Neural Indices of Heritable Impulsivity: Impact of the COMT Val158Met Polymorphism on Frontal Beta Power During Early Motor Preparation

Overview

Journal Biol Psychol

Specialty Psychiatry

Date 2024 Jun 11

PMID 38862067

Authors

Joseph P Happer

Lauren E Beaton

Laura C Wagner

Colin A Hodgkinson

David Goldman

Ksenija Marinkovic

Affiliations

Soon will be listed here.

Abstract

Studies of COMT ValMet suggest that the neural circuitry subserving inhibitory control may be modulated by this functional polymorphism altering cortical dopamine availability, thus giving rise to heritable differences in behaviors. Using an anatomically-constrained magnetoencephalography method and stratifying the sample by COMT genotype, from a larger sample of 153 subjects, we examined the spatial and temporal dynamics of beta oscillations during motor execution and inhibition in 21 healthy Met/Met (high dopamine) or 21 Val/Val (low dopamine) genotype individuals during a Go/NoGo paradigm. While task performance was unaffected, Met homozygotes demonstrated an overall increase in beta power across regions essential for inhibitory control during early motor preparation (∼100 ms latency), suggestive of a global motor "pause" on behavior. This increase was especially evident on Go trials with slow response speed and was absent during inhibition failures. Such a pause could underlie the tendency of Met allele carriers to be more cautious and inhibited. In contrast, Val homozygotes exhibited a beta drop during early motor preparation, indicative of high response readiness. This decrease was associated with measures of behavioral disinhibition and consistent with greater extraversion and impulsivity observed in Val homozygotes. These results provide mechanistic insight into genetically-determined interindividual differences of inhibitory control with higher cortical dopamine associated with momentary response hesitation, and lower dopamine leading to motor impulsivity.

References

Beaton L, Azma S, Marinkovic K . When the brain changes its mind: Oscillatory dynamics of conflict processing and response switching in a flanker task during alcohol challenge. PLoS One. 2018; 13(1):e0191200. PMC: 5766228. DOI: 10.1371/journal.pone.0191200. View

Cools R . Chemistry of the Adaptive Mind: Lessons from Dopamine. Neuron. 2019; 104(1):113-131. DOI: 10.1016/j.neuron.2019.09.035. View

Serrano J, Banks J, Fagan T, Tartar J . The influence of Val158Met COMT on physiological stress responsivity. Stress. 2019; 22(2):276-279. DOI: 10.1080/10253890.2018.1553949. View

Jana S, Hannah R, Muralidharan V, Aron A . Temporal cascade of frontal, motor and muscle processes underlying human action-stopping. Elife. 2020; 9. PMC: 7159878. DOI: 10.7554/eLife.50371. View

Barth B, Rohe T, Deppermann S, Fallgatter A, Ehlis A . Neural oscillatory responses to performance monitoring differ between high- and low-impulsive individuals, but are unaffected by TMS. Hum Brain Mapp. 2021; 42(8):2416-2433. PMC: 8090766. DOI: 10.1002/hbm.25376. View

Tsai S, Hong C, Yu Y, Chen T . Association study of a brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and personality trait and intelligence in healthy young females. Neuropsychobiology. 2004; 49(1):13-6. DOI: 10.1159/000075333. View

Marinkovic K, Beaton L, Rosen B, Happer J, Wagner L . Disruption of Frontal Lobe Neural Synchrony During Cognitive Control by Alcohol Intoxication. J Vis Exp. 2019; (144). PMC: 6677147. DOI: 10.3791/58839. View

Tang W, Jbabdi S, Zhu Z, Cottaar M, Grisot G, Lehman J . A connectional hub in the rostral anterior cingulate cortex links areas of emotion and cognitive control. Elife. 2019; 8. PMC: 6624020. DOI: 10.7554/eLife.43761. View

Buzsaki G, Logothetis N, Singer W . Scaling brain size, keeping timing: evolutionary preservation of brain rhythms. Neuron. 2013; 80(3):751-64. PMC: 4009705. DOI: 10.1016/j.neuron.2013.10.002. View

10.

Neuper C, Muller-Putz G, Scherer R, Pfurtscheller G . Motor imagery and EEG-based control of spelling devices and neuroprostheses. Prog Brain Res. 2006; 159:393-409. DOI: 10.1016/S0079-6123(06)59025-9. View

11.

Siegel M, Donner T, Engel A . Spectral fingerprints of large-scale neuronal interactions. Nat Rev Neurosci. 2012; 13(2):121-34. DOI: 10.1038/nrn3137. View

12.

Dignath D, Eder A, Steinhauser M, Kiesel A . Conflict monitoring and the affective-signaling hypothesis-An integrative review. Psychon Bull Rev. 2020; 27(2):193-216. DOI: 10.3758/s13423-019-01668-9. View

13.

Chambers C, Garavan H, Bellgrove M . Insights into the neural basis of response inhibition from cognitive and clinical neuroscience. Neurosci Biobehav Rev. 2008; 33(5):631-46. DOI: 10.1016/j.neubiorev.2008.08.016. View

14.

Adan A, Forero D, Navarro J . Personality Traits Related to Binge Drinking: A Systematic Review. Front Psychiatry. 2017; 8:134. PMC: 5532381. DOI: 10.3389/fpsyt.2017.00134. View

15.

Varga G, Szekely A, Antal P, Sarkozy P, Nemoda Z, Demetrovics Z . Additive effects of serotonergic and dopaminergic polymorphisms on trait impulsivity. Am J Med Genet B Neuropsychiatr Genet. 2012; 159B(3):281-8. DOI: 10.1002/ajmg.b.32025. View

16.

Zumarraga M, Davila R, Basterreche N, Arrue A, Goienetxea B, Zamalloa M . Catechol O-methyltransferase and monoamine oxidase A genotypes, and plasma catecholamine metabolites in bipolar and schizophrenic patients. Neurochem Int. 2010; 56(6-7):774-9. DOI: 10.1016/j.neuint.2010.02.015. View

17.

Enoch M, Xu K, Ferro E, Harris C, Goldman D . Genetic origins of anxiety in women: a role for a functional catechol-O-methyltransferase polymorphism. Psychiatr Genet. 2003; 13(1):33-41. DOI: 10.1097/00041444-200303000-00006. View

18.

Caspi A, Langley K, Milne B, Moffitt T, ODonovan M, Owen M . A replicated molecular genetic basis for subtyping antisocial behavior in children with attention-deficit/hyperactivity disorder. Arch Gen Psychiatry. 2008; 65(2):203-10. DOI: 10.1001/archgenpsychiatry.2007.24. View

19.

Muralidharan V, Aron A, Schmidt R . Transient beta modulates decision thresholds during human action-stopping. Neuroimage. 2022; 254:119145. DOI: 10.1016/j.neuroimage.2022.119145. View

20.

Tunstall M, Oorschot D, Kean A, Wickens J . Inhibitory interactions between spiny projection neurons in the rat striatum. J Neurophysiol. 2002; 88(3):1263-9. DOI: 10.1152/jn.2002.88.3.1263. View