Neurophysiological correlates of response inhibition predict relapse in detoxified alcoholic patients: some preliminary evidence from event-related potentials

Figures & data

Figure 1 Go/no-go task.

Notes: Participants were confronted with six blocks of 133 stimuli, divided in to 93 “go” trials (letter M), and 40 “no-go” trials (letter W). The letters were superimposed on two nonalcohol-related background pictures (NAC), two alcohol-related background pictures (AC), or a neutral black background (NC). Reproduced from Petit et al. Alcohol-Related Context Modulates Performance of Social Drinkers in a Visual Go/No-Go Task: A Preliminary Assessment of Event-Related Potentials. PloS One. 2012;7:e37466.¹⁴ Copyright © 2012 Petit et al.

Table 1 Clinical characteristics of patients and controls, presented as means ± standard deviation

	Patients (n=27)	Controls (n=27)	P-value
Females	7	7	1.000
Age (years)	45 (12)	45 (11)	0.876
Education level*	12 (3)	16 (2)	<0.001
Body mass index	24 (4)	26 (4)	0.089
Alcohol problems (AUDIT)	32 (7)	4 (2)	<0.001
Daily alcohol intake (U) (prior detoxification for patients)	23 (14)	0.5 (0.4)	<0.001
Smoking (% with nicotine dependence)	85	13	<0.001
Depression (BDI score)	21 (12)	7 (9)	<0.001
Anxiety traits (STAI-B)	48 (9)	38 (9)	0.001
Anxiety state (STAI-A)	49 (8)	40 (9)	0.001
Impulsivity (UPPS scale)	109 (17)	95 (19)	0.006
Degree of family history of alcoholism	1.85 (1.3)	0.22 (0.8)	<0.001

Notes:

* Number of years of education since completing primary school; one unit (U) represents 10 g of alcohol.

Abbreviations: AUDIT, Alcohol Use Disorders Identification Test; BDI, Beck Depression Inventory; STAI, State-Trait Anxiety Inventory; UPPS, urgency (lack of), premeditation, perseverance (lack of), sensation seeking.

Table 2 Reaction times (RTs) to “go” stimuli, error rates, go, no-go, and P3d amplitudes in patients and controls, presented as means ± standard deviation

	Patients	Controls	P-value
Go RTs(ms)	359 (56)	364 (58)	0.731
Omission error rates (%)	1.6 (2.1)	0.5 (0.7)	0.003*
Commission error rates (%)	22.9 (12.4)	11.4 (6.6)	<0.001†
Go P3 (μV)	9.5 (3.7)	9.6 (4.9)	0.877
No-go P3 (μV)	13.9 (4.5)	12.6 (4.6)	0.026‡
P3d (μV)	4.4 (3.1)	2.9 (3.2)	0.034‡

Notes:

* P<0.005

† P<0.001

‡ P<0.05.

Figure 2 Original go/no-go P3 waves in the patient and control groups and resulting P3d waves at the FC1, FC2, and Cz sites.

Notes: Grand averages of the go/no-go P3 waves (left side of graphs in each electrode site) picturing the similar go P3 mean amplitude waves between groups (red and blue continuous lines) and the higher no-go P3 mean waves in patients (red dotted lines) in terms of amplitudes compared to controls (blue dotted lines), underlying the higher P3d amplitudes (ie, the mean difference wave = the go P3 wave subtracted from the no-go P3 wave) in patients compared to controls (red and blue continuous lines represented on the right of graphs in each electrode site).

Table 3 Clinical characteristics of relapsers and nonrelapsers in our study, presented as means ± standard deviation

	Relapsers (n=13)	Nonrelapsers (n=14)	P-value
Females	3	4	0.745
Age (years)	39 (9)	50 (13)	0.018
Education level*	11 (2)	12 (3)	0.645
Body mass index	25 (5)	22 (3)	0.123
Alcohol problems (AUDIT)	31 (4)	32 (9)	0.846
Alcohol intake prior to detoxification (U/day)	20 (12)	24 (16)	0.517
Age of onset of alcohol misuse†	31 (11)	36 (11)	0.256
Duration of current treatment (days)	18.6 (2.8)	19.4 (1.8)	0.380
Duration of dependence‡ (years)	8 (7)	15 (9)	0.055
Number of prior detoxifications	0.6 (0.8)	3.2 (5.1)	0.086
Smoking (% with nicotine dependence)^Citation70	84	71	0.673
Depression (BDI score)	20 (9)	21 (14)	0.824
Anxiety trait (STAI-B)	47 (7)	51 (9)	0.233
Anxiety state (STAI-A)	46 (9)	49 (10)	0.470
Impulsivity (UPPS scale)	116 (14)	103 (17)	0.075
Craving before experiment	14 (2)	5 (11)	0.075
Craving after experiment	19 (33)	6 (21)	0.106
Global craving score	21 (32)	6 (14)	0.110
Degree of family history of alcoholism	1.4 (1.4)	2.2 (1.2)	0.163
Anticraving medication (% receiving treatment)	84	64	0.228
Campral	76	43	0.120
Baclofen	7	7	0.741
Antabuse	0	7	0.277
Campral + baclofen	0	7	0.519
Benzodiazepine (% of users)	30	42	0.402

Notes:

* Number of years of education since completing primary school

† age at which drinking first began to have an effect on the subject’s life of which he/she did not approve

‡ number of years that the subject fulfilled dependence criteria before assessment.

