Dive into Neuromodulation: Personalisation

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Dive into Neuromodulation: Personalisation

Ethan Kee
Ethan Kee
2020-10-16

As treatments for mental health disorders swing towards neuroscience, mental health professionals and treatment providers find themselves in the exciting position to build on recent innovations in personalised neuromodulation to provide more effective, more consistent, and more unique relief to individuals with depression.

The progression of traditional treatments for depression has slowed in the past several years. Cognitive behavioural therapy (CBT) – one of the more effective current treatments – has maintained a remission rate in the 50% range for years now, with programmes often spanning several months. While this has taken us further than before, there is room to grow. Modern pharmaceuticals, despite their prevalent usage, have met a similar fate with regards to predictability and progress. Standard dosages take anywhere from four weeks to several months to reach peak efficacy, and peak efficacy is usually comparable to that of CBT. What’s more, these popular treatment methods are both faced with the issue of severely treatment-resistant patients – a demographic that constitutes 30% of individuals who experience major depression and for whom there are still no alternatives given as standard care practice.

Research in recent years, however, has opened the door to new depression treatment methods that use neuromodulation and machine learning to offer patients a more personalised form of relief and an encouraging option for treatment-resistant patients. A Stanford study has tested a promising alternative treatment using deep brain stimulation (DBS) that could serve as a reliable supplement to traditional treatment methods. The Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) method approaches mental health disorders from a neuroanatomical level – employing an MRI to identify specific brain regions that demonstrate irregular neural activity and subsequently targeting said regions with localised transcranial magnetic stimulation (TMS).

In the SAINT study, researchers were able to associate neural patterns in certain areas of the brain with depressive symptoms and methodically stimulate those areas in efforts to alleviate the symptoms or, in some cases, induce more positive sensations. The results were highly encouraging.

According to the study design, a full dosage of this new treatment can be administered in only five days – substantially shorter than the TMS standard 6 weeks – due to a shorter stimulation duration (3 minutes versus 37 minutes) and shorter between-dose intervals. Patients began feeling the anti-depressive effects after the second or third day. The study resulted in a 90% remission rate with 70% of patients continuing to experience more than half a reduction in their depressive symptoms over a month past the initial treatment date.

These positive results validate and offer early hope for a new personalised method of depression treatment. This new brand of non-invasive deep brain stimulation is tailored to neural activity and symptoms on a patient-to-patient basis without incurring the side effects seen in earlier stimulation-based treatments.  Different from pharmaceuticals, which offer a rather one-size-fits-all solution, or CBT, which has to work backwards from symptoms, the SAINT protocol extends acute attention towards the neuroanatomical origins of depressive symptoms and is mindful of the individuality of mental health disorders. Further studies of similar approaches have even gone so far as to be “state-dependent” – meaning the stimulation is customised according to the patient’s concurrent mood.

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These general upward developments in depression treatment also offer support and direction to the Flow initiative. Flow’s transcranial direct stimulation (tCDS) operates within the same fundamental principles as the SAINT study, however utilising a low frequency, non-invasive technique. Flow’s localized and non-invasive stimulation of the dorsolateral prefrontal cortex (DLPFC) – an area indicated in depression – is poised to provide the same type of immediate and lasting relief. One question remains, however: how can this personalized, responsive treatment be transferred from the lab into the home?

Remarkable breakthroughs in brain modelling have provided an avenue by which to implement SAINT-like personalisation into a mobile and accessible device such as Flow. The brain mapping that lies at the foundation of personalised depression treatment trials was largely achieved through an MRI – an obstacle for the distribution of such treatment.

Luckily, researchers at USC’s Neural Systems Engineering & Information Processing Lab have developed technologies both to track brain activity in real time and to learn how to regulate stimulation dosages accordingly.

The malleability of depressive symptoms and patient moods means that personalised treatment is an ongoing process of monitoring brain activity and supplying the properly calibrated stimulation. The first tool that Dr. Sanechi and her colleagues at USC designed is a specialised non-invasive electric wave that can monitor an individual’s neural activity instantaneously. This technology allows doctors to see a patient’s activity at a moment’s notice without the need for an MRI.

The second innovation from the USC lab would next allow DBS to be administered remotely according to the real time brain activity. Sanechi and her colleagues tested the neural reactions of different stimuli in different brain regions with enough consistency and precision to devise algorithms that learn how an individual’s brain will respond to a spectrum of DBS dosages. The product is a machine learning technology that can process brain activity in the moment and identify the appropriate stimulation.

Together, these technologies make it possible for patients to receive real time DBS that is tailored to their present neural state, mood, and depressive symptoms – much like a neural “pace-maker”.

The advances in depression treatment that USC and Stanford have offered have deep and inspiring implications on Flow and the understanding of mental illness at large.

With regards to the latter, personalised neuromodulation allows psychiatry to venture towards a style of treatment that pays necessary attention to the personal nuances of depression and psychiatric disorders alike – a type of care not yet possible with the current diagnosis and treatment process. Patients in the discussed studies have reported feeling more comfort and resilience knowing that they are receiving treatment that is specific to them, their testimonials speak for themselves:

“I’m in a much more peaceful state of mind,” one patient of the SAINT study recounted, “able to enjoy the positive things in life with the energy to get things done.” One patient who participated in a similar study at the University of California, San Francisco remarked, “It struck me so clearly in that moment that my depression wasn’t something I was doing wrong…Every time they’d stimulate, I felt like, ‘I’m my old self, I could do the things I want to do with my life.”

As for Flow Neuroscience, our mission has always contained a similar emphasis on the individual experience. With these recent advancements, we will be able to turn this verbal mission into a tangible reality for our users. While already on the cutting edge of depression treatment with at home tCDS technology, the SAINT and USC studies offer a roadmap by which Flow can further tune our treatment to the individual user, placing the latest and greatest of psychiatric treatment in the hands of those who need it.

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