Va Os Solano Maria Teresa Master Thesis

Running head: EFFECTS OF WN, TES AND SHAM ON COGNITION 1
Influence of White Noise, tDCS, tRNS, Attentiveness and Novelty Seeking on Response
Inhibition and Working Memory
Maria Teresa Vaos Solano
Lund University
Thesis for the Master of Science in Psychology
August 2016
Supervisor
Prof. Sverker Sikstrm

EFFECTS OF WN, TES AND SHAM ON COGNITION 2
Abstract
The aim of the present study was to investigate if cognitive performance significantly and
differentially improves after the application of non-invasive brain stimulation compared to sham,
taking into consideration individual differences in attentiveness and novelty seeking. Thirty-two
healthy adolescents undertook four experimental conditions (eight participants per condition) in
which they performed a response inhibition task (Go/No-Go) followed by a visuospatial working
memory (WM) task (Corsi span). The tasks were conducted before and after the delivery of
anodal tDCS, tRNS, auditory white noise (WN) or sham over the left dorsolateral prefrontal
cortex. There was a significant improvement in WM following auditory WN. The results do not
show differential effects of tDCS, tRNS, and sham on response inhibition nor spatial WM. The
study does not support previous findings on individual differences in attentiveness influencing
results. Interestingly, a moderating and significant effect of novelty seeking was found on the
tDCS condition in the spatial WM task. Methodological limitations that may have contributed to
a lack of significant results in both tasks following tDCS and tRNS are discussed. Auditory WN
may have important implications for both healthy and at-risk populations to enhance cognition,
particularly at a crucial age for future development. Novelty seeking assessment may provide
new insights into the underlying mechanisms and differential effects of non-invasive brain
stimulation.
Keywords: cognitive enhancement, transcranial direct current stimulation (tDCS),
transcranial random noise stimulation (tRNS), auditory white noise (WN), response inhibition,
working memory (WM), attentiveness, novelty seeking, adolescents

Influence of White Noise, tDCS, tRNS, Attentiveness and Novelty Seeking on Response
Inhibition and Working Memory
Psychologists have long used cognitive training and behavioral interventions for cognitive
enhancement. However, contemporary methods are placing more emphasis on direct
interventions to modify brain function, the source from which cognitive capabilities emerge
(Cohen, 2015).
Overall, current studies from different cognitive domains demonstrate the possibility of
improving cognitive functions with non-invasive transcranial electrical stimulation (tES) like
transcranial direct current stimulation (tDCS) and transcranial random noise stimulation (tRNS)
as well as auditory white noise (WN). However, study results are inconsistent, and not much is
known about the mechanisms underlying these effects as well as the interaction of interventions
with individual differences and diverse cognitive processes.
Past studies have reported improvement in cognition with auditory WN depending on the low
or high level of attentiveness self-reported by the subjects (Sderlund, Marklund & Lacerda,
2009; Sderlund, Sikstrm, Lotuses & Sonuga-Barke, 2010; Sderlund, Sikstrm & Smart,
2007). Also, research has shown anodal stimulation of the dorsolateral prefrontal cortex (DLPF)
via tDCS enhance working memory (WM), and executive functions (EFs) in a healthy
population (Fregni et al., 2005; Fregni et al., 2006; Ohn et al., 2013; Sparing, Dafotakis, Meister,
Thirugnanasambandam & Fink, 2008). Just as in patients (Boggio et al., 2006; Boggio et al.,
2007; Nitsche, Boggio, Fregni & Pascual-Leone, 2009). However, results are conflicting and
seem to depend on numerous variables. For reviews see Brunoni et al. (2012) and Kadosh
(2013).
Besides to individual differences, the results also vary according to the type of task, the
assessment, and sample used in the study. For instance, a meta-analysis by Brunoni and
Vanderhasselt (2014), showed anodal tDCS delivered to DLPFC improved reaction time (RT)
but not accuracy in an N-back task, measuring WM. Another meta-analysis found a small benefit
of tDCS on cognition (Hill, Fitzgerald & Hoy, 2016). However, the meta-analysis performed by
Horvath, Forte and Carter (2015), found no benefits of tDCS on WM in a healthy sample.
Moreover, a meta-analysis by Dedoncker, Brunoni, Baeken and Vanderhasselt (2016), revealed
that tDCS had differential effects in healthy participants vs. patients. Healthy participants
obtained higher accuracy on cognitive tasks only with higher current densities with the effect
more pronounced in women. In contrast, neuropsychiatric samples scored greater in accuracy
when anodal tDCS was applied online vs. offline protocol tasks. Finally, tRNS has revealed
similar effects to tDCS on increasing excitability and learning facilitation (Terney, Chaieb,
Moliadze, Antal, & Paulus, 2008) but not in a WM task with a healthy population (Mulquiney,
Hoy, Daskalakis & Fitzgerald., 2011).
In addition to the mixed results mentioned above, shared and distinct neural underlying
mechanisms have been suggested for auditory WN, tDCS, and tRNS. Auditory WN has been
proposed to act through the neuromodulation of the dopamine system explained by the stochastic
resonance (SR) phenomenon (Rausch, Bauch & Bunzeck, 2014; Sikstrm & Sderlund, 2007).
TDCS and tRNS have been suggested to act via a change in voltage-gated sodium (Na) channels
(Chaieb, Antal & Paulus, 2015,) causing a depolarization in the neural membrane potential
(Bikson, Radman & Datta, 2006). Moreover, the same mechanism as in auditory WN, SR, has
been signified by Fertonani, Pirulli, and Miniussi (2011), to be working in tRNS.

