The Nuances of Norepinephrine: Investigating the Role of Salivary Alpha Amylase on tDCS - Modulated Decision Making

Abstract

The locus coeruleus - norepinephrine system (LC-NE) – a primary dispenser of norepinephrine in the brain – modulates allocation of attention used in executive functioning and reasoning through connection tracts to the prefrontal cortex (PFC); however, the changes of norepinephrine related to decision-making when affected by transcranial direct current stimulation (tDCS) are not fully understood. This obstacle is largely due to traditionally used between-subjects experimental designs that are limited in their ability to study the changes in norepinephrine across both individuals and time. For this reason, samples of salivary alpha-amylase (sAA) – a correlated biomarker of norepinephrine production – were collected within-subjects, therefore controlling for individual circadian variations of sAA. Samples consisted of one baseline measure (Collection 1) followed by three post-tDCS stimulation collections (Collection 2, 3, & 4) using equivalent time intervals. Participants’ sAA collections were repeated across three weekly visits of varying tDCS stimulation conditions: left dorsolateral prefrontal cortex (DLPFC), right DLPFC, and sham. Following each stimulation condition, participants completed a series of cognitive tasks measuring decision-making and judgement-related behavior. Stimulation condition interacted with time of salivary collection such that tDCS stimulation to the left DLPFC and sham conditions led to significant increases in sAA levels across collections. Both the sham and left DLPFC stimulation conditions demonstrated a significant sAA increase in Collection 1 to 4. Conversely, sAA levels did not increase following stimulation of the right DLPFC. Together, stimulating lateral PFC sites may differentially modulate norepinephrine release across time when controlling for individual subject variability.

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Baseline
Post 1 Post 2 Post 3
Baseline Post 1 Post 2 Post 3
Baseline
Results & FindingsIntroduction
Method
Acknowledgements
References
Discussion
Illustrated Experimental Timeline
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Salivary Collection Time
Average sAA Across Stimulation
Mean sAA Levels (U/mL)
Right DL - PFC Left DL - PFC*
Sham*
sAA Levels Across Participants
sAA Levels (U/mL)
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CRT Performance
sAA Change (U/mL)
sAA Change vs. FCI
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sAA Change vs. CRT Performance
Verbal CRTQuant. CRT * ***
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Frame Consistency Index
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EEG
Capping
Gambling
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Stimulation
Negative Frame
Positive Frame
Compumedics Neuroscan 64-Channel
Quik-Cap
CURRY Acquisition Software
A special thank you must be extended to Bailey Balloun, Analeigh Tucker, and
Christopher Beegly for their assistance with data collection and development. In
addition, thank you to Salimetrics LLC SalivaLab for their salivary analysis services.
1. Unsworth, N., Robison, M.K. (2017). A locus coeruleus-norepinephrine account of individual differences
in working memory capacity and attention control."Psychonomics Bulletin & Review,"24(4),"1282-1311.
2. Aston-Jones, G., Cohen, J.D. (2005). An integrative theory of locus coeruleus-norepinephrine
function: Adaptive gain and optimal performance. Annual Review of Neuroscience, 28(1), 403-450.
▪Results suggest that norepinephrine release of the LC-NE system following tDCS stimulation can be studied using salivary alpha-amylase to explore optimization of task
performance on select decision-making processes1,2.
▪Together, stimulating lateral PFC sites may differentially modulate norepinephrine release across time when controlling for individual subject variability.
▪Follow up studies utilizing both a more robust and diverse sample size are needed to investigate how changing sensitivities in norepinephrine sAA levels relate to changes in
prefrontal processes such as impulse control, attenuation, and analogical reasoning in both general and clinical populations (e.g., traumatic brain injury patients).
▪ 8 participants (8 Male; age M = 21 years, SD = 3.2)
▪ Participants underwent a total of 3 weekly visits, each consisting of one 20-minute
tDCS stimulation (2mA) of the right dorsolateral PFC, left DL-PFC, or sham.
▪ Afterwards, participants completed a Cognitive Reflection Task (CRT).
▪ Following EEG capping, a Financial Gambling Task (FGT) was given to measure
frame consistency in decision making.
▪ FGT was followed by a visual Stop Signal Task (SST) with varying stop signal
latencies to measure impulse inhibition in ranging difficulty.
▪ Salivary alpha amylase samples (0.25 - 1 mL) were collected in timed intervals.
▪ Norepinephrine (NE) plays a critical role in one’s arousal, attentional control, and
working memory; however, the effects of NE modulation during tDCS stimulation
remains widely unknown1.
▪ Therefore, a key objective of the study is to create a reliable protocol for salivary
alpha amylase collection (a biomarker of NE production) in order to observe the
changes of NE production with respects to tDCS stimulation.
The Nuances of Norepinephrine: Investigating the Role of Salivary
Alpha Amylase on tDCS - Modulated Decision Making
Lauren M. Kim1, Michael J. Lundie1, Matthew J. Kmiecik1, Harshith Dasara1,
& Daniel C. Krawczyk1,2
1The University of Texas at Dallas, 2The University of Texas Southwestern Medical Center at Dallas
sAA
Baseline
sAA
Post 1
sAA
Post 2
sAA
Post 3
Right DLPFC Sham Left DLPFC
Salivary Collection Time
Quantitative Example: A bat and ball cost $1.10 in total. The bat
costs $1.00 more than the ball. How much is the ball? (Ans: 5 cents)
Verbal Example: If you were running a race and passed the person in
2nd place, what place would you be in now? (Ans: 2nd place)
AB C
Stimuli
Examples