Deep TMS for Addiction

Abraham Zangen is working on developing deep transcranial magnetic brain stimulation technology to treat reward related disorders such as addiction or depression. He's got some interesting writing on his website about deep TMS and also info about his research on addiction (main page here). Being able to target the reward regions of the brain definitely brings up a lot of interesting ethical issues.

Researchers are working on a lot of new brain stimulation techniques. Other people besides Zangen are working on new types of deep TMS coils. Magnetic brain stimulation protocols such as "theta burst stimulation" could enable longer lasting brain excitability changes for a shorter stimulation duration. Controllable pulse shape TMS devices will allow for better targeting of brain regions. Ultrasonic neuromodulation could potentially enable an even greater targeting accuracy than TMS. Or perhaps it will be used in tandem with the numerous other types of brain modulation techniques (transcranial direct current stimulation, infrared stimulation). I think future goals of brain stimulation science will continue to seek longer lasting brain changes that can be induced in a shorter period of time. Also, brain stimulation tools will have much more selectivity in their manipulation capability.

A new paper about transcranial magnetic brain stimulation is available (abstract here). It discusses the mechanisms of action of TMS. The link to the paper is below.

Transcranial magnetic stimulation, synaptic plasticity and network oscillations (pdf 1.3 MB).

The basic principle of TMS is that most neuronal axons that fall within the volume of magnetic stimulation become electrically excited, trigger action potentials and release neurotransmitter into the postsynaptic neurons. What happens afterwards remains elusive, especially in the case of repeated stimulation. Here we discuss the likelihood that certain TMS protocols produce long-term changes in cortical synapses akin to long-term potentiation and long-term depression of synaptic transmission. Beyond the synaptic effects, TMS might have consequences on other neuronal processes, such as genetic and protein regulation, and circuit-level patterns, such as network oscillations. Furthermore, TMS might have non-neuronal effects, such as changes in blood flow, which are still poorly understood.

Brain Videos

I just came across a few interesting links. A new promotional video about deep transcranial magnetic stimulation (TMS) can be found here. Looks like a bit of marketing hype already (older videos about deep TMS can be found here and here). Apparently a recent trial has just been announced about using deep TMS to reduce obesity of all things, too. It sounds like they are going to treat 56 patients to see if they lose weight. I guess the main problem with this type of brain stimulation is that the effect from it may not last particularly long, even if it does have the intended effect on the brain. So we'll have to see how much utility it has in the future and whether it is really worth the expense for specific brain disorders. The blog Mind Hacks had a link to some interesting videos "The Future of Human Health". The videos cover a variety of topics such as Brain-Computer Interfaces and Building a Circuit-Diagram for the Brain.

Brain Matter Stimulation Economics

Bloomberg has a new article about deep transcranial magnetic stimulation. It sounds like they expect this non-invasive brain stimulation technique to be approved within a year.

Sofer said he expects to win the U.S. Food and Drug Administration’s approval for the device by the end of the year or the beginning of 2010.

The number of treatment sessions needed will likely be similar to the neurostar transcranial magnetic stimulation device that has already been approved.

For each treatment, Brainsway expects to receive $50, he said.

I'm not quite sure if this is what it will cost per treatment session for a patient. The neurostar TMS treatment costs $200-300 per session, for instance. So this would be quite a reduction in price if true (*This may not be the price per treatment session, just how much brainway actually gets. The actual cost per session may in fact be similar to what a neurostar TMS session costs). Also it appears that the cost of the TMS device will go down in price quite a bit.

Each unit costs the company about $80,000 to produce. Once Brainsway starts mass production, the cost will shrink to $20,000, Sofer said.

I think it would be neat if people could buy their own deep TMS device for their home. I'm not sure how realistic that possibility would be, though. Especially considering some of the possible side effects (seizures being one). Perhaps if these brain stimulation techniques continuously get cheaper and safer that could eventually become a reality.