Although many studies have investigated the effect of non-invasive brain stimulation on
cognition, past research has largely overlooked the influence that individual differences,
characteristics of the sample and cognitive tasks have in the effect of the different interventions.
Moreover, no study to date has jointly tested the influence of attentiveness, novelty seeking,
auditory WN, tDCS, tRNS on response inhibition and spatial WM on a healthy adolescent
population, with a sham and control condition.
Before describing the study in detail, a theoretical background will be introduced. The first
part provides a description of the different non-invasive brain stimulation used in the present
study, auditory WN, tDCS, and tRNS, to provide the reader with information about its principles,
evidence of impact on cognitive abilities and mechanisms. The second part substantiates the
rationale for the choice of attentiveness and novelty seeking as individual characteristics that can
influence the results. Finally, the aim and hypotheses of the study will be stated.
White Noise
Principles. Auditory WN is described as a sound that contains every frequency within the
range of human hearing (generally from 20 Hz to 20 kHz) in equal amounts. The effect of noise
has a long tradition in the study of behavior, usually portraying noise as detrimental for efficient
task performance (Broadbent, 1958). This adverse effect is supposed to be due to competition for
attentional resources. However, in non-linear and neural systems, adding an optimal level of WN
has been shown to facilitate information processing through SR (Moss, Ward & Sannita, 2004).
Previous research shows improvement in cognitive performance through stimulation with
auditory WN under particular circumstances and has been suggested to occur through SR
(Sderlund & Sikstrm, 2008). SR is a phenomenon occurring in nonlinear systems whereby
adding random noise results in better detection of a weak signal or the content of the
information. The proper amount of noise, or threshold, will improve information processing.
However, an increase of noise intensity will result in an impairment to process information
(Moss et al., 2004). McDonnell and Abbott (2009), suggest understanding SR regarding
randomness that makes a nonlinearity less detrimental to a signal (p.1).
Evidence of impact on cognitive abilities. Auditory WN has been shown to affect behavior
in healthy populations. For example, memory retrieval improved in arithmetic tasks with
auditory WN, seen on faster reaction times (RTs) (Usher & Feingold, 2000). Also, auditory WN
reduced crying time and improved vital signs in newborns undergoing painful procedures
(Karako & Trker, 2014). Further experiments showed that WN, but not control sounds,
improved recognition memory in healthy humans, selectively enhancing stimulus-driven phasic
activity in dopaminergic pathways and auditory cortex (Rausch et al., 2014).
The improvement in cognitive and behavioral tasks in subjects with ADHD by auditory WN
has also been reported. For instance, in a case study of a child diagnosed with ADHD, auditory
WN led to improvements on his writing and math assignments (Cook et al., 2015). Also, a study
by Cook, Johnson and Bradley-Johnson (2015) reported three students with ADHD that
displayed lower levels of off-task behavior when listening to WN while doing school tasks.
However, auditory WN did not have any systematic effect on assignment completion or
accuracy. Although auditory WN can benefit both a healthy and clinical population, individual
differences on attentiveness seem to affect results. Thus, auditory WN has shown beneficial
effects in subjects with low attentiveness but has been proven detrimental to persons with high
attentiveness. For example, research by Sderlund et al. (2007) and Sderlund et al. (2010),
reports children with ADHD (i.e. low attention group) stimulated with auditory WN, eliminated
the difference in performance with the control group (children with no attention problems or high
attention group) in episodic memory. Further experiments also found differential effects in the
type of tasks performed. Helps, Bamford, Sonuga-Barke and Sderlund (2014), assessed a non-
clinical sample with two non-executive functions (EFs) tasks (episodic verbal recall and delayed
verbal recognition) and two EFs tasks (visuospatial WM and Go/No-Go). The teacher rated the
participants as super, regular and sub-attentive children. They found the addition of auditory WN
particularly enhanced performance in tasks requiring EF in sub-attentive children. The results
suggest a qualitative difference between non-EF tasks and EF tasks on the assessment of
attention processes, as well as a discrimination of the effect of the noise depending on the level
of attention of subjects. Moreover, in a study combining tDCS and auditory WN, Sikstrm et al.
(2016), found differential effects in the low and high attentiveness groups. The researchers report
that stimulation with tDCS and auditory WN interacted with performance in the low but not in
the high attentiveness group in a Go/No-Go task.
In conclusion, auditory WN appears to affect positively healthy population with low levels
of attention and subjects with ADHD but seems to be detrimental for subjects with high
attentiveness. Moreover, auditory WN mainly appears to improve the execution of tasks
involving EFs.
Mechanism. The underlying neural mechanisms of SR remain unclear. However, with the
moderate brain arousal (MBA) model, Sikstrm and Sderlund (2007) attempt to explain how
random noise causes different effects on subjects with high and low attention levels. The MBA
model suggests that the amount of noise required for an optimal cognitive performance will
depend on dopamine levels. According to the MBA model, auditory WN facilitates information
processing by compensating low tonic dopamine levels in inattentive subjects or children with
ADHD (Sikstrm & Sderlund, 2007; Sderlund et al., 2010). Neurocomputational modeling of
the MBA model shows how a neural system with low dopamine levels needs a higher standard of
noise for optimal performance. Hence, the model predicts that auditory WN will be beneficial for
inattentive and ADHD children, with low levels of dopamine, but will provide more stimulation
than necessary for those with average or high attentiveness (Moss et al., 2004). Indeed, in a
recent study using behavioral and fMRI measures, auditory WN slightly improved recognition
memory and enhanced stimulus-driven phasic activity on dopaminergic networks. The results
suggest that the mechanism by which auditory WN causes benefits in cognitive tasks is via the
neuromodulation of the dopamine system (Rausch et al., 2014). Despite this, other studies have
failed to show evidence of a direct connection between the dopamine system and the effects of
WN on cognition (Baijot et al., 2016; Plsson, Sderlund, Klamer & Bergquis, 2011).
General Introduction for tES (Transcranial Electrical Stimulation)
Employing current as a therapeutic technique dates back to antiquity. The use of electric sea
creatures is reported as early as 43 AD to treat a headache, gout, hemorrhoids, and neuralgia. The
invention in 1744 of an electric portable container, made possible the storage and control of the
electrical discharges, making electrotherapy a conventional treatment to heal neuralgia,
contractions, and paralysis. In the middle of the 20th century, interest in electrical brain
stimulation was extended to use in research and psychological disorders (for a review see
Kadosh & Elliott, 2013). However, electric stimulation rapidly fell into oblivion, likely due to an
increase in popularity of pharmacological treatments. It will not be until the publication of the
study by Nitsche and Paulus (2000) that interest in electrical stimulation of the brain will resume
(Coffman, Clark & Parasuraman, 2014). A further reason why this technique, although readily
available for decades, did not gain more attention in human research, is that different parameters
like the position of the electrodes, current intensities, and stimulation duration are critical to
change cerebral excitability. Therefore, much research had to be conducted before discovering
patterns working consistently (Nitsche & Paulus, 2000).
Nowadays, tES is delivered through two or more electrodes placed on the scalp, above the area
of interest, with a low intensity between 1 to 2mA. After approximately 5 minutes of this weak
current passing through the scalp, it alters neural activity under electrodes and connected
subcortical structures (Nitsche et al., 2003; Weber, Messing, Rao, Detre, & Thompson-Schill,
2014).
Several factors, like electrode size and positioning, in addition to the intensity and duration of
the stimulation, will influence the impact of tES. By varying these parameters, different effects
are induced. Electrode positioning is critical. Even though electrical fields are comparatively
nonfocal, the placement of electrodes is associated with how much current is delivered to the
brain and what targets (Guleyupoglu, Schestatsky, Edwards, Fregni & Bikson, 2013). In tRNS,
positive and negative current fields are oscillatory rather than direct, which ensures the
application is polarity independent (Chaieb et al., 2009). The size of electrodes is also relevant,
bigger ones reducing current density, therefore diffusing the current in a larger area. Eventually,
selecting a montage will depend on the specific results the researcher wants to achieve.
The sensations caused by both real and sham tES rapidly disappear thanks to habituation
(Gandiga, Hummel, & Cohen, 2006). In a sham condition, the same level of current than in a real
condition is delivered but for a shorter time, usually 20 or 30 seconds. Such a brief induction is
not enough to produce neuronal excitability (Fritsch et al., 2010) but it causes the same tingling
in the scalp as an experimental condition.
Studies show considerable variability regarding specific characteristics of the stimulation
protocol (e.g. number of sessions, electrode placement, current intensity, and features) as well as
the type of cognitive assessment performed. This variation impacts the results and makes it
harder the interpretation of research (Saturnino, Antunes & Thielscher, 2015).
A systematic review by Elmasry, Loo and Martin (2015), reported that tES + cognitive training
enhanced performance on most of the tasks showing improvements in WM, cognitive control,
approximate number sense and mathematical skills.
A limited but growing body of literature indicates that tES is a safe, noninvasive method of
brain stimulation (Fregni, Boggio, Nitsche & Pascual-Leone, 2005). For instance, in a study with
131 healthy subjects undertaking 183 actives and 94 sham tDCS sessions, no serious adverse
effects were found (Kessler, Turkeltaub, Benson & Hamilton, 2012). For more information about
tES see review by Cohen (2015).
Transcranial Direct Current Stimulation
Principles. Transcranial direct current stimulation (tDCS) consists of the application of a
weak electric current over the scalp through the use of conductive electrodes. In tDCS, one
electrode is used as the anode (positive) and the other one as a cathode (negative). Anodal
stimulation of the motor cortex enhances excitability, while cathodal stimulation diminishes it.
The reason for this is most probably that anodal stimulation leads to neuronal depolarization and
increasing neuronal excitability while cathodal stimulation has the opposite effect, decreasing
cortical excitability through hyperpolarization (Nitsche et al., 2003).
TDCS has already been shown to modulate cortical excitability significantly and enhance
performance in numerous cognitive tasks (Coffman et al., 2014). Although this technique has
been readily available for decades, it did not gain much attention in human research till recently.
This circumstance is due to the different parameters used being critical to change cerebral
excitability
Evidence of impact on cognitive abilities. Although tDCS has been shown to improve
cognitive performance in both a healthy and clinical population, results are inconsistent.
Contradictory findings might be explained by the different parameters, like timing and placement
of the electrodes used in the studies (Martin, Liu, Alonzo, Green & Loo, 2014), together with the
diverse tasks employed for measurement.
Much research focusing on the enhancement of cognitive performance has targeted attention
processes. Many frontal areas have been shown to work in attentional processes. The right
inferior frontal gyrus (rIFG) seems to be especially critical for response inhibition. For example,
Ditye, Jacobson, Walsh and Lavidor (2012) reported that 1,5mA of anodal tDCS during 15
minutes on the rIFG combined with cognitive training improved the ability to inhibit responses
on the stop signal task (SST), a measure of response inhibition. Also, Jacobson, Javitt, and
Lavidor (2011) found 10 minutes of anodal 1mA tDCS applied at the rIFG before subjects
performed the SST, enhanced response inhibition. The study also showed that stimulation of
rIFG, but not stimulation of the right anterior gyrus, improved response inhibition. An interesting
study by Clark et al. (2012) used brain imaging together with tDCS to improve learning of tasks.
In this case, the task was the identification of concealing objects in naturalistic surroundings.
Subjects received 30 min of 2.0 mA tDCS on-line over the rIFG and right parietal cortex. TDCS
significantly improved learning and performance in comparison with a sham condition,
suggesting better selective attention and response inhibition.
Response inhibition performance also improved with anodal stimulation of the left DLPFC in
nonclinical populations. A study by Fecteau et al. (2007) reported a decrease in risk-taking, a
behavior associated with an increased inhibitory control. Similarly, Boggio et al. (2007) reported
an enhanced inhibitory response in a Go/No-Go task compared to sham. Both studies utilized an
intensity of 2mA. Another study measuring the time the gaze remained fixated on a threat in
highly trait-anxious individuals, reported that participants receiving anodal tDCS on the left
DLPFC showed a significant decrease, suggesting an improvement of attentional control
(Heeren, Baeken, Vanderhasselt, Philippot & de Raedt, 2015).
Working memory performance has also been shown to improve with tDCS. For example,
Gladwin, den Uyl, Fregni and Wiers (2012) found the application of 10 min of 1mA anodal tDCS
on the left DLPFC, improved performance in a Sternberg task measuring WM and selective
attention. Another study by Mulquiney et al., (2011) also found improvement on a 2-back WM
task. However, the improvement was just shown in RTs and not in accuracy. No effect was found
on the Sternberg task.
Moreover, Javadi and Cheng (2013) and Javadi and Walsh (2012), found significant results
with the application of 1.5mA and 1mA, respectively, anodal tDCS delivered for 20 min on the
left DLPFC in a long-term verbal memory task.
For evidence of the implication of other frontal areas in attentional processes see reviews by
Juan and Muggleton (2012) and Clark, Squire, Merrikhi and Noudoost (2015). For evidence of
the clinical efficacy of tDCS in psychiatric disorders, see review by Kekic, Boysen, Campbell
and Schmidt (2016).
Mechanism. The precise mechanisms by which tDCS influences behavior are not known,
however, previous research reports that the electrical disturbance of cortical neurons environment
caused by the delivery of tDCS, can cause the separation of electric charge within dendrites and
cell body, producing a change in membrane potential (Bikson et al., 2006).
Additionally, the after-effects of tDCS seem to depend on NMDA receptors suggesting an
interaction of tDCS with glutamatergic systems, essential for learning processes (Liebetanz,
Nitsche, Tergau & Paulus, 2002; Bliss & Collingridge, 1993. The ability to modulate occipital
alpha rhythm, which is related to cognition and WM, has also been shown with the application of
tDCS at parietooccipital locations (Zaehle, Rach & Herrmann, 2010) and the left dorsolateral
prefrontal cortex (Stagg et al., 2013).
Transcranial Random Noise Stimulation
Principles. A more recent type of tES is tRNS. Used for the first time by Terney et al.,
(2008), tRNS implies the application of alternate currents with random frequencies on the scalp.
This technique usually entails the generation of samples at a rate between 1 and 640Hz. These
samples have random current amplitudes, commonly distributed normally with a mean of 0mA.
The random electric fluctuation of the samples between positive and negative amplitudes
generate the noise in the stimulated cortical regions (Terney et al., (2008).
TRNS has been shown to boost cortical excitability (Chaieb et al., 2009; Snowball et al.,
2013; Terney et al., 2008). However, the high-frequency spectrum of tRNS (101-640Hz) but not
the low-frequency (0.1-100Hz), seems to be responsible for inducing excitability in M1 (Terney
et al., 2008). The high-frequency spectrum is also identified for the effects in the treatment of
tinnitus (Joos, De Ridder & Vanneste, 2015) and improving the perception of facial identity
(Romanska, Rezlescu, Susilo, Duchaine & Banissy, 2015).
High-frequency tRNS (101-640Hz) has benefits over tDCS because it has a higher cutaneous
perception threshold (Ambrus, Paulus, y Antal, 2010), making it easier to keep experimental
blinds. Moreover, tRNS guarantee an application independent of polarity because of its
oscillatory electric wave (Chaieb et al., 2009).
Evidence of impact on cognitive abilities. The stimulation of the primary motor cortex (M1)
during 10 minutes with tRNS resulted in a cortical excitability increase of 20-50% using the
paired-pulse paradigm (Terney et al. 2008). Moreover, Terney et al. observed an enhancement in
the acquisition and consolidation of implicit motor learning skills with a serial reaction time task
(SRTT). The tRNS lasting only five minutes can also significantly enhance cortical excitability
(Chaieb, Paulus & Antal, 2011).
Additionally, tRNS produced improvement in other domains, including perceptual learning
(Fertonani et al., 2011), number discrimination (Cappelletti et al., 2013) and mathematical
learning (Snowball et al., 2013). However, unlike tDCS (Fregni et al., 2005), tRNS did not
improve WM in a healthy population (Mulquiney et al., 2011).
The effect produced by tRNS has been shown to facilitate cortical excitability in the operating
area of both electrodes. However, in contrast to the study by Terney et al. (2008), Ho, Taylor and
Loo (2013; 2015) found that tRNS with 1mA DC offset (mean amplitude displacement from
zero) is more likely to increase cortical excitability than tRNS with zero DC offset.
The effects of tRNS, like increasing excitability and learning facilitation (Terney et al.,
2008) resemble those reported by previous studies after anodal tDCS (Nitsche & Paulus, 2000).
However, in comparison with anodal tDCS, high-frequency tRNS (100 to 640Hz) seems to
obtain a higher impact (Fertonani, Ferrari & Miniussi, 2015; Saiote, Polana, Rosenberger,
Paulus & Antal, 2013).
Mechanism. The underlying neural mechanisms of tRNS are not well-known. Fertonani et al.
(2011) suggested SR, the same mechanism that Sderlund and Sikstrm (2008) prompted to
work in auditory WN. The effect of tRNS has been shown to differ depending on the frequency
of the current delivered. For instance, tRNS, at higher frequencies ranges (100Hz-640Hz) but not
lower frequencies ranges (0.1-100Hz), has been associated with plasticity processes (Grenier et
al., 2001) and learning (Ponomarenko et al., 2008). Besides, Terney et al., (2008) postulated that
the underlying mechanisms producing excitatory after-effects are modulated through the
depolarization of voltage- gated sodium (Na) channels. Indeed, the application of tRNS has been
shown to change voltage-gated Na channels (Chaieb et al., 2015).
An essential difference exists between tDCS and tRNS. TDCS modifies the transmembrane
neuronal potential directly, opening the Na channels just once (Bindman et al., 1964). In contrast,
tRNS does not possess a component of direct current and can induce multiple ionic influxes,
modulating the firing rate of neurons and achieving higher effects (Terney et al., 2008).
Moreover, the study by Chaieb et al., (2015) showed that tRNS after-effects do not depend on
NMDA receptors as tDCS does but on the Na channels.
In sum, tRNS seems to provide with a new qualitative way to alter brain plasticity. Similar to
tDCS, it allows a painless and imperceptible excitability alteration with a noninvasive and
reversible treatment. The main advantage over tDCS is that tRNS is insensitive to polarization.
Individual Differences
The assessment of attentiveness and novelty seeking will provide valuable information on
individual differences and its interaction with response to treatment.
Attentiveness. Attentiveness is a quantitative measure used to gauge the individual level of
attention. Subjects with low attentiveness usually have learning difficulties and attention
problems and might be diagnosed with ADHD (Thomas, Sanders, Doust, Beller, & Glasziou,
2015).
Attentional processes are a necessary foundation for most higher learning and EFs (Posner &
Boies, 1971). Attention deficits are found in clinical populations across the lifespan, being an
essential feature of attention deficit hyperactivity disorder (ADHD) and traumatic brain injury
(TBI) as well as of various forms of dementia like Alzheimer dementia (Rizzo et al., 2000).
ADHD is a developmental disorder with a prevalence of 7, 2% in children and adolescents
(Rae, Sanders, Doust, Beller & Glasziou. 2015). The symptoms include inappropriate levels of
hyperactivity, impulsivity, and inattention (APA, 2013). Adolescents experiment the same
symptoms as children. However, the consequences can be more severe since they have greater
accountability and are less monitored by adults (Sibley, Kuriyan, Evans, Waxmonsky & Smith,
2014). ADHD is associated with significant deficiencies in areas including social and peer
relationships, academic attainment or emotional and cognitive performance (Tarver, Daley &
Sayal, 2014).
The symptoms of ADHD have been suggested to arise from a deficit in EFs such as response
inhibition and WM (Barkley, 1997; Castellanos & Tannock, 2002; Knudsen 2007; Pennington &
Ozonoff, 1996). A meta-analysis by Willcutt, Doyle, Nigg, Faraone and Pennington (2005)
indicates a link between ADHD and deficits on measures of response inhibition, vigilance,
spatial WM, and planning. The same shortcomings are shared for other neuropsychiatric
disorders that differ in the neural networks affected, but that might share the same underlying
mechanisms, like a deficit in cortical inhibitory neurotransmission (Demirtas-Tatlidede,
Vahabzadeh-Hagh & Pascual-Leone, 2013) and deficits in the dopaminergic system (Biederman
& Faraone, 2005).
Previous research has shown that attentiveness moderates the effect that auditory WN
(Sderlund et al., 2010; Sderlund et al., 2007) and tDCS (Sikstrm et al., 2016) exert on
cognitive processes.
Novelty seeking. Novelty seeking, a component of Cloningers Psychobiological Model of
Personality (Cloninger, Svrakic & Przybeck, 1993), has been related, like attentiveness, to the
dopaminergic system. This model is based on findings from neuroanatomy, developmental and
clinical psychology and psychiatry. Differences in the primary brain systems for procedural
learning (automatic regulation of emotional responses) versus propositional learning (individual
differences in values, goals, and self-conscious emotions) result in four temperaments, Novelty
Seeking, Harm Avoidance, Reward Dependence and Persistence, and three character constructs,
Self-directedness, Cooperativeness, and Self-transcendence. The dimensions of human
temperament are the heritable, developmentally stable, non-influenced by sociocultural learning
and emotionally based components of personality, and correlate to specific biological
characteristics of the brain. For a review see Cloninger (2004).
Most relevant for the present study is the novelty seeking element since research has found
that high levels of novelty seeking are linked with a deficit of dopaminergic transmission (Gerra
et al., 2000) and hence attention processes (Badgaiyan, Sinha, Sajjad & Wack, 2015).
Individuals with high scores on novelty seeking are characterized as impulsive, fickle, excitable,
quick-tempered, extravagant and with great exploratory behavior, while those with low scores on
novelty seeking tend to be reflective, rigid, loyal, stoic, slow-tempered and frugal (Cloninger et
al., 1993).
Purpose and Hypotheses
The aim of this study is to examine the impact that auditory WN, tDCS, and tRNS have on
response inhibition and WM in comparison with a sham condition, in an adolescent population.
Also, the current study examines whether the effect of the different stimulation conditions on
cognitive performance is dependent on individuals' self-report attentiveness and novelty seeking
personality scores. To the extent of my knowledge, this is the only study to date investigating
jointly auditory WN, tDCS, tRNS, and sham. Additionally, no study till now included an
adolescent sample. Furthermore, the assessment of individual differences in novelty seeking as a
possible moderator of the effects of the different stimulation conditions has never been done
before.
To this end, participants will be screened for attentiveness and assigned to a "low" or "high"
attentiveness group. Subjects will be randomly allocated to the different stimulation conditions,
matched on attentiveness, in a Latin square counterbalanced design. All participants will perform
two tests, a Go/No-Go task and a Corsi span task, measuring response inhibition and visuospatial
WM respectively, before and after the stimulation condition. In the tDCS and tRNS conditions,
1.5mA will be delivered, placing the anode over the left DLPFC and the cathode on the
contralateral arm. In the auditory WN condition, 77dB will be broadcasted through stereo
headphones. Finally, the sham condition will be achieved with the tDCS sham set-up that will be
explained later in full detail. An ANCOVA will be performed to compare scores across
stimulation conditions controlling for pre-intervention scores in response inhibition (accuracy
and RT) and WM span. Additionally, a series of two-way ANOVA's will be performed to
examine interaction effects of stimulation conditions and individual differences (self-report
scores on attentiveness and novelty seeking).
Based on previous research and the MBA model, it was hypothesized that attentiveness (low
vs. high) would moderate the effect that auditory WN and tDCS have on response inhibition and
spatial WM scores. Because of the absence of previous studies investigating jointly differential
effects of auditory WN, tDCS, tRNS, and sham, as well as interaction effects of novelty seeking
with stimulation conditions on an adolescent population, no further hypotheses are made.
Method
Study Recruitment and Screening

