A KCNJ6 gene polymorphism modulates theta oscillations during reward processing.

paper Primary Public

Authors: Kamarajan, Chella; Pandey, Ashwini K; Chorlian, David B; Manz, Niklas; Stimus, Arthur T; Edenberg, Howard J; Wetherill, Leah; Schuckit, Marc; Wang, Jen-Chyong; Kuperman, Samuel; Kramer, John; Tischfield, Jay A; Porjesz, Bernice
Year: 2017
Journal: International journal of psychophysiology : official journal of the International Organization of Psychophysiology
PMID: 27993610
DOI: 10.1016/j.ijpsycho.2016.12.007
PMCID: PMC5392377

Fig. 1

Schematic illustration of the monetary gambling task. Each trial starts with a choice stimulus (CS) which lasts for 800 ms and displays two amounts (10¢ or 50¢) to bet with. The participant selects one of the amounts and receives an outcome of either gain (green box) or loss (red box) for the selected amount as shown by the outcome stimulus (OS). A trial with a gain of 50¢ and the next trial with a loss of 10¢ are illustrated. The ISI between the CS and the OS is 1500 ms. Participants were required to respond to the OS within 1000 ms (i.e., response window) by selecting one of the two amounts. ERO analysis was performed on trial epochs of 1000 ms post-stimulus period after the onset of the OS (i.e., analysis window).

LLM interpretation

This figure is a schematic diagram illustrating the sequence of a monetary gambling task across multiple trials. Each trial consists of a choice stimulus (CS) presenting two bet amounts (10¢ or 50¢), followed by an outcome stimulus (OS) indicating a gain (green box) or loss (red box). The timeline specifies durations for the CS (800 ms), the inter-stimulus interval (ISI, 1500 ms), a response window (1000 ms), and an analysis window (1000 ms).

Fig. 2

Sixty-one electrodes were recorded in the current study from the surface of the scalp. Three regions, representing frontal (F3, FZ, F4), central (C3, CZ, C4), and parietal (P3, PZ, P4) electrodes were selected for statistical analyses (see shaded electrodes contributing to each of these regions).

LLM interpretation

This is a schematic diagram of an EEG electrode layout on a scalp. The figure identifies 61 electrode positions, with specific regions labeled as Frontal, Central, Parietal, Occipital, Left Temporal, and Right Temporal. Shaded circles highlight the specific electrodes (F3, FZ, F4; C3, CZ, C4; and P3, PZ, P4) selected for statistical analysis within the frontal, central, and parietal regions.

Fig. 3

Theta-band response elicited by loss (A) and gain (B) feedback in the gambling task. Log-transformed theta power (estimated marginal means) is plotted as a function of scalp region and rs702859 genotype. Bonferroni adjusted multiple comparisons of log-transformed theta power (estimated marginal means) across genotypes [AA/0 = green line; AG/1 = blue line; GG/2 = red line] at frontal, central, and parietal regions during loss (left panel) and gain condition (right panels) in all subjects. Significant differences in theta power between the genotypes (0, 1, and 2) have been marked with corresponding genotype numbers and asterisks (*p < 0.05 and **p < 0.01). Additive effect of genotype [GG > AG > AA] is seen with significant differences observed between AA and GG [GG > AA] at central (*p < 0.05) and parietal (**p < 0.01) regions during both loss and gain condition, while the gain condition additionally showed a significant difference between AG and GG [GG > AA] at the parietal region (*p < 0.05). Step-wise increase in posterior theta power as a function of minor allele(s) is shown by the difference values between frontal and parietal regions (Frontal – Parietal) within each condition and genotype, positive values represent frontal maxima and negative values parietal maxima (**p < 0.01 and ***p < 0.001). The vertical error-bars in the line graph represents 1 standard error, shown only for positive or negative direction in order to avoid any overlap with the data lines.

LLM interpretation

This figure consists of two line graphs showing log-transformed theta power across three scalp regions (Frontal, Central, Parietal) for three genotypes: AA (green), AG (blue), and GG (red), under loss (A) and gain (B) conditions. In both conditions, theta power generally increases from frontal to parietal regions for the GG genotype, while the AA genotype shows a decrease during loss. Statistical markers indicate significant differences between genotypes 0 (AA) and 2 (GG) at central and parietal regions (*p < 0.05, **p < 0.01), with the GG genotype exhibiting the highest theta power.

