TMS in Depression

Personalizing TMS therapy for the individual patient

At Nexstim we are using our decades of scientific research to help treat depression noninasivley and without the use of drugs. As the world’s leading company combining TMS with 3D imaging, we enable personalized TMS treatment with unsurpassed accuracy and precision.

Bringing accuracy and precision to TMS therapy for depression

Transcranial magnetic stimulation (TMS) stimulates the brain using small electrical fields. A coil resting against the patient’s head communicates directly with the underlying neurons of the brain. The Nexstim NBT® System uses TMS with sophisticated navigation tools to visualize the location, orientation and magnitude of the maximum stimulating E-field induced when the TMS coil is activated. We call this SmartFocusTM TMS.

Choose your Location

A non-drug option, SmartFocusTM TMS only influences the brain and doesn’t impact the rest of the body’s chemistry. In fact, TMS speaks the same language as the brain—electricity.

Targeting the left DLPFC

TMS is targeted to a region of the brain called the left DLPFC (dorso-lateral pre-frontal cortex) which is at a depth easily accessible by the normal strength of magnetic field emitted by TMS coils. It is believed that the left DLPFC is a window into a brain network including the subgenual cingulate and that stimulation of the left DLPFC has effects on the brain’s deeper limbic system. Brain imaging studies (fMRI) have shown connectivity between the stimulation site and the subgenual is a predictor of response to TMS in major depressive disorder (MDD)**. PET imaging studies in patients diagnosed with MDD have shown lower metabolism, compared to controls, in their left DLPFC regions, which supports the concept of using TMS as a therapy to increase the excitability of the left DLPFC. 

The left DLPFC has been validated as an efficacious target in several large, randomized controlled trials. The effects of TMS treatment have been shown to be dependent on the left DLPFC region receiving a sufficient “dose” of E-field each session and the sessions being repeated almost daily over many weeks. The observed effects of TMS suggest that the part of the mechanism behind TMS is neuroplasticity, the brain responding to the TMS treatment by “re-wiring” its own circuits.

**Weigand A et al. Prospective Validation That Subgenual Connectivity Predicts Antidepressant Efficacy of Transcranial Magnetic Stimulation Sites. Biol Psychiatry. 2017 Nov 10 https://www.ncbi.nlm.nih.gov/pubmed/29274805

The Nexstim NBT® System uses TMS with sophisticated navigation tools to visualize the location, orientation and magnitude of the maximum stimulating E-field induced when the TMS coil is activated. We call this SmartFocus™ TMS .

Researchers have shown that the location of the E-field in the brain is dependent on both the conductivity as well as the geometry of the underlying tissues.

Calculating the E-field location requires sophisticated modelling of tissue geometry. Nexstim uses an algorithm based on mathematically modelling the human brain as over 40,000 spheres—taking into account the brain’s shape as well as the effects of cerebrospinal fluid, grey matter and white matter on the induced E-field.

The Nexstim multi-sphere model of the brain has been scientifically-validated to accurately determine the location and orientation of the maximum induced E-field—and is the foundation for the FDA-clearance of our technology for pre-procedural planning, used in neurosurgery.**

** Krieg S (Ed.), Navigated Transcranial Magnetic Stimulation in Neurosurgery, Springer International Publishing, 2017

Personalizing the stimulation level for the individual patient

The effects of stimulation are always dependent on the intrinsic excitability state of the patient’s brain and cortex. This state is unique for each patient but can easily be measured by TMS. 
Once the motor strip has been identified, TMS is applied to the hand motor representation area, the “hand knob” with varying intensities to quantify the patient’s resting motor threshold, RMT. A patient’s RMT is defined as the minimum stimulation intensity capable of generating an MEP in 50% of given stimuli. Nexstim systems use an algorithm to ease the calculation.

It is important to carefully map for the optimal hand knob location using all the dimensions available for moving the coil, especially rotation. The goal of this mapping is to locate the site most sensitive to stimulation, otherwise the patient’s true resting-state cortical excitability cannot be determined. If the patient’s motor threshold calculation is based on measurement at an erroneous location, there is the subsequent danger of over-stimulating the cortex in therapy, as well as causing the patient unnecessary discomfort or pain.

rTMS therapy for depression is normally given at 120% of RMT. Cortical motor mapping can normally be performed at 110% of RMT, or higher.

Same dose, same location—every time.

SmartFocusTM TMS — a new noninvasive, non-drug therapy for depression.

