Brain Stimulation & Interventional Neuropsychiatry

Interventional Neuropsychiatry, Brain Stimulation and Neurofeedback

 The last decade has seen a rapid increase in methods to treat neuropsychiatric disorders beyond the traditional disciplines of psychotropic medications and psychotherapy.  In just the past few years, ‘interventional psychiatry’ programs have sprung up at academic medical centers,1, 2 and specialized clinics are providing these treatments to paying patients, oftentimes ‘off label.’  These interventions include brain stimulation, often referred to as ‘neuromodulation,’ like transcranial magnetic stimulation, currently ‘cleared’ for depression, OCD and smoking cessation by the FDA, with many other conditions under study.

             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

Realtime fMRI Neurofeedback (rtfMRI-NF)

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)

Design for rtfMRI-NF study with 3 phases

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.

Neurofeedback-enhanced cognitive reappraisal training 

Brain and Behavior Research Funding, PI: Stefanie Russman Block

This Young Investigator grant from the Brain & Behavior Research Foundation seeks to further the career of Dr. Stefanie Russman Block through a mentored research project and training plan focused on innovative neuroimaging methods and a theoretical framework of emotion dysregulation applied to anxiety disorders.  The specific research aims are to: 1) Evaluate the ability of anxiety patients to increase target activity (dmPFC) during cognitive reappraisla based on rtfMRI-nf by comparing the increase in dmPFC activity pre to post training ; 2) Determine the relationship between dmPFC recruitment and reappraisal success using the reduction in negative affective ratings compared to passive viewing pre to post training; and 3) Assess the impact of rtfMRI-nf on anxiety symptoms over one-month (exploratory). 

This study will begin recruitment for anxiety patients in February.  Check out the UM Health Research link here

Transcranial Electrical Stimulation (tES)

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).

Enhancing Neural Synchrony and Affective Cognitive Control in Bipolar Disorder using Personalized Transcranial Alternating Current Stimulation (tACS)

PI:  Ivy Tso, PhD (recently relocated to OSU)

This project provides a critical proof of concept that personalized tACS is feasible and effective in engaging the neural target of theta-gamma coupling in bipolar disorder patients, and importantly, helping them to regain cognitive control. The ultimate goal of this research is to make this innovative and customizable treatment modality widely accessible for individuals living with BD.

Funded by the Milken Institute/The Bessemer Giving Fund.  NCT05480124

Recruitment for this study has completed and data are being analyzed.  Results will be forthcoming in late 2024.

Cynthia Burton, Ph.D.

Combined Cognitive Training and Transcranial Direct Current Stimulation in Neuropsychiatric Disorders: A Systematic Review and Meta-Analysis

Treatments for cognitive dysfunction in neuropsychiatric conditions are urgently needed. Cognitive

training and transcranial direct current stimulation (tDCS) hold promise, and there is growing interest in combined ormultimodal treatments, though studies to date have had small samples and inconsistent results. Fifteen studies were included in this meta-analysis, 10 in neurodegenerative disorders and 5 in psychiatric disorders (n = 629). A wide variety of cognitive training types and outcome measures were reported. There was a small, statistically significant effect of combined treatment on measures of attention/working memory, as well as small and non–statistically significant effects favoring combined treatment on global cognition and language. These results may provide preliminary support for the efficacy of combined cognitive training and tDCS on measures of attention/working memory.  

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

Transcranial Magnetic Stimulation (TMS) 

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.

A participant experiencing the TMS set-up.

Theta Burst Transcranial Magnetic Stimulation of Fronto-Parietal Networks: Modulation by Mental State

This R21 proposal used functional magnetic resonance imaging to examine the effects of transcranial magnetic stimulation (TMS) on specific brain networks relevant for neuropsychiatric conditions. We tested the broad hypothesis that when theta-burst TMS is applied to a brain in an engaged state, frontoparietal networks appear to carry out a working memory task more efficiently.  Results in Biological Psychiatry:Cognitive Neuroscience and Neuroimaging are here. The study was pre-registered  NCT04010461, and the protocol was published here.

Diagram of TMS coil

Collaborations through National Network of Depression Centers

As a member of the Neuromodulation task group of the NNDC, I co-led an published a multi-site registry study of TMS in the NNDC network (Taylor et al 2017).  We have also published a TMS consensus guidelines through the NNDC, and in partnership with the APA (McClintock et al 2017).  Current projects include the development of embedded templates in the electronic medical record to facilitate high volume registry data collection and incorporation of data into a learning health care system.

National Network of Depression Centers

Collaboration with Michael D. Fox, M.D., Ph.D.  

Dr. Fox is Director, Center for Brain Circuit Therapeutics, Brigham and Women's Hospital. He and colleagues have published work defining TMS network targeting, to which the Taylor lab has contributed data.  See Weigand et al 2018, Siddiqi et al 2020, Siddiqi et al 2021
Michael Fox

Deep Brain Stimulation (DBS)

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. 



James Abelson, M.D., Ph.D.

Parag G. Patil, M.D., Ph.D.

Paul E. Holtzheimer, M.D., M.S.

Helen S. Mayberg, M.D.

George C. Curtis, M.D.


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