Differentiating Individuals with and without Alcohol Use Disorder Using Resting-State fMRI Functional Connectivity of Reward Network, Neuropsychological Performance, and Impulsivity Measures
Abstract
:1. Introduction
2. Materials and Methods
2.1. Sample
2.2. Neuropsychological Assessment
2.2.1. Tower of London Test (TOLT)
2.2.2. Visual Span Test (VST)
2.3. Impulsivity Scores
2.4. MRI Data Acquisition
2.5. Image Processing
2.6. Reward Network Seed Regions and rsFC Calculations
2.7. Feature Selection of FC Variables
2.8. Random Forest Classification
3. Results
3.1. Random Forests Classification
3.1.1. Classification Accuracy and Top Significant Variables
3.1.2. Distribution of Minimal Depth
3.1.3. Multi-Way Importance
3.1.4. Correlations among Rankings of RF Parameters
3.1.5. Connectivity Mapping of Significant rsFC Connections
3.2. Correlations among the Top Significant Variables
3.3. Correlations between Significant Variables and Age
3.4. Neuropsychological Scores between the Groups
4. Discussion
4.1. Altered Functional Connectivity across Reward Network in AUD Individuals
4.2. Heightened Impulsivity in AUD Individuals
4.3. Poorer Memory Span in AUD Individuals
4.4. Correlations of Significant Variables among Themselves and with Age
4.5. Limitations of the Current Study
5. Summary and Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Appendix A
F# | Feature | Detail |
---|---|---|
1. | FC_2_19 (R.VTA–L.ACC) | FC between R. Ventral Tegmental Area and L. Anterior Cingulate Cortex |
2. | FC_3_23 (L.NAc–L.PCC) | FC between L. Nucleus Accumbens and L. Posterior Cingulate Cortex |
3. | FC_6_11 (R.Amg–L.Pal) | FC between R. Amygdala and L. Pallidum |
4. | FC_6_7 (R.Amg–L.Hip) | FC between R. Amygdala and L. Hippocampus |
5. | FC_8_31 (R.Hip–L.DLP) | FC between R. Hippocampus and L. Dorsolateral Prefrontal Cortex |
6. | FC_9_12 (L.Cdt–R.Pal) | FC between L. Caudate and R. Pallidum |
7. | FC_9_13 (L.Cdt–L.Tha) | FC between L. Caudate and L. Thalamus |
8. | FC_9_18 (L.Cdt–R.PHG) | FC between L. Caudate and R. Parahippocampal Gyrus |
9. | FC_9_23 (L.Cdt–L.PCC) | FC between L. Caudate and L. Posterior Cingulate Cortex |
10. | FC_9_27 (L.Cdt–L.Ang) | FC between L. Caudate and L. Angular Gyrus |
11. | FC_12_24 (R.Pal–R.PCC) | FC between R. Pallidum and R. Posterior Cingulate Cortex |
12. | FC_13_14 (L.Tha–R.Tha) | FC between L. Thalamus and R. Thalamus |
13. | FC_13_34 (L.Tha–R.Ptm) | FC between L. Thalamus and R. Putamen |
14. | FC_16_20 (R.Ins–R.ACC) | FC between R. Insula and R. Anterior Cingulate Cortex |
15. | FC_17_31 (L.PHG–L.DLP) | FC between L. Parahippocampal Gyrus and L. Dorsolateral Prefrontal Cortex |
16. | FC_20_24 (R.ACC–R.PCC) | FC between R. Anterior Cingulate Cortex and R. Posterior Cingulate Cortex |
17. | FC_20_26 (R.ACC–R.OFC) | FC between R. Anterior Cingulate Cortex and R. Orbitofrontal Cortex |
18. | FC_20_31 (R.ACC–L.DLP) | FC between R. Anterior Cingulate Cortex and L. Dorsolateral Prefrontal Cortex |
19. | FC_21_24 (L.MCC–R.PCC) | FC between L. Middle Cingulate Cortex and R. Posterior Cingulate Cortex |
20. | FC_22_33 (R.MCC–L.Ptm) | FC between R. Middle Cingulate Cortex and L. Putamen |
21. | FC_28_29 (L.Ang–L.SPL) | FC between L. Angular Gyrus and L. Superior Parietal Lobule |