Abbreviations: AUDIT, Alcohol Use Disorders Identification Test; BDI, Beck Depression Inventory; STAI, State-Trait Anxiety Inventory; U/Day, alcohol dose unit per day; UPPS, urgency (lack of), premeditation, perseverance (lack of), sensation seeking.

Figure 3 (A) Grand averages of the P3-difference waveforms between go and no-go trials in control, relapser, and nonrelapser groups. Computation of the P3d, ie, the mean difference wave (go P3 wave subtracted from the no-go P3 wave) for control, relapser, and nonrelapser groups at the FC1, Cz, and FC2 sites. The red line represents the relapser group’s mean wave, whose amplitude was greater than the nonrelapser (blue line) and control groups (green line). (B) Mean individual P3d amplitudes in patient group. Mean difference wave (go P3 wave subtracted from the no-go P3 wave) for each patient derived from the computation of the six electrode sites (FC1, FC2, Cz, CP1, CP2, and Pz) and the three contexts (nonalcohol-related background pictures [NAC], two alcohol-related background pictures [AC], neutral black background [NC]) collapsed as a function of their abstinence status at 3-month follow-up: relapsers are represented in red, and nonrelapsers are represented in blue.

Table 4 Reaction times (RTs) to “go” stimuli, error rates, and P3d amplitudes in nonrelapsers and relapsers, presented as means ± standard deviation

	Relapsers	Nonrelapsers	P-value
Go RTs (ms)	351 (42)	367 (68)	0.449
Omission error rates (%)	1.6 (2.9)	1.6 (1.5)	0.965
Commission error rates (%)	21.2 (12.2)	24.5 (12.8)	0.496
P3d (μV)	4.4 (3.1)	2.9 (3.2)	0.026*

Notes:

* F_1,23=5.673, P=0.026; η²=0.198, observed power =0.626.

Table 5 Multiple hierarchical regression analysis examining predictors of relapse after the 3-month follow-up period

Variable	β	SE	OR (95% CI)
Step 1
UPPS scale	0.037	0.030	1.03 (0.979–1.101)
Craving	0.022	0.025	1.02 (0.973–1.074)
Medication	−0.707	1.17	0.493 (0.049–4.960)
Inhibition-error rate	−0.070	0.050	0.932 (0.844–1.029)
FHA	−0.462	0.372	0.630 (0.304–1.305)
Step 2
UPPS scale	0.061	0.038	1.06 (0.987–1.144)
Craving	0.016	0.031	1.01 (0.957–1.080)
Medication	−1.98	1.51	0.137 (0.007–2.666)
Inhibition-error rate	−0.050	0.047	0.951 (0.867–1.043)
FHA	−0.270	0.395	0.763 (0.352–1.656)
P3d amplitude	0.483	0.252	1.62 (0.988–2.657)

Notes: β represents the slope of the regression line. After a binary logistic regression model with simultaneous entry of the FHA score, craving score, UPPS scale score, P3d amplitude, inhibition-error rate, and use of anticraving medication (taking medication versus not taking medication), which significantly predicted the OR of relapse, in order to examine the unique contribution of the P3d amplitude beyond and above other variables, hierarchical regression was conducted with FHA, craving, and UPPS scores, inhibition error rate, and use of anticraving medication, entered as predictors in the first step. These variables did not predict relapse (χ²=8.168, df=5, P=0.147, Nagelkerke R²=0.348). In a second step, we entered the P3d amplitude. The addition of the P3d amplitude significantly contributed to the prediction of relapse above and beyond other variables (χ²=13.558, df=6, P=0.035, Nagelkerke R²=0.527), meaning that 52% of the variance of the relapse outcome was explained by the model. The P3d amplitude was the only variable that independently and significantly predicted the odds of relapse, with an OR of 1.620 (95% CI 0.988–2.657), Wald =3.656, P=0.05.

Abbreviations: FHA, family history of alcoholism; UPPS, urgency (lack of), premeditation, perseverance (lack of), sensation seeking; OR, odds ratio; df, degrees of freedom; CI, confidence interval; SE, standard error.

Table 6 Multivariate Cox regression analysis with stepwise backward selection examining time to relapse within the 3-month follow-up period

Variables	Significance (P-value)	β	SE	OR (95% CI)
Included in final model
UPPS scale	0.04	0.032	0.016	1.032 (1.001–1.065)
P3d amplitude	0.05	0.199	0.104	1.220 (0.995–1.497)
Not included in final model
Craving	0.50
FHA	0.12
Medication	0.16
Inhibition-error rate	0.95

Notes: β represents the slope of the regression line. The outcome variable assessed was the time to relapse within the 3-month follow-up window, and the unit of time for our analysis was 1 day. Participants remaining abstinent from alcohol by the end of the study window constituted the censored cases for this analysis. Initially, the six variables were included in the model. In a stepwise fashion, factors that showed no or limited statistically significant association with relapse adjusted for the remaining factors in the model were deleted. Two variables remained at the end: P3d amplitude and the UPPS scale score. Both variables constituted the best predictors of relapse, and they significantly and slightly significantly predicted the timing of relapse (UPPS, OR 1.032, 95% CI 1.001–1.065, P=0.04; P3d, OR 1.220, 95% CI 0.995–1.497, P=0.05).

Abbreviations: UPPS, urgency (lack of), premeditation, perseverance (lack of), sensation seeking; OR, odds ratio; CI, confidence interval; SE, standard error; FHA, family history of alcoholism.

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