Alcohol use disorder is associated with altered frontomedial phase-amplitude coupling strength during resting state.
- Authors
- Richard, C D; Porjesz, B; Meyers, J L; Bingly, A; Chorlian, D B; Kamarajan, C; Pandey, G; Anokhin, A; Brislin, S; Kuang, W; Pandey, A K; Kinreich, S
- Year
- 2026
- Journal
- Neuroimage. Reports
- PMID
- 41657495
- DOI
- 10.1016/j.ynirp.2026.100320
- PMCID
- PMC12878583
- Preprint
- Alcohol use disorder is associated with increases in frontocentral phase-amplitude coupling strength during resting state. (2025)
Considerable evidence from functional neuroimaging and EEG coherence studies indicates that individuals afflicted with alcohol use disorder (AUD) manifest aberrant patterns of connectivity, particularly in frontal brain regions. Phase-amplitude coupling (PAC) is another form of functional connectivity, reflecting the association between the phase at one frequency and amplitude changes at a higher frequency. Significant PAC differences have been reported for other substance use disorders, but it has not yet been investigated in AUD. We compared frontomedial PAC strength during resting state, eyes closed, in adult participants with severe AUD and age-matched unaffected controls from the Collaborative Study on the Genetics of Alcoholism (COGA). Comodulograms of PAC estimates between phase frequencies (0.1-13 Hz) and amplitude frequencies (4-50 Hz) were calculated for all participants. PAC differences between AUD and unaffected groups were assessed at each phase-amplitude frequency pair in comodulograms to identify clusters of significant test results, reporting only those clusters satisfying all validation and significance testing steps. Severe AUD was associated with clusters of significantly greater PAC in alpha-gamma domains of both men and women. Candidate clusters were found in theta-gamma domains of both sexes, but were only significant greater in men with AUD. Significant PAC clusters were found in the delta-gamma domain of both sexes, though women with AUD showed significant decreases in contrast to greater PAC found in men with AUD. The significant PAC clusters identified in this exploratory study could provide new insights into the dysregulation of brain connectivity underlying AUD.
Difference and significance matrix results from comodulogram analysis. [A]: comodulogram significance matrix (S-matrix) for women (left) and men (right) masked to only reveal p-values less than or equal to 0.05. PA domains of candidate clusters marked with black rectangles. PAC domains outlined in green for reference. [B]: comodulogram difference matrix results (D-matrix) by sex. [C]: PA domains of candidate clusters by sex. Cluster boundaries are marked with black rectangles. Numbering corresponds to the cluster ID in Table 2.
PA domains containing significant PAC clusters in men. Standard PA domain boundaries marked by black dotted lines. Only clusters considered for analysis were those falling within one of the standard PA domains represented on the comodulograms analyzed in this study, which include the delta-gamma, theta-gamma, alpha-gamma, delta-beta, theta-beta, alpha-beta, delta-alpha, and theta-alpha domains. These domain boundaries are based on standard EEG frequency bands of delta (0.1–3 Hz), theta (3–8 Hz), alpha (8–13 Hz), beta (13–28 Hz), and gamma (28–50 Hz). Faded regions of the comodulogram have been excluded from cluster analysis.
PA domains containing significant PAC clusters in women. Standard PA domain boundaries marked by black dotted lines. Only clusters considered for analysis were those falling within one of the standard PA domains represented on the comodulograms analyzed in this study, which include the delta-gamma, theta-gamma, alpha-gamma, delta-beta, theta-beta, alpha-beta, delta-alpha, and theta-alpha domains. These domain boundaries are based on standard EEG frequency bands of delta (0.1–3 Hz), theta (3–8 Hz), alpha (8–13 Hz), beta (13–28 Hz), and gamma (28–50 Hz). Faded regions of the comodulogram have been excluded from cluster analysis.
