Trial Outcomes & Findings for Neurobiology of Alcohol and Nicotine Co-Addiction (NCT NCT03338933)
NCT ID: NCT03338933
Last Updated: 2025-02-13
Results Overview
The DSN-back is a cognitive task used to assess working memory and attention. Participants view a sequence of letters presented on a screen, flanked by either drug-related or neutral images, and are instructed to identify matches occurring N steps earlier. Neural activation during high working memory demand condition (2-back) relative to the low working memory condition (0-back) was investigated. Inconsistent activation patterns across regions may indicate impaired neural processing in regions critical for cognitive control, emotion regulation, and reward processing, commonly reported in substance use disorders. Values closer to 0 (no change) in regions responsible for emotion regulation and cognitive control (e.g., Amygdala, ACC) may indicate reduced task-specific engagement where drug-related processes may be dominating neural activity.
Recruitment status
COMPLETED
Target enrollment
109 participants
Primary outcome timeframe
Baseline
Results posted on
2025-02-13
Participant Flow
This study was conducted in a hospital setting from 2018 to 2023.
Of 616 phone screens conducted at the VA Portland Health Care System, 171 were eligible to participate in the study, and 109 participants signed an informed consent form. 4 participants were screened out or declined participation after consent but prior to any data collection and are not included in participant flow table. Control and Nicotine group's participation was complete after baseline measurements were collected. Alcohol groups continued to next periods.
Participant milestones
| Measure |
Control Group
No history of addiction to any substance or gambling. Less than 20 lifetime cigarettes or equivalent.
magnetic resonance imaging (MRI): All subjects will undergo a baseline MRI and subjects in both alcohol groups (alcohol use disorder and combined alcohol and nicotine use disorder) will undergo a followup MRI 3 months after baseline.
|
Nicotine Group
Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-V) criteria for Nicotine Use Disorder. Current smoker, at least 10 cigarettes per day. No history of addiction to any other substance
magnetic resonance imaging (MRI): All subjects will undergo a baseline MRI and subjects in both alcohol groups (alcohol use disorder and combined alcohol and nicotine use disorder) will undergo a followup MRI 3 months after baseline.
|
Alcohol Group
DSM-V criteria for Alcohol use Disorder. At least 8 heavy drinking episodes in the past month. Abstinent for at least 2 weeks and no more than 4 weeks. Less than 20 lifetime cigarettes or equivalent. No history of addiction to any other substances or gambling.
magnetic resonance imaging (MRI): All subjects will undergo a baseline MRI and subjects in both alcohol groups (alcohol use disorder and combined alcohol and nicotine use disorder) will undergo a followup MRI 3 months after baseline.
|
Nicotine and Alcohol Group
DSM-V criteria for Nicotine Use Disorder and Alcohol Use Disorder. At least 8 heavy drinking episodes in the past month. Current smoker. Alcohol free from 2 to 4 weeks. No history of addiction to other substances or gambling.
magnetic resonance imaging (MRI): All subjects will undergo a baseline MRI and subjects in both alcohol groups (alcohol use disorder and combined alcohol and nicotine use disorder) will undergo a followup MRI 3 months after baseline.
|
|---|---|---|---|---|
|
Screening Visit
STARTED
|
31
|
28
|
13
|
33
|
|
Screening Visit
COMPLETED
|
28
|
18
|
11
|
25
|
|
Screening Visit
NOT COMPLETED
|
3
|
10
|
2
|
8
|
|
Baseline Visit
STARTED
|
28
|
18
|
11
|
25
|
|
Baseline Visit
COMPLETED
|
28
|
18
|
11
|
25
|
|
Baseline Visit
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Check-In Visit (Alcohol Groups Only)
STARTED
|
0
|
0
|
11
|
25
|
|
Check-In Visit (Alcohol Groups Only)
COMPLETED
|
0
|
0
|
8
|
15
|
|
Check-In Visit (Alcohol Groups Only)
NOT COMPLETED
|
0
|
0
|
3
|
10
|
|
Follow-up Visit (Alcohol Groups Only)
STARTED
|
0
|
0
|
8
|
15
|
|
Follow-up Visit (Alcohol Groups Only)
COMPLETED
|
0
|
0
|
7
|
13
|
|
Follow-up Visit (Alcohol Groups Only)
NOT COMPLETED
|
0
|
0
|
1
|
2
|
Reasons for withdrawal
| Measure |
Control Group
No history of addiction to any substance or gambling. Less than 20 lifetime cigarettes or equivalent.
magnetic resonance imaging (MRI): All subjects will undergo a baseline MRI and subjects in both alcohol groups (alcohol use disorder and combined alcohol and nicotine use disorder) will undergo a followup MRI 3 months after baseline.
