Introduction: Despite substantial health benefits, smoking cessation attempts have high relapse rates. Neuroimaging measures can sometimes predict individual differences in substance use phenotypes – including relapse – better than behavioral metrics alone. No study to date has compared the relative prediction ability of changes in psychological processes across prolonged abstinence with corresponding changes in brain activity. Methods: Here, in a longitudinal design, measurements were made 1 day prior to smoking cessation, and at 1 and 4 weeks post-cessation (total n = 120). Next, we tested the relative role of changes in psychosocial variables versus task-based functional brain measures predicting time to nicotine relapse up to 12 months. Abstinence was bio-verified 4–5 times during the first month. Data were analyzed with a novel machine-learning approach to predict relapse. Results: Results showed that increased electrophysiological brain activity during inhibitory control predicted longer time to relapse (c-index = 0.56). However, reward-related brain activity was not predictive (c-index = 0.45). Psychological variables, notably an increase during abstinence in psychological flexibility when experiencing negative smoking-related sensations, predicted longer time to relapse (c-index = 0.63). A model combining psychosocial and brain data was predictive (c-index = 0.68). Using a best-practice approach, we demonstrated generalizability of the combined model on a previously unseen holdout validation dataset (c-index = 0.59 vs. 0.42 for a null model). Conclusion: These results show that changes during abstinence – increased smoking-specific psychological flexibility and increased inhibitory control brain function – are important in predicting time to relapse from smoking cessation. In the future, monitoring and augmenting changes in these variables could help improve the chances of successful nicotine smoking abstinence.

1.
World Health Organization, Bloomberg Philanthropies
.
WHO report on the global tobacco epidemic, 2017: monitoring tobacco use and prevention policies
.
2017
[cited 2020 Aug 19]. Available from: http://apps.who.int/iris/bitstream/10665/255874/1/9789241512824-eng.pdf?ua=1&ua=1
2.
Hughes
JR
,
Keely
J
,
Naud
S
.
Shape of the relapse curve and long-term abstinence among untreated smokers
.
Addiction
.
2004
;
99
(
1
):
29
38
.
3.
Marti
J
.
Successful smoking cessation and duration of abstinence: an analysis of socioeconomic determinants
.
Int J Environ Res Public Health
.
2010
;
7
(
7
):
2789
99
.
4.
Pesce
G
,
Marcon
A
,
Calciano
L
,
Perret
JL
,
Abramson
MJ
,
Bono
R
, et al
.
Time and age trends in smoking cessation in Europe
.
PLoS One
.
2019
;
14
(
2
):
e0211976
.
5.
Powell
J
,
Dawkins
L
,
West
R
,
Powell
J
,
Pickering
A
.
Relapse to smoking during unaided cessation: clinical, cognitive and motivational predictors
.
Psychopharmacology
.
2010
;
212
(
4
):
537
49
.
6.
Robinson
JD
,
Li
L
,
Chen
M
,
Lerman
C
,
Tyndale
RF
,
Schnoll
RA
, et al
.
Evaluating the temporal relationships between withdrawal symptoms and smoking relapse
.
Psychol Addict Behav
.
2019
;
33
(
2
):
105
16
.
7.
Hakulinen
C
,
Hintsanen
M
,
Munafò
MR
,
Virtanen
M
,
Kivimäki
M
,
Batty
GD
, et al
.
Personality and smoking: individual-participant meta-analysis of nine cohort studies
.
Addiction
.
2015
;
110
(
11
):
1844
52
.
8.
Doran
N
,
Spring
B
,
McChargue
D
,
Pergadia
M
,
Richmond
M
.
Impulsivity and smoking relapse
.
Nicotine Tob Res
.
2004
;
6
(
4
):
641
7
.
9.
Burgess
ES
,
Brown
RA
,
Kahler
CW
,
Niaura
R
,
Abrams
DB
,
Goldstein
MG
, et al
.
Patterns of change in depressive symptoms during smoking cessation: who’s at risk for relapse
.
J Consult Clin Psychol
.
2002
;
70
(
2
):
356
61
.
10.
Piper
ME
,
Schlam
TR
,
Cook
JW
,
Sheffer
MA
,
Smith
SS
,
Loh
W-Y
, et al
.
Tobacco withdrawal components and their relations with cessation success
.
Psychopharmacology
.
2011
;
216
(
4
):
569
78
.
11.
Farris
SG
,
Zvolensky
MJ
,
Schmidt
NB
.
Smoking-specific experiential avoidance cognition: explanatory relevance to pre- and post-cessation nicotine withdrawal, craving, and negative affect
.
Addict Behav
.
2015
;
44
:
58
64
.
12.
McClure
JB
,
Bricker
J
,
Mull
K
,
Heffner
JL
.
Comparative effectiveness of group-delivered acceptance and commitment therapy versus cognitive behavioral therapy for smoking cessation: a randomized controlled trial
.
Nicotine Tob Res
.
