Improving outcome through improving cognition in Severe Mental Illness: Cognitive Remediation Training combined with transcranial Direct Current Stimulation, a pilot study.

Seven per cent of service users suffering from severe mental illness needs
long-term intensive treatment and support in a clinical setting or sheltered
living (Van Hoof et al., 2015). In this group of service users, the illness is
often chronic and characterized by an incomplete recovery (Trieman & Leff,
2002; Uggerby et al., 2011). Service users often experience problems on
multiple domains, such as persistent complaints as a result of medication
resistance (Meltzer, 1997), physical health problems (McEvoy et al., 2005) and
self-care (Wiersma et al, 2000), psychosocial (Harvey et al., 2012), and
cognitive dysfunctioning (Palmer et al., 2009; Velligan et al, 1997). The
recovery process in this group of service users is therefore complex. A
fundamental challenge in the treatment of these service users is how to deal
with cognitive dysfunctioning. Moreover, neural plasticity in service users
with SMI appears to be reduced; a factor that might hinder newly learnt
cognitive skills to sustain.

The primary goal is of this pilot study is to investigate the effects of
Computerised Interactive Remediation of Cognition - a Training for
Schizophrenia (CIRCuiTS), on the cognitive functioning of the described group
of service users. It is expected that cognitive remediation training with
CIRCuiTS will lead to improved cognitive functioning. In addition, a
non-invasive brain stimulation technique transcranial Direct Current
Stimulation (tDCS), is used to promote neural plasticity. By applying this
stimulation to neural networks simultaneously with engagement in the cognitive
tasks of CIRCuiTS, it is expected that plasticity of these networks will be
increased, resulting in longer lasting improvements in cognitive functioning
than with CIRCuiTS training only. Improvements in cognitive functioning may
subsequently positively influence daily functioning.

Participants will be randomized over two groups: CIRCuiTS in combination with
sham tDCS (group 1) or CIRCuiTS in combination with active tDCS (group 2). The
trial will start with a waiting period of 16 weeks, which will serve as the
control condition. Next, the participants will receive 16 weeks of either
CIRCuiTS + sham tDCS or CIRCuiTS + active tDCS. All sessions will be given on
an individual basis. The duration of each training session will be 30 minutes
(and 20 minutes of tDCS simultaneously in group II) and will be given twice
weekly.

Cognitive remediation training will be given with CIRCuiTS. This program is
built of computerized tasks that are mainly aimed at improving attention,
memory and planning, by training in many different ways and by learning to use
strategies to improve meta-cognition and to transfer these skills to daily life
situations. In addition, by practicing in daily life, generalization of the
newly learnt skills is stimulated.
tDCS is a non-invasive brain stimulation technique that uses two electrodes to
apply a small electrical current to alter excitability of neurons, such that it
increases or decreases spontaneous network activity, and may promote neural
plasticity. In this study, the target region is the left dorsolateral
prefrontal cortex, as an important hub of the fronto-parietal brain network.

During the baseline measurement (T0), an observational assessment for cognitive
abilities is performed by the participant's case manager (10 minutes). The case
managers are also asked to fill in a questionnaire about a participant's life
skills (10 minutes). These measures do not require effort from the participant.
The participants are asked to perform a series of cognitive tasks and two
questionnaires, which will take approximately 70 minutes. The study will follow
a stepped-wedge design in which participants will first receive care as usual
for 16 weeks (waiting period), after which participants are randomly allocated
to either 32 30-minute training sessions (16 weeks, twice weekly) with CIRCuiTS
+ prefrontal sham tDCS, or with CIRCuiTS + prefrontal active tDCS. After the
16-week waiting period and after the 16-week training period, a second (T1) and
third measurement (T2), respectively, will take place comprising the same
measurements as at T0. During the tDCS procedure, participants are exposed to a
very low electrical current of 2 mA. The use of tDCS has, to date, not resulted
in significant adverse effects, apart from mild headache or a mild tingling
sensation underneath the electrodes. The stimulation parameters are well within
international safety guidelines. To assess possible long-term effects, we will
do a follow-up measurement after six months after the intervention (T3),
similar to the other three measurements.
We hypothesize that participants in both groups improve on cognitive
functioning after the intervention period, and that participants who will
receive CIRCuiTS in combination with active tDCS will improve more than the
participants who receive CIRCuiTS + sham tDCS. Moreover, given the focus of
CIRCuiTS on the practice in daily life, we hypothesize that participants will
also improve in daily functioning. In case the results of this study indicate
that cognitive performance can be improved with CIRCuiTS, and whether or not
tDCS will lead to additional improvement, this intervention will be further
investigated in a large randomized multicenter study. If the intervention
appears to be effective, it can be implemented as standard care for service
users that need long-term support in a clinical or sheltered setting.