View

SmartFocus™ TMS creates a 3D model of the patient’s brain from an MRI head scan. With the patient comfortably seated, the MRI is co-registered to the patient’s head using the tracking system with Nexstim’s unique forehead tracker. When resting the coil against the patient’s head, the system now visualizes the coil and E-field overlaid on the 3D model of the brain. As the coil is moved, the magnitude (V/m) and orientation of the E-field relative to the cortex are dynamically calculated and displayed in real time.

Measure

Place EMG electrodes over hand muscles. Using single-pulse TMS to accurately locate the primary motor area, the SmartFocus™ TMS software quickly guides the operator to determine an optimized intensity of the TMS dose for the patient’s individual cortical excitability.

Target

The published, science-based algorithm allows accurate and reliable identification of the left DLPFC in the brain — the validated target in the cortex for treating depression.

Treat

The coil is aligned to the target and then locked in place for the treatment session. The system delivers the prescribed dose of TMS pulses while the system operator monitors treatment precision from on-screen visual feedback — in real time.

Repeat

The system automatically stores the target-finding, dosedefining and other settings needed to personalize the TMS therapy for the patient. In subsequent treatment session, SmartFocus™ TMS guidance software helps the system operator ensure the patient receives the same optimized dose at the same location and in the same orientation.

Use of navigated rTMS has the potential for a significant increase in treatment efficacy compared to non-navigated rTMS. Navigation is specifically helpful  for target stimulation over the DLPFC, but also to stimulate the various regions of the motor cortical area with anatomical and functional relevance.

Prof. JP LEFAUCHEUR, Henri Mondor University Hospital, Clinical Neurophysiology, Creteil – Paris Est, France

Visualization of the therapy in the brain inspires confidence in both the patient and the physician. 

Marja-Liisa Kemppainen, MD Department of Psychiatry, Oulu University Hospital, Finland

Indications for use and patient safety

INDICATIONS FOR USE

FDA IFU: Nexstim Navigated Brain Therapy (NBT) System 2 is indicated for the treatment of Major Depressive Disorder in adult patients who have failed to achieve satisfactory improvement from prior antidepressant medication in the current episode.

CE mark : Nexstim Navigated Brain Therapy System for depression is intended to be used for treatment of major depressive disorder (MDD) by targeting and delivering noninvasive repetitive TMS stimulation to the patient's dorsolateral prefrontal cortex.

NBT THERAPY SHOULD NOT BE GIVEN TO

  1. Patients with non-removable conductive, ferromagnetic, or other magnetic-sensitive metal anywhere in the head or within 30 cm (12 in) of the stimulation coil. Examples include cochlear implants, implanted electrodes or stimulators, aneurysm clips or coils, stents, bullet fragments, ocular implants, and stents.
  2. Patients who have an active or inactive implanted device (including device leads), including deep brain stimulators, cochlear implants, cardiac pacemakers, and vagus nerve stimulators. Contraindicated use could result in serious injury or death.
  3. Patients with increased intracranial pressure or patients with intracardiac lines, intravenous pumps, or dose calculators. 

Failure to follow these restrictions could result in serious injury or death.

RISKS AND SIDE EFFECTS

Seizures (convulsions): Cortical magnetic stimulation runs the risk of inducing seizures; although they are rare. Under ordinary clinical use, the estimated risk of seizure is approximately 1 in 30 000 treatments (0.003%) or 1 in 1000 patients (0.1%). 

Headache: The most common side effects reported during clinical trials are mild headache (~50% of TMS treatment group) and scalp pain or discomfort (35.8%). In general, headache and pain on the stimulation site have been generally mild to moderate and occurring less frequently after the first week of treatment. The reason for headache may be the tension of scalp and neck muscles due to an uncomfortable and stressful situation.

Muscle Twitching:  You may feel twitches in the muscles of your arm, leg or face during the magnetic stimulation. This is a common sensation but not hazardous. The twitches will stop when the magnetic stimulation stops.

Skin Irritation:  There is a small risk of mild skin irritation at the location where the muscle electrode sensors have been placed, but this usually consists of minor redness that will go away quickly after they are removed.

Changes in hearing:  The loud “click” produced by the TMS stimulator can cause temporary hearing changes following treatment.  This is prevented by wearing soft foam ear plugs during treatment. No problems with hearing due to TMS have ever occurred when earplugs have been properly worn

INEFFECTIVE TREATMENT

There is no evidence that single therapy sessions would improve mood.  rTMS treatment effects in reducing depression are temporary, and patients may need to continue other forms of depression therapy. Relapse into depression is likely without follow-up treatment. Notify your doctor in case of worsening depression or suicidality.