As a result of improved treatment, the survival rate of children diagnosed with a brain tumor has increased considerably . As a consequence, neurocognitive long-term effects of the tumor and the treatment are reported more often, including deficits in attention, processing speed, and memory [2–4]. Radiotherapy, chemotherapy, tumor location, and longer time since diagnosis are related to worse neurocognitive functioning [5, 6]. A major consequence of these impairments is the decline in ability to acquire new skills and information, which leads to an increasing gap in the development between patients and their peers. This, in turn, has its impact on educational results, vocational success and may compromise social competence and quality of life .
Butler and Mulhern have emphasized that interventions should be developed to improve neurocognitive functioning and subsequently improve future perspectives of these children . Interventions that are considered relevant for survivors with cancer-related brain injury are cognitive remediation and pharmacotherapy [9, 10]. A cognitive remediation program, using techniques from three disciplines: brain injury rehabilitation, special education and clinical psychology, has been developed and tested by Butler and colleagues . Participants in the randomized controlled trial were 161 survivors of a childhood cancer, whose malignancy and/or treatment involved the central nervous system. The results showed improvements in caregiver reported attention and academic achievement, although the effect sizes were modest. Van ‘t Hooft et al. have investigated the effects of a cognitive training program on neurocognitive function with a randomized controlled trial, enrolling 38 patients with acquired brain injury, including 14 brain tumor survivors . The training program consisted of memory and attention exercises, in combination with cognitive behavioral training. The children in the treatment group showed sustained positive effects on memory and attention functioning until six months after the training, but not on processing speed.
Regarding pharmacotherapy, it has been suggested that survivors of childhood cancer may benefit from stimulant medication as used in the treatment of attention deficit hyperactivity disorder (ADHD). Attention deficits in survivors of brain tumors are likely to improve by methylphenidate. Mulhern and colleagues found improvements of attention in 37 long term survivors of a malignant brain tumor after methylphenidate . In a randomized placebo-controlled double-blinded trial including 32 survivors of a brain tumor (n=25) or acute lymphoblastic leukemia (n=7), Thompson et al. found that methylphenidate led to improved sustained attention . A drawback of pharmacotherapy is the possibility of side effects, e.g. sleep disturbance, weight loss, anxiety, and sadness . Also, this medication does not lead to a sustained effect unless the patient continues the pharmacotherapy.
The limited current available options warrant the search for alternatives. Neurofeedback is a relatively new form of therapy, which has never been investigated in pediatric brain tumor survivors. Neurofeedback is a behavioral intervention that is based on the principles of operant conditioning. During the therapy the patient is presented with real-time feedback on his or her brainwaves, as measured by one or more electrodes on the scalp. The patient is reinforced when the brain produces a certain desired wave. Reinforcement may comprise seeing a movie or hearing music. The desired brain wave is determined by a quantified electro encephalogram (qEEG), which is conducted prior to the training.
The effects of neurofeedback have been discovered serendipitously by Sterman, when cats having received feedback of 12–15 Hz on the motor cortex showed to be less susceptible to epileptic seizures . There is a large body of scientific research documenting the effectiveness of neurofeedback for the treatment of diverse pathological conditions as summarized in comprehensive reviews, including ADHD, traumatic brain injury and schizophrenia [15–19].
Strehl et al. showed that children with ADHD were able to learn to regulate their brain activity by neurofeedback . After training, significant improvements in behavior, attention, and IQ scores were found. All changes proved to be stable at six months follow-up after the end of training. Hodgson et al. conclude in their meta-analysis on nonpharmacological interventions for ADHD that neurofeedback resulted in significant improvements of DSM-IV symptoms of ADHD, neurocognitive functioning and behavior . In a comparative study researchers found that the positive effects of neurofeedback for children with ADHD were superior to a computerized attention training at six months follow up . However, to date there is a lack of published studies that employ a randomized placebo-controlled double-blind design when investigating neurofeedback .
Brain tumor survivors differ from ADHD patients, as they have structural brain damage caused by the tumor, surgery, radiotherapy and/or chemotherapy. An indication that neurofeedback might be effective in pediatric brain tumor survivors may be derived from the results of studies into the effects of neurofeedback in patients with traumatic brain injury. A review of Thornton and colleagues  describes a total of 44 studies (12 RCT, 16 comparative, 16 correlation) with traumatic brain injury patients reporting improved attention, cognitive flexibility, cognitive performance, and problem solving after neurofeedback, providing strong initial support for the idea that neurofeedback could be used in patients with structural brain damage. Subsequently, Aukema and colleagues conducted a pilot study into the feasibility of neurofeedback on 9 brain tumor survivors in our hospital . This study demonstrated that it was feasible to use neurofeedback with brain tumor survivors. All participants completed the training and were positive about the training they received, as they would recommend it to others. Patients reported decreased subjective fatigue after the training. Also the test results showed that processing speed improved in 6 out of 9 patients. These findings warranted the set up of a larger study into the effectiveness of neurofeedback for pediatric brain tumor survivors.
The current paper describes the protocol of the PRISMA study (pediatric research on improving speed, memory, and attention); a randomized controlled double-blind trial, approved by the medical ethical committee of the Academic Medical Centre in Amsterdam. The primary aim of the PRISMA study is to investigate the efficacy of neurofeedback for improving neurocognitive functioning after treatment for a pediatric brain tumor. Secondary, we hypothesize that subsequent to the expected neurocognitive changes achieved with neurofeedback, children will experience improved psychosocial functioning . Neurocognitive functioning will be investigated by tests administered to the patient. Psychosocial functioning will be measured using patient-reported as well as caregiver and teacher reported questionnaires. Assessments will take place pre and post training, as well as six months post training, in order to examine the long-term effects of the training. Comparing the effects of neurofeedback to placebo feedback will assess efficacy of neurofeedback. Pre training results obtained with the brain tumor survivors will be compared to a control group of healthy siblings, to assess the level of dysfunction on the measures used in this study.