Stimulating Self-Regulation: A Review of Non-invasive Brain Stimulation Studies of Goal-Directed Behavior

Abstract

Self-regulation enables individuals to guide their thoughts, feelings, and behaviors in a purposeful manner. Self-regulation is thus crucial for goal-directed behavior and contributes to many consequential outcomes in life including physical health, psychological well-being, ethical decision making, and strong interpersonal relationships. Neuroscientific research has revealed that the prefrontal cortex plays a central role in self-regulation, specifically by exerting top-down control over subcortical regions involved in reward (e.g., striatum) and emotion (e.g., amygdala). To orient readers, we first offer a methodological overview of tDCS and then review experiments using non-invasive brain stimulation techniques (especially transcranial direct current stimulation) to target prefrontal brain regions implicated in self-regulation. We focus on brain stimulation studies of self-regulatory behavior across three broad domains of response: persistence, delay behavior, and impulse control. We suggest that stimulating the prefrontal cortex promotes successful self-regulation by altering the balance in activity between the prefrontal cortex and subcortical regions involved in emotion and reward processing.

Full text

fnbeh-12-00337 January 16, 2019 Time: 18:45 # 1
REVIEW
published: 18 January 2019
doi: 10.3389/fnbeh.2018.00337
Edited by:
Antonella Gasbarri,
University of L’Aquila, Italy
Reviewed by:
Jacqueline M. Barker,
Drexel University, United States
Davide Crivelli,
Catholic University of Sacred Heart,
Italy
*Correspondence:
Nicholas J. Kelley
nicholasjkelley@gmail.com
Received: 09 March 2018
Accepted: 21 December 2018
Published: 18 January 2019
Citation:
Kelley NJ, Gallucci A, Riva P,
Romero Lauro LJ and Schmeichel BJ
(2019) Stimulating Self-Regulation:
A Review of Non-invasive Brain
Stimulation Studies of Goal-Directed
Behavior.
Front. Behav. Neurosci. 12:337.
doi: 10.3389/fnbeh.2018.00337
Stimulating Self-Regulation: A
Review of Non-invasive Brain
Stimulation Studies of Goal-Directed
Behavior
Nicholas J. Kelley1*, Alessia Gallucci2, Paolo Riva2, Leonor Josefina Romero Lauro2and
Brandon J. Schmeichel3
1Department of Psychology, Northwestern University, Evanston, IL, United States, 2Department of Psychology, University
of Milano-Bicocca, Milan, Italy, 3Department of Psychological and Brain Sciences, Texas A&M University, College Station,
TX, United States
Self-regulation enables individuals to guide their thoughts, feelings, and behaviors
in a purposeful manner. Self-regulation is thus crucial for goal-directed behavior
and contributes to many consequential outcomes in life including physical
health, psychological well-being, ethical decision making, and strong interpersonal
relationships. Neuroscientific research has revealed that the prefrontal cortex plays a
central role in self-regulation, specifically by exerting top-down control over subcortical
regions involved in reward (e.g., striatum) and emotion (e.g., amygdala). To orient
readers, we first offer a methodological overview of tDCS and then review experiments
using non-invasive brain stimulation techniques (especially transcranial direct current
stimulation) to target prefrontal brain regions implicated in self-regulation. We focus
on brain stimulation studies of self-regulatory behavior across three broad domains of
response: persistence, delay behavior, and impulse control. We suggest that stimulating
the prefrontal cortex promotes successful self-regulation by altering the balance in
activity between the prefrontal cortex and subcortical regions involved in emotion and
reward processing.
Keywords: transcranial direct current stimulation, self-regulation, emotion-regulation, goal-directed behavior,
dorsolateral prefrontal cortex
INTRODUCTION
At least since Walter Mischel’s seminal work on delay of gratification (Mischel, 1958;Mischel et al.,
1972), the practical and the theoretical implications of self-regulation have been important topics of
study in psychological science (Carver and Scheier, 1982;Metcalfe and Mischel, 1999;Muraven and
Baumeister, 2000). Self-regulation refers to the conscious and non-conscious processes that enable
individuals to guide their thoughts, feelings, and behaviors in a purposeful manner. Self-regulation
is crucial for goal-directed behavior and has been related to many consequential outcomes in life
including physical and mental health, psychological well-being, ethical decision making, and strong
interpersonal relationships. Likewise, failures at self-regulation are thought to contribute to alcohol
and drug addiction, personal debt, obesity, and other outcomes that carry both personal and societal
costs (for a review, see Vohs and Baumeister, 2016). Because of its consequences for so many crucial
outcomes, the scientific study of self-regulation spans many of subfields in psychological science
and frequently centers on a relatively simple question: How can we improve self-regulatory abilities?
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One possible answer is by stimulating the brain with electrical
current. Self-regulation is typically assessed with laboratory
analogs of common challenges encountered in daily life, such
as persisting at difficult tasks, choosing between immediate
versus more delayed rewards, and managing emotional impulses.
These examples represent paradigmatic forms of self-regulation,
namely persistence, or the sustained performance of aversive
behavior (e.g., tolerating pain, coping with failure); delay
behavior, which refers to choices that favor more long-
term investments at the expense of short-term gains; and
impulse control, which involves the purposeful inhibition of
emotive response tendencies. Below we focus on these three
paradigmatic forms of self-regulation and review experiments
that have used brain stimulation techniques to try to improve
them. We then consider inconsistencies in findings, address
unresolved questions, and point to new directions for future
research.
Neural Correlates of Self-Regulation
Convergent evidence from social, cognitive, and affective
neuroscience research reveals that the interplay between the
prefrontal cortex and subcortical threat and reward processing
is crucial for self-regulation (for a review see: Heatherton and
Wagner, 2011;Kelley et al., 2015b;Berkman, 2017;Wagner and
Heatherton, 2017). Numerous studies have associated successful
self-regulation with top-down control from the prefrontal cortex
over subcortical regions involved in reward and threat processing
(e.g., Dambacher et al., 2014;Giuliani et al., 2014;Vijayakumar
et al., 2014;Lopez et al., 2017). By contrast, self-regulatory failure
occurs when top-down control is diminished or when the balance
in activity favors threat and reward systems (e.g., Demos et al.,
2012;Wagner and Heatherton, 2012;Wagner et al., 2013;Chester
and DeWall, 2014;Lopez et al., 2014;Meyer and Bucci, 2016).
As an illustrative example, in a 40-year longitudinal follow-
up with children who participated in Mischel’s seminal delay of
gratification work, children who successfully delayed gratification
exhibited preferential recruitment of the prefrontal cortex (PFC)
during a task requiring inhibitory control as adults. In contrast,
children who were unsuccessful at delaying gratification showed
preferential recruitment of the ventral striatum in a delay task
as adults (Casey et al., 2011). These findings highlight the
importance of the balance or relative activity levels in the
prefrontal cortex and subcortical regions, respectively, and how
shifts in this balance can tip the scales between short-term and
long-term goal regulation.
Several models of emotion regulation similarly emphasize
the balance in activity between prefrontal and subcortical brain
regions. For example, Ochsner and Gross (2007) proposed a
seminal model of emotion that distinguishes between bottom-
up affective processing, mediated by limbic system structures
such as amygdala, and top-down appraisal processes that
involve prefrontal regions. Success at cognitive reappraisal,
a form of emotion regulation that involves generating cool
cognitive representations of affective states or changing the
meaning of emotional events, is associated with increased activity
in dorsomedial and dorsolateral prefrontal cortices, alongside
corresponding decreases limbic system (i.e., amygdala) activity.
Another relevant model of emotion regulation highlighted
the key role of a cortico-subcortical network consisting in a
dorsal system and a ventral system (Phillips, 2003;Phillips et al.,
2008). The dorsal system encompasses the hippocampus, the
dorsal regions of anterior cingulate gyrus, and the DLPFC and is
involved in executive functions, particularly planning, attention
control, and effortful regulation of affective states. The ventral
system includes the amygdala, the insula, the ventral striatum,
the anterior cingulated cortex, the orbitofrontal cortex, and the
ventrolateral prefrontal cortex (VLPFC) and is predominantly
recruited for the automatic regulation of affective reactions and
for the recognition of emotional valence of stimuli.
Consistent with and prior to these models of emotion
regulation, Botvinick and colleagues (Cohen et al., 2000;
Botvinick et al., 2001, 2004;Shenhav et al., 2013) discussed
cortical-subcortical balance as it relates to cognitive control.
Cognitive control refers to a constellation of functions that
orient cognitive subsystems to perform difficult and novel
tasks (Botvinick et al., 2004). Botvinick and colleagues’ conflict
monitoring hypothesis proposed that response conflict activates
cortical brain regions (i.e., the dorsal ACC), thereby signaling
the need for conflict resolution to facilitate effective behavior
(see MacDonald et al., 2000;Botvinick et al., 2001;Ochsner
et al., 2009). The theoretical models reviewed above suggest that
regulation of both cognition and emotion is contingent upon
the balance in activity between cortical and subcortical regions.
Brain stimulation techniques targeting cortical regions may
thus influence self-regulation by influencing cortical-subcortical
balance.
Overview and Goals
We propose that non-invasive brain stimulation targeting the
prefrontal cortex holds promise for improving human self-
regulation. To orient the reader to neuromodulation, we first
provide a methodological overview of transcranial direct current
stimulation (tDCS) – one of the most popular brain stimulation
techniques in psychological science. Then we review behavioral
evidence that non-invasive brain stimulation targeting the
PFC may enhance three paradigmatic forms of self-regulation:
persistence, delay behavior, and impulse control (see Table 1). We
conclude our review by highlighting inconsistencies in findings,
unresolved questions, and new directions for future research.