Future Transcranial Magnetic Stimulation Devices

I came across some interesting patent (applications) about potential future transcranial magnetic stimulation devices in a forum. This first patent uses magnetic fields coupled with what sounds like acoustic stimulation. I'm a little unsure of what exactly that means, but it sounds like this could potentially enable scientists to stimulate very small (1 cm) structures located deep within the brain. I assume this would allow a much greater focal accuracy and targeting ability than the deep transcranial magnetic stimulation I previously mentioned on this blog. Deep TMS may stimulate a larger brain area so it may be somewhat limited in its utility for certain brain disorders.

"A system is disclosed for the diagnostic or therapeutic treatment of a patient's neural tissues. The system includes at least a means to directly or indirectly acoustically expose or acoustically displace at least a first tissue portion. The system further includes a means to impose, directly or indirectly, an electromagnetic, electrical, magnetic or optical field on at least a second neural tissue portion. The combined or cooperative action of the acoustic exposure/displacement and the field, whether sequentially or simultaneously applied, causes at least one diagnostically or therapeutically useful mechanism."

The second patent has some information about "stereotactic transcranial magnetic stimulation" (sTMS). This also sounds similar in principle to Brainsway's deep transcranial magnetic stimulation. Instead of having an electromagnetic field generated from a single coil, they use multiple coils with 3 on the sides of the head and one on the top of the head. This would mean there would be less unbearable stimulation of more cortical brain areas. The problem with a single coil is that the magnetic field would need to be way too high to stimulate deeper brain structures. So brain areas near to the surface of the brain would be stimulated too much, leading to pain and potentially seizures.

"The present invention provides for Stereotactic Transcranial Magnetic Stimulation (sTMS) at predetermined locations with the brain or spinal cord and incorporates an array of electromagnets arranged in a specified configuration where selected coils in the array are pulsed simultaneously. Activation of foci demonstrated by functional MRI or other imaging techniques can be used to locate the neural region affected. Imaging techniques can also be utilized to determine the location of the designated targets."

So this stereotactic transcranial magnetic stimulation would likely have more focal accuracy and would also be coupled with real time brain imaging. This would allow scientists to simultaneously manipulate brain functioning and watch the resulting effects on an fMRI.

"Several patents and patent applications relate to such areas as electromagnetic coil design, simultaneous monitoring of EEG, simultaneous monitoring with functional MRI, and specific clinical applications."

The third patent has a coil that is constantly moving around the head. This would mean that no single area on the surface of the brain would be stimulated too much. This would also avoid over stimulation of surface brain areas and allow researchers to target deeper structures.

"Techniques for applying electromagnetic energy to deep, targeted areas without overwhelming other areas are provided. One or more coils are moved relative to a target area and magnetic fields are applied to the target from multiple coil locations. As a result, the aggregate electromagnetic energy applied to the target over time is greater than surrounding areas. Additionally, a model for testing and treatment planning is provided."

If these transcranial magnetic stimulation devices get patented they may have the potential for improved brain manipulation. They may serve as a new treatment modality in conjunction with the numerous other methods of changing brain chemistry that are already available.

Deep TMS and Bipolar Disorder

Brainsway (the company that is developing the new deep transcranial magnetic stimulation technology) has recently gotten results from a new clinical trial using this device on depressed bipolar patients. Bipolar disorder is a cyclical mental illness. People who have this disorder can have moods that range from euphoric mania to suicidal depression. Bipolar mania and hypomania are often associated with negative outcomes as a patient's behavior can become bizarre and irrational.

According to the write up, brainsway said that 80% of patients responded to the treatment with 50% experiencing a significant improvement. When they say significant improvement I'm guessing that they mean a 50% or greater reduction in depressive symptoms. This seems like a surprisingly high improvement rate for this disorder so I'm somewhat skeptical.

It looks like they may have selected bipolar patients who have more treatment resistant depression for the trial so that would make that reduction even more surprising.

"Medication resistance to at least two different antidepressant treatments, defined as resistance to a minimum of 2 antidepressant drug trials of adequate dose and duration in the current episode or previous episodes defined as a minimum level of 3 on the ATHF per antidepressant drug-trial."

Treating bipolar depression is fairly difficult because antidepressant treatment can cause them to switch into a manic or hypomanic state. So managing bipolar depression is often much less successful than reducing the symptoms associated with manic episodes. It sounds like this new treatment was successful without the propensity for causing switching.