|
Nicotine Group
Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-V) criteria for Nicotine Use Disorder. Current smoker, at least 10 cigarettes per day. No history of addiction to any other substance
magnetic resonance imaging (MRI): All subjects will undergo a baseline MRI and subjects in both alcohol groups (alcohol use disorder and combined alcohol and nicotine use disorder) will undergo a followup MRI 3 months after baseline.
|
Alcohol Group
DSM-V criteria for Alcohol use Disorder. At least 8 heavy drinking episodes in the past month. Abstinent for at least 2 weeks and no more than 4 weeks. Less than 20 lifetime cigarettes or equivalent. No history of addiction to any other substances or gambling.
magnetic resonance imaging (MRI): All subjects will undergo a baseline MRI and subjects in both alcohol groups (alcohol use disorder and combined alcohol and nicotine use disorder) will undergo a followup MRI 3 months after baseline.
|
Nicotine and Alcohol Group
DSM-V criteria for Nicotine Use Disorder and Alcohol Use Disorder. At least 8 heavy drinking episodes in the past month. Current smoker. Alcohol free from 2 to 4 weeks. No history of addiction to other substances or gambling.
magnetic resonance imaging (MRI): All subjects will undergo a baseline MRI and subjects in both alcohol groups (alcohol use disorder and combined alcohol and nicotine use disorder) will undergo a followup MRI 3 months after baseline.
|
|---|---|---|---|---|
|
Screening Visit
Lost to Follow-up
|
1
|
3
|
1
|
4
|
|
Screening Visit
Screen fail after consent
|
2
|
7
|
1
|
4
|
|
Check-In Visit (Alcohol Groups Only)
Lost to Follow-up
|
0
|
0
|
2
|
9
|
|
Check-In Visit (Alcohol Groups Only)
Deemed no longer eligible due to changes in health
|
0
|
0
|
1
|
1
|
|
Follow-up Visit (Alcohol Groups Only)
Could not complete in-person items due to COVID-19 shutdown
|
0
|
0
|
1
|
2
|
Baseline Characteristics
Neurobiology of Alcohol and Nicotine Co-Addiction
Baseline characteristics by cohort
| Measure |
Control Group
n=28 Participants
No history of addiction to any substance or gambling. Less than 20 lifetime cigarettes or equivalent.
magnetic resonance imaging (MRI): All subjects will undergo a baseline MRI and subjects in both alcohol groups (alcohol use disorder and combined alcohol and nicotine use disorder) will undergo a followup MRI 3 months after baseline.
|
Nicotine Group
n=18 Participants
Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-V) criteria for Nicotine Use Disorder. Current smoker, at least 10 cigarettes per day. No history of addiction to any other substance
magnetic resonance imaging (MRI): All subjects will undergo a baseline MRI and subjects in both alcohol groups (alcohol use disorder and combined alcohol and nicotine use disorder) will undergo a followup MRI 3 months after baseline.
|
Alcohol Group
n=11 Participants
DSM-V criteria for Alcohol use Disorder. At least 8 heavy drinking episodes in the past month. Abstinent for at least 2 weeks and no more than 4 weeks. Less than 20 lifetime cigarettes or equivalent. No history of addiction to any other substances or gambling.
magnetic resonance imaging (MRI): All subjects will undergo a baseline MRI and subjects in both alcohol groups (alcohol use disorder and combined alcohol and nicotine use disorder) will undergo a followup MRI 3 months after baseline.
|
Nicotine and Alcohol Group
n=25 Participants
DSM-V criteria for Nicotine Use Disorder and Alcohol Use Disorder. At least 8 heavy drinking episodes in the past month. Current smoker. Alcohol free from 2 to 4 weeks. No history of addiction to other substances or gambling.
magnetic resonance imaging (MRI): All subjects will undergo a baseline MRI and subjects in both alcohol groups (alcohol use disorder and combined alcohol and nicotine use disorder) will undergo a followup MRI 3 months after baseline.
|
Total
n=82 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
28 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
25 Participants
n=4 Participants
|
82 Participants
n=21 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Age, Continuous
|
34.86 years
STANDARD_DEVIATION 11.4 • n=5 Participants
|
38.67 years
STANDARD_DEVIATION 8.6 • n=7 Participants
|
41.45 years
STANDARD_DEVIATION 6.8 • n=5 Participants
|
40.88 years
STANDARD_DEVIATION 8.7 • n=4 Participants
|
38.41 years
STANDARD_DEVIATION 9.7 • n=21 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
24 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
20 Participants
n=4 Participants
|
58 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
9 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
23 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
22 Participants
n=4 Participants
|
69 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
5 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
25 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
23 Participants
n=4 Participants
|
65 Participants
n=21 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
5 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
|
Region of Enrollment
United States
|
28 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
25 Participants
n=4 Participants
|
82 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: BaselinePopulation: Participants were removed from analysis due to too much motion, performing the task incorrectly, or did not perform the task during the MRI session.
