The field of brain stimulation, both non-invasive and invasive technologies, has been a hotbed of activity and innovation, given the wide variety of methods to deliver energy to the brain and alter neurocircuitry.  The ‘parameter space’ of brain stimulation – various combinations of where and how energy is delivered to neural tissue --  is extremely large, meaning that many opportunities exist to develop interventions with therapeutic effects.  This space also includes interventions delivered while patients are engaged in a specific task, such as the currently approved treatment for OCD which delivers stimulation to the medial frontal cortex while a patient is being exposed to compulsion-eliciting stimuli. 

Interventional psychiatry as an emerging discipline also includes the use of anti-depressant treatments, such as ketamine3 and brexanalone,4 administered in controlled settings via intravenous injection over a few sessions.  Because of their fast-acting effects and the need to deliver treatment via infusion, they have required a new, ‘interventional’ mindset in the psychiatric treatment of depression.  More recent experimental work with hallucinogenic agents, such as MDMA and psilocybin, has introduced another limited session, rapid-acting intervention for patients with PTSD, depression and chronic pain.5  Notably, these sessions require specially-trained therapists to manage a patient’s experience and ensure a therapeutic benefit (and not a ‘bad trip’).  Techniques to manage the behavior of a patient receiving the intervention are a critical part of interventional psychiatry, such as combining pharmacotherapy with a psychotherapeutic intervention, e.g. combined treatment of exposure therapy with single doses of d-cycloserine to enhance extinction.6

There is another area of experimental therapeutics, not traditionally associated with interventional psychiatry, involving behavioral training, often coupled with feedback derived from real-time measurement of brain activity. A large body of literature and many commercially available applications use ‘brain training,’ which, at its most basic, is conceived of as ‘brain exercises,’ particularly popular for persons suffering from, or concerned about, the cognitive losses associated with dementia and aging. In spite of the many commercial programs available, evidence for efficacy of these programs, beyond the acute effects of practice, is mixed, although carefully-done studies have demonstrated proof-of-concept that training with adaptive rewards induce performance enhancing neuroplasticity.7  Behavioral training also occurs with feedback from ongoing physiological processes. The  field of ‘neurofeedback,’ uses EEG and functional MRI to guide patients to enhance or suppress electrical or hemodynamic activity. The ‘autogenic’ or ‘operant’ modulation of EEG was described 50 years ago,8 and commercially-available, proprietary systems have been offered therapeutically for several decades, although neurofeedback clinics operate largely without the evidence base of rigorous clinical trials.  However, with more recent scientific attention in the last decade, the field has expanded rapidly (see Figure and Nature Reviews Neuroscience article by Sitaram  and colleagues 9). The advent of real-time functional MRI (rtfMRI) has demonstrated reliable methodologies to link voluntary subjective states with changing activity in specific neural structures.10-12 It is these activities of brain training and neurofeedback, usually not including in academic Interventional Psychiatry programs, where we see opportunity to advance the field by developing an initiative that links brain stimulation, pharmacologic interventions, brain training and neurofeedback, i.e.  ‘Interventional Neuropsychiatry.’

The Taylor lab is just beginning its forays into rtfMRI-NF, and future plans include expansion into EEG neurofeedback.

Targeting large-scale networks in depression with real-time fMRI neurofeedback

R21 MH134035-01 (PI: S.F. Taylor)

To develop improved treatments for depression, as well as other psychiatric disorders, this proposal will build upon findings from functional magnetic resonance imaging (fMRI) studies that large scale networks in the brain are “out of balance” in depression. We will  Using a relatively new technique with fMRI, patients with depression will perform an attention-focusing task while getting real-time feedback of brain network activity to help them bring their networks back into a more balanced, and healthy, state.

In Aim 1, during an initial (localizer) MRI session, network participation in this network switching task will be evaluated, testing the hypothesis that the salience network is engaged by a 'Rest FocusTask' (RFT). For Aim 2, participants will be randomized to receive either valid NF from the personalized network activated by the switching task during the localizer session, or they will receive sham NF. We will test the hypothesis that real, compared to sham NF, will increase activation in the RFT, and that the NF task will increase SN connectivity.  NCT05934604 (Phase 1 & 2, healthy participants), NCT06050070 (Phase 3, depressed patients).

Recruitment for Phase 3 of this study will begin February 2024. See this UM HealthResearch link for more info.

Transcranial Electrical Stimulation consists of deliver mild current (usually powered by a 9-volt battery) to the scalp, of which some portion enters the brain and has been shown to affect a variety of brain functions, including therapeutic benefits.  Our lab is beginning to engage with these approaches.  One form uses direct current, and it is called transcranial direct current stimulation (tDCS).  The other form uses alternating current, and it is called transcranial alternating current stimulation (tACS).

Burton CZ, Garnetta EO, Capellarib E, Chang S, Tso IF, Hampstead BM, Taylor SF, Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, published online 13 October 2022  10.1016/j.bpsc.2022.09.014

I have been engaged with non-invasive brain stimulation, primarily using transcranial magnetic stimulation (TMS), both as an experimental tool (Demeter 2016; Khammash 2019 & 2019) and a treatment for depression (Taylor et al 2017; McClintock et al, 2018). In collaboration with Eric Michielson in the College of Engineering, we have also characterized e-field strengths of TMS coils (Gomez et al, 2015). Work has included studies of neural mechanisms and predictors of repetitive TMS (rTMS) for depression (Taylor et al, 2018, Light et al, 2019, Fan et al, 2019). 

We currently offer clinical TMS for depression, available through our TMS service in the Department of Psychiatry.

In 1999, I joined a team, which included Geroge Curtis and James Abelson -- the first group in North America to use deep brain stimulation in a psychiatric patient, a man with OCD, and we went on to show promising effects of stimulation to the internal capsule/ventral striatum (Abelson et al, 2005). In collaboration neurosurgeon Dr. Parag Patil, we participated in an industry-sponsored study of DBS in area 25 white matter for the treatment of refractory depression (Holtzheimer et al, 2017), a target derived from brain imaging work of Helen Mayberg and colleagues. 

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