The use of Virtual Reality for Cognitive Rehabilitation Following Acquired Brain Injury

The reported prevalence of cognitive disorders after acquired brain injury
(ABI) in at least one or multiple domains ranges from 10-93% (van der Naalt et
al., 1999; van Kessel et al., 2017; Nys et al., 2005; Nys et al., 2007; de
Haan, Nys & van Zandvoort, 2006; Tatemichi et al., 1994, Rasquin et al., 2004).
Cognitive disorders have a negative influence on both performance on *activity*
and *participation* level (van der Kemp et al., 2017; van Velzen et al., 2009;
Nys et al., 2005).

Research has demonstrated the importance of rehabilitation following ABI.
However, despite benefits, conventional ABI rehabilitation is focused on
learning compensation strategies as opposed to recovery of cognitive functions
(e.g. learning how to deal with the problems and limitations, but not solving
them; Laver, George, Thomas, Deutsch & Crotty, 2015). This is also the case for
recovery of activities of daily life (ADL). Furthermore, conventional ABI
rehabilitation poses several limitations: it is time consuming, costly, labor
and resource intensive, reliant upon the adherence of a patient, limited in
availability subject to location, and has a modest effect (Saposnik, 2016).

Research has demonstrated that rehabilitation following ABI can facilitate
recovery of cognitive functions, even years following the injury (Miltner,
2016; Laver et al., 2015; Rohling, Faust, Beverly & Demakis, 2009; Cappa et
al., 2005; Cicerone et al., 2000, Cicerone et al., 2005). Repetitive, task and
goal-oriented training has been shown to improve cognition and ADL on a
functional level for those who have experienced an ABI. However, there remains
a need for further investigation and the development of rehabilitation
protocols or tools that can help in extending conventional rehabilitation to
overcome its limitations.

Over the past ten years, research has emerged regarding the use of VR as a
rehabilitation tool for ABI, suggesting that it is a feasible and useful option
that may improve cognition, ADL, and physical and emotional deficits leading to
disability, while reducing costs and resources (Spreij, Visser-Meily, Sibbel,
Gosselt & Nijboer, 2020; Spreij, Gosselt, Visser-Meily & Nijboer, 2020; Gamito
et al., 2017; Laver et al., 2015). Conventional rehabilitation protocols
typically take place in a controlled environment, while VR aims to simulate
settings one may encounter in daily life (e.g. possesses higher ecological
validity), which may be attributed to an immersive and dynamic setting (e.g.
many external distractors and time-pressure) (Negu* et al., 2016; Nijboer,
2017). VR simulations create an environment in which stimuli can be fully
controlled and adjusted to a person*s level of functioning (Bohil et al., 2011;
Nijboer, 2017). Finally, VR offers the ability to register every individual*s
actions, and may serve as a measure of cognitive function on *activity* level
(Nijboer, 2017; Rizzo et al., 2004). Therefore, research suggests that VR
simulations are a promising addition to rehabilitation following ABI, and that
this will enhance not only cognitive outcomes, but ADL, IADL (instrumental
activities of daily living) and quality of life (Qol).

Research has shown that serious games (e.g. the gamification of tasks) and the
ability to include incremental levels of difficulty can serve as a motivating
factor (Hamari et al., 2014; Hense et al., 2014), increasing the likelihood of
intense and repetitive practice in an entertaining method. The current research
will allow participants to train cognitive functions following an ABI, using
this novel approach: a VR serious game named Koji*s Quest in addition to
conventional rehabilitation.

The main aim of the current study is to examine if there is a treatment effect
in the cognitive domains assessed in the condition where patients receive a
rehabilitation program with conventional therapy plus Koji's Quest, and compare
this effect to those receiving only conventional therapy. Furthermore, the
current study aims to examine if treatment effects are comparable between
inpatient and outpatient groups.

Hypotheses:
1. Inpatient Group: It is expected that complementing conventional
rehabilitation by training with Koji's Quest will have a greater treatment
effect on cognition than the treatment effect of conventional rehabilitation
alone (from T1 to T2).

Outpatient Group: It is expected that complementing conventional rehabilitation
by training with Koji's Quest will have a greater treatment effect on level of
function in terms of ADL than the treatment effect of conventional
rehabilitation alone (from T1 to T2).

2. It is expected that there will be no significant difference in the treatment
effects found between inpatient and outpatient groups.

3. It is expected that interactions between scores on the NPO, questionnaires,
demographic factors, and medical factors will contribute to the treatment
effect observed in both inpatient and outpatient groups.