The DSN-back is a cognitive task used to assess working memory and attention. Participants view a sequence of letters presented on a screen, flanked by either drug-related or neutral images, and are instructed to identify matches occurring N steps earlier. Neural activation during high working memory demand condition (2-back) relative to the low working memory condition (0-back) was investigated. Inconsistent activation patterns across regions may indicate impaired neural processing in regions critical for cognitive control, emotion regulation, and reward processing, commonly reported in substance use disorders. Values closer to 0 (no change) in regions responsible for emotion regulation and cognitive control (e.g., Amygdala, ACC) may indicate reduced task-specific engagement where drug-related processes may be dominating neural activity.
Outcome measures
| Measure |
Control Group
n=26 Participants
No history of addiction to any substance or gambling. Less than 20 lifetime cigarettes or equivalent.
magnetic resonance imaging (MRI): All subjects will undergo a baseline MRI and subjects in both alcohol groups (alcohol use disorder and combined alcohol and nicotine use disorder) will undergo a followup MRI 3 months after baseline.
|
Nicotine Group
n=8 Participants
Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-V) criteria for Nicotine Use Disorder. Current smoker, at least 10 cigarettes per day. No history of addiction to any other substance
magnetic resonance imaging (MRI): All subjects will undergo a baseline MRI and subjects in both alcohol groups (alcohol use disorder and combined alcohol and nicotine use disorder) will undergo a followup MRI 3 months after baseline.
|
Alcohol Group
n=5 Participants
DSM-V criteria for Alcohol use Disorder. At least 8 heavy drinking episodes in the past month. Abstinent for at least 2 weeks and no more than 4 weeks. Less than 20 lifetime cigarettes or equivalent. No history of addiction to any other substances or gambling.
magnetic resonance imaging (MRI): All subjects will undergo a baseline MRI and subjects in both alcohol groups (alcohol use disorder and combined alcohol and nicotine use disorder) will undergo a followup MRI 3 months after baseline.
|
Nicotine and Alcohol Group
n=17 Participants
DSM-V criteria for Nicotine Use Disorder and Alcohol Use Disorder. At least 8 heavy drinking episodes in the past month. Current smoker. Alcohol free from 2 to 4 weeks. No history of addiction to other substances or gambling.
magnetic resonance imaging (MRI): All subjects will undergo a baseline MRI and subjects in both alcohol groups (alcohol use disorder and combined alcohol and nicotine use disorder) will undergo a followup MRI 3 months after baseline.
|
|---|---|---|---|---|
|
Brain Activation During Functional Magnetic Resonance Imaging (fMRI) in Response to a Stress Modulated Cue Induced Craving Task (DSNBACK)
Anterior Cingulate Cortex
|
-26.1562 Percent signal change
Standard Deviation 163.7528
|
-45.2123 Percent signal change
Standard Deviation 142.7251
|
18.4989 Percent signal change
Standard Deviation 119.7023
|
-8.8848 Percent signal change
Standard Deviation 93.3926
|
|
Brain Activation During Functional Magnetic Resonance Imaging (fMRI) in Response to a Stress Modulated Cue Induced Craving Task (DSNBACK)
Amygdala
|
-37.6450 Percent signal change
Standard Deviation 101.1780
|
-72.3998 Percent signal change
Standard Deviation 160.9536
|
-36.6553 Percent signal change
Standard Deviation 143.9042
|
-17.9994 Percent signal change
Standard Deviation 119.2175
|
|
Brain Activation During Functional Magnetic Resonance Imaging (fMRI) in Response to a Stress Modulated Cue Induced Craving Task (DSNBACK)
Hippocampus
|
-31.8272 Percent signal change
Standard Deviation 106.1173
|
-45.4345 Percent signal change
Standard Deviation 124.8141
|
-69.7126 Percent signal change
Standard Deviation 115.1060
|
-37.1105 Percent signal change
Standard Deviation 135.3652
|
|
Brain Activation During Functional Magnetic Resonance Imaging (fMRI) in Response to a Stress Modulated Cue Induced Craving Task (DSNBACK)
Insula
|
-0.7322 Percent signal change
Standard Deviation 152.9914
|
-73.3807 Percent signal change
Standard Deviation 160.7811
|
61.6090 Percent signal change
Standard Deviation 138.2172
|
-42.4399 Percent signal change
Standard Deviation 146.2034
|
|
Brain Activation During Functional Magnetic Resonance Imaging (fMRI) in Response to a Stress Modulated Cue Induced Craving Task (DSNBACK)
Medial Orbital Frontal Cortex
|
-35.9220 Percent signal change
Standard Deviation 52.9373
|
-22.4666 Percent signal change
Standard Deviation 55.9283
|
37.5445 Percent signal change
Standard Deviation 95.7412
|
-12.6343 Percent signal change
Standard Deviation 42.7803
|
|
Brain Activation During Functional Magnetic Resonance Imaging (fMRI) in Response to a Stress Modulated Cue Induced Craving Task (DSNBACK)
Nucleus Accumbens
|
-56.2479 Percent signal change
Standard Deviation 193.2017
|
-121.6585 Percent signal change
Standard Deviation 258.8531
|
-133.8492 Percent signal change
Standard Deviation 123.4497
|
-40.6751 Percent signal change
Standard Deviation 112.4257
|
PRIMARY outcome
Timeframe: BaselinePopulation: Participants were removed from analysis due to too much motion, performing the task incorrectly, or did not perform the task during the MRI session.
