The Effect of tDCS on the Consolidation of Fear Extinction Memory

Exposure therapy is a prevalent method in the treatment of anxiety disorders.
However, for many patients this extinction-based treatment is not, or only
partially, beneficial (McNally, 2007). In anxiety research, classical fear
conditioning and extinction paradigms are commonly used to study the nature of
fear responses. In a conditioning phase, a neutral stimulus (CS) is paired with
an unconditioned aversive stimulus (US) and will be repeatedly presented. At
the end of the conditioning phase, presentation of the previously neutral
stimulus (CS+) will elicit a fear response even in the absence of the US. In an
extinction phase, the CS+ will be repeatedly presented without the US which
will result in a new safety memory of the previously aversive stimulus. The
recall of this fear extinction memory is typically tested 24 hours later.
Previous studies have shown that the recall of fear extinction memories is
dysfunctional in individuals with anxiety disorders (e.g. post-traumatic stress
disorder) indicating that the consolidation of the extinction memory is
impaired (Milad et al., 2009). In recent studies, transcranial direct current
stimulation (tDCS) has been shown to have the capacity of impacting the
consolidation of memories. tDCS might therefore provide a new means to
facilitate the effects of extinction-based therapies.
It is generally considered that anodal tDCS increases neuronal excitability
while cathodal stimulation decreases neuronal excitability of the stimulated
area (ref). However, while this polarity effect has been consistently observed
when tDCS was applied over motor areas, heterogenous effects have been found
in tDCS studies investigating its effect on cognitive functions (Jacobson et
al., 2011). In cognitive tasks, anodal stimulation was found to consistently
cause excitatory effects, inhibitory effects, however, were not observed after
cathodal stimulation.
Only few studies have investigated the impact of tDCS on fear memories. In a
recent study, Asthana et al. (2013) showed that cathodal transcranial direct
current stimulation (tDCS) over the right dorsolateral prefrontal cortex
(dlPFC) disrupts the consolidation of conditioned fear memories when compared
to sham stimulation. Anodal tDCS over the right dlPFC was shown to enhance fear
memories (as measured by skin conductance responses) when applied after the
presentation of a reminder of the previous learned fearful stimulus (Mungee et
al., 2013). The effect of tDCS on the consolidation of fear extinction
memories has not been investigated. The aim of this research is to investigate
whether transcranial direct current stimulation over the right dorso-lateral
prefrontal cortex (dlPFC) enhances the consolidation of extinction memory when
administered directly after extinction training. This is of clinical
significance for the successful treatment of anxiety disorders.

To evaluate the effect of tDCS (anodal and cathodal) to the right dorso-lateral
prefrontal cortex on the consolidation of fear extinction memory in healthy
volunteers as compared to sham tDCS (control) as measured by
psychophysiological measures (SCR and startle response). It is anticipated that
anodal stimulation will facilitate the consolidation of extinction memory while
cathodal stimulation will disrupt/interfere with extinction memory
consolidation.

The present study is a placebo-controlled double-blind design. Volunteers will
participate in three sessions in an observational study. On day 1, participants
will perform a Pavlovian conditioning paradigm with a neutral stimulus and an
aversive stimulus paired with a mild electric stressor. On the second day,
participants will undergo an extinction paradigm. Subsequently, subjects will
receive tDCS (anodal or cathodal) or sham stimulation to the dorso-lateral
prefrontal cortex. On day 3, participants will perform an extinction recall and
reinstatement paradigm which will involve a mild electric stressor. The first
session will last approximately 45min, the second 60min, and the third session
will last for approximately 45 min. All study sessions will be performed at the
Psychiatry Department of the AMC. Subjects* personality variables will be
assessed using several questionnaires.
As directionality of anodal and cathodal tDCS stimulation is not yet fully
established, both polarities will be investigated.

transcranial direct current stimulation

The proposed tDCS procedure is safe and does not carry any significant risk.
Safety guidelines will be followed to ensure participant*s safety. Potential
side-effects of tDCS are itching and tingling sensations under the electrodes
(Nitsche et al., 2008). tDCS will be applied with a current intensity of 1mA
over a time period of 20 min. For sham stimulation, the current will be ramped
up and then down again to simulate the feeling of active stimulation.
Volunteers can withdraw from the study at any given time and there are no
direct benefits for the participants.