Transcranial Magnetic Stimulation for Hallucinations

A majority of hallucinations found in people who have schizophrenia are auditory in nature. Schizophrenics may hear voices that do not exist in reality. They can sometimes make disparging commentary towards the person and can be very distressing. The amount of patients that hear auditory hallucinations are in the range of 50 to 70 percent of schizophrenics. For auditory hallucinations, the left temporoparietal cortex has been show to have increased activity. Transcranial magnetic stimulation has been used to reduce activity in that area of the brain. By selectively reducing activity here, scientists are able to reduce the amount of non real voices a person hears.

Other types of hallucinations outside the range of auditory (visual, sensory) are much rarer. You can read an interesting case study about using transcranial magnetic stimulation to reduce coenesthetic hallucinations in a single patient here. The coensthetic hallucinations consisted of having a feeling of undergoing electric shocks and also a feeling of having alien objects moving inside the person's pelvis/thorax/abdomen. These would definitely be very disturbing and troubling hallucinations to have to endure. They are possibly much more frightening than regular auditory hallucinations.

The patient actually benefited from 10 daily sessions of fMRI guided low frequency transcranial magnetic stimulation. They directed the TMS pulse over a brain area called the somatosensory cortex to reduce neuron activity their. This person had previously been treatment resistant to anti-psychotic therapy. The authors of the paper linked overactivation in the somatosensory cortex to the type of sensory hallucination that the person was experiencing.

I think this shows that TMS has a pretty good selectivity and scientists may be able to treat many currently treatment resistant patients. Brain areas can be selectively targeted for deactivation/activation as I have mentioned in the past. Better characterization of the changes induced by TMS by using real time brain imaging should help obtain even better responses.

Deep TMS Device Test

Brainsway, the company creating the new deep TMS device, has just gotten the go ahead from the FDA to start a multi-center clinical trial of their new TMS device on depressed patients. They will test it on patients for 20 sessions over the course of 4 weeks. The sessions will last 20-minutes each and will help the symptoms of major depression. The deep TMS will be able to stimulate more regions of the brain with electromagnetism than the neuronetics TMS device that just recently got FDA clearance. The neuronetics device can only penetrate 1-2 cms deep into the brain. The new study is expected to begin in january 2009. It will be conducted at several sites such as Columbia University, Howard University, Johns Hopkins University Medical Center, Davis Hospital and UCLA. According to Brainsway, the effectiveness of this treatment has lasted for as long as 24 weeks. Here is what area of the brain they will target.

Includes 20 patients.These patients will be given 4 weeks (5 days a week) of deep TMS, 20 minutes each session, to the prefrontal cortex bilateraly using H2 coil, in frequency of 0.1 HZ, with intensity of 120 % of motor threshold. H2-coil is designed to stimulate deep prefrontal brain regions bilaterally (without any preferencefor either hemisphere). The effective part of the coil, which has contact with the patient's scalp, includes 10 strips of 14-22 cm length.These strips are oriented in a right-left direction (lateral-medial axis).This coil is destined to stimulate lateral-medial neuronal fibers.

Trials for other brain disorders will likely follow. They may eventually test this device for the treatment of strokes, schizophrenia, bipolar disorder, addiction, and post traumatic stress disorder. I think this will also become a novel research tool that will find increasing use in the future.

Transcranial Magnetic Stimulation Awakens Coma Patient

Researchers have recently used transcranial magnetic stimulation TMS to awaken a coma victim. TMS has been used by researchers for a variety of brain disorders in the past, altering brain activity by sending a magnetic pulse through a person's skull. The 26 year old man had been in a car accident and had suffered a traumatic head insult. He had been in a coma and had not improved for quite some time. Researchers used TMS to simulate his brain generating an electric current in a targeted brain region. The doctors discovered that the patient aroused after undergoing 15 TMS treatment sessions. The patient began speaking a few choice words and was also able to move his eyes. The TMS was used to activate brain cells in an area of the brain called the right dorsolateral prefrontal cortex.