This outcome measures resting-state functional connectivity (rsFC) of the striatum using seed-based analysis of resting-state fMRI data. FC values, expressed as Fisher z-transformed correlation coefficients, quantify the strength of synchronization between the striatum seed region and other brain areas. Positive values indicate synchronized activity, while negative values reflect anticorrelation. Altered rsFC of the striatum, a hub for reward processing, habit formation, and executive control, is linked to alcohol and nicotine use disorders and may indicate impaired regulation of cravings and heightened sensitivity to substance-related cues. Investigating rsFC patterns may identify biomarkers of addiction severity, predict treatment outcomes, and inform potential therapeutic targets.
Outcome measures
| Measure |
Control Group
n=25 Participants
No history of addiction to any substance or gambling. Less than 20 lifetime cigarettes or equivalent.
magnetic resonance imaging (MRI): All subjects will undergo a baseline MRI and subjects in both alcohol groups (alcohol use disorder and combined alcohol and nicotine use disorder) will undergo a followup MRI 3 months after baseline.
|
Nicotine Group
n=10 Participants
Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-V) criteria for Nicotine Use Disorder. Current smoker, at least 10 cigarettes per day. No history of addiction to any other substance
magnetic resonance imaging (MRI): All subjects will undergo a baseline MRI and subjects in both alcohol groups (alcohol use disorder and combined alcohol and nicotine use disorder) will undergo a followup MRI 3 months after baseline.
|
Alcohol Group
n=5 Participants
DSM-V criteria for Alcohol use Disorder. At least 8 heavy drinking episodes in the past month. Abstinent for at least 2 weeks and no more than 4 weeks. Less than 20 lifetime cigarettes or equivalent. No history of addiction to any other substances or gambling.
magnetic resonance imaging (MRI): All subjects will undergo a baseline MRI and subjects in both alcohol groups (alcohol use disorder and combined alcohol and nicotine use disorder) will undergo a followup MRI 3 months after baseline.
|
Nicotine and Alcohol Group
n=8 Participants
DSM-V criteria for Nicotine Use Disorder and Alcohol Use Disorder. At least 8 heavy drinking episodes in the past month. Current smoker. Alcohol free from 2 to 4 weeks. No history of addiction to other substances or gambling.
magnetic resonance imaging (MRI): All subjects will undergo a baseline MRI and subjects in both alcohol groups (alcohol use disorder and combined alcohol and nicotine use disorder) will undergo a followup MRI 3 months after baseline.
|
|---|---|---|---|---|
|
Brain Activation During Resting State MRI.
Anterior Cingulate Cortex (ACC)
|
0.1817 correlation coefficient
Standard Deviation 0.1460
|
0.1858 correlation coefficient
Standard Deviation 0.1576
|
0.1729 correlation coefficient
Standard Deviation 0.0973
|
0.1308 correlation coefficient
Standard Deviation 0.0959
|
|
Brain Activation During Resting State MRI.
Amygdala
|
0.1293 correlation coefficient
Standard Deviation 0.1124
|
0.1216 correlation coefficient
Standard Deviation 0.1148
|
0.0232 correlation coefficient
Standard Deviation 0.0903
|
0.0930 correlation coefficient
Standard Deviation 0.0682
|
|
Brain Activation During Resting State MRI.
Hippocampus
|
0.0391 correlation coefficient
Standard Deviation 0.0998
|
0.0746 correlation coefficient
Standard Deviation 0.1068
|
0.0255 correlation coefficient
Standard Deviation 0.0791
|
0.0348 correlation coefficient
Standard Deviation 0.0609
|
|
Brain Activation During Resting State MRI.
Insula
|
0.2297 correlation coefficient
Standard Deviation 0.1390
|
0.3139 correlation coefficient
Standard Deviation 0.1958
|
0.2134 correlation coefficient
Standard Deviation 0.1306
|
0.2386 correlation coefficient
Standard Deviation 0.1829
|
|
Brain Activation During Resting State MRI.
