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TMS 2025: Rewiring Recovery

TMS 2025: Rewiring Recovery

What’s New in Neuromodulation, Protocols, and Interventional Psychiatry

Umar Latif, MD
June 28, 2025

Mechanism of Action: What Happens During TMS?
Next-Generation TMS Protocols: Faster, More Person …
Expanding Clinical Applications: Beyond Depression
TMS Tech Innovations: Engineering the Future of Br …
- Further reading and references

Transcranial Magnetic Stimulation (TMS) is now a core treatment in interventional psychiatry. No longer reserved only for medication-resistant cases, TMS is moving earlier into standard care pathways. In 2025, technology and protocol advances are accelerating, reshaping what’s possible in therapeutic neuromodulation.

What’s especially notable is how thought leaders are advancing evidence-informed practices that push beyond the constraints of traditional FDA-approved protocols and insurance models. Guided by neuroscience, clinical observation, and early-stage data, they’re refining TMS delivery in real time—prioritizing outcomes, access, and individualized care.

This blog highlights the latest innovations in TMS, from updated protocols and mechanisms of action to emerging applications across psychiatry, addiction, PTSD, and dementia.

Mechanism of Action: What Happens During TMS?

Our understanding of the neurophysiology of how TMS works has deepened in recent years, reshaping how we think about therapeutic neuromodulation. At its most fundamental level, TMS uses magnetic pulses to stimulate specific regions of the brain, causing neurons to fire, triggering a cascade of electrical and chemical signaling that strengthens connections across brain circuits.

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"Neurons that fire together, wire together.”

While the core mechanism is conceptually simple, the physiological effects unfold at multiple levels: from individual neurons to synaptic communication, to large-scale functional networks and long-term neuroplastic changes, as well as changes in cerebral blood flow and glucose metabolism and neurotransmitter release.

Cellular Level: TMS-induced electrical currents depolarize neurons, leading to the firing of action potentials that trigger specific intracellular signaling pathways. These pathways mediate the strength and plasticity of inter-neuronal connections, potentially altering information processing and storage within the brain.
Synaptic Level: TMS alters the release of neurotransmitters, particularly glutamate and GABA, affecting synaptic strength and plasticity. This leads to long-term potentiation (LTP) or long-term depression (LTD) of synaptic transmission, depending on whether the inter-neuronal connections are strengthened or weakened.
Network Level: TMS modifies the functioning and interconnections of extensive neural networks by altering neuronal excitability and synaptic connectivity. This can selectively modify the excitability of specific brain regions, resulting in changes in the functioning of interconnected regions and ultimately affecting the activity of entire networks. There are 3 functional networks relevent to psychiatry: the default mode network, which is active at rest and stands out when daydreaming or mind-wandering, the salience network which tells our brain to pay attention to things in the outside world, and the central executive network which kicks in when we’re solving problems or focusing on tasks.
Neuroplasticity and BDNF: A key mechanism behind TMS's therapeutic effects involves neuroplasticity—the brain's ability to reorganize itself by forming new neural connections. TMS has been shown to enhance the secretion of Brain-Derived Neurotrophic Factor (BDNF), a critical mediator of neuronal plasticity that contributes to the brain's capacity to adapt and modify. Research indicates that TMS can increase BDNF levels in the prefrontal cortex and other brain regions, with this effect potentially being more pronounced in individuals with depression or other psychiatric disorders. This BDNF-mediated neuroplasticity may explain the lasting therapeutic benefits observed after TMS treatment courses.
Subgenual Anterior Cingulate Cortex (sgACC): A deeper dive highlights the role of the subgenual anterior cingulate cortex (sgACC), a central node in depression-related circuitry. Its bidirectional connections with the prefrontal cortex are a key target of TMS. Recent studies suggest that modulation of DLPFC-sgACC connectivity may predict rTMS treatment responsiveness and explain individual variability in outcomes.

Next-Generation TMS Protocols: Faster, More Personalized, and with better outcomes.

Intermittent Theta Burst Stimulation (iTBS)

Modern TMS is faster without compromising effectiveness. FDA-cleared Intermittent Theta Burst Stimulation (iTBS) delivers high-frequency bursts in just minutes and has been shown to be non-inferior to traditional rTMS. This advancement enables accelerated protocols like SAINT.

Personalized TMS Therapy: qEEG MeRT protocol

Magnetic e-Resonance Therapy (MeRT) is a personalized, data-driven TMS approach guided by EEG and ECG findings. Unlike standard TMS, MeRT tailors frequency and intensity based on individual brainwave patterns. MeRT stimulation typically uses two-thirds the energy of standard TMS, focusing on synchronization rather than stimulation intensity. The protocol typically follows three core steps:

EEG/EKG Recording: A 10-minute qEEG and EKG assess brainwave activity, heart rate, and brain-heart coherence.
Braincare™ Analysis: Proprietary software compares data to a large normative database to identify dysfunction and generate a personalized report.
Individualized TMS Therapy: Patients typically receive 30-minute sessions, five days per week for a month, targeting specific circuits.

Watch Prof. Alexander T. Stack explain how brain state and timing influence outcomes
A Study on EEG-based biomarkers predicting TMS entrainment
A Study on individual alpha frequency as a predictive biomarker in deep vs. standard TMS

SAINT Protocol: Stanford Accelerated Intelligent Neuromodulation Therapy

A major breakthrough in the field, the SAINT protocol condenses a full course of TMS into five days, offering rapid relief for patients in crisis. Clinical results have been remarkable. Watch Dr. Nolan Williams present SAINT. The protocol includes:

50 total sessions (10 per day) over 5 consecutive days
Utilizes iTBS for time efficiency
fcMRI targeting to precisely locate the left DLPFC

ONE-D Protocol: Single-Day Neuroplasticity Boost!