22. | ExcMovMade_All | Overall excess moves beyond the minimum moves required to solve the puzzle |
23. | AvgPicTime_All | Overall average pickup time to solve the puzzle |
24. | AvgTotTime_All | Overall average total time to solve the puzzle |
25. | TotTrlTime_All | Overall total trial time within each puzzle type |
26. | AvgTrlTime_All | Overall average trial time across trials per puzzle type |
27. | TotCor_Fw | Total number of correctly performed trials in forward sequence |
28. | TotCor_Bw | Total number of correctly performed trials in backward sequence |
29. | Span_Fw | Maximum span or sequence-length achieved in forward sequence |
30. | Span_Bw | Maximum span or sequence-length achieved in backward sequence |
31. | TotAvgTime_Fw | Total average time taken across all trials performed in forward sequence |
32. | TotAvgTime_Bw | Total average time taken across all trials performed in backward sequence |
33. | TotCorAvgTime_Fw | Total correct average time taken across all correct trials in forward sequence |
34. | TotCorAvgTime_Bw | Total correct average time taken across all correct trials in backward sequence |
35. | BIS_AI | Barratt Impulsiveness Scale, Attentional Impulsivity Score |
36. | BIS_MI | Barratt Impulsiveness Scale, Motor Impulsivity Score |
37. | BIS_NP | Barratt Impulsiveness Scale, Non-planning Impulsivity Score |
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Variable | AUD | CTL | ||||
---|---|---|---|---|---|---|
N * | Mean | SD | N * | Mean | SD | |
Age (in years) | 30 | 41.42 | 7.31 | 30 | 27.44 | 4.74 |
Education (in Years) | 30 | 11.93 | 2.35 | 30 | 15.77 | 1.87 |
Age of onset (regular alcohol use) | 30 | 15.77 | 2.58 | 12 | 20.50 | 3.80 |
Alcohol: Drinks/day (heavy alcohol use period) | 30 | 12.08 | 10.02 | 12 | 2.88 | 1.93 |
Alcohol: Days/month (heavy alcohol use period) | 30 | 20.30 | 9.01 | 12 | 3.35 | 3.64 |
Alcohol: Drinks (last 6 months) | 30 | 2.68 | 6.61 | 18 | 2.61 | 1.98 |
Alcohol: Days (last 6 months) | 30 | 3.97 | 8.02 | 18 | 2.94 | 3.62 |
Length of Abstinence (in months) | 30 | 22.43 | 28.16 | 18 | 1.9 | 4.99 |
Tobacco: Times/day (last 6 months) | 20 | 9.90 | 5.80 | 6 | 2.33 | 1.63 |
Tobacco: Days/month (last 6 months) | 20 | 28.35 | 4.83 | 6 | 14.17 | 13.82 |
Marijuana: Times in last 6 months | 10 | 98.80 | 91.38 | 4 | 18.75 | 27.61 |
ROI | Brain Region | Notation | Location | MNI Coordinates | ||
---|---|---|---|---|---|---|
X | Y | Z | ||||
1 | L. Ventral Tegmental Area | L.VTA | Subcortical | −4 | −16 | −14 |
2 | R. Ventral Tegmental Area | R.VTA | Subcortical | 4 | −16 | −14 |
3 | L. Nucleus Accumbens | L.NAc | Subcortical | −8 | 10 | −10 |
4 | R. Nucleus Accumbens | R.NAc | Subcortical | 8 | 10 | −10 |
5 | L. Amygdala | L.Amg | Subcortical | −24 | −2 | −14 |
6 | R. Amygdala | R.Amg | Subcortical | 24 | −2 | −14 |
7 | L. Hippocampus | L.Hip | Subcortical | −28 | −10 | −22 |
8 | R. Hippocampus | R.Hip | Subcortical | 28 | −10 | −22 |
9 | L. Caudate | L.Cdt | Subcortical | −13 | 15 | 9 |
10 | R. Caudate | R.Cdt | Subcortical | 13 | 15 | 9 |
11 | L. Pallidum | L.Pal | Subcortical | −18 | −2 | −4 |
12 | R. Pallidum | R.Pal | Subcortical | 18 | −2 | −4 |
13 | L. Thalamus | L.Tha | Subcortical | −8 | −12 | 6 |
14 | R. Thalamus | R.Tha | Subcortical | 8 | −12 | 6 |