Ethical approval was obtained from the authors supervisor professor at Lund University and
Psychology Ethics Committee. Written consent was obtained from the schools head teacher on
behalf of the students, and from the students themselves. Before the beginning of the study,
parents were sent information letters about the study and were given the option to opt their
children out. Three parents opt their children out of the study. All students were recruited from an
international school in Malmo, Sweden. All students, from school years MYP4 and MYP5 (76
students aged 15 to 17 years) were offered an informative session, without stating the
hypotheses, and were given the option to voluntarily and confidentially participate. Fifty-eight
students volunteer and were screened for level of attention using the Adult Attention-
Decit/Hyperactivity Disorder ADHD Self-Report Scale (ASRS v1.1) Symptom Checklist
(Kessler et al. 2005). After screening, 32 participants, 16 with the highest and 16 with the lowest
scores in attention levels were selected. Participants were randomly assigned to four groups of
equal size (8 subjects for each condition) matched on attentiveness. Conditions were
counterbalanced with a Latin square to control for order effects. A scheduled date and time was
mailed to the teachers and the participants for them to go to a class on school grounds for around
40 minutes. The study was conducted during two consecutive weeks, Monday to Friday, from
8:30 to 14:30h.
Participants
In total, 32 healthy adolescents volunteers participated, 21 male and 11 females (mean age =
15.44 years, SD = .56 years). All participants, except one, were right-handed. Subjects had
international backgrounds with eight different nationalities. However, all of them had been in an
English speaking school for at least five years, and their English language skills were excellent.
Procedure and Material

