Context

Although a wide variety of treatment methods for depression exist, these have been found insufficiently adequate to treat a substantial proportion of patients suffering from depression (Rush et al., 2006). While neurofeedback shares some components with currently existing treatment methods such as psychological and pharmacological treatment, it also offers some unique benefits. Nevertheless, only one study other than our pilot study (Linden et al., 2012) has investigated fMRI-based neurofeedback in depression. The results from that study cannot establish whether neurofeedback can alleviate symptoms of depression as only short-term mood changes were assessed (Young et al., 2014). Other drawbacks of this study are that group allocation was not randomised, that there was a significant difference in proportion of co-morbid diagnoses between the experimental and control group and that the study did not control for the amount of positive feedback provided to both groups.

Various other novel methods to alleviate symptoms of depression are currently being investigated as well. One example is transcranial magnetic stimulation (TMS), which has now received FDA approval for treatment-resistant

depression (George & Aston-Jones, 2010). However, mixed results have been published about the efficacy of TMS (Herrmann & Ebmeier, 2006; Rodriguez- Martin et al., 2001), it can be experienced as uncomfortable and the most commonly applied placebo condition does not match the sensation induced by actual TMS pulses. Nevertheless, TMS might have a positive effect on depression as well as on certain cognitive functions such as verbal fluency and working memory (Moreines, McClintock, & Holtzheimer, 2011). Some findings have suggested a positive effect of vagus nerve stimulation (VNS) on depression. This method requires the implantation of electrodes and a generator and is thus relatively invasive. However, improvements in depression have been found even long after its administration (Marangell et al., 2002). Another technique proposed to treat depression is transcranial direct current stimulation (tDCS), although the clinical benefits for depression have so far only been tested in pilot studies (Nitsche, Boggio, Fregni, & Pascual-Leone, 2009). These findings thus still have to be replicated in larger randomised controlled trials.

The aforementioned methods do not explicitly target the cognitive emotion regulation system related to depression. A recent study reported a noteworthy alternative to improve emotion regulation, namely via emotional working memory training (Schweizer, Grahn, Hampshire, Mobbs, & Dalgleish, 2013). The study found that the same frontoparietal circuit that was involved in the cognitive regulation of affect played a role in working memory tasks. The affective dual n-back task used by Schweizer et al. (2013) is less likely to target the cognitive emotion regulation system that can potentially ameliorate depression than neurofeedback training. Patients namely did not have to engage in the effortful regulation of their mood but instead had to identify whether the presented affective face or word matched the affective stimuli presented n positions back. Another important advantage of the neurofeedback paradigm proposed for treating depressed patients is the presence of feedback which can guide their dysfunctional emotion regulation system.

Various studies have investigated the application of imaging-based neurofeedback in other clinical syndromes such as chronic pain (DeCharms et al., 2005), Parkinson’s disease (Subramanian et al., 2011), tinnitus (Haller,

Birbaumer, & Veit, 2010), stroke (Sitaram et al., 2012) and schizophrenia (Ruiz et al., 2013). Although increasingly more pilot studies of clinical applications of imaging-based neurofeedback have been published in recent years, this technique is clearly still in its infancy and its full potential still has to be uncovered. Future studies might demonstrate the feasibility of applying this method to for instance addiction and autism as well and are likely to provide more insight in its value in clinical settings.

Apart from a potential role in the treatment of various disorders, the advantages that neurofeedback training provides as a research tool must not be forgotten. The (parametric) modulation of brain activation that can be achieved via neurofeedback can provide useful insights in brain-behaviour relations. Related to this, the study described in Chapter 4 investigated the effect of activity changes in higher order visual areas on perception. Although no perceptual changes were found, these may have been present but not picked up by the selected measures of perception. This study did however confirm the findings of Weiskopf et al. (2004) and incorporated two important improvements. First of all, it was shown that healthy participants can learn to differentially activate higher visual areas, mediated not by eye movement but by imagery techniques. Conversely, Weiskopf et al. had selected two brain areas with relatively unrelated functions. While the SMA has a more direct bearing to motor functions, the PPA is more involved in scene encoding. Our study employed two areas that were both involved in higher order visual processing, thereby increasing the task difficulty. Secondly, in contrast to Weiskopf et al. and many other neurofeedback studies to date, our study excluded a confounding effect of eye movement. Moreover, we collected physiological data to account for any variation in for instance heart rate during the self-regulation and count condition. Despite the known effects of physiology on the blood oxygenation level dependent (BOLD) response (Birn, Murphy, Handwerker, & Bandettini, 2009), neuroimaging-based neurofeedback studies rarely collect these measures. Future studies should show more awareness of potentially confounding variables and take appropriate measures. Any other directions for future studies will be discussed next.