I have always wanted to do the most good with my abilities. On this path, I studied to become a doctor, all the while thinking I would work in global health. I spent a year in Kenya and came to realize that there is much work to be done, but many of the problems are "upstream" in both ideas coming from "the West" and in medical systems. I came back to the US and discovered a love for neuroscience and nurtured my interests in the big questions. I became a psychiatrist and have come to believe the greatest impact can be made in mental health and specifically depression.
We are in the midst of a revolution in psychiatry. Our treatments have been slow and only partly effective. Now, we are starting to better understand the brain and have highly-effective, fast-acting treatments. Building on earlier work on the Stanford Intelligent Neuromodulation Therapy (SAINT), in October 2021, our team showed that a 5-day targeted TMS treatment (Stanford Neuromodulation Therapy, SNT) brought 79% of patients into remission from treatment-resistant depression. This work shows not just a new single treatment, but validates a new approach in psychiatry.
My passion is to develop and deliver these new treatments to those who need them most.
- Transcranial Magnetic Stimulation
- Accelerated TMS
- Treatment Resistant Depression
- Interventional Psychiatry
- Cognitive Behavioral Therapy
Clinical Assistant Professor, Psychiatry and Behavioral Sciences
Medical Education: Stanford University School of Medicine (2014) CA
Board Certification: American Board of Psychiatry and Neurology, Psychiatry (2018)
Residency: Stanford University Adult Psychiatry Residency (2018) CA
Stanford Neuromodulation Therapy (SNT): A Double-Blind Randomized Controlled Trial.
The American journal of psychiatry
OBJECTIVE: Depression is the leading cause of disability worldwide, and half of patients with depression have treatment-resistant depression. Intermittent theta-burst stimulation (iTBS) is approved by the U.S. Food and Drug Administration for the treatment of treatment-resistant depression but is limited by suboptimal efficacy and a 6-week duration. The authors addressed these limitations by developing a neuroscience-informed accelerated iTBS protocol, Stanford neuromodulation therapy (SNT; previously referred to as Stanford accelerated intelligent neuromodulation therapy, or SAINT). This protocol was associated with a remission rate of 90% after 5 days of open-label treatment. Here, the authors report the results of a sham-controlled double-blind trial of SNT for treatment-resistant depression.METHODS: Participants with treatment-resistant depression currently experiencing moderate to severe depressive episodes were randomly assigned to receive active or sham SNT. Resting-state functional MRI was used to individually target the region of the left dorsolateral prefrontal cortex most functionally anticorrelated with the subgenual anterior cingulate cortex. The primary outcome was score on the Montgomery-Asberg Depression Rating Scale (MADRS) 4 weeks after treatment.RESULTS: At the planned interim analysis, 32 participants with treatment-resistant depression had been enrolled, and 29 participants who continued to meet inclusion criteria received either active (N=14) or sham (N=15) SNT. The mean percent reduction from baseline in MADRS score 4 weeks after treatment was 52.5% in the active treatment group and 11.1% in the sham treatment group.CONCLUSIONS: SNT, a high-dose iTBS protocol with functional-connectivity-guided targeting, was more effective than sham stimulation for treatment-resistant depression. Further trials are needed to determine SNT's durability and to compare it with other treatments.
View details for DOI 10.1176/appi.ajp.2021.20101429
View details for PubMedID 34711062
- A Strong Emergence Hypothesis of Conscious Integration and Neural Rewiring INTERNATIONAL PHILOSOPHICAL QUARTERLY 2020; 60 (1): 97–115
Identification of Common Neural Circuit Disruptions in Emotional Processing Across Psychiatric Disorders.
The American journal of psychiatry
OBJECTIVE: Disrupted emotional processing is a common feature of many psychiatric disorders. The authors investigated functional disruptions in neural circuitry underlying emotional processing across a range of tasks and across psychiatric disorders through a transdiagnostic quantitative meta-analysis of published neuroimaging data.METHODS: A PubMed search was conducted for whole-brain functional neuroimaging findings published through May 2018 that compared activation during emotional processing tasks in patients with psychiatric disorders (including schizophrenia, bipolar or unipolar depression, anxiety, and substance use) to matched healthy control participants. Activation likelihood estimation (ALE) meta-analyses were conducted on peak voxel coordinates to identify spatial convergence.RESULTS: The 298 experiments submitted to meta-analysis included 5,427 patients and 5,491 control participants. ALE across diagnoses and patterns of patient hyper- and hyporeactivity demonstrated abnormal activation in the amygdala, the hippocampal/parahippocampal gyri, the dorsomedial/pulvinar nuclei of the thalamus, and the fusiform gyri, as well as the medial and lateral dorsal and ventral prefrontal regions. ALE across disorders but considering directionality demonstrated patient hyperactivation in the amygdala and the hippocampal/parahippocampal gyri. Hypoactivation was found in the medial and lateral prefrontal regions, most pronounced during processing of unpleasant stimuli. More refined disorder-specific analyses suggested that these overall patterns were shared to varying degrees, with notable differences in patterns of hyper- and hypoactivation.CONCLUSIONS: These findings demonstrate a pattern of neurocircuit disruption across major psychiatric disorders in regions and networks key to adaptive emotional reactivity and regulation. More specifically, disruption corresponded prominently to the "salience" network, the ventral striatal/ventromedial prefrontal "reward" network, and the lateral orbitofrontal "nonreward" network. Consistent with the Research Domain Criteria initiative, these findings suggest that psychiatric illness may be productively formulated as dysfunction in transdiagnostic neurobehavioral phenotypes such as neurocircuit activation.