2020
;
22
(
3
):
354
62
.
13.
Stewart
JL
,
May
AC
,
Paulus
MP
.
Bouncing back: brain rehabilitation amid opioid and stimulant epidemics
.
Neuroimage Clin
.
2019
;
24
:
102068
.
14.
Moeller
SJ
,
Paulus
MP
.
Toward biomarkers of the addicted human brain: using neuroimaging to predict relapse and sustained abstinence in substance use disorder
.
Prog Neuropsychopharmacol Biol Psychiatry
.
2018
;
80
(
Pt B
):
143
54
.
15.
Wilcox
CE
,
Abbott
CC
,
Calhoun
VD
.
Alterations in resting-state functional connectivity in substance use disorders and treatment implications
.
Prog Neuropsychopharmacol Biol Psychiatry
.
2019
;
91
:
79
93
.
16.
Yip
SW
,
Kiluk
B
,
Scheinost
D
.
Toward addiction prediction: an overview of cross-validated predictive modeling findings and considerations for future neuroimaging research
.
Biol Psychiatry Cogn Neurosci Neuroimaging
.
2020
;
5
(
8
):
748
58
.
17.
Houston
RJ
,
Schlienz
NJ
.
Event-related potentials as biomarkers of behavior change mechanisms in substance use disorder treatment
.
Biol Psychiatry Cogn Neurosci Neuroimaging
.
2018
;
3
(
1
):
30
40
.
18.
Versace
F
,
Lam
CY
,
Engelmann
JM
,
Robinson
JD
,
Minnix
JA
,
Brown
VL
, et al
.
Beyond cue reactivity: blunted brain responses to pleasant stimuli predict long-term smoking abstinence
.
Addict Biol
.
2012
;
17
(
6
):
991
1000
.
19.
Luijten
M
,
Kleinjan
M
,
Franken
IHA
.
Event-related potentials reflecting smoking cue reactivity and cognitive control as predictors of smoking relapse and resumption
.
Psychopharmacology
.
2016
;
233
(
15–16
):
2857
68
.
20.
Steele
VR
,
Fink
BC
,
Maurer
JM
,
Arbabshirani
MR
,
Wilber
CH
,
Jaffe
AJ
, et al
.
Brain potentials measured during a go/NoGo task predict completion of substance abuse treatment
.
Biol Psychiatry
.
2014
;
76
(
1
):
75
83
.
21.
Whelan
R
,
Garavan
H
.
When optimism hurts: inflated predictions in psychiatric neuroimaging
.
Biol Psychiatry
.
2014
;
75
(
9
):
746
8
.
22.
Piper
ME
,
Bullen
C
,
Krishnan-Sarin
S
,
Rigotti
NA
,
Steinberg
ML
,
Streck
JM
, et al
.
Defining and measuring abstinence in clinical trials of smoking cessation interventions: an updated review
.
Nicotine Tob Res
.
2019
;
22
(
7
):
1098
106
.
23.
Brown
RA
,
Lejuez
CW
,
Kahler
CW
,
Strong
DR
,
Zvolensky
MJ
.
Distress tolerance and early smoking lapse
.
Clin Psychol Rev
.
2005
;
25
(
6
):
713
33
.
24.
Shadel
WG
,
Martino
SC
,
Setodji
C
,
Cervone
D
,
Witkiewitz
K
,
Beckjord
EB
, et al
.
Lapse-induced surges in craving influence relapse in adult smokers: an experimental investigation
.
Health Psychol
.
2011
;
30
(
5
):
588
96
.
25.
Kirchner
TR
,
Shiffman
S
,
Wileyto
EP
.
Relapse dynamics during smoking cessation: recurrent abstinence violation effects and lapse-relapse progression
.
J Abnorm Psychol
.
2012
;
121
(
1
):
187
97
.
26.
Bricker
JB
,
Mull
KE
,
Kientz
JA
,
Vilardaga
R
,
Mercer
LD
,
Akioka
KJ
, et al
.
Randomized, controlled pilot trial of a smartphone app for smoking cessation using acceptance and commitment therapy
.
Drug Alcohol Depend
.
2014
;
143
:
87
94
.
27.
Farris
SG
,
Zvolensky
MJ
,
DiBello
AM
,
Schmidt
NB
.
Validation of the avoidance and inflexibility scale (AIS) among treatment-seeking smokers
.
Psychol Assess
.
2015
;
27
(
2
):
467
77
.
28.
Oostenveld
R
,
Praamstra
P
.
The five percent electrode system for high-resolution EEG and ERP measurements
.
Clin Neurophysiol
.
2001
;
112
(
4
):
713
9
.
29.
Rueda-Delgado
LM
,
O’Halloran
L
,
Enz
N
,
Ruddy
KL
,
Kiiski
H
,
Bennett
M
, et al
.
Brain event-related potentials predict individual differences in inhibitory control
.
Int J Psychophysiol
.
2021
;
163
:
22
34
.
