Brain Activity Patterns in Persons With Spinal Cord Injury and Neuropathic Pain After a Virtual Walking Training Program

The aim of this pilot study is to explore the association of changes in pain perception with changes in brain activity (functional Magnetic Resonance Imaging (fMRI)) and metabolic (Magnetic Resonance Spectroscopy (MRS)) patterns of individuals with SCI and chronic NeP after a Virtual Walk (VW) therapy. The brain activity patterns will be assessed in resting state and under a specific task, before and after a VW training program, done as part of the clinical routine, as well as at a four weeks follow-up.

The results of this pilot study will serve as basis for a bigger project that aims to investigate and compare brain activity and long-term effects of non-immersive VW therapy on chronic NeP in individuals with SCI (traumatic SCI with chronic NeP at- or below level, complete or incomplete) taking into account confounding factors such as time since injury, level of injury and type of NeP.

This pilot study consists of specific assessments at four different time points (T0=screening, T1=baseline, pre measurement, T2=post measurement, T3=four week follow-up).

The physiotherapeutical assessment at T0 involves the evaluation of the imagery capacity. At T1, the participant will be assessed for baseline measures before starting with the VW training. At T2 (after the last VW training) and at T3 (four weeks after the last VW training), the participant will be assessed for outcome measures.

Sociodemographic and clinical characteristics (age, sex, education level, workability, age at injury, lesion level, comorbidities, complications, concomitant injuries, SCI pain basic dataset 2.0 and medication) will be collected in the screening/recruitment phase but only used after receiving informed consent from each participant.

Participants will undergo a non-invasively MRI examination without application of contrast agents. The functional activity of the brain will be assessed by a blood oxygenation level-dependent (BOLD) fMRI. The metabolic profile will be assessed non-invasively by means of single voxel MRS. Prior to the fMRI and MRS measurements, a high-resolution anatomical MRI will be performed, which serves for tissue segmentation and planning purposes.

The MRI will consist out of the following sequences conducted in an MRI scanner (six minutes duration each):

1. MRS sequence: The metabolic profile will be assessed with single voxel spectroscopy in the Anterior Cingulate Cortex and the Thalamus.
2. Resting-state fMRI: The participant will stay rested with open eyes and does not have to perform a specific task.
3. Task-based fMRI: In an on-off scheme, a sequence of neutral (not pain related) pictures on a screen, mounted outside of the MRI machine will be shown. The pictures will change every 20 seconds in a random order to keep the participant alert.
4. Task-based fMRI: In an on-off scheme, a sequence of pain-related pictures on a screen, mounted outside of the MRI machine will be shown. The pictures will change every 20 seconds in a random order to keep the participant alert.
5. Resting-state fMRI: The participant will stay rested with open eyes and does not have to execute a task.

The pain images shown during the task-based fMRI are a validated set of pictures.

The participants will receive a pain diary. This pain diary is filled in daily for the one-week period before the baseline assessments, during the VW therapy and in the week before the last assessments at T3. To minimise the risk of missing data in the pain diary the participants will be called one week before T3 and get reminded to fill in the pain diary.

Before starting with the VW therapy the participants will first perform a subitem of the standardised Graded Motor Imagery (GMI) training over four weeks, five times a day using the Recognise Foot App and the Recognise Hand App. The participants will train their capacity to perform a left-right discrimination for hands and feet. This training will help to improve the therapeutic effect of the following VW therapy program, by improving the imagery capacity. Reaction time as well as accuracy while performing a left-right discrimination task will be measured. More than 80% correct answers and a reaction time of less than two seconds is interpreted as good imagery capacity. The imagery capacity will be assessed right before the start of the discrimination training, after two weeks and after four weeks. This serves on one hand as information about participant characteristics and on the other hand as a control mechanism that each participant keeps performing this training.

After the discrimination training, the participants will perform a non-immersive VW therapy program at the pain clinic, which consists of five sessions of 10 to 20 minutes per week, over a two-week period, then three treatments per week for the following two weeks and finally in the last two weeks only two treatments per week are scheduled. This is the standard protocol for this kind of therapy and is not changed in any way for the participants of the MRI study. For the VW, the participants will sit on an electric wheelchair in front of a canvas with an integrated camera. The camera films the participant's head and trunk, which are then projected on the canvas, overlapping with the recording of the feet of an actor walking. This way the participants will see themselves walk through a forest from a third-person view. To improve the embodiment, the participants will be asked to swing their arms in the rhythm of the gait and imagine that they are walking themselves through the forest. In addition to this, the chair moves minimally in the frontal plane to imitate the natural movements of the pelvis while walking.

Eligibility Criteria:
Inclusion Criteria:

* Passed neurological, physiotherapeutic and psychological assessments and team decision to take part on VW
* Age ≧ 18
* Traumatic SCI (\> 1 year) confirmed by MRI or CT
* Neuropathic at or below level spinal cord injury pain for at least 3 months diagnosed by a neurologist following the CanPain Clinical Practice Guidelines and ISCIP classification
* Good German skills (understand questionnaires and instructions)
* Ability to draw with a pen
* Ability to swing the arms

Exclusion Criteria:

* Claustrophobia
* Non-acceptance of the paraplegia
* Psychiatric disorders
* Epilepsy
* Other neurological, psycho-logical or cognitive impairments
* Pregnancy
* Spasticity that would interfere with MRI
* Extensive dose of opioids