View details for DOI 10.1176/appi.ajp.2019.18111271
View details for PubMedID 31964160
Global connectivity and local excitability changes underlie antidepressant effects of repetitive transcranial magnetic stimulation.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
Repetitive transcranial magnetic stimulation (rTMS) is a commonly used treatment for major depressive disorder (MDD). However, our understanding of the mechanism by which TMS exerts its antidepressant effect is minimal. Furthermore, we lack brain signals that can be used to predict and track clinical outcome. Such signals would allow for treatment stratification and optimization. Here, we performed a randomized, sham-controlled clinical trial and measured electrophysiological, neuroimaging, and clinical changes before and after rTMS. Patients (N = 36) were randomized to receive either active or sham rTMS to the left dorsolateral prefrontal cortex (dlPFC) for 20 consecutive weekdays. To capture the rTMS-driven changes in connectivity and causal excitability, resting fMRI and TMS/EEG were performed before and after the treatment. Baseline causal connectivity differences between depressed patients and healthy controls were also evaluated with concurrent TMS/fMRI. We found that active, but not sham rTMS elicited (1) an increase in dlPFC global connectivity, (2) induction of negative dlPFC-amygdala connectivity, and (3) local and distributed changes in TMS/EEG potentials. Global connectivity changes predicted clinical outcome, while both global connectivity and TMS/EEG changes tracked clinical outcome. In patients but not healthy participants, we observed a perturbed inhibitory effect of the dlPFC on the amygdala. Taken together, rTMS induced lasting connectivity and excitability changes from the site of stimulation, such that after active treatment, the dlPFC appeared better able to engage in top-down control of the amygdala. These measures of network functioning both predicted and tracked clinical outcome, potentially opening the door to treatment optimization.
View details for DOI 10.1038/s41386-020-0633-z
View details for PubMedID 32053828
- Self-control "in the wild": Experience sampling study of trait and state self-regulation SELF AND IDENTITY 2019; 18 (5): 494–528
Identification of Common Neural Circuit Disruptions in Cognitive Control Across Psychiatric Disorders.
American journal of psychiatry
Cognitive deficits are a common feature of psychiatric disorders. The authors investigated the nature of disruptions in neural circuitry underlying cognitive control capacities across psychiatric disorders through a transdiagnostic neuroimaging meta-analysis.A PubMed search was conducted for whole-brain functional neuroimaging articles published through June 2015 that compared activation in patients with axis I disorders and matched healthy control participants during cognitive control tasks. Tasks that probed performance or conflict monitoring, response inhibition or selection, set shifting, verbal fluency, and recognition or working memory were included. Activation likelihood estimation meta-analyses were conducted on peak voxel coordinates.The 283 experiments submitted to meta-analysis included 5,728 control participants and 5,493 patients with various disorders (schizophrenia, bipolar or unipolar depression, anxiety disorders, and substance use disorders). Transdiagnostically abnormal activation was evident in the left prefrontal cortex as well as the anterior insula, the right ventrolateral prefrontal cortex, the right intraparietal sulcus, and the midcingulate/presupplementary motor area. Disruption was also observed in a more anterior cluster in the dorsal cingulate cortex, which overlapped with a network of structural perturbation that the authors previously reported in a transdiagnostic meta-analysis of gray matter volume.These findings demonstrate a common pattern of disruption across major psychiatric disorders that parallels the "multiple-demand network" observed in intact cognition. This network interfaces with the anterior-cingulo-insular or "salience network" demonstrated to be transdiagnostically vulnerable to gray matter reduction. Thus, networks intrinsic to adaptive, flexible cognition are vulnerable to broad-spectrum psychopathology. Dysfunction in these networks may reflect an intermediate transdiagnostic phenotype, which could be leveraged to advance therapeutics.
View details for DOI 10.1176/appi.ajp.2017.16040400
View details for PubMedID 28320224