Uses of Deep TMS

I had previously mentioned the new deep transcranial magnetic stimulation (deep TMS) created by the company brainsway that is currently undergoing several clinical trials. This specific technology can excite or inhibit more areas of the brain than conventional TMS. Regular TMS is basically limited the brain's outer layer, the neocortex, and can only reach about 1 to 2 centimeters into the brain. So it is limited in its ability to affect many brain areas. The new deep tms can stimulate inner brain areas without inducing unbearable magnetic fields cortically. This device currently has almost magical properties and it is somewhat difficult to distinguish company hype from real clinical benefit. I'm not sure at this point how selective this targeting technique is. I think it will be fairly difficult to selectively turn on or off specific brain areas without having unintentional effects. However this technology is certainly promising for a number of brain disorders.

Researchers are testing the device to treat obesity. They are targeting the hypothalamus which is a deeper brain structure. The hypothalamus secretes various hormones and is involved in the metabolic processes of the body. This area is involved with weight gain, so by stimulating this area researchers may allow a person to shed the pounds without actually having to do anything. Researchers have already performed trials using deep brain stimulation devices to target this area. Apparently they have found that stimulation of this area has an impact on animal weight gain in tests. So it should be interesting if they can get a weight loss response by targeting this area.

They are also testing the deep TMS on alzhiemer's patients. Alzheimer's patients undergo a fairly precipitous cognitive decline over the course of the disease and current treatments leave a lot to be desired. Researchers have found that by using deep TMS, they were able to positively improve a person's spatial memory. For alzhiemer's patients, they are targeting an area of the brain called the dorsal septal region that has cholinergic nuclei. Presumably they are targeting the cholinergic nuclei to increase the neurotransmitter acetylcholine that is often deficient in patient's with alzhiemer's. I'm doubtful that the deep tms will have a huge impact on alzhiemer's patients. There are already drugs that increase acetylcholine and their efficacy is fairly limited. It seems improbable that the deep TMS will have much impact on the alzhiemer's disease process. However it may be able to improve specific symptoms of alzhiemer's temporarily. They have already tested it on single alzhiemers patients and claimed that it improved visual memory, executive functions and orientation. I think any improvements will likely be fairly limited in scope.

The researchers are also testing it to reduce auditory hallucinations in people with schizophrenia. Approximately 5o to 70 percent of schizophrenic patients hear voices that aren't really there. This can be extremely distressing and frightening as the voices can often be mean or disparaging to the person. The voices can range from commentary about the person life to verbal commands. The left temporoparietal cortex has been shown to be activated during auditory hallucinations. A recent meta-analysis has shown that using conventional TMS at a frequency of 1-Hz to this area is superior to sham in treating auditory hallucinations. Several deeper brain areas located in thalamic, limbic and paralimbic regions have been shown to be activated when a person is experiencing auditory hallucinations. So decreasing activity in these areas may lead to a reduction in hearing voices. Presumably they are going to target several of these other areas that have now become available for stimulation. I think the evidence for conventional TMS on auditory hallucinations is already pretty sound, so this new technology may allow an even greater improvement in these symptoms.

Researchers are testing this device for depression and negative schizophrenia (both have similar symptoms). It appears that they are targeting deeper prefrontal areas. The left dorsolateral prefrontal cortex in the front part of the brain has been stimulated with conventional TMS. Researchers have found this to have a good mood elevating effect and it also leads to a reduction in negative schizophrenic symptoms. With the new deeper TMS they may be able to target deeper into this specific area of the brain and get a better antidepressant response by stimulating more neurons that were previously out of reach. Stimulating this area may improve a person's interest, motivation, mood and attention. I am under the impression that they are also going to directly target the brain's reward system as well by stimulating areas like the nucleus accumbens. This will be done to improve the ability to experience pleasure in drug addicts, depressed patients and schizophrenics. Overall this technology sounds almost too good to be true. Imagine having this treatment performed on you to make you lose weight, allow you to quit your addictions and improve your mood and pleasure. All of this would be done non-invasively without the need for brain surgery. I will certainly be keeping an eye out for future developments of this new way to manipulate brain functioning.