A METHODOLOGICAL OVERVIEW OF
tDCS
Effects of weak electrical currents on brain and neuronal function
were first described more than two centuries ago (Priori, 2003;
Nitsche et al., 2008;Zago et al., 2008). Systematic studies
with animals showed the efficacy of inducing modifications,
enhancements, or diminutions of cortical activity by delivering
weak direct currents to the brains of laboratory rats. Specifically,
passing currents through the scalp polarized the brain region
beneath the electrodes and altered the firing rate of neurons.
These effects were detected immediately after the stimulation and
seemed to last beyond the stimulation period (Bindman et al.,
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TABLE 1 | Study features, stimulation parameters, and key outcomes of all studies reviewed.
N Time
(min)
Size
(cm2)
Current
(mA)
Montage Design Outcome
Persistence
20 5 35 2 Sham, anode L DLPFC, M1, V1 W Anode L DLPFC increased pain thresholds (Boggio et al.,
2008)
12 20 35 2 Sham, anode and cathode tDCS over L
and R DLPFC
W Anode R DLPFC increased tolerance to heat (Mylius et al.,
2012)
40 20 15 2 Anode and cathode tDCS over the L
and R DLPFC
W Anode L DLPFC decreased pain (Mariano et al., 2015)
79 20 16 2 Sham, anode L DLPFC, and cathode L
DLPFC
B Cathode L DFLPFC increased pain tolerance (Powers et al.,
2018)
Delay behavior
14 20 9 1.6 Sham, anode L DLPFC/cathode R
DLPFC, cathode L DLPFC/anode R
DLPFC
W Anode L DLFPC increased preference for immediate
rewards (Hecht et al., 2012)
24 20 35 1.5 Sham, anode L DLPFC/cathode R
OFC, cathode L DLPFC/anode R OFC
W Both types of active stimulation increased preference for
larger-but-later rewards (Nejati et al., 2018)
23 20 35 2 Sham, anode L DLPFC/cathode R
DLPFC, and cathode L DLPFC/anode
R DLPFC
W Anode R DLPFC decreased food cravings, visual attention
toward desserts, and consumption (Fregni et al., 2008)
19 20 35 2 Sham and cathode L DLPFC/anode R
DLPFC
W Anode R DLPFC decreased food cravings but not
consumption (Goldman et al., 2011)
10 20 35 2 Sham and cathode L DLPFC/anode R
DLPFC
W Anode R DLPFC reduced consumption and modulated the
N2, P3a, and P3b ERP components (Lapenta et al., 2014)
17 20 25 2 Sham and cathode L DLPFC/anode R
DLPFC
W Anode R DLPFC reduced cravings for sweet but not savory
foods or consumption (Kekic et al., 2014)
30 20 35 2 Daily sham or anode R DLPFC for
5 days
B Anode R DLPFC reduced food cravings up to 30 days later
(Ljubisavljevic et al., 2016)
30 20 25 2 Sham and cathode L DLPFC/anode R
DLPFC
W Anode R DLPFC reduced cravings and consumption
(Burgess et al., 2016)
Impulse control
20 15 5.3 0.45 Sham, anode L DLPFC, and anode R
DLPFC
W Anode R DLPFC combined with a cognitive reappraisal task
reduced negative emotions (Pripfl and Lamm, 2015)
96 20 25/35 1.5 Sham or anode R VLPFC B Anode R VLPFC reduced the perceived intensity of negative
emotions (Vergallito et al., 2018)
60 15 35 2 Sham, cathode L DLPFC/anode R
DLPFC, or anode L DLPFC/cathode R
DLPFC
B Anode L DLPFC caused more aggression in angry
participants (Hortensius et al., 2012)
32 12.5 35 2 Sham or anode R DLPFC B Anode R DLPFC reduced proactive aggression in men
(Dambacher et al., 2014)
64 21.75 35 1.5 Sham, cathode L IFG/anode R IFG, and
anode L IFG/cathode R IFG
B No effect of IFG stimulation on response inhibition or
aggression (Dambacher et al., 2015b)
90 15 35 2 Sham, cathode L DLPFC/anode R
DLPFC, and anode L DLPFC/cathode
R DLPFC
B Anode R DLPFC increased rumination (Kelley et al., 2013)
202 15 35 2 Sham, cathode L DLPFC/anode R
DLPFC, and anode L DLPFC/cathode
R DLPFC
B Anode R DLPFC sped up motive incongruent responses
(Kelley and Schmeichel, 2016)
14 20 32 2 Five days of twice daily anode L
DLPFC/cathode R DLPFC
N/A Anode L DLPFC reduced sadness up to 30 days after
treatment (Ferrucci et al., 2009)
10 20 35 1 Daily sham or anode L tDCS B Anode L DLPFC reduced depressive symptoms (Fregni
et al., 2006)
23 5 35 2 Sham, anode L DLPFC, M1, V1 W Anode L DLPFC increased accuracy in identifying positive
pictures (Boggio et al., 2009)
80 20 35 2 Sham and anode R IFG B Anode R IFG decreased sustained fear and skin
conductance levels to unpredictable threats (Herrmann
et al., 2017)
(Continued)
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TABLE 1 | Continued
N Time
(min)
Size
(cm2)
Current
(mA)
Montage Design Outcome
45 30 25 1 Sham and either cathode L DLPFC/anode R
DLPFC, or anode L DLPFC/cathode R DLPFC
W Anode L DLPFC improved performance and decreased
cortisol among participants high in ma anxiety (Sarkar et al.,
2014)
47 20 25 1 Sham and anode L DLPFC B Anode L DLPFC enhanced fear memories (Mungee et al.,
2014)
17 20 25 1 Sham and cathode R DLPFC B No effect of cathode R DLPFC on fear memories (Mungee
et al., 2016)
80 20 25/35 1.5 Sham and anode R VLPFC B Anode R VLPFC reduced aggression after social exclusion
(Riva et al., 2012)
79 15 25/35 1.5 Sham and anode R VLPFC B Anode R VLPFC reduced negative feelings after social
exclusion (Riva et al., 2014a)
20 25/50 1.5 Sham and anode R VLPFC B Anode R VLPFC reduced unproved aggression in
violent-game players (Riva et al., 2017)
92 15 35 2 Sham, cathode L DLPFC/anode DLPFC, and
anode L DLPFC/cathode R DLPFC
B Anode L DLPFC increased jealousy after social exclusion
(Kelley et al., 2015a)
16 20 35 1 Sham and anode L DLPFC W Negative pictures rated less negative after anode tDCS over
the L DLPFC (Peña-Gómez et al., 2011)
48 20 35/100 1.5 Sham and anode R DLPFC B Anode R DLPFC enhanced cognitive control during
emotion regulation (Feeser et al., 2014)
35/12 20 35 2 S1: Bilateral DLPFC S2: Unilateral DLPFC B Bilateral DLPFC tDCS modulated decision making (Fecteau
et al., 2007b)
36 35 2 Sham, cathode L DLPFC/anode DLPFC, and
anode L DLPFC/cathode R DLPFC
B Anode R DLPFC reduced risk taking (Fecteau et al., 2007a)
16 19 35 2 Sham, cathode DLPFC/anode R DLPFC, and
anode L DLPFC/cathode R DLPFC
W Anode stimulation over the R DLPFC reduced risky
decision-king (Cheng and Lee, 2016)
30 25 25 2 Twice daily sham or anode R DLPFC/cathode L
DLPFC for 5 days
B Active tDCS paired with the cognitive task reduced
risk-taking This effects persisted 2 months (Gilmore et al.,
2017)
20 15 25 1.5 Sham or anode R DLPFC/cathode L DLPFC B Anode R DLPFC caused greater R DLPFC-whole brain
connectivity which was associated with reduced risk-taking
(Wacker et al., 2008)
24 15 35 1 Anode and cathode R DLPFC or anode and
cathode L DLPFC
W Anode DLPFC (either L or R) led to reduced risk taking on a
driving simulation (Beeli et al., 2008)
DLPFC, dorsolateral prefrontal cortex; VLPFC, ventrolateral prefrontal cortex; L, left; R, right; B, between-subjects; W, within-subjects.
1964;Gartside, 1968;Hattori et al., 1990;Islam et al., 1995).
Early research in human samples investigated the application
of electrical currents in mood disorders treatment, with some
evidence suggesting a reduction in symptoms of depression and
mania (Costain et al., 1964;Carney, 1969). But subsequent studies
and null findings contributed to skepticism in the efficacy of
running weak electrical currents into the brain as an effective tool
for symptom reduction (Lolas, 1977;Nitsche et al., 2003b). More
recently, researchers have shed light on bidirectional, time, and
polarity-dependent excitability changes following tDCS (Priori
et al., 1998;Nitsche and Paulus, 2000).
How Does tDCS Work?
The tDCS device consists of an electric stimulator, which delivers
a constant current and an isolation current, linked to a pair
of electrodes positioned on the scalp over cortical regions
of interest. The electrodes, namely an anode and a cathode,
are typically covered by sponges soaked in NaCI solution (or
electrode cream) to increase conductivity, reduce resistance,
and improve the homogeneity of the electric field under the
electrodes.
