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Neuromodulation Therapies – Exciting New Development


There are now two well-researched neuromodulation therapies that are specifically designed to alter activity in brain circuits that exhibit abnormal activity in specific psychiatric disorders.   Transcranial Magnetic Stimulation (TMS) and Deep Brain Stimulation (DBS) were developed specifically with an understanding of neuroanatomy and the physiology of neural networks as a guide. Though DBS is a very exciting area of research with great promise for treating the most severe and treatment-resistant of psychiatric disorders, it requires brain surgery for the implantation of electrodes, so the remainder of this article will focus on TMS, which is non-invasive and therefore can be used far more widely, including at Mind Therapy Clinic.

Through neuroscience research examining brain lesions and using functional neuro-imaging methods (e.g. fMRI, which looks at regional patterns of blood oxygen usage that correlate with the activity of the neurons in each brain structure), we now know a great deal about the abnormalities in brain function that occur in various psychiatric disorders.  Transcranial Magnetic Stimulation (TMS) uses a powerful electromagnet that generates a strong magnetic field pulse which induces the neurons underlying the brain region being stimulated to fire action potentials (the discrete electrical firings that occur in brain cells to send information between one another). Depending on the frequency (Hz) and pattern (rTMS vs Theta Burst Stimulation, TBS) of the magnetic pulses, TMS can either stimulate the brain region to become more active or less active, by increasing or decreasing the synaptic connectivity the region exhibits with other brain regions.  These changes in neural plasticity are mediated by mechanisms called Long-Term Potentiation (LTP) and Long-Term Depression (LTD), which are dependent upon the NMDA receptor mentioned earlier in the newsletter, and they can be made long lasting through repetition of the treatment multiple times a week over a period of 4-8 weeks (5-6 weeks on average).

A very exciting development in the past month was the FDA approval of a 3 minute TMS treatment protocol called iTBS for the treatment of depression. The cutting-edge-neuroscience-informed psychiatrists at Mind Therapy Clinic have been using the iTBS treatment protocol on depression patients ever since we began using TMS, as the data suggesting its efficacy were very strong for years before the FDA finally acted to approve the technique.  iTBS uses bursts of 3 high-frequency (50 Hz) magnetic pulses recurring 5 times per second for 2 seconds (with an 8 second pause between stimulation trains). This novel stimulation paradigm has been demonstrated to produce a robust antidepressant response in a much shorter time frame, and given shorter duration, iTBS treatment can be offered for a significantly lower price, thus making TMS treatment much more widely available to patients with treatment-resistant depression, or simply those depressed patients who cannot or will not tolerate medication side effects or the notion of becoming “dependent” on psychiatric drugs.

Neuroscience research has shown that mental illnesses such as depression, OCD, and schizophrenia have characteristic patterns of neural network activity that have deviated from the normal patterns.  For instance, in depression there is deficient activity in the left prefrontal cortex as well as increased connectivity within the Default Mode Network discussed above (among other changes). In individuals with schizophrenia who experience auditory hallucinations, there is excessive activity of Wernicke’s Area of the cortex (critical for speech comprehension and syntax/semantics), as well as increased connectivity between this area and the amygdala, which has such a critical role in emotional processing.  TMS can be used to alter the abnormal electrochemical activity in these brain circuits, and the specific regions to be stimulated were chosen based upon knowledge of the neural network abnormalities in the disorders.

In depression, we stimulate a region of the brain called the Left DLPFC (dorsolateral prefrontal cortex), which is critical for the cognitive processing of emotional experience.  The activity in this region can be increased with Cognitive Behavioral Therapy (CBT), but it also can be directly increased using TMS with a high frequency of magnetic pulses (10 Hz rTMS or iTBS).  There is such strong scientific evidence for this TMS treatment of depression that it is FDA approved for treating depression that hasn’t responded to medications (FDA requires only 2 failed antidepressant trials, but in order to get prior authorization from most of the health insurance companies, a patient typically has to have failed at least 4 antidepressant medication trials).  This makes TMS a great treatment option for patients whose depression has failed to respond to antidepressants or augmentation agents, patients who have been unable to tolerate psychiatric medications due to side effects, or patients who are wary of becoming “dependent” upon psychiatric medications.

Considering the neuroscience of both TMS and Cognitive Behavioral Therapy (CBT) , in addition to the clinical trials that have specifically examined the combination of TMS with CBT, there is ample reason to suggest that combining TMS with a course of psychotherapy can have synergistic benefits, and this is what would likely be recommended at Mind Therapy Clinic to maximize therapeutic benefits.  Though the FDA has only approved TMS for treatment-resistant depression and OCD, there have been many clinical trials investigating its use for the treatment of several other psychiatric disorders, and if a patient is interested in possibly pursuing this mode of treatment for a condition other than depression, their Mind Therapy Clinic psychiatrist would base the decision about whether to pursue this cutting-edge treatment upon clinical trials that have been conducted using the technology.  Other than depression, TMS has strongest evidence to support treatment of OCD (deep TMS just FDA approved to treat OCD!), auditory hallucination in schizophrenia that have failed to fully respond to medications, and mild cognitive impairment (MCI).

It is worth briefly mentioning that new treatment methods are under investigation using TMS.  Deep TMS is already FDA approved for treatment-resistant depression (and now OCD!) and this form of TMS may work better for certain patients (and vice versa).  Perhaps the most intriguing avenue of investigation is using paired pulse TMS, which uses two separate TMS coils for repeated stimulation to the brain with an interval of time between the two TMS magnets firing that can directly induce quite robust changes in neural connectivity between two different areas of the cortex (by exploiting the mechanisms of LTP or LTD, i.e. “Neurons the fire together, Wire together”.)  This paired pulse TMS technique would also have the advantage of selectively altering the synaptic connection strength between two nodes of a neural network, whereas current TMS methods merely increase or decrease the activity (“excitability”) of a single area of cortex and indiscriminately strengthen or weaken all of the region’s connections to other brain regions.

If you know of anyone who may be interested in pursuing TMS, and unsure whether TMS may be indicated for you, your loved one, or your patient, feel free to contact us to discuss your case.

Neuroscience-Informed Psychotherapy

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