Participants were individually greeted by the experimenter and invited to go through a safety
questionnaire and consent form. They were further asked to clarify practical and ethical concerns
(Bostrom & Sandberg, 2009). No participant showed any safety issue. Subjects were invited to
sit in a comfortable chair in front of a laptop. The room was well aired and naturally lighted. The
experimenter explained the procedure and that further instruction would be appearing on the
computer monitor. The experimenter remained in the room to assist if necessary but sitting away
from the participant to avoid distraction.
Two laboratory tests, one response inhibition (Go/No-Go task) and one visuospatial WM task
(Corsi span) were employed. These tasks were presented in a fixed order and lasted
approximately 12 minutes. Afterward, subjects were set with headphones or the tES device,
depending on condition. In the sham condition, tDCS, set-up to sham, was used as it provides
with a better sham experience. After starting the stimulation (tES, sham, or auditory WN), a
questionnaire was given to the participants, the short version of the Temperament and Character
Inventory-Revised (TCI-R 48), which takes 7 to 10 minutes to complete. This time has been
shown to be enough for tES to alters neural activity under electrodes and connected subcortical
structures (Nitsche et al., 2008; Weber et al., 2014). When finished filling up the questionnaire,
subjects proceeded to perform the two cognitive tasks again. Participants completed the tasks
with the same experimenter present.
TES. Electrical stimulation was delivered by a battery-driven constant-current stimulator (v2
32Bit ARM Microprocessor, foc.us) through two (3.5 x 3.5; 12.25 cm2) saline-soaked sponges
with conductive electrodes. Anodal and cathodal electrodes were respectively placed
approximately at F3 (1020 EEG International System) and contralateral arm locations. The
placement was chosen following research proving these sites to be ideal for cognitive and
behavioral studies (Chaieb et al., 2009; Nitsche et al., 2003). Active stimulation was applied for
20 minutes with a 20-second ramp- up and ramp-down period. For sham stimulation, the current
was switched on for 30 seconds with a ramp time of 10 seconds and then switched off. For the
sham condition tDCS was used because subjects can feel better the sensation of the current than
with the tRNS, which has a higher cutaneous perception threshold (Ambrus et al., 2010), making
them think they are in an active condition. For tDCS, a current of 1.5mA and 20V was delivered.
For tRNS, a 1.5mA current with a DC offset set at zero producing a current that fluctuated
between 1.5 and 1.5 mA and with a high-frequency range (101-640 Hz) was delivered (Woods,
2016).
Auditory WN. The auditory WN was delivered binaurally, during all the experimental
condition, using headphones and an MP3 player. The output signal was set to 77dB based on
earlier studies (Baijot et al., 2016).
Cognitive tasks. Subjects participated in a Go/No-Go task followed by a visuospatial WM
spam task before and during the stimulation session. The Psychology Experiment Building
Language (PEBL), an open source, free application software, was used to program and deliver
the cognitive tasks. (Mueller & Piper, 2014).
Go/No-Go task. The Go/No-Go task is a computerized test measuring response time and
response inhibition included in the PEBL. During this task, participants were required to watch a
sequential presentation of letters and respond to a target letter by pressing the right shift button
on a laptop keyboard. The presentation began with instructions on a 17" computer monitor where
participants clicked enter to continue. Next, a screen with a 2 2 array of four stars (one in each
square of the matrix) was shown. A single letter (P or R) was then presented in one of the squares
for 500 ms with an interstimulus interval of 1,500 ms. In the first condition, (P-Go), subjects had
to press the right shift button when the target letter "P" appeared, and withhold their response to
the non-target letter "R". In the second condition, (R-Go), participants had to press the right shift
in response to the target letter "R", and withhold their response to the non-target letter "P". The
ratio of targets to non-targets was 80:20 in both conditions. A total of 320 trials, 160 in each
condition, were presented with practice trials before the task. Behavioral performance was
assessed by calculating accuracy, the number of errors in omission and commission both in the
Go and the No-Go conditions. The duration of the entire Go/No-Go task was approximately 10
minutes, including instructions and practice trials.
Corsi span task. The Corsi span task is a visuospatial WM task widely used for the
assessment of visuospatial short-term memory, both in clinical practice and in experimental
research settings. The Corsi test also relies heavily on memory for temporal information, because
the block sequences must be recalled in the proper sequential order (Kessels, van Zandvoort,
Postma, Kappelle & de Haan, 2000). The computerized Corsi span task used in the present study
was programmed using the PEBL. The trial started with the instructions for the task shown on a
17" screen. After the participant had pressed enter, an array of 9 blue squares (each 3 3 cm in
size) showed on a black background during 1000 ms. Then, the squares highlighted by flashing
in yellow for 1000 ms, before reverting to blue in a sequence of blocks, which the participant has
to repeat subsequently in the correct sequential order clicking them with the mouse. Two trials
were given per block sequence of the same length. If at least one of these was repeated correctly,
the next two trials of a sequence of an increased length were administered. Therefore, by
increasing the length of the sequences, the capacity of the visuospatial short-term memory was
measured. Series started at length 2 and gradually increased up to a maximum of 9. The trial
concluded when the subject did not reproduce the two sequences of equal length. The Total Score
(the product of the Block Span and the number of correct trials) was computed for each
participant. The duration of the task was for approximately 3 minutes.
Questionnaires. In order to assess individual differences in attentiveness and novelty
seeking, two self-report questionnaires were used.
ASRS-v1.1. The Adult Attention-Decit/Hyperactivity Disorder ADHD Self-Report Scale
(ASRS) v1.1 Symptom Checklist, is an 18-item scale developed in conjunction with the World
Health Organization (WHO), and the Workgroup on Adult ADHD as a valid self-assessment of
ADHD symptoms (Kessler et al. 2005). The questions in the ASRS v1.1 are consistent with the
Diagnostic and Statistical Manual of Mental Disorder (DSM-IV) criteria for the assessment of
ADHD symptoms in adults. This screening instrument consists of part A, with six questions that
have been found to be the most predictive of the symptoms. Part B comprises the remaining
twelve questions and provides with additional cues and information about the frequency of the
symptoms (Kessler et al., 2005). A study by Adler et al. (2012), contrasted the (ADHD) Self-
Report Scale (ASRS) v1.1 Symptom Checklist with the clinician-administered ADHD Rating
Scale (ADHD-RS) in adolescents with ADHD with a mean age of 15 years. The results of the
study suggest that the ASRS v1.1 is an internally consistent and valid self-report scale for the
assessment of adolescents.
TCI-R 48. Cloninger (1999) developed the Temperament and Character Inventory-Revised to
measure seven personality dimensions. The shortened version TCI-R 48, used in this study, is a
48-item self-administered questionnaire designed to measure four temperaments, Novelty
Seeking, Harm Avoidance, Reward Dependence, and Persistence, and three characters, Self-
directedness, Cooperativeness, and Self-transcendence. The response option format of the TCI-R
48 ranged from 1 = definitely false to 5 = definitely true.