Transcranial direct current stimulation differs from other
brain stimulation techniques, such as transcranial electrical
stimulation (TES) and transcranial magnetic stimulation (TMS),
because tDCS does not induce action potentials in neuronal
membrane. Instead, tDCS transiently modifies spontaneous
neuronal excitability by depolarizing or hyperpolarizing neurons’
resting membrane potentials, producing ionic concentration
shifts within the extracellular fluid (Creutzfeldt et al., 1962;
Purpura and McMurtry, 1965). Anodal stimulation typically
depolarizes local neurons, which in turn will require less dendritic
input to fire, whilst cathodal stimulation hyperpolarizes neurons’
typical resting membrane potentials so that increasing dendritic
input is required (Nitsche and Paulus, 2000). This mechanism of
action generally occurs both during stimulation and for a short
period of time (<5 min) thereafter.
Transcranial direct current stimulation has been found
to involve more complex mechanisms including long-term
potentiation (LTP) and long-term depression (LTD) mechanisms
at the synaptic level, affecting hyper-communicative activity
through the anode and hypo-communicative activity through
the cathode. These tDCS-driven changes in LTP and LTD may
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be mediated by a number of synaptic mechanisms including:
NMDA (N-methyl-D-aspartate) receptors, GABAergic activity,
glutamatergic activity, intracellular CA2+concentration, brain-
derived neurotrophic factor (BDNF) secretion, and tropomyosin-
related kinase B (TrkB) activation (Liebetanz et al., 2002;Nitsche
et al., 2003a, 2004;Stagg et al., 2009;Fritsch et al., 2010;Stagg and
Nitsche, 2011). Also, non-synaptic mechanisms, such as changes
in pH and transmembrane proteins, seem to be involved in
long-term effects of tDCS (Ardolino et al., 2005).
Parameters Influencing Stimulation
Efficacy
The efficacy of eliciting changes in brain activity using tDCS
depends on several physical parameters including current
density, stimulation duration, and the orientation and focality of
the electrical field. These parameters constitute the tDCS dosage.
Current Density
Current density represents the ratio between current strength
(normally up to 2 mA) and electrode size (normally reference
electrode varies from 25 to 35 cm2). Current density determines
the delivered electrical field strength (Purpura and McMurtry,
1965).
Stimulation Duration
Stimulation duration refers to the amount of time participants
undergo stimulation. It is based on LTP and LTD mechanisms
and is related to the occurrence and length of aftereffects.
Generally, keeping current density constant, brief exposure to
tDCS stimulation (few seconds) does not induce long-lasting
effects, whereas tDCS stimulations of about 10 min (up to 30 min)
typically do elicit aftereffects (Nitsche et al., 2003c;Ardolino et al.,
2005).
Orientation of the Electric Field
The orientation of the electric field normally depends on
electrodes’ polarity and position. As already described, tDCS
produces polarity-dependent effects whereby anodal stimulation
increases the activity of the stimulated area, whereas cathodal
stimulation decreases it. Several studies of both the primary
motor and visual cortices have found that different electrode
positions modulate different neuronal groups and elicit different
evoked potentials (Priori et al., 1998;Antal et al., 2004;Accornero
et al., 2007) suggesting that electrode position is a crucial tDCS
parameter.
Indeed, not only may electrode position affect the amount of
current delivered to the brain and the direction of current flow,
but also it may determine effects on the targeted brain region, due
to electrical field interactions associated with neuronal geometry
(Nitsche and Paulus, 2000;Nitsche et al., 2008). Whereas the
coupling of anodal-excitatory and cathodal-inhibitory effects
is well established in the sensorimotor domain, evidence gets
more controversial when addressing higher cognitive functions
(Jacobson et al., 2012). This lack of consistency between
sensorimotor and cognitive functions is at this output level. It is
not that the inconsistencies arise from differences in the effects
of stimulation on sensorimotor cortices versus prefrontal cortices
themselves. In other words, the inconsistency is not the result in
differences in the effects of the stimulation protocol on activity
or function but rather the consequence of those changes. Indeed,
when dealing with more complex functions, likely represented
by large and interconnected neural networks comprising both
excitatory and inhibitory connections, it is more difficult to
obtain a predictable outcome, hence it is not always the case that
anodal tDCS leads to an enhancement (e.g., better performance
in a task) and cathodal tDCS leads to a diminution of the assessed
cognitive function (Fertonani and Miniussi, 2017).
Induced Electric Field Focality
Another important tDCS parameter is the induced electric field
focality. Generally, large electrodes and bipolar scalp electrode
arrangements limit tDCS focality (Gandiga et al., 2006), in part
because large electrodes may alter activity in areas adjacent to
the stimulated region. Moreover, with an intracephalic montage,
the so-called reference electrode (the secondary electrode with
regard to a specific experimental setting), being located on the
scalp, is not entirely inert. The lack of spatial focality of tDCS
effects suggests the need for arrangements to increase focality.
For instance, to increase tDCS focality it is possible to use smaller
target electrodes. Another option is to increase the reference
electrode size so that, due to decreased current density, it becomes
practically inert. Alternatively, using an extracephalic montage
may increase stimulation focality (Nitsche et al., 2007, 2008;
Ferrucci et al., 2008), although in this case the spread of current
flow could be hardly traceable. In any case, widespread (non-
focal) effects of tDCS should be taken into account, considering
that functionally active cortical targets may be more susceptible to
excitability changes induced by tDCS. Lack of spatial focality may
undermine tDCS effectiveness in performing cortical mapping,
but the idea that widespread cortical networks are affected by
tDCS could explain the strength of the observed behavioral
effects, in some cases lasting for months after several stimulation
sessions are performed, thus supporting the possible benefits of
this technique for clinical applications.
Underlying Neural Activity
Studies using fMRI to assess online and offline tDCS effects have
found that anodal and cathodal stimulation elicit, respectively, an
increment and a decrement of perfusion in a wide set of brain
areas, including cortical and subcortical structures, even at some
distance from the target area (e.g., Stagg et al., 2013). Similarly,
computational models of current flow have indicated that strong
electric fields occur not only underneath and near the stimulating
electrodes but also in the regions between them (Miranda et al.,
2013). Consistent with the computational modeling studies noted
above, recent findings have observed tDCS effects on both
structural and functional connectivity (Romero Lauro et al., 2014,
2016;Pisoni et al., 2017).
Practical Considerations
Sham Stimulation
Regarding its practical applications, tDCS, allows for more
effective placebo stimulation-controlled studies compared to
TMS where notable issues with placebo effects and limited
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blinding success (Duecker and Sack, 2015). Placebo (sham)
stimulation can be delivered for few seconds and subjects
experience the same physical sensations as real stimulation
(e.g., itching sensation), without substantial neural or behavioral
effects (Gandiga et al., 2006;Nitsche et al., 2008).
Individual Differences
Another practical consideration concerns individual differences.
Following seminal work in the tDCS literature (e.g., Nitsche
et al., 2008) we recommend that participants be matched on
individual differences like sex or age that can influence tDCS
efficacy (Pitcher et al., 2003;Kuo et al., 2006;Quartarone et al.,
2007;Chaieb et al., 2008). In addition to demographic factors,
researchers should also consider whether participants respond to
tDCS protocols. In two motor cortex studies, anodal stimulation
increased cortical excitability in 50–64% of participants (Wiethoff
et al., 2014;López-Alonso et al., 2015). These individual
differences highlight the need to develop more robust stimulation
protocols and well-powered studies which can systematically test
for the moderating role of individual differences.
Safety
Transcranial direct current stimulation is a safe and non-invasive
neuromodulatory technique. Several neuroimaging and EEG
studies have demonstrated that tDCS does not cause adverse
effects on the brain (Nitsche et al., 2004;Iyer et al., 2005).
The most common side effects include mild tingling sensations,
moderate fatigue and light itching sensations, especially at
stimulation onset (e.g., Poreisz et al., 2007) and stimulation
sessions up to 50 min do not cause serious consequences (Nitsche
et al., 2008). Moreover, ramping up and ramping down current at
the beginning and at the end of a stimulation session is useful to
avoid brief retinal phosphenes or startle-like phenomenon caused
by sudden neuronal firings.
To summarize, tDCS is a safe, inexpensive, well-tolerated,
and easy to use. Its physiological consequences have led to an
increasing interest in using tDCS to alter psychological processes.
With an appreciation for the history and mechanics of tDCS, the
next section will explore the consequences of prefrontal tDCS
psychological processes in the domain of self-regulation.
TRANSCRANIAL DIRECTION CURRENT
STIMULATION AND SELF-REGULATION
Persistence
Self-regulation enables individuals to guide their thoughts,
feelings, and behaviors in a goal-directed fashion. Self-regulation
can be aversive both physically and psychologically. Goal directed
behavior often entails persistence, including the sustained
performance of aversive behavior. For example, physical exercise
sometimes elicits short-term pain or physical discomfort but
also brings more long-term appearance- and health-related
benefits. Individuals who are better able to endure the discomfort
presumably exercise longer and more frequently. As a result,
these same individuals may be more successful at achieving their
fitness goals. Other situations may require individuals to endure
psychologically aversive states in the interest of accomplishing
one’s goals. For example, academic and occupational successes
may entail many failed attempts to solve complex problems. The
ability to endure these aversive states seems likely to facilitate
goal-directed behavior and thus may constitute an important
facet of self-regulation.
Pain Tolerance
Research suggests that the DLPFC is a key brain region for
various aspect of pain, including pain tolerance (see Seminowicz
and Moayedi, 2017). Consistent with this viewpoint, several
studies have used prefrontal tDCS to modulate the experience of
pain in laboratory tasks. For example, Mylius et al. (2012) found
that anodal tDCS over the right DLPFC increases tolerance to
heat pain as measured by the temperature of a thermode applied
to the forearm. Similar results were obtained by Boggio et al.