Fig. 4

Theta power (in µV2) across genotypes (rs702859) during loss (panel-set A) and gain (panel-set B). Within these panel-sets, TF plots (middle panels showing x-axis with time in ms and y-axis with frequency in Hz for the loss and gain conditions at FZ and PZ electrodes) and head maps of absolute (left panels) and Z-scores (right panels) are illustrated. The dotted vertical line (at 0 ms) in the TF plots represents the onset of outcome stimulus. The smaller rectangles within the TF plots represent the TFROI of theta power (3.5–7.5 Hz within 200–500 ms) post outcome stimulus. During evaluation of loss as well as gain, there is an additive effect of genotypes [GG > AG > AA] with increasing power corresponding the number of minor allele(s) in central and parietal regions. Subtle topographic differences across genotypes (i.e., minor allele(s) contributing to posteriorization of theta power) are also shown.

LLM interpretation

This figure presents time-frequency (TF) plots and topographic head maps of theta power ($\mu\text{V}^2$) for three genotypes (AA, AG, GG) during loss (Panel A) and gain (Panel B) conditions. The TF plots show frequency (Hz) over time (ms) at FZ and PZ electrodes, with a defined region of interest (ROI) between 200–500 ms and 3.5–7.5 Hz. The head maps display absolute power (left) and Z-scores (right), illustrating an additive increase in theta power and a shift toward posterior regions as the number of minor alleles increases (GG > AG > AA).

Fig. A1

ERP waveforms (panels in columns 2, 3, and 4) flanked by P3 topography (panels in columns 1 and 5) across the genotypes (panels in rows) during loss and gain outcome. The group with minor allele(s) have displayed higher P3 amplitude than the group homozygous for the major allele [GG/AG > AA], prominently at the posterior region, during evaluation of loss as well as gain. Peak P3 amplitude values (in µV) for gain (green) and loss (red) are shown within the panels of ERP waveforms. The dotted vertical line (at 0 ms) in the waveform panels represents the onset of outcome stimulus. Uniform color scales have been used for all the head plots.

LLM interpretation

This figure consists of a grid of ERP waveforms (columns 2-4) and P3 topography head plots (columns 1 and 5) across three genotypes (0-AA, 1-AG, 2-GG) for "Loss" and "Gain" outcomes. The waveforms plot amplitude ($\mu$V) against time (ms) at FZ, CZ, and PZ electrodes, with green lines representing gain and red lines representing loss. Topography plots use a uniform color scale (0 to 16 $\mu$V) to show spatial distribution, with higher P3 amplitudes visible in the posterior regions for the AG and GG genotypes compared to the AA genotype.

Fig. A2

Theta power (in µV2) across genotypes (rs702859) and age groups during loss (left columns) and gain condition (right columns). Additive effect of genotypes [GG > AG > AA] with increasing power corresponding the number of minor allele(s) in adolescent (17–18 years) and adult (19–25 years) groups is shown during evaluation of loss as well as gain. The adolescents show more theta power and more diffused posterior topography than adults in each genotype group (top three rows) and in the combined sample (bottom row of head maps). Uniform color scales have been used for all the head plots.

LLM interpretation

This figure consists of a grid of EEG topographic head maps showing theta power ($\mu V^2$) across two conditions (Loss and Gain), two age groups (17–18 and 19–25 years), and three genotypes (AA, AG, GG), with a final row showing the combined sample (All). The color scale indicates that theta power increases from blue (0) to red (18), with the highest power observed in the GG genotype and the 17–18 age group. Across both conditions, there is a visible additive increase in power from AA to AG to GG, and adolescents exhibit more intense and diffused posterior activity compared to adults.