Medial Orbital Frontal Cortex (OFC)
|
0.0469 correlation coefficient
Standard Deviation 0.0398
|
0.0574 correlation coefficient
Standard Deviation 0.0420
|
0.0726 correlation coefficient
Standard Deviation 0.0456
|
0.0327 correlation coefficient
Standard Deviation 0.0397
|
|
Brain Activation During Resting State MRI.
Lateral OFC
|
0.0769 correlation coefficient
Standard Deviation 0.0739
|
0.1212 correlation coefficient
Standard Deviation 0.0826
|
0.0969 correlation coefficient
Standard Deviation 0.0587
|
0.0770 correlation coefficient
Standard Deviation 0.0655
|
|
Brain Activation During Resting State MRI.
Bilateral Middle Frontal Gyrus
|
-0.0501 correlation coefficient
Standard Deviation 0.0996
|
-0.0128 correlation coefficient
Standard Deviation 0.1573
|
0.0393 correlation coefficient
Standard Deviation 0.0580
|
-0.0184 correlation coefficient
Standard Deviation 0.0974
|
|
Brain Activation During Resting State MRI.
Rostral ACC
|
0.1610 correlation coefficient
Standard Deviation 0.1664
|
0.2674 correlation coefficient
Standard Deviation 0.1721
|
0.2327 correlation coefficient
Standard Deviation 0.1361
|
0.1293 correlation coefficient
Standard Deviation 0.1124
|
|
Brain Activation During Resting State MRI.
Caudal ACC
|
0.1884 correlation coefficient
Standard Deviation 0.1459
|
0.1574 correlation coefficient
Standard Deviation 0.1361
|
0.1598 correlation coefficient
Standard Deviation 0.1027
|
0.1323 correlation coefficient
Standard Deviation 0.1121
|
|
Brain Activation During Resting State MRI.
Bilateral Anterior Insula
|
0.2561 correlation coefficient
Standard Deviation 0.1766
|
0.3575 correlation coefficient
Standard Deviation 0.2270
|
0.2477 correlation coefficient
Standard Deviation 0.1456
|
0.2817 correlation coefficient
Standard Deviation 0.1945
|
|
Brain Activation During Resting State MRI.
Bilateral Dorsal Anterior Insula
|
0.3803 correlation coefficient
Standard Deviation 0.2124
|
0.4823 correlation coefficient
Standard Deviation 0.2517
|
0.3249 correlation coefficient
Standard Deviation 0.1984
|
0.3775 correlation coefficient
Standard Deviation 0.2760
|
|
Brain Activation During Resting State MRI.
Bilateral Ventral Anterior Insula
|
0.1541 correlation coefficient
Standard Deviation 0.1739
|
0.2554 correlation coefficient
Standard Deviation 0.2228
|
0.1852 correlation coefficient
Standard Deviation 0.1200
|
0.2039 correlation coefficient
Standard Deviation 0.1538
|
|
Brain Activation During Resting State MRI.
midbrain
|
0.0037 correlation coefficient
Standard Deviation 0.1067
|
0.0390 correlation coefficient
Standard Deviation 0.0987
|
0.0380 correlation coefficient
Standard Deviation 0.0903
|
0.0306 correlation coefficient
Standard Deviation 0.1308
|
|
Brain Activation During Resting State MRI.
Right Dorsal Lateral Prefrontal Cortex
|
0.0251 correlation coefficient
Standard Deviation 0.1323
|
0.0504 correlation coefficient
Standard Deviation 0.1995
|
0.0074 correlation coefficient
Standard Deviation 0.0267
|
0.1052 correlation coefficient
Standard Deviation 0.1409
|
|
Brain Activation During Resting State MRI.
Sub Callosal Cortex
|
0.0224 correlation coefficient
Standard Deviation 0.0582
|
0.0673 correlation coefficient
Standard Deviation 0.0489
|
0.1034 correlation coefficient
Standard Deviation 0.0738
|
0.0495 correlation coefficient
Standard Deviation 0.0533
|
PRIMARY outcome
Timeframe: BaselinePopulation: Participants were removed from analysis due to too much motion, performing the task incorrectly, or did not perform the task during the MRI session.
This outcome measures cortical thickness (millimeters) across brain regions using structural MRI. Cortical thickness reflects the integrity of gray matter and is influenced by factors such as neurodegeneration, plasticity, and development. Reductions in cortical thickness, particularly in prefrontal and limbic regions, are associated with impaired cognitive control, emotion regulation, and decision-making in substance use disorders.