(2008), who found that excitatory stimulation of the left DLPFC
increases pain thresholds. Taken together, these findings suggest
that stimulation to the prefrontal cortex in either hemisphere may
increase pain tolerance – a classic form of self-regulation.
More recently, a study by Mariano et al. (2016) applied
anodal versus sham tDCS during both a cold pressor task
and a breath holding task (see also Mariano et al., 2015, for
similar work probing the dorsal anterior cingulate cortex).
These two tasks represent commonly used laboratory pain
paradigms. Participants’ pain ratings were assessed before and
after stimulation using the Defense and Veterans Pain Rating
Scale (DVPRS), which asks participants to rate their pain on an
11-point visual analog scale from 0 = no pain to 10 = severe pain.
Ratings were obtained after the first 7 min of tDCS in each testing
block and immediately after the cold pressor and breath holding
tasks. Stimulation did not influence performance on the cold
pressor task as measured by threshold, tolerance, or endurance,
nor did it influence breath holding time. However, anodal
stimulation over the left DLPFC decreased the experience of pain
as measured by the DVPRS. This study suggests that excitatory
stimulation of the DLPFC may influence pain perception.
Another relevant pilot study by Powers et al. (2018) paired
anodal, cathodal, or sham stimulation over the left DLPFC with
either pain education or a 3-min audio recording designed
to mimic key components of Cognitive-Behavioral Therapy
for pain. Afterward, participants completed five trials of a
heat tolerance pain test. Regardless of which intervention was
paired with tDCS, cathodal stimulation over the left DFLPFC
increased pain tolerance. But several limitations in this study
mar the interpretability of the results. First, the study included
6 experimental conditions with 79 total participants, resulting
in small sample sizes in each condition and thus relatively
low statistical power to detect anything but very large effects
of tDCS. Second, the electrode montage involved placing the
anode or cathode over the F3 region and the other electrode
on the right shoulder. The study by Mariano et al. (2016)
reviewed above, which found reduced pain experience but not
increased pain tolerance, used the mastoid as a reference, whereas
the study by Mylius and colleagues, which found increased
pain tolerance, involved placing the reference electrode over
the contralateral supraorbital area. Thus, inconsistencies in the
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electrode montages used across studies of prefrontal tDCS and
pain, along with differences in methods used to induce and
measure pain, hamper our ability to draw clear conclusions about
the effects of tDCS on pain experience and pain tolerance.
Delay Behavior
Often one’s end goals are situated far in the future, and pursuing
such goals comes at the cost of satisfying more immediate desires.
Saving for the future comes at the cost of spending today.
Maintaining a healthy physique comes at the expense of delicious
desserts. Academic achievement often comes at the expense of
fraternization. Delay behavior refers to choices that favor more
long-term investments at the expense of short-term gains. To the
extent that individuals stifle or subdue their immediate urges, the
better they are in striving toward their long-term goals.
Delay Discounting
Delay discounting refers to the reduction in the present value
of a reward with delayed receipt. The basic idea is that the
valuation of rewards degrades over time. So, for example, gaining
$10 today would typically be valued more than gaining $10 in a
month from today. For each unit of time increase in the delay
to receipt, the value of a reward decreases (or is discounted)
by a non-fixed proportion. In other words, the effect of delay
on value is not the same across the range of delays. At short
delays value decreases less steeply, whereas at longer delays
value degrades more steeply. A hyperbolic discounting function
captures the pattern that at shorter delays reward valuation
degrades less than it does at longer delay periods. The steepness
of the slope within this hyperbolic model reflects the extent to
which people prefer smaller-but-immediate (compared to larger-
but-delayed) rewards. A steep slope (i.e., a larger hyperbolic k)
reflects a stronger preference for smaller-but-immediate rewards.
A less steep slope (i.e., a smaller hyperbolic k) reflects a
stronger preference for larger-but-delayed rewards. Typically,
a preference for smaller-but-immediate rewards is thought to
reflect impulsivity (poor self-regulation) whereas a preference for
larger-but-delayed rewards is thought to reflect self-control (good
self-regulation).
Hecht et al. (2012) paired prefrontal tDCS with a delay
discounting task. Specifically, participants received anodal right
DLPFC/cathodal left DLPFC, cathodal right DLPFC/anodal left
DLFPC, or sham stimulation. They observed a greater preference
for smaller-but-sooner rewards when participants had received
anodal stimulation over the left DLFPC, suggesting that this
pattern of stimulation increased impulsivity or reduced self-
regulation. Similar results have been obtained in TMS studies
disrupting right DLPFC activity (Figner et al., 2010;Smittenaar
et al., 2013). More recently, a study by Nejati et al. (2018)
paired DLPFC stimulation with OFC stimulation prior to a
delay discounting task. Specifically, participants received sham
stimulation, anodal left DLPFC/cathodal right OFC, and cathodal
left DLPFC/anodal right OFC. They observed that relative to
sham stimulation, both active stimulation conditions caused a
greater preference for delayed rewards as reflected in a smaller
kvalue. The results of this study hinge upon the interaction
between the DLPFC and OFC and as a result we cannot
determine to what extent they were driven by the DLPFC (or
OFC). Because of this, the study by Nejati and colleagues differs
in a critical way from the discounting studies reviewed above as
those studies speak moreso to the role of hemispheric asymmetry
in discounting behavior. Thus, the majority of evidence here
suggests that stimulation to shift the balance in neural activity
toward the left prefrontal cortex increases delay discounting in
a manner that suggests poorer self-regulation.
Food Choice
Food choice and eating entail delay behavior insofar as
choosing nutritious foods (e.g., vegetables) over tempting ones
(e.g., chocolate cake) represents a choice favoring long-term
investments in health at the expense of a short-term hedonic
gain. Fregni et al. (2008) compared excitatory right DLPFC
stimulation (cathode over F3/anode over F4), excitatory left
DLPFC stimulation (anode over F3/cathode over F4), and sham
stimulation in the context of food. Self-report measures of
food craving and craving in response to food in the laboratory
were assessed before and after tDCS. Additionally, after tDCS,
participants had their gaze patterns recorded while they viewed
an array of nature scenes and images of tempting foods (e.g.,
desserts). Last, participants had the opportunity to ingest foods
and the number of calories ingested was recorded. Results
indicated that excitatory right DLPFC stimulation decreased food
cravings, decreased visual attention toward tempting desserts,
and decreased caloric consumption relative sham stimulation.
Goldman et al. (2011) conducted a similar experiment in
a group of healthy individuals with frequent food cravings.
Participants viewed food images from the International Affective
Picture System (IAPS; Lang et al., 2008) before and after tDCS.
Additionally, after stimulation, participants were free to eat a
variety of tempting foods including chips, cookies, chocolate,
and donuts. Consistent with the results of Fregni et al. (2008),
Goldman and colleagues found that excitatory right DLPFC
stimulation (cathode over F3/anode over F4) decreases food
cravings, especially for sweets. Unlike the study by Fregni
et al., however, the study by Goldman et al. did not find that
tDCS influences food consumption. Thus, stimulation over the
right prefrontal cortex appears to influence self-regulation in
the context of desire for tempting foods but has seemingly
inconsistent effects on consumption.
More recently, a study by Lapenta et al. (2014) found that
excitatory stimulation over the right DLPFC reduces caloric
ingestion and food intake (e.g., cakes and sweets). Additionally,
after stimulation participants completed a GO/NO-GO task while
EEG was recorded. Excitatory stimulation over the right DLPFC
modulated the N2, P3a, and P3b ERP components. All three of
these components have been implicated in successful inhibitory
control during GO/NO-GO tasks (e.g., Albert et al., 2013).
This study thus provides more direct evidence that tDCS over
prefrontal cortex influences regulatory mechanisms, which in
turn influence food choice behavior.
Kekic et al. (2014) compared excitatory right DLPFC
stimulation (cathode over F3/anode over F4) to sham stimulation
as participants completed both a food craving questionnaire and
a food challenge task before and after stimulation. The food
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challenge task consisted of two parts. First, participants watched
two short videos of tempting foods (e.g., chocolate). Next, each
of the foods from the videos was made available to participants
in the laboratory. At this point participants rated their desire
to eat and emotional reactions to each of the presented foods.
After stimulation, participants were left alone with the foods and
instructed to eat what they would like while the experimenter was
out of the room. Consistent with past research (e.g., Fregni et al.,
2008;Goldman et al., 2011), excitatory right DLPFC stimulation
reduced cravings for sweet but not savory foods on the food
challenge task. Much like the findings from Goldman et al. these
effects did not extend to influence actual consumption during the
free eating portion of the task. Kekic et al. further reported that
the tDCS-driven reductions in cravings were more pronounced
among participants with low (versus high) delay discounting
tendencies. This pattern suggests that it was easier to modulate
food-related cravings in individual relatively low in impulsivity
(high in self-control).
Ljubisavljevic et al. (2016) explored the consequences of
repeated stimulation over the DLPFC on food craving. In their
study, participants received excitatory right DLPFC stimulation
for five consecutive days. Replicating past research, a single
session of excitatory right DLPFC stimulation reduced the
intensity of food craving. The effects of five consecutive days of
stimulation reduced cravings both immediately and 30 days later.