Analytical Strategy
In the dependent variables, measures of RTs and accuracy for response inhibition (Go/No-Go
task) and span spam for WM (Corsi span task) were obtained.
The distribution of the scores on response inhibition and WM of the four conditions were
examined with descriptive statistics (median, mean, standard deviation) and boxplots. If the
normality and equal variance assumptions were satisfied, the inferential statistical procedures
performed was the analysis of covariance ANCOVA for equal sample sizes, and Tukey's HSD, to
see which groups are significantly different. The pre-test (performance of the task without
stimulation), was the variable acting as covariate so as to adjust for pre-test differences. All
statistical tests were two-sided. All outliers (3 SD from the group mean score for each condition)
and any missing data was replaced with the group mean for that condition. A p-value of 0.05
was considered statistically significant. The one-way analysis of variance, ANCOVA, was
chosen over a mixed ANOVA because the study is looking for differences in the mean between
conditions and not for interaction effects between conditions and pre-post-tests. Moreover, a
mixed ANOVA analysis could be misleading as suggested by Dimitrov and Rumrill (2003). To
determine the reliability of group mean differences, as there are several groups or conditions,
performing multiple t-tests would not be convenient because the probability of a Type I error
would increase with each comparison between groups. An analysis of covariance, ANCOVA,
control for that error in the comparison of the four groups. If a statistically significant difference
was found, a Post Hoc test, Tukey, was used to establish between which groups were the
differences. The standard deviation and sample means of these groups will be reported. If
significant differences were found, the degree to which the IV and DV's were related was
assessed reporting the effect size or eta squared.