4. It is expected that effects of training will be robust after a 3 month
follow up (T3). It is expected that individuals with ABI will not show further
improvement from their most recent testing session (T2), however, will be
improved from baseline (T1) in the inpatient group.

5. It is expected that effects of training will be robust after a 3 month
follow up (T3). It is expected that individuals with ABI will not show further
improvement from their most recent testing session (T2), however, will be
improved from baseline (T1) in the outpatient group.

Primary objective:

Inpatient Group:
The primary objective of the research with the inpatient group is to assess
whether there is a treatment effect in cognition (at T2) compared to baseline
(T1) using conventional rehabilitation, as compared to conventional
rehabilitation with the addition of training with Koji's Quest.

Outpatient Group:
The primary objective of the research with the outpatient group is to assess
whether there is a treatment effect at the level of function in terms of ADL
(at T2) compared to baseline (T1) using conventional rehabilitation, as
compared to conventional rehabilitation with the addition of training with
Koji's Quest.

Secondary objectives:
To examine the extent to which inpatient versus outpatient treatment effects in
cognition differ from baseline (T1) to post intervention (T2).

Sub-questions:
- Which factors contribute to whether an individual has a treatment effect or
not, e.g., demographic factors, medical factors, performance on
neuropsychological tests (NPO), and performance on questionnaires?
- After a 3 month follow up (T3), how robust are the treatment effects for the
inpatient group (if any) found compared to T2?
- After a 3 month follow up (T3), how robust are the treatment effects for the
outpatient group (if any) found compared to T2?

The current study is designed as a single-blind randomized controlled trial.
Randomization will be done through a block design with a 1:1 allocation ratio.
Participants will be assigned to blocks based upon their gender and age. Within
the blocks, the participants will be randomly allocated to either the
experimental or the control group by computer generated sequences. Block
randomization will be completed by a data analyst with no clinical ties to the
current study.

The current study is a between-and-within subjects repeated measures trial. We
will include 142 ABI inpatients who are currently receiving treatment at a
facility, and 142 ABI outpatients who currently are living at home and are
either receiving treatment outside of their facility or no treatment.

Both patient groups will consist out of an experimental group (n = 71) and a
control group (n = 71). The control group consists of patients with ABI who
will receive conventional rehabilitation, whereas the experimental group will
receive conventional rehabilitation concurrently to training with Koji's Quest.

The training tasks associated with each cognitive domain in the VR
intervention, Koji's Quest, will be randomized to control for order effects and
balance the fatigue associated with time spent during rehabilitation (i.e. if
selective attention is always trained first and executive functioning is always
trained last, the participant*s training may be impacted by fatigue rather than
reflect cognitive ability). The cognitive training software will be programmed
to randomly select the order of the cognitive training tasks.
See protocol section 3: Study Design for further details.

The ABI inpatient and outpatient groups will either receive solely conventional
rehabilitation (control group) or conventional rehabilitation with the addition
of training with Koji's Quest (experimental group). The intervention will last
for 6 weeks - 3 times per week, in sessions of 30 minutes. Individuals in the
control groups will be waitlisted and will be offered the ability to train with
Koji's Quest as well following the conclusion of their participation in the
study.

Participation is voluntary in all subjects and participants are free to
withdraw from the study at any time, while still receiving compensation. There
are minimal risks associated with participation in this study, namely some
individuals may experience dizziness as a result of using virtual reality (VR).
All questionnaires and neuropsychological tests administered to both inpatient
and outpatient groups will have a maximum duration of 90 minutes. Training
sessions using VR will last approximately 30 minutes per session.Both groups
may have the benefit of a treatment effect that enhances their cognitive
functions and activities of daily life (ADLs) if the intervention is
successful. Participants will also be contributing to furthering scientific
discovery.

Inpatient group:
Burden and inconvenience are minimal considering the inpatient group will be
recruited and participate at the center they are currently undergoing treatment
in. Furthermore, to minimize burden, as much information as possible regarding
demographics, medical information, and scores on relevant screenings, NPO, and
questionnaires will be gathered from electronic patient files (EPFs).

Outpatient group:
Use of the intervention at home will minimally inconvenience the outpatient
group as they will still follow their scheduled conventional rehabilitation,
and are able to follow the VR training protocol during times that are suitable
for them. Their NPO can be administered by a qualified researcher either at the
facility where the outpatient receives treatment, or at their place of
residence. Questionnaires can be filled in independently and with a proxy at
home as well.