The craving reductions were most pronounced for fast foods
and desserts. These effects were not moderated by participants’
weight at the beginning of the study, nor did the stimulation
protocol influence weight assessed 30 days later. Another study
using a repeated stimulation design found that stimulation for
8 straight days reduced both self-reported appetite and caloric
consumption during a free eating buffet on the last day of
stimulation (Jauch-Chara et al., 2014).
Inspired by the evidence linking excitatory right DLPFC
stimulation to reductions in food cravings, Burgess et al.
(2016) extended this body of research by testing a sample of
participants with clinical or subclinical binge eating disorder.
They observed that excitatory right DLPFC stimulation not only
reduced cravings across food categories but also decreased desire
to binge eat and decreased food consumption. In summary,
research using tDCS to influence delay behavior has occasionally
tested delay discounting for monetary rewards, and the evidence
suggests that a left lateralized pattern of prefrontal stimulation
induces a more impulsive preference for immediate rewards.
Even more studies have concentrated on the domain of food
craving and food consumption. Much of this work has found that
excitatory stimulation over the right DLPFC decreases cravings
for unhealthy foods, and in some cases this stimulation pattern
also decreased actual consumption.
Why does tDCS seem more likely to reduce craving but not
consumption as the studies above suggest? It may be that cravings
or subjective responses are easier to modulate with tDCS (and
other interventions) than consumption or behavior. The fact that
more of the studies reviewed above find craving effects than
consumption effects is consistent with this view.
In the case of studies where cravings are reduced but
not reduced consumption, in these studies it may be the
case that craving was not reduced enough to reduce eating.
Additional consumption without craving (or low levels of
craving) may reflect a form of dysregulation suggesting
more automatic/habitual factors may influence consumption
independent of craving (e.g., mindless eating). These reasons
suggest that many contextual factors may make detecting links
between impulse and consumption more difficult.
Impulse Control
Impulse control involves the inhibition of emotive response
tendencies. It plays a key role in diverse behavioral domains
including emotion regulation, prosocial behavior, and risk taking.
Emotion Regulation
Emotions are not always functional. For example, emotions
may work against one’s goals when they are expressed at
the wrong time or at an inappropriate level of intensity
(Taylor and Liberzon, 2007). Emotion regulation refers to
the conscious and non-conscious processes individuals use
to influence the intensity, variety, and duration of their
emotions (Gross, 1998, 2001). Antecedent-focused emotion
regulation strategies aim to modulate emotional responses
before they solidify, whereas response-focused strategies aim
to modulate emotional responses that have already been
initiated (Gross, 1998, 2001). Neurobiological models of emotion
regulation distinguish between bottom-up emotion regulation
(e.g., expressive suppression) mediated by limbic system
structures, such as amygdala, and top-down emotion regulation
(e.g., cognitive reappraisal), which involves prefrontal regions
(e.g., Ochsner and Gross, 2007).
Current neural models of emotion regulation (e.g., Phillips,
2003;Phillips et al., 2008) further distinguish between
deliberate, conscious emotion regulation processes, which
involve specifically the DLPFC, and more automatic, implicit
regulation, which predominantly recruits the VLPFC (Chaiken
and Trope, 1999;Strack and Deutsch, 2004;Mauss et al., 2007).
Although emotion regulation typically recruits a wide range of
cortical and subcortical structures, the DLPFC and the VLPFC
constitute two central hubs in emotion regulation processes.
These two regions contribute also to other forms of self-control,
including motor control, risk-taking behavior regulation, task
switching, response inhibition, and conflict monitoring (Braver
et al., 2003;Aron et al., 2004;Berkman et al., 2009).
Evidence from fMRI research regarding the contributions
of VLPFC and DLPFC to emotion regulation paved the way
for the application of non-invasive brain stimulation to these
regions to investigate stimulation effects on both explicit and
implicit control strategies. For instance, one study tested the
hypothesis that a top-down form of antecedent-focused emotion
regulation – cognitive reappraisal – involves DLPFC. Indeed,
anodal tDCS over the right DLPFC combined with a cognitive
reappraisal task reduced negative emotions (but not positive
emotions or craving) compared to anodal tDCS over the left
hemisphere and sham stimulation (Pripfl and Lamm, 2015). This
pattern of finding corroborates the widely established role of
the right hemisphere in painful or aversive feelings (Canli et al.,
1998;Kalisch et al., 2006;Baek et al., 2012;Herrmann et al.,
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2016, 2017;Salas et al., 2016;Mattavelli et al., 2017), but in this
case stimulation to increase activity over right DLPFC reduced
negative emotions. This perspective is further supported by the
evidence that anodal tDCS over the right VLPFC, compared with
sham stimulation, reduces the perceived intensity of negative (i.e.,
fear, anxiety, and sadness) but not positive or neutral emotions
induced by film clips (Vergallito et al., 2018). In this study,
participants were not explicitly instructed to apply any regulation
strategy, suggesting a role for the VLPFC in incidental or implicit
emotion regulation. In the next paragraphs we review tDCS
effects on negative emotions, empathy, and social pain. Most of
the reported studies have tested tDCS application on prefrontal
cortex, mainly on DLPFC and VLPFC.
Anger and Aggression
Anger and aggression are associated with the activation of
the behavioral approach system (Harmon-Jones and Sigelman,
2001;Harmon-Jones, 2003). The behavioral approach system is
associated with greater left than right frontal cortical activity
(Wacker et al., 2008;Zinner et al., 2008;Harmon-Jones
et al., 2010). Using tDCS in laboratory aggression paradigms,
several researchers have found additional support for a causal
relationship between greater relative left frontal cortical activity
and approach motivation.
Hortensius et al. (2012) asked participants to write a short
essay on a controversial topic (e.g., abortion) before receiving
insulting feedback on their essay from another ostensibly real
participant. After writing the essay but before receiving the
insulting feedback, participants received 15 min of tDCS. By
random assignment some participants received stimulation to
increase in relative left frontal cortical excitability (anodal over
F3/cathode over the F4), increase in relative right frontal
cortical excitability (cathode over F3/anode over F4), or sham
stimulation. After tDCS, participants played a competitive
reaction time game against the purported insulter. The game
was based on the Taylor aggression paradigm (Taylor, 1967).
Aggression was operationalized as the duration and intensity of
a noxious noise blast given to the other participant. Participants
also reported how much anger they felt both pre- and post-insult.
Results indicated that after receiving tDCS to increase relative left
frontal cortical activity, individuals behaved more aggressively
toward the other participant, but only when they also reported
high insult-related anger. In other words, stimulation to increase
relative left frontal activity strengthened the link between anger
and aggression.
Dambacher et al. (2015b) also combined tDCS over the
DLFPC with the Taylor aggression paradigm. They found that
stimulation to increase relative right frontal activity reduced
aggression. Taken together with the results of Hortensius et al.
(2012), these results suggest that manipulating frontal asymmetry
with tDCS can modulate aggressive behaviors in a manner
consistent with previous correlational work linking aggression
to relative left frontal asymmetry: increasing relative left frontal
activity increases aggression (especially among angry individuals;
Hortensius et al., 2012) whereas increasing relative right frontal
activity reduces aggression using the same Taylor aggression
paradigm (Dambacher et al., 2015b). Unfortunately, Dambacher
and colleagues did not include a condition to increase relative left
frontal activity, so, they were unable to test whether increased left
frontal activity increases aggressive behavior, as was the case for
angry individuals in the study by Hortensius et al. (2012).
One difference between the results of Hortensius et al. (2012)
and Dambacher et al. (2015b) is that the former found a main
effect of tDCS on aggressive behavior whereas the latter did
not. Rather, Hortensius et al. found a moderated pattern of
results whereby anodal stimulation over the left DLPFC/cathodal
stimulation over the right DLPFC increased aggression only
for those high in insult-related anger. The studies differed
insofar as Dambacher et al.’s study included two experimental
conditions, whereas Hortensius study included three conditions.
Moreover, another study (Dambacher et al., 2015a) did not
find an effect of stimulation condition on aggressive behavior.
Although this latter study did include all three stimulation
conditions as in Hortensius et al. (2012), stimulation occurred
over the F7/F8 prefrontal regions, whereas Hortensius et al. and
Dambacher stimulated over the F3/F4 prefrontal regions. Thus,
methodological differences preclude a direct comparison of these
studies. Despite modest support for the effect of asymmetrical
frontal cortical activity on aggressive behavior, further research
is needed.
One common response to negative emotions, like anger,
is rumination, which is an automatic cognitive process
characterized by repetitive and distressful thoughts (Denson
et al., 2006;Wade et al., 2008). Parallel literatures on depression
(e.g., Heller et al., 1995;Nolen-Hoeksema, 2000) and anger (e.g.,
Bushman, 2002) have developed competing hypotheses about
how rumination relates to lateralized patterns of prefrontal
cortical activity. The depression literature links rumination to
an increase in right frontal cortical activity, whereas the anger
literature links rumination to an increase in left frontal cortical
activity.
A study by Kelley et al. (2013) tested these two competing
hypotheses by delivering anodal or cathodal tDCS over the
right or left frontal cortex while participants received negative
(insulting) ratings on their essay writing. Results supported
the rumination-depression literature in showing that anodal
stimulation over the right frontal cortex, compared with the
other stimulation conditions, caused enhanced rumination. This
study left open the question of what this increase in rumination
means. One option flowing from the rumination-depression
literature is that an increase in right lateralized frontal brain
activity reflects an increase in avoidance motivation; the stronger
the avoidance motivation, the greater the rumination. Another
possibility, which may align with the rumination-aggression
literature, is that the increase in right frontal activity reflects
an increase in inhibition rather than avoidance motivation.