Additionally, with the aim of investigating interactions between individual differences
(attentiveness and novelty seeking) and stimulation conditions, a two-way between-subjects 42
ANOVA was performed, one for attentiveness and one for novelty seeking, for each dependent
variable. For this end, a high-low group for attentiveness and novelty seeking was established
depending on the scores, and the difference between pre and post-test scores was computed for
all dependent variables.
Results
Analysis of Covariance for Differential Effects
Three ANCOVAs (one for each dependent variable) were run to determine the effect of sham,
auditory WN, tRNS and tDCS on post-intervention scores in visuospatial WM, response
inhibition accuracy and response inhibition RT after controlling for pre-intervention scores.
Visuospatial WM. There was a linear relationship between pre- and post-intervention spatial
WM scores for each intervention type, as assessed by visual inspection of a scatterplot. There
was homogeneity of regression slopes as the interaction term was not statistically significant, F
(3, 24) = 1.805, p = .173. Standardized residuals for the interventions were normally distributed,
as assessed by Shapiro-Wilk's test (p > .05). There was homoscedasticity, as evaluated by the
standardized residuals plotted against the predicted values. There was homogeneity of variances,
as determined by Levene's test of homogeneity of variance (p = .598). There were no outliers in
the data, as assessed by no cases with standardized residuals greater than 3 standard deviations.
Adjusted means are presented unless otherwise stated. Post-intervention spatial WM scores were
higher in the auditory WN group (M = 85.50, SE = 7.44), tRNS group (M = 63.32, SE = 7.55)
and tDCS group (M = 76.01, SE = 7.32) compared to the sham group (M = 47.40, SE = 7.31).
After adjustment for pre-intervention spatial WM scores, there was a statistically significant
difference in post-intervention spatial WM scores between the conditions, F (3, 27) = 49.777, p
= .007, partial 2 = .356.
Post hoc analysis was performed with a Bonferroni adjustment. Post-intervention spatial WM
scores were statistically significantly greater in the auditory WN group (M = 85.50, SE = 7.44)
compared to the sham group (M = 47.40, SE = 7.31), a mean difference of 38.10, 95% CI [8.44,
67.76], p = .007. Post-intervention spatial WM scores were marginally statistically significantly
greater in the tDCS group than in the sham group, a mean difference of 28.61, 95% CI [-.83,
58.06], p = .061. No statistically significant differences were found between the tRNS and sham
group, a mean difference of 15.91, 95% CI [-14.10, 45.94], p = .857 (see Table 1).
Table1
Adjusted and Unadjusted Stimulation Condition Means and Variability for Posttest Spatial
Working Memory Scores with Pre-Test Spatial Working Memory Scores as a Covariate
Unadjusted Adjusted
N M SD M SE
Sham 8 46.75 22.72 47.40 7.31
tRNS 8 70.88 20.08 63.32 7.65
tDCS 8 74.75 24.77 76.01 7.32
WN 8 79.88 31.75 85.50 7.44
Note: N = number of participants, M = Mean, SD = Standard Deviation, SE = Standard Error, tRNS = Transcranial
Random Noise Stimulation, tDCS = Transcranial Direct Current Stimulation, WN = Auditory White Noise.
Response inhibition accuracy. There was a linear relationship between pre- and post-
intervention spatial WM scores for each intervention type, as assessed by visual inspection of a
scatterplot. There was homogeneity of regression slopes as the interaction term was not
statistically significant, F (3, 24) = .269, p = .847. Standardized residuals for the interventions
were normally distributed, as assessed by Shapiro-Wilk's test (p > .05). There was
homoscedasticity, as assessed by visual inspection of the standardized residuals plotted against
the predicted values. There was homogeneity of variances, as assessed by Levene's test of
homogeneity of variance (p = .868). There were no outliers in the data, as assessed by no cases
with standardized residuals greater than 3 standard deviations except in one instance, ID = 5
with a standardized residual of 3.35. It is decided to keep the outlier for further analysis because
the results of the analysis were not substantially affected.
Adjusted means are presented, unless otherwise stated. Post-intervention response inhibition
accuracy (number of omissions plus commissions errors) scores were similar in all conditions:
auditory WN group (M = 23.91, SE = 2.83), tRNS group (M = 26.95, SE = 2.90), tDCS group (M
= 24.06, SE = 2.85) and sham group (M = 24.55, SE = 2.85). After adjustment for pre-
intervention intervention response inhibition accuracy scores, there was not a statistically
significant difference in post-intervention response inhibition accuracy scores between the
conditions, F (3, 27) = 2.36, p = .871, partial 2 = .026 (See Table 2).
Table2
Adjusted and Unadjusted Stimulation Condition Means and Variability for Posttest Response
Inhibition Accuracy Scores with Pre-Test Posttest Response Inhibition Accuracy Scores as a
Covariate
Unadjusted Adjusted
N M SD M SE
Sham 8 26.63 15.15 24.65 2.85
tRNS 8 22.88 9.62 26.95 2.90
tDCS 8 26.25 11.23 24.06 2.85
WN 8 23.75 13.60 23.91 2.83
Response inhibition RT. There was a linear relationship between pre- and post-intervention
spatial WM scores for each intervention type, as assessed by visual inspection of a scatterplot.
There was homogeneity of regression slopes as the interaction term was not statistically
significant, F (3, 24) = .158, p = .924. Standardized residuals for the tDCS and tRNS conditions
were normally distributed, as assessed by Shapiro-Wilk's test (p > .05). However, standard
residuals for auditory WN and sham conditions were not normally distributed, Shapiro-Wilk's
test (p < .05). Because the one-way ANCOVA is relatively robust to deviations from normality
and the sample sizes are equal, it is decided to run the test as non-normality does not affect Type
I error rate substantially. There was homoscedasticity, as assessed by visual inspection of the
standardized residuals plotted against the predicted values. There was homogeneity of variances,
as assessed by Levene's test of homogeneity of variance (p = .624). There were no outliers in the
data, as assessed by no cases with standardized residuals greater than 3 standard deviations
except in one instance, ID = 5 with a standardized residual of 3.07. It is decided to keep the
outlier for further analysis because the results of the analysis were not substantially affected.
Adjusted means are presented unless otherwise stated. Post-intervention response inhibition RTs
were similar in all conditions: auditory WN group (M = 501.65, SE = 17.74), tRNS group (M =
470.71, SE = 17.73), tDCS group (M = 480.17, SE = 17.82) and sham group (M = 494.75, SE =
17.70). After adjustment for pre-intervention response inhibition RTs, there was not a statistically
significant difference in post-intervention response inhibition RTs between the conditions, F (3,
27) = .623, p = .606, partial 2 = .065 (see Table 3).

Table3
Adjusted and Unadjusted Stimulation Condition Means and Variability for Posttest Response
Inhibition RT Scores with Pre-Test Posttest Response Inhibition RT Scores as a Covariate
Unadjusted Adjusted
N M SD M SE
Sham 8 494.46 55.23 494.75 17.70
tRNS 8 473.04 42.34 470.71 17.73
tDCS 8 475.53 38.71 480.17 17.82
WN 8 504.25 71.45 501.65 17.74
Two-Way ANOVAs for Interaction Effects
To further investigate if the effect of the distinct stimulation depends on individual
differences, subjects were classified in a low or high attentiveness group and a low or high
novelty seeking group. A two-way between-subjects 42 ANOVA was performed, one for
attentiveness and one for novelty seeking, for each dependent variable (visuospatial WM,
response inhibition accuracy and response inhibition RT). For the dependent variables, the
difference between scores in the pre-test and post-test was computed. Subjects were assigned to
the low and high attentiveness group depending on the scores obtained in the ASRS-v1.1. The
subjects with scores from 1 to 17 were included in the high attention group (N = 17), and
subjects with scores from 18 to 34, in the low attention group (N = 15). Similarly, subjects were
assigned to the low or high novelty seeking group depending on the scores obtained in the TCI-R
48. The subjects with scores from 15 to 27 were included in the low novelty seeking group (N =
19), and subjects with scores from 28 to 41 (N = 13), in the high novelty seeking group. The two
independent variables were stimulation condition (auditory WN, tDCS, tRNS and Sham) and
attentiveness (low and high attentiveness) for the first ANOVA and low and high novelty seeking
for the second ANOVA. Residual analysis was performed to test the assumptions of the two-way
ANOVA. Inspection of a boxplot assessed outliers, normality, was assessed using Shapiro-Wilk's
normality test for each cell of the design and homogeneity of variances by Levene's test.
Attentiveness interaction with stimulation condition on spatial WM. There were no
outliers; residuals were normally distributed (p > .05), and there was homogeneity of variances
(p =. 278).
The interaction effect between stimulation condition and low-high attentiveness group for spatial
WM score was not statistically significant F (2, 24) = .855, p = .478, partial 2 = .097.
Therefore, an analysis of the main effects for stimulation condition and low-high attentiveness
group was performed, which indicated that the main effect of stimulation condition was
statistically significant, F (3, 24) = 4.988, p = .008, partial 2 = .384. There was no statistically
significant main effect of low-high attentiveness group on spatial WM score, F (1, 24) = .000, p
= .984, partial 2 = .000. All pairwise comparisons were run where reported 95% confidence
intervals and p-values are Bonferroni-adjusted. The marginal means of spatial WM scores for
auditory WN, tDCS, tRNS and sham low and high attentiveness group were 29.267 (SE = 8.024),
18.375 (SE = 7.769), 1.875 (SE = 7.769) and -10.500 (SE = 7.769), respectively.
Auditory WN stimulation was associated with a mean spatial WM score 39.767, 95% CI [7.655,
71.878] higher than the sham condition, a statistically significant difference, p = .010. The effect
of the stimulation conditions on spatial WM was not different for subjects classified as low or
high attentiveness.
Novelty seeking's interaction with stimulation condition on spatial WM. There were no
outliers as assessed by studentized residual value not greater than 2.5. Data was normally
distributed, as evaluated by Shapiro-Wilk's test (p > .05). There was homogeneity of variances,
as assessed by Levene's test for equality of variances (p =. 653).
There was a statistically significant interaction between stimulation condition and low-high level
of novelty seeking on spatial WM scores, F (3, 24) = 3.086, p = .046, partial 2 = .278.
Therefore, an analysis of simple main effects for stimulation condition was performed with
statistical significance receiving a Bonferroni adjustment and being accepted at the p < .025
level. There was a statistically significant difference in mean spatial WM scores between the low
and high novelty seeking group in the tDCS condition. In the tDCS condition, mean spatial WM
scores for the high novelty seeking group was 37.00 (SD = 24.99) and -.25 (SD = 6.46) for the
low novelty seeking group, a statistically significant mean difference of 37.25, 95% CI [8.70,
75.80], F (1, 24) = 7.252, p = .013, partial 2 = .232.
All pairwise comparisons were run for each simple main effect with reported 95% confidence
intervals and p-values Bonferroni-adjusted within each simple main effect. Spatial WM scores
for auditory WN, tRNS, tDCS and sham conditions in the high novelty seeking group were 27.33
(SD = 17.01), 2.50 (SD = 12.02), 37.00 (SD = 24.99) and -20.75 (SD = 28.76), respectively. The
high novelty seeking group, in the sham stimulation condition, had a statistically significantly
lower mean spatial WM score than the high novelty seeking group on the auditory WN, -48.08,
95% CI [-91.03, -5.12], p = .022, and the high novelty seeking group in the tDCS condition,
-57.75, 95% CI [-97.51, -17.98], p = .002. Mean spatial WM scores for auditory WN, tRNS,
tDCS and sham conditions for the low novelty seeking group were 31.20 (SD = 8.74), 1.66 (SD =
7.98), -.25 (SD = 9.78), and -.25 (SD = 9.78), respectively. No statistically significant differences
on mean spatial WM scores were found between stimulation conditions in the low novelty
seeking group.
The effect of tDCS on spatial WM was different for subjects classified as low or high
attentiveness. Subjects in the high novelty seeking group had statistically significantly higher
scores on spatial WM, compared to the subjects in the low novelty seeking group, with the
delivery of tDCS (see Figure 1).
80
Mean differences between pre and post test
60 Low NS High NS
40
on spatial WM scores
20
0
Sham tRNS tDCS WN
-20
-40
-60
Figure 1. Mean differences scores on spatial working memory between pre and posttest for
all stimulation conditions in both the Low and High novelty seeking (NS) groups. Error bar
denotes one standard deviation around the mean.
Attentiveness interaction with stimulation condition on response inhibition accuracy.
There were no outliers; residuals were normally distributed (p > .05), and there was homogeneity
of variances (p = .843).
There was not statistically significant interaction between stimulation condition and attentiveness
for response inhibition accuracy scores, F (3, 24) = .836, p = .487, partial 2 = .095. Therefore,
an analysis of the main effect for attentiveness was performed. There was not statistically
significant main effect of attentiveness on response inhibition accuracy scores, F (1, 24) = 0.902,
p = .352, partial 2 = .036.
Novelty seeking's interaction with stimulation condition on response inhibition accuracy.
of variances (p =.182).
for response inhibition accuracy scores, F (3, 24) = .503, p = .684, partial 2 = .059. Therefore,
an analysis of the main effect for novelty seeking was performed. There was not statistically
significant main effect of novelty seeking on response inhibition accuracy scores, F (1, 24) =
0.632, p = .435, partial 2 = .026.
Attentiveness's interaction with stimulation condition on response inhibition RT. There
were no outliers; residuals were normally distributed (p > .05), and there was not homogeneity of
variances (p =.043). However, it is decided to proceed with the analysis because group sample
sizes are equal, there is normality, and the ratio of the largest group variance to the smallest
group variance is less than 3. Under these circumstances, to run the two-way ANOVA it is
somehow robust to the heterogeneity of variance (Jaccard, 1998).
for response inhibition RT scores, F (3, 24) = 2.32, p = .101, partial 2 = .225. Therefore, an
analysis of the main effect for attentiveness was performed. There was not statistically
significant main effect of attentiveness on response inhibition RT scores, F (1, 24) = 1.46, p
= .239, partial 2 = .057