| Name | Type |
|---|---|
| Adjacent motor regions local | anatomy |
| alcohol | phenotype |
| Alcohol Use Disorder | phenotype |
| alpha band | phenotype |
| alpha-beta domain local | phenotype |
| Alpha-beta domain local | anatomy |
| alpha-gamma domain local | anatomy |
| alpha-gamma domain local | phenotype |
| Alpha-gamma domain local | anatomy |
| Alpha-gamma domain local | phenotype |
| alpha-gamma PAC | phenotype |
| AUD | phenotype |
| AUD group local | cohort |
| AUD groups local | cohort |
| AUD study cohort local | cohort |
| autism spectrum disorder | phenotype |
| basolateral amygdala | anatomy |
| beta band | phenotype |
| beta/gamma boundaries local | anatomy |
| Beta-gamma PAC local | phenotype |
| Bradykinesia | phenotype |
| brain | anatomy |
| brain function | phenotype |
| brain structure | anatomy |
| Candidate clusters local | cohort |
| cerebral hemispheres | anatomy |
| Cluster W16 local | anatomy |
| Cluster W17 local | anatomy |
| cocaine | phenotype |
| COGA sample | cohort |
| Cognitive functioning scores local | phenotype |
| Collaborative Study on the Genetics of Alcoholism (COGA) | cohort |
| compulsive behavior | phenotype |
| compulsivity | phenotype |
| conditioned place preference | phenotype |
| conditioned place preference (CPP) local | phenotype |
| control group | cohort |
| controls | cohort |
| craving | phenotype |
| deep brain stimulation | drug |
| delta-alpha domain local | phenotype |
| Delta-alpha domain local | anatomy |
| delta band | phenotype |
| delta-beta domain local | phenotype |
| delta-gamma domain local | anatomy |
| delta-gamma domain local | phenotype |
| Delta-gamma domain local | anatomy |
| Delta-gamma M2 cluster local | phenotype |
| Delta-gamma PAC local | phenotype |
| DSM-5 local | drug |
| EEG coherence local | other |
| EEG theta frequency band local | anatomy |
| Emotional face discrimination local | phenotype |
| experimental group | cohort |
| forehead | anatomy |
| Freezing of gait local | phenotype |
| frontal cortex | anatomy |
| frontal midline | anatomy |
| frontomedial brain regions local | anatomy |
| frontomedial channel FZ local | anatomy |
| Frontomedial EEG channel FZ local | anatomy |
| Frontoparietal executive control networks local | anatomy |
| Fz | anatomy |
| GABA agonists local | drug |
| gamma band | phenotype |
| healthy controls | cohort |
| healthy functioning local | phenotype |
| heavy drinking | phenotype |
| heroin addicted rats local | cohort |
| human brain | anatomy |
| impulsivity | phenotype |
| Insomnia disorder local | phenotype |
| Left executive control networks local | anatomy |
| Levodopa | drug |
| Low beta-gamma PAC local | phenotype |
| M15 cluster local | anatomy |
| M2 local | cohort |
| M3 local | cohort |
| M4 local | cohort |
| M6 local | cohort |
| male mice | cohort |
| male rats | cohort |
| medial prefrontal cortex | anatomy |
| men | cohort |
| methamphetamine | drug |
| midfrontal channel FZ local | anatomy |
| Mild cognitive impairment | phenotype |
| motor cortex | anatomy |
| Motor symptoms local | phenotype |
| neurological disorders | phenotype |
| non-drinkers | phenotype |
| nose | anatomy |
| nucleus accumbens | anatomy |
| obsessive-compulsive disorder | phenotype |
| OCD | phenotype |
| opioid | drug |
| opioid dependence | phenotype |
| PAC | phenotype |
| PAC domains local | phenotype |
| PAC magnitude local | phenotype |
| PAC strength local | phenotype |
| PA domain local | phenotype |
| PA domains local | phenotype |
| palatable food local | drug |
| parietal cortex | anatomy |
| Parieto-frontal circuits local | anatomy |
| Parkinson's disease | phenotype |
| PD patients local | cohort |
| phase-amplitude coupling | phenotype |
| Phase Amplitude Coupling local | phenotype |
| Phase-amplitude coupling (PAC) local | phenotype |
| physical dependence | phenotype |
| prefrontal cortex | anatomy |
| prelimbic area of mPFC local | anatomy |
| prelimbic cortex | anatomy |
| prelimbic cortex (mPFC) local | anatomy |
| psychiatric disorders | phenotype |
| reward-related sensory cues local | phenotype |
| Salience brain networks local | anatomy |
| Seeking behaviors local | phenotype |
| severe alcohol use disorder | phenotype |
| Severe Alcohol Use Disorder cohort local | cohort |
| Severe AUD group local | cohort |
| sex | phenotype |
| sleep quality | phenotype |
| Sober participants local | cohort |
| study cohort | cohort |
| substance abuse | phenotype |
| substance use | phenotype |
| SUNY Downstate Health Sciences University local | cohort |
| theta-alpha domain local | phenotype |
| Theta-alpha domain local | anatomy |
| Theta-alpha domain cluster 8 local | phenotype |
| theta band | phenotype |
| theta-beta domain local | phenotype |
| Theta-beta domain local | anatomy |
| theta-gamma clusters local | anatomy |
| theta-gamma domain local | anatomy |
| theta-gamma domain local | phenotype |
| Theta-gamma domain local | anatomy |
| Theta-gamma domain local | phenotype |
| Theta-gamma PAC local | phenotype |
| theta-gamma PAC strength local | phenotype |
| theta-gamma phase-amplitude coupling (theta-gamma PAC) local | phenotype |
| theta oscillations | phenotype |
| typical adult brain local | phenotype |
| unaffected | phenotype |
| Unaffected control group local | cohort |
| unaffected group | cohort |
| Unaffected participants local | cohort |
| Unmedicated Parkinson's disease patients local | cohort |
| Ventrolimbic corticostriatal regions local | anatomy |
| W16 cluster local | anatomy |
| W17 cluster local | anatomy |
| W6 local | cohort |
| W7 local | cohort |
| W8 local | cohort |
| wave 2 | cohort |
| withdrawal | phenotype |
| women | cohort |
| Women with Alcohol Use Disorder cohort local | cohort |
No uploaded files.
No papers in this knowledge base cite this source.
No citations found for this source.