Therefore, when considering the increasing of right frontal cortex
activity, anger is still experienced, but inhibited; conversely
left frontal cortex activation is linked to an approach-oriented
motivation. Consistent with the latter interpretation, Kelley et al.
observed an association between rumination and behavioral
inhibition sensitivity (BIS; Carver and White, 1994), which is
thought to reflect inhibition more so than avoidance (e.g., Neal
and Gable, 2017).
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A follow-up study further explored the consequences of
excitatory tDCS over the right DLPFC for inhibitory processing.
A meta-analysis of neuroimaging studies using a Go/No-Go
task found a broad pattern of right frontal cortical activation
during response inhibition (Swick et al., 2011). A separate EEG
literature has often found that right lateralized frontal EEG alpha
asymmetry is associated with exaggerated avoidance-motivated
reactions to aversive events (Tomarken et al., 1990;Dawson et al.,
1992;Wheeler et al., 1993;Kalin et al., 1998;Coan et al., 2001).
These literatures suggest competing hypotheses regarding the
psychological correlates of activity in the right frontal lobe.
Kelley and Schmeichel (2016) used tDCS to test the competing
hypotheses. One hypothesis, flowing from the frontal EEG
literature, is that excitatory stimulation over the right DLPFC
should increase avoidance motivation. A second hypothesis,
flowing from the neuroimaging findings, is that excitatory
stimulation over the right DLPFC should increase response
inhibition. The key to differentiating these two hypotheses is to
test the effects of stimulation over right DLPFC on the inhibition
of avoidance-oriented impulses. Kelley and Schmeichel paired
tDCS with an approach-avoidance task whereby participants
enacted motive incongruent motor responses to appetitive and
aversive IAPS images. Specifically, participants in the positive
emotion condition pushed away positive images whereas those
in the negative emotion condition pulled negative images toward
them. These responses require inhibitory control insofar as
avoiding rewards and approaching threats requires one to
override a predominant response tendency.
The results revealed that anodal stimulation over the right
frontal cortex facilitates the inhibition of both approach-
incongruent and avoidance-incongruent responding. These
results are not readily explained by an increase in avoidance
motivation. Indeed, an increase in avoidance motivation would
have slowed the enactment of an avoidance-incongruent
response. But Kelley and Schmeichel (2016) found that
stimulation over the right DLPFC sped up both avoidance- and
approach-incongruent responding. This study thus supported the
hypothesis that increasing right frontal cortical activity increases
response inhibition.
Sadness
Several studies have concentrated on testing tDCS efficacy
in sadness regulation, which has important implications for
considering tDCS as a treatment device for major depression.
Indeed, it has been widely observed that major depression is
associated with an asymmetry in prefrontal cortical activity,
specifically hypoactivity in the left DLPFC and hyperactivity in
the right DLPFC. For instance, one study found that five sessions
of bilateral, twice-a-day tDCS over the DLFC (anode left/cathode
right) decreased self-reported sadness in a group of patients with
severe, drug-resistant major depression. These improvements
lasted up to a month after the end of the treatment (Ferrucci
et al., 2009). These findings are in line with a growing body of
evidence that tDCS can be effective for treating the symptoms of
major depression (for a review, see Nitsche et al., 2009). Indeed, a
randomized, double-blinded, sham-controlled study found mood
symptoms ameliorations after five session of active prefrontal
tDCS in a group of newly diagnosed patients (Fregni et al.,
2006b). Moreover, a study by Boggio et al. (2009) found that
a single tDCS session over prefrontal cortex, but not occipital
or sham tDCS, improved accuracy in identifying emotionally
positive visual material in a sample of participants with major
depression.
Fear
Another major, consequential negative emotion is fear. Fear plays
a crucial role in the onset and maintenance of chronic pain (Riva
et al., 2014b) and several mental disorders, including anxiety and
post-traumatic stress disorder (Mungee et al., 2014). Regarding
fear regulation, one study using an unpredictable threat paradigm
found that anodal tDCS over right prefrontal cortex decreased
sustained fear and skin conductance levels in the context of
unpredictable threats (Herrmann et al., 2017). This finding lends
additional support to the idea that right PFC activation increases
response inhibition rather than avoidance motivation. Another
study, this one using a bipolar montage over the DLPFC with the
anode over the left DLPFC and cathode over the right DLPFC,
found improved reaction times on simple arithmetic decisions
and decreased cortisol concentrations among participants high
in math anxiety (Sarkar et al., 2014).
On the other hand, a recent tDCS study on the consolidation
of fear memories observed that greater right frontal cortical
activity may enhance fear-related responding. Mungee et al.
(2014) paired a fear-conditioning paradigm with either cathodal
stimulation (i.e., stimulation to decrease activity) over the
right dorsolateral prefrontal cortex, anodal stimulation (i.e.,
stimulation to increase activity) over the right dorsolateral
prefrontal cortex, or sham stimulation. Fear was measured via
skin conductance responses to the conditioned stimulus. Results
revealed that anodal stimulation over the right dorsolateral
prefrontal cortex increased memory for the conditioned
feared stimulus as measured via skin conductance responses.
These results suggested that increasing activation of the
right dorsolateral prefrontal cortex increases fear memory
consolidation (see also Mungee et al., 2016). However, this
study did not simultaneously pair anodal stimulation to the
right dorsolateral prefrontal cortex with cathodal stimulation to
the left dorsolateral prefrontal cortex to create an asymmetric
pattern of activity, as was done in the studies described in
the previous paragraphs in this section. Given that the effects
of anodal stimulation over the right dorsolateral prefrontal
cortex in conjunction with cathodal stimulation over the left
dorsolateral prefrontal cortex have yet to be tested in the
study of fear memory consolidation, the causal relationship
between greater relative right frontal cortical asymmetry and
avoidance motivation remains unclear. Collectively, the evidence
on prefrontal tDCS effects on the regulation of fear-related
responses remains mixed. Future studies should clarify the extent
to which excitatory stimulation over the right DLPFC helps or
hinders fear regulation.
Social Pain
Social pain refers to the hurt feelings caused by rejection or
ostracism from the group. These aversive social experiences
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generally cause negative emotions and result in a loss of sense
of belonging, control, and self-esteem (Williams, 2009). Some
studies have found a role for the dorsal anterior cingulated
cortex (dACC) and the right VLPFC in experienced and observed
social exclusion conditions, suggesting the presence of a partially
overlapping neural network involved both in physical and social
pain (Eisenberger et al., 2003;Kross et al., 2007;Wager et al.,
2008;Masten et al., 2009). The right VLPFC, in addition to being
broadly involved in emotion regulation, has also been found to
have a crucial role also in regulating the pain associated with
social exclusion (Onoda et al., 2010).
These findings have lead researchers to test the effects of tDCS
over brain regions involved in social pain regulation, mainly the
right VLPFC. For example, participants in a study by Riva et al.
(2012) received 15 min of anodal tDCS over the right VLPFC. At
the end of the stimulation, participants were randomly assigned
to be included or excluded in a virtual ball-tossing game called
Cyberball (Williams et al., 2000). In the inclusion condition,
subjects received a ball the same number of times as the other two
players, whereas in the exclusion condition participants received
the ball only on the first throws. Actually, participants did not
play with real players; a computer program controlled the ball.
Results revealed that anodal tDCS over right VLPFC, compared
to sham stimulation, reduced levels of pain and hurt feelings
among excluded subjects.
In a similar study, the same research group (Riva et al.,
2014a) tasted the effects of tDCS on behavioral aggression
following social inclusion or exclusion condition in the Cyberball
paradigm. Participants received anodal or sham stimulation
during the Cyberball game. At the end of the stimulation, subjects
had to choose the amount of hot sauce for their ostensible
partners to taste. This is the well-validated hot-sauce paradigm
for studying aggression (e.g., Lieberman et al., 1999). Findings
indicated that increasing right VLPFC cortical activity with tDCS
reduced behavioral aggression among excluded participants, who
were no more aggressive than included ones. These findings
were replicated in a subsequent study (Riva et al., 2017), which
found that brain polarization through anodal tDCS over the
right VLPFC reduced unprovoked aggression as measured by the
Taylor aggression paradigm (Taylor, 1967).
Similar results were obtained by Kelley et al. (2015a), who also
paired a Cyberball game with prefrontal tDCS. In this modified
version of the game, participants first chose a partner from
a group of images of eight opposite-sex individuals. A third
Cyberball player was assigned by the experimenter and was
always the same sex as the participant. Harmon-Jones et al. (2009)
had found that this Cyberball game evokes jealousy and that
self-reported jealousy after being excluded by a desired partner
correlates with relative left frontal cortical activity. Kelley et al.
had participants choose a partner in the modified Cyberball
paradigm and play a practice version of the game before receiving
15 min of tDCS in one of three conditions: excitatory left DLPFC
stimulation (anode over F3/cathode over the F4), excitatory
right DLPFC stimulation (cathode over F3/anode over F4), or
sham stimulation. Stimulation to increase relative left frontal
cortical activity increased self-reported jealousy. Because the
direct manipulation of cortical excitability with tDCS produced
the same outcome as the correlational finding reported Harmon-
Jones et al. (2009), this study suggests that tDCS over the
dorsolateral prefrontal cortex does indeed modulate emotive
responses associated with social exclusion and asymmetric frontal
cortical activity.
