How fMRI-Guided TMS Therapy Works
fMRI-TMS Compared
to Standard TMS
We believe that without fMRI to guide the treatment plan, we would be administering TMS in the one-size-fits-all approach. Standard TMS uses this one-size-fits-all approach that is over 20 years old.
Step 1 fMRI: 
Acquire high-resolution functional (fMRI brain images). fMRI allows detection for each individual of a unique pattern of active brain areas (Nodes) and inter-Node connections, which comprise a variety of networks each with different functions.
STEP 2 ANALYSIS:
After reviewing thousands of the individual’s fMRI images, the clinical team will identify the unique pattern of network anomalies, which would include abnormal node function and/or abnormal internode and intranode connections.
STEP 3 COMPUTATION:
Once the networks to be treated are identified, the appropriate TMS coil will be selected and the appropriate TMS stimulation will be computed. This includes the site of stimulation and type of coil to be used (based on focality and depth), as well as the parameters which determine results of stimulation, e.g. increasing or decreasing strength of nodes and networks. Parameters include the strength of the magnetic pulse as well as their frequency and the number of pulses administered during a session, and subsequent sessions
STEP 4: TMS TREATMENT DELIVERY:
Stimulation will be performed with a state of the art TMS device (MagPro® X100 with MagOption Magnetic Stimulator) and Neuronavigation (Localite TMS Navigator: MRI based, Real-Time Neuro-Navigation, Spectra). This will assure the appropriate placement of the stimulator at the initial and following treatment sessions. Since Neuronavigation will be done in real-time during the treatment, it will ensure that the stimulator will be in the right position during the entire session even in the presence of head movements.
Our TMS Protocols
By applying repeated pulses (repetitive TMS) at high-frequencies (e.g., >5 Hz), one can excite underlying cortical activity and low-frequency (e.g., <5 Hz) can result in inhibitory changes. The effects of TMS can propagate beyond the stimulation site, through connectivity, impacting a distributed network of brain regions, making the use of resting state functional connectivity (rsFC) a powerful tool for assessing the connectivity, and guiding the optimal coil position regarding the targeted area.
In determining the intensity of the pulse, we use a pulse with intensity at 100-120% above the patient motor threshold (MT). Depending on the coil being used, Theta Burst stimulation is applied in 50 Hz triplet bursts five times per second. It is an intermittent Theta Burst Stimulation (iTBS), which means that the stimulation is delivered in a cycle of approximately 2 seconds on and 8 seconds off over a period of 3 minutes.
- During a typical treatment session, the patient receives a total of 600 pulses and 200 bursts. This treatment is known to increase neuronal firing in this region, and as a result, increases brain activity and functional connectivity in the target region modulating the neural circuit.
- Inhibitory Theta Burst stimulation is applied in 50 Hz triplet bursts five times per second. It is a continuous Theta Burst Stimulation (cTBS), which means that the stimulation is delivered continuously over a period of 40 s (600 pulses total). This protocol decreases neuronal firing which results in decreased regional brain activity and functional connectivity in the brain regions that need to be slowed down, modulating the neural circuit.
Precise Treatments Results in Longer
Lasting Wellness
Identifying an individual’s poorly functioning network through fMRI is only one part of the path to wellness. The other ingredient is delivering the TMS treatment to the precise location of that network.
We do so with an advanced guidance system that was originally developed for neurosurgery… where millimeters of precision are required. The system is called Infra-red Navigation and it delivers the TMS treatment precisely to the identified brain network.
Unlike Standard TMS, where a one-size-fits-all approach is used to select and direct the TMS coil, our system uses the unchanging anatomical features of the individual’s face (landmarks) for registration, and real-time navigation to direct the treatment. This technology allows Neurotherapeutix to provide the treatment precisely where it is needed for each treatment.
Consistency is important; with each TMS treatment the network we are “re-training” needs the same treatment, at the same precise location for it to begin to normalize its connectivity. Therefore, millimeters are important in TMS, and infrared Neuronavigation is one of the reasons for our greater success and longer-lasting wellness.
Human Growth & Brain Development
Connectivity in the Brain
Human growth is accompanied by brain development of each of the four regions of the brain and the connectivity of these regions through brain networks. The four brain regions are the Cerebrum, Cerebellum, Brainstem and the Diencephalon. Let’s make this simpler…, think of each of four brain regions as states and connectivity as roads or highways in each state. These highways connect different areas of the state, and highways connect one state to another state. Just like highway 66 connects cities in the same state and connects one state to another…, we call this inter and intra network connectivity. Intra– within the same brain region, and inter– from one brain region to another. (Ever hear of inter-state commerce?) Just like highways, these networks have poor connections, and these poor connections can exist in the same brain region and from one region to the next.
Networks and Nodes
Figure A is a typically functioning brain network. It consists of two networks joined by a central node. Each of the nodes is connected in either positive or negative polarity depending upon the brain functioning required. A well, functioning network includes: Solid connectivity between nodes. No weak or missing connections. Varied node’s connections intensity. Some have greater connectivity intensity and others have secondary connectivity intensity. Node connection polarity can be positive or negative. Nodes can change in magnitude (connectivity strength), sign (connectivity positive/negative) or be lost/gained as the strength changes above/below a threshold (network membership). In the Figure, red edges represent positive connections and blue edges, negative connections.
Neuroplasticity
Neuroplasticity refers to the ability of the brain to change and remold itself over time. There are changes at all stages of the life span related to learning or changes associated with normal aging (e.g., maturation). Brain networks also change due to injury (e.g., stroke), neurodevelopmental (e.g., autism) and neurodegenerative (e.g., dementia) disorders. Not all changes are related to cognitive deficits or disorders, there are also changes that are considered “compensatory” (e.g., recover/retain brain function).
Brain stimulation (e.g., Transcranial Magnetic Stimulation) can influence/modulate the brain configuration during development or after brain injuries by changing the dynamics in brain networks’ activity and, in the long term, changing functional and structural connectivity. Removing/adding synapses is called “structural connectivity” while adjusting the weight of an existing synapse is called “functional connectivity”.
Every Individual is Unique
Every individual with a brain disorder has a unique network connection problem that needs to be uncovered and treated. We identify the unique issue by fMRI imaging. Through fMRI imaging, we can identify the poorly performing network and treat that network directly. Standard TMS uses a one-size-fits-all approach. We target the exact network, in the unique location that is causing brain disorder.
Would you like to know more?
Every human baby is born with about 100 billion neurons. Connections among neurons begin in-utero but speed up after birth.
At birth, babies have about 10 trillion (synapses) connections. At 6-months old, their connections have multiplied by 20-fold. By one year old, babies already have 1,000 trillion synapses (1 with 15 zeros). These brain connections are made through experiences that involve simple tasks—like grasping a toy rattle and focusing on the details of mom’s face.
These brain network connections are not simple – they are complex in how they communicate internally and to other brain networks. Brain networks are constructed by grouping together nodes. Nodes are hubs that create the pathways within the network.
When we look at images from a patient’s fMRI we see what nodes are working and what nodes are not. From this analysis, we can target TMS to the network node or nodes that are not performing correctly.
References
Kaiser M. Changing Connectomes: Evolution, Development, and Dynamics in Network Neuroscience. 1st ed. The MIT Press, 2020. 259 pp
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