Published in The Neuropsychotherapist Issue #1
Normally, successful psychotherapy depends on the art of modulating memory contents, such as in fear extinction. The common understanding has followed the model that such memory modulation or learning processes in general lead to lasting changes at the level of our synapses. However, it is now clear that the key factor in conveying such neuroplastic changes is long-term potentiation, and that inhibition of long-term potentiation will lead to a worsening of learning performance. In this light, it is not surprising that an exaggerated long-term depression has been observed in animal models of various psychiatric disorders with memory disturbances.
Based on the observations that first, learning is key in psychotherapy and second, learning processes lead to neuroplastic changes on a synaptic level, one might expect that interventions and manipulations with the capacity to enhance long-term potentiation or inhibit long-term depression processes will have the potential to improve those elements of psychotherapy which crucially rely on learning processes. Consequently, numerous substances have been investigated with regard to their potential to boost learning processes. Among them is D-cycloserine, a substance initially developed as a tuberculosis antibiotic, which binds at the glycine binding site of the (glutamatergic) N-methyl-D-aspartate receptor as a co-agonist. In this role, D-cycloserine upregulates long-term potentiation in the hippocampus of rats. These observations translated successfully into studies in human beings. Here, declarative and hippocampal learning processes across different modalities were improved, and—of importance in the context of the present topic—the efficacy of classical psychotherapeutic techniques such as exposure was increased. Administered alone, however, D-cycloserine did not result in any improvement, indicating a lack of effectiveness of this compound in the absence of psychotherapy. Other substances with comparable effects are currently under investigation, and most big pharmaceutical companies have at least one compound in the pipeline aimed at improving learning processes. From my perspective, it is very likely that at least one of those compounds will enter the market within the next decade and that they will be marketed as neuroenhancers. The public and academic discussion concerning the ethical aspects of improving learning processes, both generally and in the context of psychotherapy by pharmaceutical interventions, has already begun. This discussionis often dominated by two contrasting positions: one in favor, stating that neuroenhancement does not pose a serious moral problem where compounds are efficacious and well tolerated, and one opposing, arguing that broad availability will lead to serious medical problems such as addiction or an irresistible social pressure to use such agents. It will be interesting to see how society positions itself in the day these compounds actually become available.
Besides pharmacological interventions, we have neuromodulatory interventions; and here especially, non-invasive brain stimulation techniques constitute a second approach to boosting memory processes. The principle of non-invasive brain stimulation techniques such as transcranial magnetic stimulation or direct current stimulation is to influence superficial cortical structures with an electromagnetic field. Depending on the stimulation parameters, this intervention can facilitate or inhibit the activity of underlying neuronal structures. In most cases the lateral, prefrontal cortex is the target region, and its stimulation might elevate mood or interfere with working memory processes. More specifically, it has been demonstrated in some studies that electric or electromagnetic stimulation can result in better working memory performance in a valence-specific manner. The impact of such stimulation protocols on the efficacy of psychotherapeutic interventions is yet to be determined, but studies dealing with the impact of brain stimulation on exposure therapy and cognitive-behavioral therapy are currently underway. Notably, brain stimulation is capable of influencing not only learning-dependent symptoms but also others such as an attentional bias in patients suffering from affective disorders.
To date, most studies on pharmacological and electromagnetic augmentations of psychotherapy have focused on efficacy. However, before these can be applied on a broader basis, a tolerability profile as well as the identification of augmentation-sensitive fields of psychotherapy need to be addressed in more detail. That said, augmented psychotherapy is a wonderful example of how thinking beyond disciplinary boundaries can open up new therapeutic avenues for the benefit of our patients.
Malek Bajbouj M.D.
Professor of Psychiatry and Affective Neuroscience at the Department of Psychiatry, Charité, Berlin, Germany. Co-director, Dahlem Institute for Neuroimaging of Emotion, Berlin, Germany. Adjunct Professor, Department of Psychology, Freie Universität Berlin, Germany