Collectively, these studies highlight the effects of tDCS
over the prefrontal cortex on regulating responses to social
exclusion. This work may have clinical implications for disorders
characterized by maladaptive responses to social exclusion (e.g.,
borderline personality disorder). Future research should test the
extent to which the increased negative affect and autonomic
arousal (Kopala-Sibley et al., 2012) and inappropriate coping
strategies and impulsive behaviors (Dixon-Gordon et al., 2011;
Coifman et al., 2012) associated with these disorders can be
modified by tDCS.
Empathy
Recently, some research has observed that personal physical
suffering and empathy for the pain of others share the
same neural network, involving prefrontal cortex as well as
somatosensory cortex, anterior cingulate cortex, amygdala, and
anterior insula (Eisenberger, 2012). To investigate the role of
prefrontal cortex in empathic pain regulation, Boggio et al.
(2009) conducted a study in which participants judged the
unpleasantness of pictures showing human beings under painful
conditions. Anodal tDCS was applied over the left DLPFC, the
primary motor cortex, and the primary visual cortex (control
site) in three experimental sessions. Findings revealed decreased
unpleasantness and discomfort during anodal stimulation over
left DLPFC compared to sham stimulation. Moreover, compared
to a previous study in which tDCS was delivered together
with an electrical peripheral stimulation (Boggio et al., 2008),
no significant effects were found in the primary motor
cortex stimulation condition, suggesting that DLPFC specifically
contributes to the emotional processing of empathic pain.
These findings were expanded by a similar study comparing
emotional reactions to negative, positive, and neutral human
pictures (Peña-Gómez et al., 2011). This study found that anodal
tDCS over the left DLPFC reduces only painful and not positive
or neutral affects. Based on previously mentioned neural models
(Phillips, 2003;Phillips et al., 2008;Kohn et al., 2014) and
previous neuroimaging evidences regarding DLPFC involvement
in more cognitive forms of emotion regulation (Blair et al.,
2007;Boggio et al., 2007a;Ochsner et al., 2009;Peña-Gómez
et al., 2012), the authors suggested that increasing activity in the
DLPFC may enhance cognitive control of emotional reactions.
Moreover, the tDCS effect was more noticeable for participants
with higher subclinical scores on the introversion personality
dimension, perhaps due to their enhanced ability to control
emotion expression, which correlates with the increased cortical
activity, compared with extraverts, especially in the frontal lobes
(Suslow et al., 2010).
A similar finding was reported also by Feeser et al.
(2014), who applied anodal tDCS over the right DLPFC while
participants applied cognitive reappraisal strategies to down-
or up-regulate the emotions elicited by negative or neutral
pictures. Skin conductance responses were also assessed. Anodal
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tDCS, compared to sham stimulation, increased emotional and
autonomic reactions when the reappraisal instruction was to
upregulate emotions and decreased emotional and autonomic
responses when participants attempted down-regulation. Taken
together, the studies reviewed here implicate DLPFC and VLPFC
in emotion regulation when observing or experiencing painful
situations, thereby highlighting the feasibility of tDCS application
for the study of pain and empathy for pain.
Risk Taking
In addition to emotion and mood manipulations, another way
researchers have explored the consequences of prefrontal brain
stimulation on emotion regulation is by studying risk taking.
Risk taking involves the possibility of punishment or potential
harm in the pursuit of rewards or goal-relevant actions. From an
emotion-regulation perspective, risk-taking involves managing
the emotions associated with the anticipation of winning and
losing. In a seminal tDCS study, Fecteau et al. (2007a) used tDCS
over the DLPFC during a risk task (Rogers et al., 1999). Across
100 trials of a gambling task, participants viewed 6 horizontal
boxes. Some boxes were blue, and some were pink, and the
ratio of blue to pink boxes varied from trial to trial. The ratio
could be 5:1, 4:2, or 3:3. Of the two options, the high likelihood
option was always associated with a small reward whereas the
low likelihood option was always associated with a large reward.
Participants were to indicate which color box contained a token.
Each trial selecting the winning color box earned a reward
but selecting the incorrect color box incurred a penalty. Larger
rewards were always paired with riskier decisions such that
correctly choosing a pink box with a low win probability (1/6)
would result in a large reward whereas making that same choice
and losing was associated with same magnitude of a loss. Thus,
participant’s tendency to choose high-risk/unlikely rewards over
low risk/likely rewards was the measure of risk-taking. Results
indicated that excitatory right DLPFC stimulation increased the
number of participants earned by decreasing risk taking on the
task. These results suggest that excitatory stimulation over the
right DLPFC tilted participants toward safer, less risky choices,
as though they were less tempted by the larger, riskier rewards.
These findings have been partially replicated by Cheng and Lee
(2016), who found that the excitatory stimulation over the right
DLPFC influences performance on the Risky Gains Task (RGT;
Paulus et al., 2003), but not on the Balloon Analogue Risk Task
(BART; Lejuez et al., 2002). Regarding the RGT task, participant’s
goal was to win as many points as possible. To accomplish
this goal, they made quick (1 s) decisions between taking a
reward (i.e., points) now or waiting for a larger point value later.
However, this later-but-larger reward also came with the risk of
being punished (i.e., losing points equivalent to the later-but-
larger reward). Risk-taking was quantified as the rate at which
participants selected trials for which punishment was possible
whereas safe decision-making was the rate at which participants
chose point values with no possibility of punishment. The effect
of excitatory right DLPFC stimulation on risky (but not safe)
trials was moderated by individual differences in impulsivity,
such that greater risk-taking was associated with greater (versus
lower) impulsivity. More recently these results have recently
been conceptually replicated in a clinically impulsive sample.
Gilmore et al. (2017) paired excitatory stimulation over the right
DLPFC (twice a day for 5 days) with a balloon analog risk
taking (BART) task. They found that excitatory stimulation over
the right DLPC reduced risk-taking by 46%. This diminished
risk-taking persisted at a two-month follow-up.
Another study probed the underlying neurocircuitry that may
be driving the changes in risk taking. Weber et al. (2014) used
excitatory stimulation over the right DLPFC, prior to functional
MRI during which participants completed the BART. They found
that excitatory stimulation over the right DLPFC increased
activity in the right DLPFC and the ACC as well. Additionally,
this pattern of stimulation also influenced how these two
regions connected with the rest of the brain. Specifically,
greater right DLPFC-whole brain connectivity was associated
with diminished risk-taking on the BART. These results suggest
that the diminished risk-taking linked to excitatory right DLPF
stimulation influences the neurocircuitry implicated in successful
self-regulation.
In addition to laboratory risk-taking paradigms, an innovative
study paired prefrontal tDCS with a more ecologically valid form
of risk taking: driving behavior. In a driving simulator study, Beeli
et al. (2008) observed that excitatory stimulation of the DLPFC
(either left or right) led participants to keep a safer distance
behind a lead driver and reduced the number of speeding errors.
This pattern of stimulation did not influence average speed or
revolutions per minute. These results are broadly consistent with
reduced risk taking, but they differ from the risk-taking findings
reviewed above in a crucial way: the electrode montage used.
Whereas the risk-taking studies described above paired excitatory
stimulation over the right DLPFC with inhibitory stimulation
over the left DLPFC, the study be Beeli and colleagues placed the
cathode over the ipsilateral mastoid. Because of this difference
in electrode montages it is unclear to what extent these results
are comparable to the risk-taking studies above. Future studies
should explore the extent to which anodal right DLPFC/cathodal
left DLPFC stimulation influences risk-taking in this domain.
In summary, numerous studies have observed enhanced
self-regulation after anodal tDCS over right DLPFC (cathodal
over left). Improved self-regulation manifested in a variety of
ways including greater pain tolerance, healthier food choices,
less impulsive decision-making, improved emotion regulation,
reduced anger and aggression, less sadness and fear, more
empathy, and less risk taking. Collectively, these results anodal
tDCS over right DLPFC may be one tool that shows promise in
helping individuals live happier, healthier lives.
Limitations and Future Directions
We have reviewed evidence suggesting that non-invasive brain
stimulation over the prefrontal cortex may improve human self-
regulation. First, we detailed a methodological review of tDCS
highlighting that tDCS is a safe, inexpensive, and easy to use
technique that can be used to study higher-order cognition,
emotion, and clinical phenomena. We also reviewed stimulation
parameters that may help or hinder tDCS efficacy including
current density, stimulation duration, and the orientation and
focality of the electrical field. Second, we reviewed findings
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from experiments observing that non-invasive brain stimulation
over the PFC can enhance three paradigmatic forms of self-
regulation: persistence, delay behavior, and impulse control.
Although the current review focused predominantly on tDCS,
other techniques such as low energy neurofeedback (e.g., Ochs,
2006) and transcranial ultrasound (e.g., Tufail et al., 2011) also
represent low-cost, non-invasive techniques for investigating the
causal role of neural activation in various forms of self-regulation.
Although much of this review highlighted the ability of
brain stimulation to promote self-regulation, under the right
circumstances brain stimulation may also undermine self-
regulation. For example, we highlighted studies wherein
excitatory stimulation over the right DLPFC enhances
inhibition (e.g., Kelley and Schmeichel, 2016) whereas excitatory
stimulation over the left DLPFC increases approach motivated
negative emotions like anger (e.g., Hortensius et al., 2012)
and jealousy (e.g., Kelley et al., 2015a,b). These contrasting
findings imply that excitatory tDCS is not an unmitigated
good that improves self-regulation in all cases. In fact, these
findings emphasize the need to identify precise stimulation
parameters that help versus hinder self-regulation. Below, we
discuss inconsistencies, unresolved questions, and new directions
emanating from the above review.
tDCS Dosage
The efficacy of eliciting changes in brain activity using tDCS
depends on several physical parameters including current
density, stimulation duration, and the orientation and focality
of the electrical field. These parameters constitute the tDCS
dosage. As we noted above, different electrode positions modulate
different neuronal groups and elicit different evoked potentials
in the case of primary motor cortex and primary visual cortex
stimulation, respectively (Priori et al., 1998;Antal et al., 2004;
Accornero et al., 2007), and these different electrode positions
may also determine effects on the targeted brain region due to
electrical field interactions associated with neuronal geometry
(Nitsche and Paulus, 2000;Nitsche et al., 2008).