15 | L. Insula (anterior) | L.Ins | Subcortical | −30 | 17 | −15 |
16 | R. Insula (anterior) | R.Ins | Subcortical | 30 | 17 | −15 |
17 | L. Parahippocampal Gyrus | L.PHG | Cortical | −24 | −39 | −12 |
18 | R. Parahippocampal Gyrus | R.PHG | Cortical | 27 | −39 | −12 |
19 | L. Anterior Cingulate Cortex | L.ACC | Cortical | −6 | 44 | 10 |
20 | R. Anterior Cingulate Cortex | R.ACC | Cortical | 6 | 44 | 10 |
21 | L. Mid-Cingulate Cortex | L.MCC | Cortical | −6 | 2 | 40 |
22 | R. Mid-Cingulate Cortex | R.MCC | Cortical | 6 | 2 | 40 |
23 | L. Posterior Cingulate Cortex | L.PCC | Cortical | −6 | −46 | 30 |
24 | R. Posterior Cingulate Cortex | R.PCC | Cortical | 6 | −46 | 30 |
25 | L. Orbitofrontal Cortex | L.OFC | Cortical | −32 | 42 | −16 |
26 | R. Orbitofrontal Cortex | R.OFC | Cortical | 32 | 42 | −16 |
27 | L. Angular Gyrus | L.Ang | Cortical | −45 | −58 | 30 |
28 | R. Angular Gyrus | L.Ang | Cortical | 45 | −58 | 30 |
29 | L. Superior Parietal Lobule | L.SPL | Cortical | −24 | −68 | 56 |
30 | R. Superior Parietal Lobule | R.SPL | Cortical | 24 | −68 | 56 |
31 | L. Dorsolateral PFC | L.DLP | Cortical | −44 | 38 | 19 |
32 | R. Dorsolateral PFC | R.DLP | Cortical | 44 | 38 | 19 |
33 | L. Putamen | L.Ptm | Subcortical | −27 | 5 | −6 |
34 | R. Putamen | R.Ptm | Subcortical | 27 | 5 | −6 |
Feature | Mean Minimum Depth | No. of Nodes | Accuracy Decrease | Gini Decrease | No. of Trees | Time a Root | p-Value | Direction |
---|---|---|---|---|---|---|---|---|
BIS Motor Impulsivity | 1.3824 | 348 | 0.0170 | 2.0202 | 319 | 94 | 1.87E-19 | A > C |
FC_3_23 (L.NAc–L.PCC) | 1.9354 | 330 | 0.0130 | 1.6903 | 295 | 74 | 1.82E-15 | A > C |
FC_16_20 (R.Ins–R.ACC) | 2.0062 | 326 | 0.0149 | 1.5132 | 291 | 57 | 1.23E-14 | C > A |
BIS Non-planning | 1.7619 | 319 | 0.0187 | 1.6830 | 294 | 74 | 3.05E-13 | A > C |
FC_2_19 (R.VTA–L.ACC) | 2.0561 | 313 | 0.0040 | 1.4706 | 274 | 58 | 4.23E-12 | C > A |
FC_20_26 (R.ACC–R.OFC) | 2.2513 | 299 | 0.0101 | 1.3203 | 272 | 45 | 1.24E-09 | C > A |
FC_6_7 (R.Amg–L.Hip) | 2.3798 | 275 | 0.0063 | 1.1669 | 258 | 41 | 4.40E-06 | C > A |
FC_9_12 (L.Cdt–R.Pal) | 2.5018 | 268 | 0.0039 | 0.9725 | 255 | 29 | 3.26E-05 | C > A |
FC_20_24 (R.ACC–R.PCC) | 2.4732 | 266 | 0.0054 | 1.0002 | 249 | 28 | 5.58E-05 | C > A |
FC_13_14 (L.Tha–R.Tha) | 2.5681 | 252 | 0.0023 | 0.9843 | 233 | 40 | 0.0016 | C > A |
FC_12_24 (R.Pal–R.PCC) | 2.8735 | 249 | 0.0022 | 0.8844 | 223 | 20 | 0.0030 | A > C |
FC_9_13 (L.Cdt–L.Tha) | 2.7035 | 249 | 0.0056 | 0.9541 | 228 | 34 | 0.0030 | C > A |
FC_13_34 (L.Tha–R.Ptm) | 2.7980 | 247 | 0.0053 | 0.9212 | 234 | 24 | 0.0044 | C > A |
FC_8_31 (R.Hip–L.DLP) | 2.9451 | 238 | 0.0047 | 0.8020 | 217 | 20 | 0.0220 | A > C |
Feature | AUD (N = 30) | CTL (N = 30) | § ALL (N = 60) | |||
---|---|---|---|---|---|---|
r | p | r | p | r | p | |
FC_2_19 (R.VTA–L.ACC) | −0.08 | 0.6744 | 0.22 | 0.2449 | 0.03 | 0.8131 |
FC_3_23 (L.NAc–L.PCC) | 0.16 | 0.3949 | −0.21 | 0.2693 | 0.02 | 0.8956 |
FC_6_7 (R.Amg–L.Hip) | −0.02 | 0.8993 | 0.38 | 0.0374 *○ | 0.11 | 0.4225 |
FC_8_31 (R.Hip–L.DLP) | 0.16 | 0.3977 | 0.27 | 0.1489 | 0.20 | 0.1276 |
FC_9_12 (L.Cdt–R.Pal) | 0.16 | 0.3964 | −0.01 | 0.9583 | 0.09 | 0.5079 |
FC_9_13 (L.Cdt–L.Tha) | −0.15 | 0.4430 | 0.05 | 0.7812 | −0.06 | 0.6349 |
