Mental Health Neuroscience Programme

To survive, organisms maintain homeostasis by predicting, detecting, and regulating their internal state: am I thirsty? Hungry? In pain? Patients with mental ill-health frequently report disturbances in one or more homeostatic domains, including motivation, appetite, and sleep. For many patients, current treatments are profoundly limited in treating these homeostatic disruptions. The field is missing a framework to translate scientific discoveries in homeostatic processes into new potential treatments (or improvements in existing treatments) for mental health conditions. My MRC Programme develops and tests such a framework.

First, we are exploring whether disruptions in bodily processes, such as circadian rhythm or inflammation affect our brain’s ability to learn, a key process underpinning symptoms in psychiatric disorders. Next, we are developing a new brain stimulation approach that could alter the brain’s awareness of the body’s state. This could be helpful for patients who have disruptions in their sensation of internal signals, such as sickness or hunger. Finally, we are also testing new ways of improving psychological therapy using homeostatic augmentations, such as medications given directly before the therapy. This will allow us to move from basic laboratory science toward improved mental health treatment, identifying which domains have the most clinical potential, and which interventions will work for which patients.

The goal of the Mental Health Neuroscience Programme at the MRC CBU is to exploit the potential of cognitive neuroscience to improve mental health treatment.
To survive, organisms maintain homeostasis by predicting, detecting, and regulating their internal state. Many neuropsychiatric disorders show profound disruptions in homeostatic processes, including motivational drive, appetite, and interoception. The scientific aim of the Mental Health Neuroscience Programme over the next quinquennium is to elucidate the role of homeostatic mechanisms in mental health disorders, and their clinical potential as treatment targets.
The programme has three interlinked objectives: (1) discover homeostatic mechanisms driving mental health disorders; (2) disrupt putative sources of these processes in experimental medicine studies; and (3) determine the treatment potential of homeostatic interventions. Dr Nord’s group employs methods from experimental psychology, cognitive neuroscience, computational psychiatry, and physiology, with a particular focus on causal approaches (psychopharmacology, non-invasive brain stimulation, and psychological interventions).
Over the next quinquennium, Dr Nord’s team will develop novel experimental assays to probe body-brain learning in a number of domains: motivational drive (led by research assistant Quentin Dercon), circadian rhythm (led by PhD student Sara Mehrhof), inflammation (led by PhD student Alicia Smith), and appetite (led by investigator scientist Hugo Fleming). Together, these studies will build a new theoretical model of homeostatic learning in mental health disorders. These assays will also be tested as predictors of individual vulnerability to symptoms of mental ill-health. Over the next ten years, the most promising assays will be tested as putative biomarkers of treatment response in early-stage clinical trials.
To advance the second objective of the programme, Dr Nord’s team will also employ causal methods to disrupt homeostatic mechanisms. The central methodological component of this stream will be neurostimulation, in particular, the development of offline transcranial ultrasound stimulation (tUS) protocols in humans (led by research assistant Alec Sargood, in collaboration with Rik Henson, Ajay Halai, and Matt Lambon Ralph)
The third stream of the programme focuses on biological routes to improve psychological therapy. New models or treatments for disorders are only truly translational if clinicians and patients use them, so clinical collaboration and patient experience is at the crux of this work. This includes reverse translation studies revealing the neurocomputational basis of psychological therapy, as well as collaborative work on novel therapeutic augmentations (in collaboration with Tim Dalgleish).

The underlying framework of Dr Nord’s programme is translation from discovery science through experimental medicine studies and into early-stage clinical testing. This contributes to the long-term strategy of Dr Nord’s programme: providing a theoretical and methodological framework that links psychological and biological models of mental health disorders, to eventually improve the precision and effectiveness of mental health treatment.