The ONE-D trial pushes acceleration to its limits, delivering TMS in a single day! This approach showed promising results in treatment-resistant depression and introduces a potential emergency-use paradigm for neuromodulation. Watch Dr. Jonathan Downar discusses ONE-D. The one day protocol includes:

20 iTBS sessions (600 pulses each at 120% MT), spaced every 30 minutes
Targeted at left DLPFC using a heuristic scalp method
Pre-treatment includes off-label low-dose d-cycloserine (125 mg) and lisdexamfetamine (20 mg) to enhance neuroplasticity

Expanding Clinical Applications: Beyond Depression

TMS now extends beyond depression. New protocols and emerging evidence have broadened its clinical use across multiple conditions:

Post-Traumatic Stress Disorder (PTSD): Individually guided neuromodulation shows potential benefits for veterans and special operator populations. Evidence supports symptom reduction when targeting TBI-related neural circuits. Frontiers in Neurology | PubMed

Substance Use Disorders (SUDs): TMS has shown promise as an adjunct intervention. Trials show reduced cravings and use across cocaine, methamphetamine, tobacco, alcohol, stimulants, and smoking cessation. Effects appear linked to modulation of dopamine pathways and prefrontal-striatal circuits. Cochrane Review | Cocaine | Methamphetamine | Craving | Dopamine | Striatal Imaging | Smoking Cessation

Alzheimer’s and Dementia: Preliminary data suggest benefits from long-term rTMS targeting the precuneus, improving cognition and network function. Alz Res | Psychology Today Summary | PubMed

TMS + Ketamine: Combining TMS with low-dose ketamine may enhance antidepressant effects, especially in treatment-resistant patients. This approach leverages ketamine’s NMDA modulation alongside TMS-induced neuroplasticity. PMC Review

TMS + Hypnosis (SHIFT Protocol): The Stanford SHIFT protocol demonstrates that targeted TMS can temporarily increase hypnotizability, opening new avenues for pain and behavioral interventions. In one RCT, two 46-second bursts of 800 pulses to the left DLPFC produced statistically significant, albeit transient, changes in hypnotic suggestibility. SHIFT Study - Nature

TMS + Mindfulness and Meditation: Audio-guided mindfulness during TMS sessions, especially through MBCT protocols, may enhance treatment by aligning attentional and affective circuits. Pilot studies show improved outcomes in mood, stress, and mindfulness. Frontiers Study

TMS-Assisted Psychotherapy: Emerging models integrate TMS with psychotherapeutic interventions to amplify cognitive and emotional processing. Conceptual frameworks propose sequential or concurrent use.

Autism Spectrum Disorder: Studies suggest that EEG biomarkers—including endophenotypes linked to MTHFR gene variation—may help identify autism subtypes responsive to TMS. PubMed | SAGE Open Report

TMS Tech Innovations: Engineering the Future of Brain Stimulation

Advances in TMS tech are reshaping how—and where—we deliver brain stimulation, ushering in a new era of scalable, personalized care—from quieter coils to precision-guided stimulation.

Engineered Precision: Device-level innovation is making TMS more targeted, tolerable, and adaptable:

Modular Pulse Synthesizers enable custom pulse shaping, allowing clinicians to selectively engage specific neural populations.
Noise‑Reducing Coils ease discomfort while maintaining high magnetic output—supporting patient adherence.

Deep Brain Stimulation with TMS: Traditionally, TMS could only stimulate superficial cortical layers. But new work from the National Institute of Mental Health (NIMH) suggests that individualized brain mapping may enable clinicians to steer stimulation toward deeper brain structures, expanding the range of treatable conditions.

TMS and Virtual Reality: Pairing TMS with immersive virtual environments is showing promise across domains. This approach merges neuromodulation with experiential retraining—potentially strengthening both cognitive and emotional circuits simultaneously.

In stroke rehabilitation, combining rTMS with VR training improves cognitive functions like memory, language, and executive processing beyond standalone interventions.
In mental health and addiction, VR-TMS protocols are under study for enhancing outcomes in food addiction, alcohol use, schizophrenia, phobias, and PTSD.

Precision Targeting with Neuroimaging: Clinics are increasingly incorporating neuroimaging-guided personalization into their protocols. MRI‑guided neuronavigation and TMS‑fMRI co‑stimulation support real-time mapping of brain activity and functional connectivity.

Real-time EEG guided Closed-Loop TMS: Unlike traditional open-loop stimulation, closed-loop TMS adapts in real time by monitoring brain activity through EEG, MEG, or fMRI and delivering pulses precisely when the brain is most receptive. This state-dependent approach may enhance efficacy while minimizing side effects

AMPA Portable TMS: AMPA’s portable TMS system delivers clinic-grade neuromodulation in a compact form that fits into two suitcases. With camera-guided coils enabling built-in neuronavigation and no need for external tracking equipment, it offers accurate, intuitive targeting and streamlined setup for clinicians working in remote or mobile settings.

Wearable TMS: Wearable TMS may sound like science fiction—but it’s becoming real. Imagine a headband or cap delivering neuromodulation anywhere—home, office, or clinic—without bulky equipment. Though still in early development, this innovation hints at a future where daily, personalized brain stimulation is as accessible as wearing a Fitbit.