Abstract
Introduction
Stimulant drugs are thought to alter processing of rewarding stimuli. However, the mechanisms by which they do this are not fully understood.
Method
In this study we used EEG to assess effects of single doses of methamphetamine (MA) on neural responses during anticipation and receipt of reward in healthy volunteers. Healthy young men and women (N = 28) completed three sessions in which they received placebo, a low MA dose (10 mg) or a higher MA dose (20 mg) under double blind conditions. Subjective and cardiovascular measures were obtained, and EEG was used to assess brain activity during an electrophysiological version of the Monetary Incentive Delay (eMID) task.
Results
EEG measures showed expected patterns during anticipation and receipt of reward, and MA produced its expected effects on mood and cardiovascular function. However, MA did not affect EEG responses during either anticipation or receipt of rewards.
Conclusions
These findings suggest that the effects of MA on EEG signals of reward processing are subtle, and not related to the drug’s effects on subjective feelings of well-being. The findings contribute to our understanding of the neural effects of MA during behaviors related to reward.
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Data availability
Data is available raw or processed, upon request to the corresponding author.
Notes
Two major issues with results suggest the PCA was not successfully able to separate the RewP from the preceding FB-P2 and subsequent FB-P3. First, although TF4SF1 is consistent with FB-P2, the next adjacent factor, TF5SF1, does not resemble the RewP. For example, TF4SF1 peaks at 176 ms around FCz and shows no difference between Reward Win and Lose conditions, consistent with the FB-P2. But the next adjacent factor, TF5SF1, does not align with RewP effects in ERP waveform, peaks too early (224 ms at FCz), and is greatest for Reward Lose (vs. Win). These results suggest that while TF4SF1 likely reflects the FB-P2, TF5SF1 may not reflect the RewP but rather some combination of overlapping FB-P2 and RewP activity. In support, one recent PCA study reported the RewP PC factor was not significantly modulated by outcome valence (Clayson et al. 2019), suggesting temporospatial PCA may be unable to adequately separate feedback-related ERPs in some cases.
Second, two positive PCs emerged in the FB-P3 time window: TF7SF1 and TF2SF1. Numerous studies have identified two P3-related ERP components: an earlier, frontal P3a reflecting early attention and a later, parietal P3b reflecting stimulus categorization (Polich 2007). One previous reward processing study used PCA to separate the FB-P3 into the FB-P3a and FB-P3b after feedback and produced PC factor distributions strikingly similar to the present results (Glazer et al. 2020). Consistent with this prior study, the current results suggest TF2SF1 corresponds to the FB-P3b. However, unlike this previous study, the current results suggest PCA was unable to successfully separate the RewP from the FB-P3a. While TF7SF1 may reflect the FB-P3a, it rather resembles the RewP in peak latency and electrode (276 ms at Cz), is greatest for Reward Win (vs. Lose), and lines up with expected RewP effects in the ERP waveform. These results suggest it is likely that TF5SF1 and TF7SF1 PC factors contain overlapping activity corresponding to the RewP and FB-P3a, respectively.
Results suggest it is likely that substantial temporal overlap remained after PCA among TF4SF1, TF5SF1, and TF7SF1, presumably reflecting the FB-P2, RewP, and FB-P3a. Further complicating interpretation, one negative PC emerged (TF12SF1) consistent with the peak latency, scalp topography, and polarity of the feedback-related negativity (FRN). While the RewP reflects a positive ERP deflection after better-than-expected feedback, a negative ERP deflection called the FRN may index worse-than-expected feedback in the same time window (Proudfit 2015, Holroyd et al. 2008, 2011). Although most reward processing studies using PCA do not report a negative deflection consistent with the FRN, some previous studies have done so and are consistent with the present results (Valadez et al. 2016, Valadez 2019). The present results suggest temporospatial PCA of feedback-related ERPs may produce more complex PC distributions than previously reported. Future studies should consider comprehensive reporting of all PCs in the FB-P2/RewP/FB-P3 time window to better interpret and understand the rapid cascade of feedback-related ERPs.
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This research was supported by National Institute on Drug Abuse grant DA02812.
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CJH – analysis, interpretation, writing.
JG – analysis, interpretation, writing.
RL – design, interpretation.
RN –analysis, interpretation.
HdW – design, analysis, interpretation, writing.
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HdW serves on the Board of Directors of PharmAla Biotech and has served as Scientific Advisor to Awakn Life Sciences, Gilgamesh Pharmaceuticals and Mind Foundation. These roles are unrelated to the research reported here. CJH, JEG, IT, MK, and RL have no conflicts of interest to disclose.
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Haggarty, C.J., Glazer, J.E., Nusslock, R. et al. Lack of effect of methamphetamine on reward-related brain activity in healthy adults. Psychopharmacology 241, 181–193 (2024). https://doi.org/10.1007/s00213-023-06475-8
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DOI: https://doi.org/10.1007/s00213-023-06475-8