Outcome measures
| Measure |
Control Group
n=29 Participants
No history of addiction to any substance or gambling. Less than 20 lifetime cigarettes or equivalent.
magnetic resonance imaging (MRI): All subjects will undergo a baseline MRI and subjects in both alcohol groups (alcohol use disorder and combined alcohol and nicotine use disorder) will undergo a followup MRI 3 months after baseline.
|
Nicotine Group
n=12 Participants
Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-V) criteria for Nicotine Use Disorder. Current smoker, at least 10 cigarettes per day. No history of addiction to any other substance
magnetic resonance imaging (MRI): All subjects will undergo a baseline MRI and subjects in both alcohol groups (alcohol use disorder and combined alcohol and nicotine use disorder) will undergo a followup MRI 3 months after baseline.
|
Alcohol Group
n=9 Participants
DSM-V criteria for Alcohol use Disorder. At least 8 heavy drinking episodes in the past month. Abstinent for at least 2 weeks and no more than 4 weeks. Less than 20 lifetime cigarettes or equivalent. No history of addiction to any other substances or gambling.
magnetic resonance imaging (MRI): All subjects will undergo a baseline MRI and subjects in both alcohol groups (alcohol use disorder and combined alcohol and nicotine use disorder) will undergo a followup MRI 3 months after baseline.
|
Nicotine and Alcohol Group
n=22 Participants
DSM-V criteria for Nicotine Use Disorder and Alcohol Use Disorder. At least 8 heavy drinking episodes in the past month. Current smoker. Alcohol free from 2 to 4 weeks. No history of addiction to other substances or gambling.
magnetic resonance imaging (MRI): All subjects will undergo a baseline MRI and subjects in both alcohol groups (alcohol use disorder and combined alcohol and nicotine use disorder) will undergo a followup MRI 3 months after baseline.
|
|---|---|---|---|---|
|
Brain Cortical Thickness Assessed During MRI
Right inferior parietal cortex
|
2.5510 mm
Standard Deviation 0.0803
|
2.5175 mm
Standard Deviation 0.0953
|
2.4377 mm
Standard Deviation 0.0324
|
2.4774 mm
Standard Deviation 0.5158
|
|
Brain Cortical Thickness Assessed During MRI
Left caudal anterior cingulate
|
2.6111 mm
Standard Deviation 0.2171
|
2.5421 mm
Standard Deviation 0.1780
|
2.5472 mm
Standard Deviation 0.2005
|
2.6560 mm
Standard Deviation 0.5697
|
|
Brain Cortical Thickness Assessed During MRI
Left inferior parietal cortex
|
2.4885 mm
Standard Deviation 0.0862
|
2.4414 mm
Standard Deviation 0.0675
|
2.3881 mm
Standard Deviation 0.0586
|
2.4132 mm
Standard Deviation 0.5030
|
|
Brain Cortical Thickness Assessed During MRI
Left rostral anterior cingulate
|
2.7960 mm
Standard Deviation 0.1675
|
2.7058 mm
Standard Deviation 0.1977
|
2.7173 mm
Standard Deviation 0.1454
|
2.7150 mm
Standard Deviation 0.5749
|
|
Brain Cortical Thickness Assessed During MRI
Left rostral middle frontal cortex
|
2.4701 mm
Standard Deviation 0.0898
|
2.4315 mm
Standard Deviation 0.0752
|
2.3740 mm
Standard Deviation 0.0794
|
2.4406 mm
Standard Deviation 0.5069
|
|
Brain Cortical Thickness Assessed During MRI
Left supramarginal cortex
|
2.6022 mm
Standard Deviation 0.1315
|
2.5550 mm
Standard Deviation 0.0838
|
2.4669 mm
Standard Deviation 0.0656
|
2.5375 mm
Standard Deviation 0.5283
|
|
Brain Cortical Thickness Assessed During MRI
Right caudal anterior cingulate
|
2.4662 mm
Standard Deviation 0.1935
|
2.4350 mm
Standard Deviation 0.1495
|
2.3582 mm
Standard Deviation 0.1392
|
2.4452 mm
Standard Deviation 0.5130
|
|
Brain Cortical Thickness Assessed During MRI
Right rostral anterior cingulate
|
2.8013 mm
Standard Deviation 0.1454
|
2.6618 mm
Standard Deviation 0.2390
|
2.6828 mm
Standard Deviation 0.1466
|
2.7507 mm
Standard Deviation 0.5852
|
|
Brain Cortical Thickness Assessed During MRI
Right rostral middle frontal cortex
|
2.3994 mm
Standard Deviation 0.1024
|
2.3699 mm
Standard Deviation 0.0777
|
2.3103 mm
Standard Deviation 0.0640
|
2.3443 mm
Standard Deviation 0.4864
|
|
Brain Cortical Thickness Assessed During MRI
Right supramarginal cortex
|
2.6165 mm
Standard Deviation 0.1221
|
2.5694 mm
Standard Deviation 0.0666
|
2.4713 mm
Standard Deviation 0.0701
|
2.5312 mm
Standard Deviation 0.5261
|
PRIMARY outcome
Timeframe: BaselinePopulation: Participants were removed from analysis due to too much motion, performing the task incorrectly, or did not perform the task during the MRI session.