Novelty seeking's interaction with stimulation condition on response inhibition RT.
of variances (p = .184).
There was not statistically significant interaction between stimulation condition and novelty
seeking for response inhibition RT scores, F (3, 24) = 1.39, p = .267, partial 2 = .149.
Therefore, an analysis of the main effect for novelty seeking was performed. There was not
statistically significant main effect of novelty seeking on response inhibition RT scores, F (1, 24)
= .505, p = .484, partial 2 = .021.
Discussion
This study investigated the effect of auditory WN, tRNS and tDCS (over the left DLPFC) on
response inhibition and spatial WM together with the interaction of the stimulation conditions
with individual differences in attentiveness and novelty seeking. The performance of response
inhibition and WM tasks after auditory WN, tDCS, and tRNS was compared to performance
after the sham condition, with the scores on the cognitive tasks before the application of
stimulation conditions, acting as a control variable. Individual self-report scores on attentiveness
and novelty seeking were investigated as moderator variables of any significant effect. Accuracy
and RT were assessed for response inhibition with a Go/No-Go task. Spatial WM was assessed
with a Corsi visuospatial span task.
Differential effects of stimulation conditions
The application of tRNS and tDCS resulted in no significant change on any of the outcome
measures compared to sham when controlling for pre-intervention performance. However, it is
noteworthy that the study found marginally statistically significant difference in spatial WM
between tDCS and the sham condition, with higher scores after intervention with tDCS than
sham on spatial WM span. The results do not agree with previous studies reporting enhancement
of response inhibition and WM after application of tDCS on the left DLPFC (Boggio et al.,
2007). However, differences in the intensity, 1.5mA in the present study vs. 2mA in the study by
Boggio et al., and differences in the tasks employed to measure WM, a visuospatial WM task in
this study vs. a Sternberg task in the study by Gladwin et al. (2012), might explain discrepancies.
The results cannot be due to a lack of sensitivity of the outcomes measures as the Go/No-Go task
has been used extensively in previous studies and a visual inspection of the raw data revealed
neither ceiling nor flooring effects. On the other hand, this study is in agreement with prior
research that found the application on the left DLPFC of tDCS and tRNS (Mulquiney et al.,
2011) did not affect performance on response inhibition and WM tasks.
The auditory WN stimulation condition did yield a significant increase in the span of spatial
WM while it did not impact task accuracy or RT on the response inhibition Go/No-Go task,
compared with the sham condition. These results cannot be explained by the effects of pre-
existing group differences in response inhibition and WM because the use of ANCOVA corrected
for these effects. Results reveal a difference in the processes underlying response inhibition and
spatial WM. The investigation of the neural correlations underlying these processes can reveal
differential mechanisms involved in the various forms of brain stimulation. Moreover, the fact
that only the auditory WN stimulation condition yield a significant increase in spatial WM scores
over tDCS and tRNS suggests that auditory WN underlying mechanisms are not the same as
those that are at stake in tDCS and tRNS. An alternative explanation is that the placement of the
electrodes over the left DLPFC was not ideal to target response inhibition processes. Indeed, in
previous research reporting effects of tDCS on a Go/No-Go task measuring response inhibition,
the anodal electrode was placed above the rIFG, (Sikstrm et al., 2016). However, the effect was
only showed on RT and not accuracy.
Interaction Effects
The additional analyses of the interaction between the different stimulation conditions and the
low-high attentiveness groups on the performance on spatial WM and response inhibition
revealed no significant results. These findings do not concur with the hypothesis of the present
study nor with previous studies by Helps et al. (2014) and Sikstrm et al. (2016) that found
attentiveness moderates the effect of auditory WN and tDCS on a Go/No-Go task, measuring
response inhibition. However, unlike the present study, they did not use a sham condition to
avoid placebo effects, did not control for pre-intervention scores and conditions were not
counterbalanced. Nevertheless, the results do agree with Sikstrm et al. (2016) not finding any
interaction effects of attentiveness with auditory WN and tDCS on a spatial WM task. Although
the results of the current study do not agree with recent research, differences in the assessment of
attentiveness, self-report in the present study vs. parents and teachers report in the study by
Helps et al. (2014), might account for the conflicting results.
A relevant finding of the present study is that individual differences in novelty seeking
moderates the effect of tDCS on a spatial WM task. To date, this is the only known study that has
investigated the moderating effect that individual differences in novelty seeking have on different
stimulation conditions on measures of response inhibition and spatial WM. A significant increase
in spatial WM scores was found in the high vs. low novelty seeking group with the delivery of
anodal tDCS over the left DLPFC compared to the sham condition. Also relevant is the finding
that auditory WN stimulation, unlike tDCS, affects both, the low and high novelty seeking
groups, significantly improving their scores on spatial WM compared to the sham condition.
Although a significant correlation between novelty seeking and attentiveness has been
established in previous studies as well as the present one, r =.483, p= .005, the results indicate a
substantial discrimination between attentiveness and novelty seeking that could help to elucidate
the underlying working mechanisms of auditory WN and tDCS.
The involvement of the dopaminergic system on attentiveness (Biederman & Faraone, 2005),
novelty seeking (Bodi et al. 2009) and WM (Takeuchi et al., 2015) has been long established.
Even more, the MBA model (Sikstrm & Sderlund, 2007) explains how individual differences
in the dopaminergic system can lead to differential effects of auditory WN. However, the results
of the current study suggest that novelty seeking measures might be more sensible than
attentiveness to detect such differential effects.
Another intriguing finding of this study is the distinction between response inhibition and WM.
With auditory WN and tDCS exclusively affecting spatial WM and not response inhibition.
A possible alternative explanation to the MBA model (Sikstrm & Sderlund, 2007) could be
accounted for by the multiple-component theory of WM (Baddeley & Hitch 1974), the state-
based models of WM (Cowan, 2001) and the load theory of cognition (Lavie, 1995).
The multiple-component model of WM (Baddeley & Hitch 1974) describes two distinct
processes, WM storage, and control. Auditory WN might work allowing to expand the storage
capacity of WM. On the other hand, tDCS might affect the control process.
The WM storage is better explained by state-based models (Cowan, 2001; DEsposito & Postle,
2015; Fuster, 2014; Jonides, Lacey & Nee, 2005). These models are grounded in the idea that
mental representations are brought into WM by attentional selection. According to these models
(attention models), both attended and unattended sounds cause the occurrence of contents that
occupy resources in WM. The maintenance and processing of these sound-related contents in
WM would engage attentional resources that would no longer be available for other tasks. The
findings of the current study suggest that the application of auditory WN might help to disregard
distracting sounds that otherwise would occupy resources in WM, regardless of individual
differences. This effect can be explained by the Load Theory of Attention and Cognitive
Control (Lavie, 1995; Lavie, Hirst, de Fockert & Viding, 2004). The theory states that the level
of information irrelevant to the main task that is processed will depend on the amount of
perceptual load that the primary task involves. When a task with a high perceptual load
consumes all available capacity, the perception of stimuli irrelevant to the task is reduced or
eliminated. Conversely, when a task has a low perceptual load, available capacity allows the
perception of irrelevant stimuli (Parks, Hilimire & Corballis, 2011).
Cross-modal interactions between the visual and auditory perceptual systems are well-
documented (Spence, 2010). This study substantiates these findings as auditory WN influenced a
visuospatial WM task and might have contributed to eliminating distraction and expanding the
storage capacity of WM.
On the other hand, tDCS might affect the control process of WM. A critical mechanism of
WM function is the synchronization of the prefrontal cortex (PFC) with activity in other brain
regions. Top-down control signals from PFC have been suggested to enhance task-relevant
information and suppress task-irrelevant information (DEsposito & Postle, 2015). Therefore, the
stimulation on the left DLPFC with tDCS might differentially help to synchronize the activity of
PFC with other areas in individuals with higher scores in novelty seeking.
Some potential limitations of the present study require consideration. The current study
describes a relatively small sample size, meaning that the study may have lacked the power
needed to detect reliably changes in the response inhibition measures employed. Additionally,
despite the exact counterbalancing of the sessions achieved following randomization and the
matching of groups on attentiveness, other variables may have interfered with the equivalence of
the groups. Although no differences were found in age, gender, education level and novelty
seeking between groups.
In addition to addressing the limitations above through employing larger sample sizes, with
respect to tDCS and tRNS, in future studies, it may also be advantageous to alter the placement
of the electrodes, current density, and range as well as the time of off-line and online application
when employing this form of stimulation. In this study, the same intensity,1.5mA was delivered
for tDCS and tRNS, but past studies have shown increased brain excitability with tRNS only
with higher current density in comparison with tDCS (Moliadze, Antal & Paulus, 2010). It is
therefore suggested to increase current intensity when using tRNS. Additionally, tRNS with DC
offset of 1mA has been shown to be more efficient than tRNS with zero DC offset (Ho, Taylor &
Loo, 2013; 2015). However, the statistical proprieties of tRNS with zero DC offset (used in the
current study) are more similar to the random frequencies of auditory WN, thus more appropriate
to test if auditory WN and tRNS share the same working mechanism, SR (Fertonani et al., 2011).
Future studies on differential effects of non-invasive brain stimulation might find helpful to
assess novelty seeking in addition to attentiveness. The results of the present study suggest the
assessment of this component may provide valuable information on individual differences and its
interaction with response to treatment. For instance, to explore which of the two novelty
seeking's sub-dimensions -- exploratory excitability (drive for novel experience) and
impulsiveness (careless decision-making) -- interacts with tDCS to affect results could enable
further specification of personality and character differences interacting with stimulation.