FC_12_24 (R.Pal–R.PCC) | 0.01 | 0.9579 | −0.09 | 0.6402 | −0.03 | 0.8298 |
FC_13_14 (L.Tha–R.Tha) | −0.26 | 0.1616 | −0.02 | 0.9168 | −0.15 | 0.2588 |
FC_13_34 (L.Tha–R.Ptm) | 0.07 | 0.7127 | 0.12 | 0.5196 | 0.09 | 0.5002 |
FC_16_20 (R.Ins–R.ACC) | −0.19 | 0.3149 | 0.09 | 0.6203 | −0.07 | 0.6062 |
FC_20_24 (R.ACC–R.PCC) | −0.05 | 0.7849 | 0.01 | 0.9574 | −0.03 | 0.8195 |
FC_20_26 (R.ACC–R.OFC) | 0.19 | 0.3182 | 0.11 | 0.5460 | 0.16 | 0.2110 |
BIS_NP (Non-planning) | 0.03 | 0.8936 | 0.21 | 0.2644 | 0.09 | 0.4815 |
BIS_MI (Motor Impulsivity) | 0.23 | 0.2121 | 0.12 | 0.5432 | 0.20 | 0.1268 |
AUD | CTL | F | p | |||
---|---|---|---|---|---|---|
Mean | SD | Mean | SD | |||
ExcMovMade_All | 15.04 | 17.02 | 7.83 | 6.66 | 4.43 | 0.0402 * |
AvgPicTime_All | 3.09 | 1.09 | 2.81 | 0.96 | 1.02 | 0.3167 |
AvgTotTime_All | 5.16 | 1.58 | 4.72 | 1.64 | 1.01 | 0.3199 |
TotTrlTime_All | 482.60 | 178.18 | 404.24 | 139.05 | 3.29 | 0.0755 |
AvgTrlTime_All | 22.98 | 8.48 | 19.25 | 6.62 | 3.29 | 0.0755 |
TotCor_Fw | 7.00 | 2.58 | 10.21 | 2.78 | 19.06 | 0.0001 ++ |
TotCor_Bw | 6.31 | 3.02 | 8.31 | 1.87 | 8.95 | 0.0042 * |
Span_Fw | 5.44 | 1.33 | 6.83 | 1.36 | 14.25 | 0.0004 ++ |
Span_Bw | 4.65 | 1.44 | 5.52 | 0.95 | 7.02 | 0.0106 * |
TotAvgTime_Fw | 26.72 | 9.13 | 28.31 | 10.53 | 0.35 | 0.5591 |
TotAvgTime_Bw | 17.72 | 9.39 | 17.79 | 10.01 | 0.00 | 0.9791 |
TotCorAvgTime_Fw | 38.15 | 12.39 | 32.48 | 8.07 | 4.06 | 0.0490 * |
TotCorAvgTime_Bw | 28.93 | 13.92 | 27.16 | 10.66 | 0.28 | 0.5963 |
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Kamarajan, C.; Ardekani, B.A.; Pandey, A.K.; Kinreich, S.; Pandey, G.; Chorlian, D.B.; Meyers, J.L.; Zhang, J.; Bermudez, E.; Kuang, W.; et al. Differentiating Individuals with and without Alcohol Use Disorder Using Resting-State fMRI Functional Connectivity of Reward Network, Neuropsychological Performance, and Impulsivity Measures. Behav. Sci. 2022, 12, 128. https://doi.org/10.3390/bs12050128
Kamarajan C, Ardekani BA, Pandey AK, Kinreich S, Pandey G, Chorlian DB, Meyers JL, Zhang J, Bermudez E, Kuang W, et al. Differentiating Individuals with and without Alcohol Use Disorder Using Resting-State fMRI Functional Connectivity of Reward Network, Neuropsychological Performance, and Impulsivity Measures. Behavioral Sciences. 2022; 12(5):128. https://doi.org/10.3390/bs12050128
Chicago/Turabian StyleKamarajan, Chella, Babak A. Ardekani, Ashwini K. Pandey, Sivan Kinreich, Gayathri Pandey, David B. Chorlian, Jacquelyn L. Meyers, Jian Zhang, Elaine Bermudez, Weipeng Kuang, and et al. 2022. "Differentiating Individuals with and without Alcohol Use Disorder Using Resting-State fMRI Functional Connectivity of Reward Network, Neuropsychological Performance, and Impulsivity Measures" Behavioral Sciences 12, no. 5: 128. https://doi.org/10.3390/bs12050128
APA StyleKamarajan, C., Ardekani, B. A., Pandey, A. K., Kinreich, S., Pandey, G., Chorlian, D. B., Meyers, J. L., Zhang, J., Bermudez, E., Kuang, W., Stimus, A. T., & Porjesz, B. (2022). Differentiating Individuals with and without Alcohol Use Disorder Using Resting-State fMRI Functional Connectivity of Reward Network, Neuropsychological Performance, and Impulsivity Measures. Behavioral Sciences, 12(5), 128. https://doi.org/10.3390/bs12050128