Fractional Anisotropy (FA) is a scalar metric derived from diffusion-weighted MRI that quantifies the degree of directional dependence (anisotropy) of water diffusion in brain white matter, with values ranging from 0 (isotropic diffusion) to 1 (maximally anisotropic diffusion). Increases in FA may reflect greater white matter organization and integrity, while decreases often indicate microstructural damage, demyelination, or axonal loss. FA measurements were averaged within predefined regions of interest (ROIs) to assess the integrity of white matter in various brain regions associated with cognitive, motor, and emotional processing. Decreased FA in tracts such as the corpus callosum or prefrontal pathways may reflect impaired communication between brain regions involved in reward processing and cognitive control in substance use disorders.
Outcome measures
| Measure |
Control Group
n=19 Participants
No history of addiction to any substance or gambling. Less than 20 lifetime cigarettes or equivalent.
magnetic resonance imaging (MRI): All subjects will undergo a baseline MRI and subjects in both alcohol groups (alcohol use disorder and combined alcohol and nicotine use disorder) will undergo a followup MRI 3 months after baseline.
|
Nicotine Group
n=10 Participants
Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-V) criteria for Nicotine Use Disorder. Current smoker, at least 10 cigarettes per day. No history of addiction to any other substance
magnetic resonance imaging (MRI): All subjects will undergo a baseline MRI and subjects in both alcohol groups (alcohol use disorder and combined alcohol and nicotine use disorder) will undergo a followup MRI 3 months after baseline.
|
Alcohol Group
n=3 Participants
DSM-V criteria for Alcohol use Disorder. At least 8 heavy drinking episodes in the past month. Abstinent for at least 2 weeks and no more than 4 weeks. Less than 20 lifetime cigarettes or equivalent. No history of addiction to any other substances or gambling.
magnetic resonance imaging (MRI): All subjects will undergo a baseline MRI and subjects in both alcohol groups (alcohol use disorder and combined alcohol and nicotine use disorder) will undergo a followup MRI 3 months after baseline.
|
Nicotine and Alcohol Group
n=15 Participants
DSM-V criteria for Nicotine Use Disorder and Alcohol Use Disorder. At least 8 heavy drinking episodes in the past month. Current smoker. Alcohol free from 2 to 4 weeks. No history of addiction to other substances or gambling.
magnetic resonance imaging (MRI): All subjects will undergo a baseline MRI and subjects in both alcohol groups (alcohol use disorder and combined alcohol and nicotine use disorder) will undergo a followup MRI 3 months after baseline.
|
|---|---|---|---|---|
|
Brain White Matter Integrity as Assessed by Fractional Anisotropy During MRI
Forceps Major
|
0.4167 Unitless
Standard Deviation 0.1984
|
0.3996 Unitless
Standard Deviation 0.1497
|
0.4030 Unitless
Standard Deviation 0.1900
|
0.4044 Unitless
Standard Deviation 0.1930
|
|
Brain White Matter Integrity as Assessed by Fractional Anisotropy During MRI
Forceps Minor
|
0.3794 Unitless
Standard Deviation 0.1809
|
0.3657 Unitless
Standard Deviation 0.1374
|
0.3574 Unitless
Standard Deviation 0.1685
|
0.3589 Unitless
Standard Deviation 0.1718
|
|
Brain White Matter Integrity as Assessed by Fractional Anisotropy During MRI
Left Anterior Thalamic Radiation
|
0.3474 Unitless
Standard Deviation 0.1653
|
0.3362 Unitless
Standard Deviation 0.1257
|
0.3356 Unitless
Standard Deviation 0.1582
|
0.3334 Unitless
Standard Deviation 0.1592
|
|
Brain White Matter Integrity as Assessed by Fractional Anisotropy During MRI
Right Anterior Thalamic Radiation
|
0.3450 Unitless
Standard Deviation 0.1642
|
0.3337 Unitless
Standard Deviation 0.1247
|
0.3331 Unitless
Standard Deviation 0.1570
|
0.3306 Unitless
Standard Deviation 0.1578
|
|
Brain White Matter Integrity as Assessed by Fractional Anisotropy During MRI
Left Inferior fronto-occipital fasciculus
|
0.3536 Unitless
Standard Deviation 0.1684
|
0.3388 Unitless
Standard Deviation 0.1268
|
0.3383 Unitless