Deep TMS Clinical Trial

Recently, Brainsway (the company developing the new deep transcranial magnetic stimulation technology) has successfully completed an open label trial on depressed patients. It looks like about 45% of the patients showed a significant response (50% or greater reduction in depressive symptoms) with this treatment. That is a fairly high response rate, and these patients were treatment resistant and had failed at least two prior antidepressants. Comparatively, the response rate in a neuronetics trial for conventional TMS was around 24% (also done with treatment resistant patients). Now Brainsway plans on having a larger double-blind trial to test the efficacy of its device and obtain FDA approval, which could happen in a year or two. Brainsway is also testing its device to improve the cognitive symptoms of schizophrenia, cannabis addiction, post traumatic stress disorder and bipolar disorder.

Deep Transcranial Magnetic Stimulation

A main goal of brain research is to be able to selectively excite or inhibit any area of the brain. A new technology called deep transcranial magnetic therapy is being developed by a company called Brainsway that may finally allow scientists to do just that. Conventional transcranial magnetic stimulation (TMS) has been around since 1985 and has shown a lot of promise in treating various mental illnesses. TMS has been used by researchers to activate or deactivate specific areas of the brain by sending a magnetic pulse through the skull. This magnetic pulse generates an electric current in a targeted brain area and this can cause either excitation or inhibition of neuron firing depending on the frequency of the pulse that is used. High frequency pulses excite neurons while low frequency pulses inhibit neuronal firing. So specific brain areas can be either activated or deactivated. The main problem with existing transcranial magnetic devices is that they can only reach 1 to 2 centimeters into the brain. This has meant that researchers have only been able to target the outer layer of the brain (the neocortex) that is located in close proximity to the skull. The new deep TMS allows targeted electrical stimulation of brain areas that are not within reach of conventional TMS devices.

A documentary about this technology is in production and you can some trailers from it here, here and here. The documentary appears to be entitled "Invisible Mind Fields" (renamed Electric Mind) and looks like it will follow a clinical trial of depressed patients undergoing a course of treatment with this new technology. According to the write-up from the filmaker's website it looks as if a transhumanist element will be added to the film. Here's a quote about the film, link here (pdf file removed).

"The prospect of manipulating our minds with machines has for decades been considered a cybernetic fantasy belonging to the realm of literature and cinema, now, after "softening up" by advances in science and science fiction, far fewer people find the notion of neuro-enhancement troublesome. Its potential clients are not just the radicals who long for a post-human future, but ordinary people who grew up in the information age."

The company making this device has already tested it on healthy volunteers and claimed that it improved their mood. So the transhumanist label may be warranted considering it has the capacity to make "normal" people's lives more worthwhile. Brainsway's strategy to get FDA approval appears to be using the deep TMS device to target deeper brain areas related to the brain's reward system. Direct electrical stimulation of the nucleus accumbens has been shown to be rewarding. In animal and human subjects, electrodes have been implanted directly within the nucleus accumbens by scientists. However, doing this requires risky brain surgery. With this new technology, psychiatrists may eventually be able to electrically stimulate the nucleus accumbens non-invasively without unecessarily stimulating other cortical brain areas.

Other areas of the brain can also be targeted selectively. This device has the potential to ameliorate several conditions like depression, schizophrenia, bipolar disorder, obesity, addiction and autism. It seems like this technology could potentially allow scientists to activate or deactivate multiple brain regions at once. Application of this technology in the future may lead to an unprecedented ability to create new modes of brain functionality. Scientists still have plenty of research to do with conventional TMS, but this new technology could open up a whole new era in brain manipulation. Targeting specific areas of the brain may allow researchers to improve a person's memory or concentration. Conventional TMS has already been used to bring out savant like creative abilities in normal subjects and reduce the detrimental affect of sleep deprivation. So in the future, TMS may be able to enhance aspects of human intelligence or creativity. In sum, this new deep TMS technology has a number of potentional uses and could significantly improve our ability to manipulate the brain.