#	Section	Preview
20	2. Methods — 2.5. Genotyping	Genotyping was performed at Washington University School of Medicine in St. Louis on an OpenArray…
21	2. Methods — 2.5. Genotyping	heterozygosities were computed in PLINK (Purcell et al., 2007) using data on founders only included…
22	2. Methods — 2.6. Statistical Analyses	Log-transformed ERO theta power, representing frontal (F3, FZ, F4), central (C3, CZ, C4), and…
23	2. Methods — 2.6. Statistical Analyses	the EEG data is to use multivariate tests within a repeated-measures design (Bell and Cuevas, 2012),…
24	3. Results — 3.1. Theta EROs across genotypes	Mean age across genotype groups [AA = 19.29; AG = 19.25; GG = 19.41] was not significantly…
25	3. Results — 3.1. Theta EROs across genotypes	2.70; SE = 0.02). Genotype × region interaction effect indicated that theta differences between…
26	3. Results — 3.1. Theta EROs across genotypes	Bonferroni adjusted pairwise comparisons across genotypes, as derived from the estimated marginal…
27	3. Results — 3.2. Topography of theta power across genotypes	Time-frequency (TF) plots and head maps of theta power across the genotypes during loss and gain…
28	4. Discussion	The major findings of the current study are 1) an additive genotypic effect of the KCNJ6 SNP on the…
29	4. Discussion — 4.1. Genotypic Effects on Theta EROs	The major finding of the current study is that genotypic variations in the KCNJ6 SNP (rs702859)…
30	4. Discussion — 4.1. Genotypic Effects on Theta EROs	Our results also showed topographic differences of theta power across genotype during the loss…
31	4. Discussion — 4.1. Genotypic Effects on Theta EROs	In a previous study of theta EROs during loss and gain in the same monetary gambling task, we…
32	4. Discussion — 4.1. Genotypic Effects on Theta EROs	group, regardless of genotype. Furthermore, the subgroups with minor allele(s) (AG and GG) showed a…
33	4. Discussion — 4.1. Genotypic Effects on Theta EROs	in the course of development (Yordanova and Kolev, 1998, 2009). Therefore, given these suggested…
34	4. Discussion — 4.1. Genotypic Effects on Theta EROs	region, followed by central and parietal regions. Further studies are needed to ascertain the…
35	4. Discussion — 4.2. Role of KCNJ6 / GIRK2 in neurocognitive (dys)function and disorders	KCNJ6 gene encodes G-protein-coupled inwardly rectifying potassium channel 2 (GIRK2) which is one of…
36	4. Discussion — 4.2. Role of KCNJ6 / GIRK2 in neurocognitive (dys)function and disorders	Down syndrome (Thiery et al., 2003; Harashima et al., 2006; Cramer et al., 2010). Alterations in…
37	4. Discussion — 4.2. Role of KCNJ6 / GIRK2 in neurocognitive (dys)function and disorders	were susceptible to spontaneous and provoked seizures (cf. Hallmann et al., 2000). A recent study…
38	4. Discussion — 4.3. Role of KCNJ6 / GIRK2 in modulating alcohol actions and addiction	Studies reporting alcohol modulation of GIRK channels have been well-documented (for a recent…
39	4. Discussion — 4.3. Role of KCNJ6 / GIRK2 in modulating alcohol actions and addiction	controls (Blednov et al., 2001; Hill et al., 2003), suggesting that GIRK2 may be mediating the…

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In this knowledge base

Title	Year	PMID
Alcohol reverses the effects of KCNJ6 (GIRK2) noncoding variants on excitability of human glutamatergic neurons.	2023	36207584

External

Title	Authors	Journal	Year	Link
Chronic ethanol exposure in mice evokes pre- and postsynaptic deficits in GABAergic transmission in ventral tegmental area GABA neurons.	Mitten EH et al.	—	2025	→
Pharmacogenomic and Pharmacomicrobiomic Aspects of Drugs of Abuse.	Borrego-Ruiz A et al.	—	2025	→
Whole Genome Sequencing of Pedigrees With High Density of Substance Use and Psychiatric Disorders: A Meeting Report.	Hill SY et al.	—	2025	→
A critical review of ethanol effects on neuronal firing: A metabolic perspective.	Popova D et al.	—	2024	→
Upregulated GIRK2 Counteracts Ethanol-Induced Changes in Excitability and Respiration in Human Neurons.	Prytkova I et al.	—	2024	→
5. Collaborative Study on the Genetics of Alcoholism: Functional genomics.	Gameiro-Ros I et al.	—	2023	→
Alcohol reverses the effects of KCNJ6 (GIRK2) noncoding variants on excitability of human glutamatergic neurons.	Popova D et al.	—	2023	→
Impairments in hippocampal oscillations accompany the loss of LTP induced by GIRK activity blockade	Contreras A et al.	—	2023	—
Impairments in hippocampal oscillations accompany the loss of LTP induced by GIRK activity blockade.	Contreras A et al.	—	2023	→
The collaborative study on the genetics of alcoholism: Brain function.	Meyers JL et al.	—	2023	→
The collaborative study on the genetics of alcoholism: Genetics.	Johnson EC et al.	—	2023	→
Enhanced GIRK2 channel signaling in Down syndrome: A feasible role in the development of abnormal nascent neural circuits.	Kleschevnikov AM	—	2022	→
Therapeutic potential of targeting G protein-gated inwardly rectifying potassium (GIRK) channels in the central nervous system.	Jeremic D et al.	—	2021	→
KCNJ6 variants modulate reward-related brain processes and impact executive functions in attention-deficit/hyperactivity disorder.	Ziegler GC et al.	—	2020	→
Network preservation reveals shared and unique biological processes associated with chronic alcohol abuse in NAc and PFC.	Vornholt E et al.	—	2020	→