30.
Etter
J
.
Assessment of the accuracy of salivary cotinine readings from NicAlert strips against a liquid chromatography tandem mass spectrometry assay in self‐reported non‐smokers who passed carbon monoxide but failed NicAlert validation
.
Addiction
.
2019
;
114
(
12
):
2252
6
.
31.
Whelan
R
,
Watts
R
,
Orr
CA
,
Althoff
RR
,
Artiges
E
,
Banaschewski
T
, et al
.
Neuropsychosocial profiles of current and future adolescent alcohol misusers
.
Nature
.
2014
;
512
(
7513
):
185
9
.
32.
Steck
H
,
Krishnapuram
B
,
Dehing-Oberije
C
,
Lambin
P
,
Raykar
VC
.
On ranking in survival analysis: bounds on the concordance index
.
Advances in neural information processing systems
.
2007
;
20
.
33.
Moreno Padilla
M
,
O’Halloran
L
,
Bennett
M
,
Cao
Z
,
Whelan
R
.
Impulsivity and reward processing endophenotypes in youth alcohol misuse
.
Curr Addict Rep
.
2017
;
4
(
4
):
350
63
.
34.
Falk
EB
,
Berkman
ET
,
Whalen
D
,
Lieberman
MD
.
Neural activity during health messaging predicts reductions in smoking above and beyond self-report
.
Health Psychol
.
2011
;
30
(
2
):
177
85
.
35.
Wiers
CE
,
Cabrera
EA
,
Tomasi
D
,
Wong
CT
,
Demiral
ŞB
,
Kim
SW
, et al
.
Striatal dopamine D2/D3 receptor availability varies across smoking status
.
Neuropsychopharmacology
.
2017
;
42
(
12
):
2325
32
.
36.
Celma-Merola
J
,
Abella-Pons
F
,
Mata
F
,
Pedra-Pagés
G
,
Verdejo-Garcia
A
.
Self-changing behaviour in smoking cessation linked to trait and cognitive impulsivity
.
Addiction
.
2018
;
113
(
1
):
107
12
.
37.
McCarthy
DE
,
Bold
KW
,
Minami
H
,
Yeh
VM
,
Rutten
E
,
Nadkarni
SG
, et al
.
Reliability and validity of measures of impulsive choice and impulsive action in smokers trying to quit
.
Exp Clin Psychopharmacol
.
2016
;
24
(
2
):
120
30
.
38.
Garey
L
,
Farris
SG
,
Schmidt
NB
,
Zvolensky
MJ
.
The role of smoking-specific experiential avoidance in the relation between perceived stress and tobacco dependence, perceived barriers to cessation, and problems during quit attempts among treatment-seeking smokers
.
J Contextual Behav Sci
.
2016
;
5
(
1
):
58
63
.
39.
Bricker
JB
,
Watson
NL
,
Mull
KE
,
Sullivan
BM
,
Heffner
JL
.
Efficacy of smartphone applications for smoking cessation: a randomized clinical trial
.
JAMA Intern Med
.
2020
;
180
(
11
):
1472
80
.
40.
Gifford
EV
,
Kohlenberg
BS
,
Hayes
SC
,
Antonuccio
DO
,
Piasecki
MM
,
Rasmussen-Hall
ML
, et al
.
Acceptance-based treatment for smoking cessation
.
Behav Ther
.
2004
;
35
(
4
):
689
705
.
41.
Serre
F
,
Fatseas
M
,
Swendsen
J
,
Auriacombe
M
.
Ecological momentary assessment in the investigation of craving and substance use in daily life: a systematic review
.
Drug Alcohol Depend
.
2015
;
148
:
1
20
.
42.
Serre
F
,
Fatseas
M
,
Denis
C
,
Swendsen
J
,
Auriacombe
M
.
Predictors of craving and substance use among patients with alcohol, tobacco, cannabis or opiate addictions: commonalities and specificities across substances
.
Addict Behav
.
2018
;
83
:
123
9
.
43.
Hiscock
R
,
Bauld
L
,
Amos
A
,
Fidler
JA
,
Munafò
M
.
Socioeconomic status and smoking: a review
.
Ann N Y Acad Sci
.
2012
;
1248
(
1
):
107
23
.
44.
Jollans
L
,
Boyle
R
,
Artiges
E
,
Banaschewski
T
,
Desrivières
S
,
Grigis
A
, et al
.
Quantifying performance of machine learning methods for neuroimaging data
.
Neuroimage
.
2019
;
199
:
351
65
.
45.
Lundberg
SM
,
Lee
S-I
.
A unified approach to interpreting model predictions
. In:
Guyon
I
,
Luxburg
UV
,
Bengio
S
,
Wallach
H
,
Fergus
R
,
Vishwanathan
S
, et al
, editors.
Advances in neural information processing systems 30 (NIPS 2017)
.
Curran Associates, Inc.
;
2017
. p.
4765
74
.
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