Conclusion
The current study does not support the MBA model suggestion that both auditory WN and
current stimulation interact with individual differences in attentiveness on cognitive
performance. The results prompt to tRNS, tDCS and auditory WN targeting different
mechanisms and processes. A possible explanation of the results is that auditory WN allows
more capacity in the WM storage and that tDCS helps to activate or synchronized top-down
control signals that could be deficient in individuals with a high score in novelty seeking. The
lack of effect of tRNS, in contrast to auditory WN and tDCS, further indicates a different
working mechanism. Novelty seeking interaction with tDCS further opens new possibilities for
future studies to investigate differential effects and underlying mechanisms of the diverse
non/invasive brain stimulations.

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Running head: EFFECTS OF WN, TES AND SHAM ON COGNITION 1

Inhibition and Working Memory

Maria Teresa Vaos Solano

Thesis for the Master of Science in Psychology

Prof. Sverker Sikstrm

Keywords: cognitive enhancement, transcranial direct current stimulation (tDCS),

working memory (WM), attentiveness, novelty seeking, adolescents

Inhibition and Working Memory

enhancement. However, contemporary methods are placing more emphasis on direct

with individual differences and diverse cognitive processes.

Moreover, a meta-analysis by Dedoncker, Brunoni, Baeken and Vanderhasselt (2016), revealed

more pronounced in women. In contrast, neuropsychiatric samples scored greater in accuracy

Hoy, Daskalakis & Fitzgerald., 2011).

been signified by Fertonani, Pirulli, and Miniussi (2011), to be working in tRNS.

population, with a sham and control condition.

Previous research shows improvement in cognitive performance through stimulation with

(Sderlund & Sikstrm, 2008). SR is a phenomenon occurring in nonlinear systems whereby

However, an increase of noise intensity will result in an impairment to process information

randomness that makes a nonlinearity less detrimental to a signal (p.1).

improved recognition memory in healthy humans, selectively enhancing stimulus-driven phasic

activity in dopaminergic pathways and auditory cortex (Rausch et al., 2014).

particularly enhanced performance in tasks requiring EF in sub-attentive children. The results

the high attentiveness group in a Go/No-Go task.

attentiveness. Moreover, auditory WN mainly appears to improve the execution of tasks

General Introduction for tES (Transcranial Electrical Stimulation)

electrical discharges, making electrotherapy a conventional treatment to heal neuralgia,

patterns working consistently (Nitsche & Paulus, 2000).

in the scalp as an experimental condition.

Studies show considerable variability regarding specific characteristics of the stimulation

harder the interpretation of research (Saturnino, Antunes & Thielscher, 2015).

approximate number sense and mathematical skills.

tES see review by Cohen (2015).

Transcranial Direct Current Stimulation

Principles. Transcranial direct current stimulation (tDCS) consists of the application of a

cortical excitability through hyperpolarization (Nitsche et al., 2003).

diverse tasks employed for measurement.

significantly improved learning and performance in comparison with a sham condition,

suggesting better selective attention and response inhibition.

nonclinical populations. A study by Fecteau et al. (2007) reported a decrease in risk-taking, a

DLPFC showed a significant decrease, suggesting an improvement of attentional control

(Heeren, Baeken, Vanderhasselt, Philippot & de Raedt, 2015).

on the Sternberg task.

left DLPFC in a long-term verbal memory task.

and Schmidt (2016).

cell body, producing a change in membrane potential (Bikson et al., 2006).

Additionally, the after-effects of tDCS seem to depend on NMDA receptors suggesting an

prefrontal cortex (Stagg et al., 2013).

Transcranial Random Noise Stimulation

the low-frequency (0.1-100Hz), seems to be responsible for inducing excitability in M1 (Terney

(Romanska, Rezlescu, Susilo, Duchaine & Banissy, 2015).

blinds. Moreover, tRNS guarantee an application independent of polarity because of its

oscillatory electric wave (Chaieb et al., 2009).

(Chaieb, Paulus & Antal, 2011).

Additionally, tRNS produced improvement in other domains, including perceptual learning

improve WM in a healthy population (Mulquiney et al., 2011).

Paulus & Antal, 2013).

shown to change voltage-gated Na channels (Chaieb et al., 2015).

NMDA receptors as tDCS does but on the Na channels.

individual differences and its interaction with response to treatment.

Attentiveness. Attentiveness is a quantitative measure used to gauge the individual level of

ADHD is a developmental disorder with a prevalence of 7, 2% in children and adolescents

mechanisms, like a deficit in cortical inhibitory neurotransmission (Demirtas-Tatlidede,

& Faraone, 2005).

Novelty seeking. Novelty seeking, a component of Cloningers Psychobiological Model of