupled brains of individuals have been increasingly represented by inter-brain synchronization (IBS) when they coordinate with each ...

Dual-Task Stroop Paradigm for Detecting Cognitive Deficits in High-Functioning Stroke Patients

General clinical cognitive assessment scales are not sensitive enough to cognitive impairment in high-functioning stroke patients. The dual-task assessment has advantages for identifying cognitive deficits in high-functioning stroke patients and has been gradually applied in clinical assessment and cognitive training. Moreover, the Stroop paradigm has higher sensitivity and specificity for attentional assessment than conventional clinical cognitive assessment scales. Therefore, this study presents the dual-task assessment based on the Stroop paradigm to identify cognitive deficits in high-functioning stroke patients. This study demonstrates a single- and dual-task evaluation based on the Stroop paradigm and confirms its feasibility through case experiments and synchronized functional near-infrared spectroscopy evaluation. The Stroop reaction time and correct rate are used as the main indicators to evaluate the cognitive level of the subjects. This study protocol aims to provide new ideas to figure out the ceiling effect in general clinical assessment failure for high-functioning stroke patients.

Clinical assessment scales are notsensitive enough to cognitive dysfunction in high-functioning stroke patients. The dual-task paradigm presents advantages and potential in the assessment and cognitive training of cognitive dysfunction. The study here proposes a dual-task Stroop paradigm to identify cognitive dysfunction in high-functioning stroke patients.

General clinical cognitive assessment scales are not sensitive enough to cognitive impairment in high-functioning stroke patients. The dual-task ...

A Visuospatial Planning Task Coupled with Eye-Tracker and Electroencephalogram Systems

The planning process, characterized by the capability to formulate an organized plan to reach a goal, is essential for human goal-directed behavior. Since planning is compromised in several neuropsychiatric disorders, the implementation of proper clinical and experimental tests to examine planning is critical. Due to the nature of the deployment of planning, in which several cognitive domains participate, the assessment of planning and the design of behavioral paradigms coupled with neuroimaging methods are current challenges in cognitive neuroscience. A planning task was evaluated in combination with an electroencephalogram (EEG) system and eye movement recordings in 27 healthy adult participants. Planning can be separated into two stages: a mental planning stage in which a sequence of steps is internally represented and an execution stage in which motor action is used to achieve a previously planned goal. Our protocol included a planning task and a control task. The planning task involved solving 36 maze trials, each representing a zoo map. The task had four periods: i) planning, where the subjects were instructed to plan a path to visit the locations of four animals according to a set of rules; ii) maintenance, where the subjects had to retain the planned path in their working memory; iii) execution, where the subjects used eye movements to trace the previously planned path as indicated by the eye-tracker system; and iv) response, where the subjects reported the order of the visited animals. The control task had a similar structure, but the cognitive planning component was removed by modifying the task goal. The spatial and temporal patterns of the EEG revealed that planning induces a gradual and lasting rise in frontal-midline theta activity (FM&#952;) over time. The source of this activity was identified within the prefrontal cortex by source analyses. Our results suggested that the experimental paradigm combining EEG and eye-tracker systems was optimal for evaluating cognitive planning.

The study of cognitive planning combining EEG and eye-tracking systems provides a multimodal approach to investigate the neural mechanisms that mediate cognitive control and goal-directed behavior in humans. Here, we describe a protocol for investigating the role of brain oscillations and eye movements in planning performance.

The planning process, characterized by the capability to formulate an organized plan to reach a goal, is essential for human goal-directed behavior. Since ...

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

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