Whereas the coupling of anodal-excitatory and cathodal-
inhibitory effects is well established in the sensorimotor domain,
the evidence pertaining to higher cognitive functions is more
controversial (Jacobson et al., 2012). Indeed, when dealing with
more complex functions represented by large and interconnected
neural networks comprising both excitatory and inhibitory
connections, it is more difficult to obtain predictable outcomes –
especially when different electrode montages have been used
across studies. Hence it is not always the case that anodal tDCS
leads to an enhancement (e.g., better performance in a task) and
cathodal tDCS leads to a diminution of the assessed cognitive
function (Fertonani and Miniussi, 2017).
To illustrate this point, consider the studies above on physical
pain tolerance. These studies found increased pain tolerance as
the result of excitatory stimulation of the right DLPFC (Mylius
et al., 2012), excitatory stimulation over the left DLPFC (Boggio
et al., 2008;Mariano et al., 2016), and inhibitory stimulation
over the left DLPFC (Powers et al., 2018). Of the four studies
we reviewed, three difference electrode montages were used.
Notably, the study by Powers and colleagues, unlike the other
pain studies, paired tDCS with clinical interventions. These
methodological differences likely contributed to the differences
in results across studies and thus makes interpreting the effects
of tDCS difficult. Future studies should more precisely optimize
the stimulation protocols that accentuate versus undermine self-
regulation for easier comparison across studies.
More broadly, however, the findings from the pain studies
are congruent with the findings from studies of other self-
regulatory domains in suggesting that stimulation over right
DLPFC facilitates self-regulation. Whether such stimulation is
most profitably paired with inhibitory (cathodal) stimulation
over left DLPFC remains to be seen. And the effects of excitatory
(anodal) stimulation over left DLPFC on self-regulation are even
more uncertain, with some studies finding better and some
finding worse self-regulation after excitatory stimulation over left
DLPFC.
Individual Differences
Another inconsistency in past research concerns individual
differences. Despite seminal work suggesting that participants
should be matched on individual differences like sex or age that
can influence tDCS efficacy (Pitcher et al., 2003;Kuo et al., 2006;
Quartarone et al., 2007;Chaieb et al., 2008;Nitsche et al., 2008),
many of the studies reviewed above did not use this strategy, and
we recommend future studies implement matching procedures to
reduce error variance and increase power to detect tDCS effects.
In addition to demographic factors, which may subtly
influence tDCS efficacy, many of the studies we reviewed also
did not consider the extent to which participants are responsive
to tDCS. Previous research has found that between 50 and
64 percent of participants are responsive to tDCS protocols,
which leaves a substantial proportion of individuals who are not
particularly responsive to tDCS (Wiethoff et al., 2014;López-
Alonso et al., 2015). Studies that include non-responders and
studies that do not systematically test for differences between
responders and non-responders many obscure effects of tDCS on
regulatory behavior. Further, only few studies have considered
individual differences traits, though these are also likely to
moderate tDCS effects. For example, the study by Kekic et al.
(2014) found that tDCS-driven reductions in food craving were
more pronounced among participants with low (versus high)
delay discounting tendencies. Evidence of this sort highlights
the need to develop more robust stimulation protocols in well-
powered studies that can systematically test for the moderating
role of individual differences.
Impulse-Behavior Relationship
Another inconsistency in the research reviewed above concerns
whether changes in emotive responding extend to changes in
behavior. We summarized evidence that tDCS may alter food
craving without altering food consumption (although sometime
consumption changes, too; e.g., Fregni et al., 2008). Similarly,
we summarized evidence that changes in emotional responses
(e.g., anger) may occur in both the absence of and presence of
corresponding changes in behavior.
The path from impulse to behavior entails multiple
determinants, and thus impulses and behaviors may diverge for
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several reasons. Practical considerations including variability
in stimulation dosage may explain why tDCS sometimes does
and sometimes does not influence behavior. For example, one
important aspect of the tDCS dosage is electrode size. The
study by Kekic et al. (2014) who did not find effects on food
consumption used 25 cm2electrodes whereas Fregni et al. (2008)
used 35 cm2electrodes. Smaller electrodes are more spatially
precise compared to larger electrodes. The larger electrodes
may affect distal brain regions that are less affected in studies
using smaller electrodes possibly accounting for why the study
by Fregni et al. founds effects on consumption, but Kekic did
not. Beyond these practical considerations idiosyncratic food
preferences may have played a role in the inconsistent results. The
studies assessing compulsion offered actual food to participants,
but those foods were not specifically tailored to the participant.
Instead participants were offered foods that are generally (but
not universally) well liked, such as chips, cookies, and chocolate.
This may be problematic insofar as some participants may not
prefer any of the food options offered by the experimenter.
Future studies using more ecologically valid measures of food
consumption and others types of regulatory behavior (e.g.,
naturalistic observation) may prove useful in clarifying the
extent to which tDCS-induced changes in emotions/impulses
influence subsequent behavior. However, we must also consider
the possibility that cravings/subjective states are more readily
influenced by tDCS, whereas behaviors may be harder to change
as they have a multiple of determinates above and beyond the
preceding subjective state.
How Does tDCS Effect Underlying Brain Activity?
The effects of tDCS on underlying brain activity are not well
understood and subject to ongoing debate. It remains to be seen
how tDCS affects brain activity and how these changes relate
to changes in self-regulation. One way to advance research on
this topic is to pair concurrent measures of brain function with
electrical stimulation. Candidate neural processes mediating links
between tDCS and self-regulation include changes in prefrontal
EEG alpha and functional connectivity between the prefrontal
cortex and subcortical regions.
Prefrontal Alpha
One potential mediator driving many of the effects reported in
the current review is EEG alpha activity. Specifically, lateralized
patterns of alpha activity may reflect a person’s motivational
orientation with left lateralized EEG alpha activity reflecting
approach-motivation (Tomarken et al., 1992;Harmon-Jones and
Allen, 1997, 1998;Sutton and Davidson, 1997;Harmon-Jones
and Sigelman, 2001;Harmon-Jones et al., 2002, 2006;Coan and
Allen, 2003;Harmon-Jones, 2007) and right lateralized pattern
of EEG alpha activity has been linked to withdrawal or avoidance
motivation (Davidson et al., 1990;Tomarken et al., 1990;Dawson
et al., 1992;Kalin et al., 1998;Coan et al., 2001). Self-regulatory
failure tends to occur when individuals have strong impulses
such as strong impulses to engage in approach or avoidance
motivated behavior. Likewise successful self-regulation tends to
occur when impulses are weaker. To the extent that asymmetric
patterns of alpha activity in the frontal cortex reflect the strength
of appetitive and aversive impulses they may be a good candidate
linking tDCS to changes in self-regulation.
Indirect support for the role of EEG alpha activity in tDCS
effects comes from parallel findings using EEG and tDCS,
respectively, to study the emotion of jealousy. Harmon-Jones
et al. (2009) found that feelings of jealousy during a Cyberball
game correlate with greater left frontal alpha activity, and Kelley
et al. (2015a,b) found the same pattern by manipulating (rather
than measuring) brain activity with tDCS. More specifically,
Kelley et al. observed that excitatory stimulation of the right
DLPFC paired with inhibitory stimulation of the left DLPFC
increases feelings of jealousy during a Cyberball game. By finding
the congruent effects with both measured and manipulated brain
activity, the pair of results together suggest that EEG alpha
activity may mediate the link between prefrontal tDCS and
behavioral self-regulation.
In an innovative new study, Vöröslakos et al. (2018) developed
an intersectional short-pulse (ISP) stimulation paradigm in
cadaver and rodent studies. ISP delivers shorts bursts (less than
10 µs) of high intensity stimulation from multiple electrode
pairs centered on a stimulation site of interest. ISP thus offers
superior spatial focality plus higher current densities (7–9 MA)
more easily tolerated than traditional tDCS paradigms (>2 MA),
with relatively low charge densities and scalp sensations. Pairing
Vöröslakos and colleagues then paired ISP with concurrent EEG
measurement and observed that tDCS affects the amplitude
of simultaneously recorded EEG alpha waves. This work
provides an important example of how technical studies in
mouse and cadaver models can be used to improve existing
tDCS protocols. Future research should consider implementing
innovate stimulation paradigms like ISP to increase the efficacy of
existing stimulation paradigms and to trace the neural mediators
of tDCS effects.
Functional Connectivity
The self-regulation findings we reviewed may also be mediated
by frontal cortical-subcortical interactions. Due to its high
spatial resolution, functional MRI is perhaps best suited to
probe such possibilities. Research along these lines has already
begun. Weber et al. (2014) administered excitatory stimulation
over the right DLPFC prior to functional MRI of a risk-taking
task. They found that excitatory stimulation over the right
DLPFC influences how the right DLPFC connects to the rest
of the brain. Specifically, stronger right DLPFC-whole brain
connectivity and