Towards precision treatment with brain stimulation for depressive disorders

Non-invasive brain stimulation, using electric currents or magnetic pulses, offers a promising treatment for people with depressive disorders. However these treatments are not effective for all people. This project will aim to understand and to overcome some of this variability, and to establish best practice for the use of brain stimulation.

This project has one primary aim: to improve the efficacy of brain stimulation-based treatments for depressive disorders.

***Background***

Depressive disorders are a very common class of disorders, with 3% of people in the UK reporting a depressive symptom in the past week (McManus et al, 2016). Most disorders are treated in a stepped-care pathway, with less invasive treatments, such as talking therapies, giving way to more invasive procedures, such as surgery, if people do not respond at each stage. It has been suggested that non-invasive brain stimulation could offer a safe treatment option, either on its own or alongside another therapy.

There are measureable brain differences in depressed people compared to healthy people. For example, when people with depression are scanned with functional magnetic resonance imaging (fMRI), there is an imbalance in the activity of the prefrontal cortex, with the left side relatively under-active, and the right side relatively over-active (Heller & Nitscke, 1997). One strategy for treatment would therefore be to alter brain activity in one or both sides of the prefrontal cortex.

Although there is justifiable excitement about the use of brain stimulation in mood disorders, there is considerable variation in how people respond to treatment. This is true for all treatments, but here we have the opportunity to study and to address this variability and non-response. Some of the variability is likely to come from individual differences in head anatomy and in how the brain’s functional areas are located, others may be related to individual physiological and endocrine stress responses that alter the activity of specific brain areas. The project will contribute to scientific and healthcare knowledge by improving protocols for brain stimulation to increase their efficacy.

***Scientific approach***

Here at Manchester Met we have devices that can alter brain activity. Transcranial magnetic stimulation (TMS) delivers pulses of magnetic energy that target small regions of the brain. Transcranial electric stimulation (tES) uses weak electric currents to target wider areas. Both have been suggested as treatments for mood disorders, and TMS has NICE and FDA approval as a treatment for depression (https://www.nhs.uk/conditions/clinical-depression/treatment/). We have also invested in functional near-infrared spectroscopy (fNIRS) to measure brain activity and physiological equipment. In addition, electroencephalography (EEG) recording of the electrical activity of the brain will provide wider and faster information regarding neural activity.

The strategy of this project will be:
- to use brain imaging while performing a neuropsychological task in order to locate a specific area that will be a target for brain stimulation;
- To stimulate the specific area; and
- Immediately afterwards record stress responses and brain activity.

In one possible study, people will take part in a task that activates emotion-processing areas, while having brain activation measured (EEG/fNIRS). The precise location on the scalp where the greatest amount of activation is found will be used as the target for brain stimulation (TMS/tDCS). In this way, a person-specific target is used, rather than a less-precise population-level estimate.

For some disorders it will not be practical to recruit a patient population within the studentship, so the project will also focus on improving emotional processing and regulation in a healthy population. This strategy has been used by the lead supervisor, in enhancing mood in a non-depressed sample of young adults (Austin et al., 2016).