Rationale: Individuals with spinal cord injury (SCI) suffer from accelerated cognitive aging. In able-bodied individuals, a vast amount of studies have shown that exercise interventions can improve cognitive function. Myokines (i.e. factors released into the blood stream from muscle cells) are considered one of the mediators of this beneficial effect. Neuromuscular electrical stimulation (NMES), used to replace or support muscle training in disabled individuals with poor exercise possibilities, was shown to elicit a large release of myokines (in some studies larger than following voluntary exercise). However, so far, the effects of NMES on cognitive function have never been studied before. In fact, only one study has previously investigated the effect of exercise on cognitive function in persons with SCI.

Objective: The primary aim is to assess to what extent a 12 week intervention with NMES to the quadriceps muscles of people with SCI can change their performance on a set of cognitive tests. Secondarily, the investigators will measure to what extent NMES to the quadriceps muscles of people with SCI induces changes in blood levels of the myokine brain-derived neurotrophic factor (BDNF), which is considered a potential mediator of the exercise-cognition effect, facilitating neuroplastic processes.

Study design: A single case experimental design (SCED) with sequential multiple baseline time series and a single-armed prospective study design, with a random duration of the baseline phase ranging from 3 to 6 weeks, an intervention phase of 12 weeks, and a 12 week period without measurements, followed by a follow-up phase of 3 weeks; in addition to a single-armed prospective study design.

Study population: Individuals (n = 15) aged 18 years and older with a chronic SCI (>1y post-injury) and with visible or palpable contraction of the quadriceps muscles upon NMES will be recruited at the rehabilitation centre of Adelante in Hoensbroek, the Netherlands.

Intervention: The study participants will receive 30min of NMES using surface electrodes on the quadriceps muscles three times per week for a total duration of 12 weeks.

Main study parameters/endpoints: The primary outcome is cognitive function changes which will be measured using a secured smartphone application (e.g. m-Path). Secondary outcome measures are changes in the blood myokine levels of BDNF and changes in cognitive outcome scores on an verbal cognitive test battery.

Inclusion Criteria:

• Persons with spinal cord injury
• Completeness of injury: American Spinal Injury Association (ASIA) Impairment Scale (AIS) A, B or C
• Level of injury: L2 or higher
• At least 18 years old
• Chronic stage (> 1 year) since injury
• No previous surgery to the quadriceps muscles
• Intact hand function
• Able to use apps on smartphone (i.e. participants should have their own smartphone and should not have disabilities that impair them to operate it independently)
• Able to follow the instructions of placing the surface electrodes of the NMES device correctly or to have someone else put the electrodes for them
• Dutch as a native language

Exclusion Criteria:

• Malignant processes, or history of undergoing chemotherapy, or history of radiotherapy to the head
• No visible or palpable contraction of the quadriceps muscle upon electrical stimulation
• Intolerance to electrical stimulation of the quadriceps muscle
• Recent or current participation in an electrical stimulation-induced exercise or therapy program in which regular electrical stimulation was given (up to 6 months prior to study inclusion)
• Known neurodegenerative disorder, such as Alzheimer's disease or Parkinson's disease
• Known psychiatric disorder, such as major depressive disorder or bipolar disorder
• Current pressure ulcer
• History of severe autonomic dysreflexia
• Metal implants in the electrical stimulation area
• Intrathecal baclofen (ITB) device
• Pregnancy

All information will be coded and kept behind locked doors.