Standard Deviation 0.1595
|
0.3374 Unitless
Standard Deviation 0.1614
|
|
Brain White Matter Integrity as Assessed by Fractional Anisotropy During MRI
Right Inferior fronto-occipital fasciculus
|
0.3574 Unitless
Standard Deviation 0.1702
|
0.3436 Unitless
Standard Deviation 0.1287
|
0.3422 Unitless
Standard Deviation 0.1614
|
0.3417 Unitless
Standard Deviation 0.1632
|
|
Brain White Matter Integrity as Assessed by Fractional Anisotropy During MRI
Left Temporal Superior longitudinal fasciculus
|
0.3535 Unitless
Standard Deviation 0.1683
|
0.3389 Unitless
Standard Deviation 0.1269
|
0.3392 Unitless
Standard Deviation 0.1600
|
0.3387 Unitless
Standard Deviation 0.1620
|
|
Brain White Matter Integrity as Assessed by Fractional Anisotropy During MRI
Right Temporal Superior longitudinal fasciculus
|
0.3460 Unitless
Standard Deviation 0.1647
|
0.3338 Unitless
Standard Deviation 0.1251
|
0.3340 Unitless
Standard Deviation 0.1574
|
0.3330 Unitless
Standard Deviation 0.1592
|
|
Brain White Matter Integrity as Assessed by Fractional Anisotropy During MRI
Left Corticospinal tract
|
0.3909 Unitless
Standard Deviation 0.1860
|
0.3790 Unitless
Standard Deviation 0.1418
|
0.3826 Unitless
Standard Deviation 0.1804
|
0.3800 Unitless
Standard Deviation 0.1812
|
|
Brain White Matter Integrity as Assessed by Fractional Anisotropy During MRI
Right Corticospinal tract
|
0.3870 Unitless
Standard Deviation 0.1841
|
0.3766 Unitless
Standard Deviation 0.1407
|
0.3802 Unitless
Standard Deviation 0.1792
|
0.3780 Unitless
Standard Deviation 0.1802
|
|
Brain White Matter Integrity as Assessed by Fractional Anisotropy During MRI
Left cingulate gyrus
|
0.3831 Unitless
Standard Deviation 0.1826
|
0.3697 Unitless
Standard Deviation 0.1385
|
0.3662 Unitless
Standard Deviation 0.1726
|
0.3652 Unitless
Standard Deviation 0.1747
|
|
Brain White Matter Integrity as Assessed by Fractional Anisotropy During MRI
Right cingulate gyrus
|
0.3758 Unitless
Standard Deviation 0.1789
|
0.3647 Unitless
Standard Deviation 0.1364
|
0.3705 Unitless
Standard Deviation 0.1747
|
0.3662 Unitless
Standard Deviation 0.1751
|
|
Brain White Matter Integrity as Assessed by Fractional Anisotropy During MRI
Left Uncinate fasciculus
|
0.3219 Unitless
Standard Deviation 0.1533
|
0.3136 Unitless
Standard Deviation 0.1177
|
0.3104 Unitless
Standard Deviation 0.1464
|
0.3057 Unitless
Standard Deviation 0.1463
|
|
Brain White Matter Integrity as Assessed by Fractional Anisotropy During MRI
Right Uncinate fasciculus
|
0.3231 Unitless
Standard Deviation 0.1538
|
0.3120 Unitless
Standard Deviation 0.1172
|
0.3148 Unitless
Standard Deviation 0.1484
|
0.3073 Unitless
Standard Deviation 0.1470
|
|
Brain White Matter Integrity as Assessed by Fractional Anisotropy During MRI
Left Inferior longitudinal fasciculus
|
0.3552 Unitless
Standard Deviation 0.1692
|
0.3388 Unitless
Standard Deviation 0.1269
|
0.3408 Unitless
Standard Deviation 0.1607
|
0.3421 Unitless
Standard Deviation 0.1636
|
|
Brain White Matter Integrity as Assessed by Fractional Anisotropy During MRI
Right Inferior longitudinal fasciculus
|
0.3522 Unitless
Standard Deviation 0.1677
|
0.3392 Unitless
Standard Deviation 0.1272
|
0.3399 Unitless
Standard Deviation 0.1603
|
0.3393 Unitless
Standard Deviation 0.1621
|
|
Brain White Matter Integrity as Assessed by Fractional Anisotropy During MRI
Left Hippocampus
|
0.3572 Unitless
Standard Deviation 0.1705
|
0.3464 Unitless
Standard Deviation 0.1300
|
0.3493 Unitless
Standard Deviation 0.1649
|
0.3441 Unitless
Standard Deviation 0.1645
|
|
Brain White Matter Integrity as Assessed by Fractional Anisotropy During MRI
Right Hippocampus
|
0.3750 Unitless
Standard Deviation 0.1786
|
0.3677 Unitless
Standard Deviation 0.1377
|
0.3617 Unitless
Standard Deviation 0.1706
|
0.3635 Unitless
Standard Deviation 0.1737
|
Adverse Events
Control Group
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Nicotine Group
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Alcohol Group
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Nicotine and Alcohol Group
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place