Apparently the patient had only been give a 20 to 40 percent chance of recovery. After each TMS session he improved by an incremental amount. I think that TMS may be used for people with brain damage in the future. Researchers are now testing deep TMS for stroke patients to improve functioning and I think brain damage should follow. Transcranial direct current stimulation also has the potential to do the same thing.

I think that overall this treatment modality will be fairly limited for the treatment of traumatic brain injuries. While this specific case is interesting, TMS is not magic. It cannot repair brain damage itself. However, it may be able to activate underactive brain regions and restore some functioning in specific patients.

You can read the whole story here.

Transcranial Magnetic Stimulation Gains FDA Clearance

Transcranial magnetic stimulation (TMS), a method of non-invasively stimulating the brain, has just recently gained clearance for the treatment of major depression. This is one of the first FDA clearances of TMS for a brain disorder. TMS has actually been around quite some time (since 1985) and has shown considerable promise for treating a variety of brain disorders. TMS has been used by scientists to deactivate or activate specific regions of the brain's outer layer (the neocortex) by sending multiple magnetic pulses through a person's skull using a TMS device. These magnetic pulses are able to create an electric current in a very targeted brain region. This electric current can then cause either an inhibition or an excitation of the underlying brain tissue depending on which frequency of the TMS pulse that is used. High frequency magnetic pulses are able to excite brain tissue while lower frequency pulses tend to decrease brain activity. So specific brain regions may be selectively activated or deactivated. Brain disorders often have hyperactive or hypoactive activity in specific regions, and TMS is able to selectively adjust this brain activity non-invasively.

I think approval for other conditions will follow after this success. Neuronetics, the company marketing the TMS device, had actually tried in 2007 to get approval but failed quite spectacularly. Neuronetics has previously showed the results from a different TMS trial to a board of several FDA advisors in 2007. For that specific trial, the clinical outcome was measured by a reduction in major depression scores on the Montgomery-Asberg Depression Rating Scale (MADRS) symptom score after undergoing a treatment with TMS for six weeks. Symptoms for major depression include profound sadness, apathy and an inability to experience pleasure.

In that previous trial the TMS failed to distinguish itself from the sham/fake TMS for improving depression symptoms. The mean decrease in the MADRS symptom scores was approximately 5.6 points in the active transcranial magnetic stimulation group of patients and about 3.2 points in the sham/fake TMS group of patients. Unfortunately for the company Neuronetics, the p-value after 6 weeks was just .058. A p-value (see statistics) that is less than .05 is the difference between the active and sham TMS that is considered statistically significant. So the difference between fake and real treatment was just not enough to prove efficacy. Neuronetics had also tried to compare the efficacy of TMS to ECT, which is a bad move. ECT has a much greater mood elevating effect than TMS and they are not comparable. TMS, though, has almost no side effects in comparison to numerous side effects with ECT or antidepressants, which is a huge plus. ECT causes a brain seizure and requires a person to undergo anaesthesia. ECT has a drastic effect on the functioning of the entire brain. TMS on the other hand can be performed on a person while they are totally awake and is fairly painless. So TMS does have advantages to both ECT and antidepressants. Neuronetics had to do another trial in order to get better results and satisfy the FDA. It appears that they were successful in convincing the FDA.

Neuronetics, Inc., a privately-held medical device company and a leader in the field of neuromodulation, announced today that the U.S. Food and Drug Administration (FDA) has cleared its NeuroStar TMS (Transcranial Magnetic Stimulation) Therapy system for the treatment of depression. NeuroStar TMS Therapy® is specifically indicated for the treatment of Major Depressive Disorder in adult patients who have failed to achieve satisfactory improvement from one prior antidepressant medication at or above the minimal effective dose and duration in the current episode. In clinical trials with NeuroStar TMS Therapy, these patients had been treated with a median of 4 medication treatment attempts, one of which achieved criteria for adequate dose and duration.

You can read the data from the clinical trial at this website. The success from the new trial seems to be partially due to "adjusting" the outcome parameters a little. Notice that the end point this time was 4 weeks and not 6 weeks. However, it is possible that they amped up the amount of TMS excitation that the patients received as well for a better effect.

The primary efficacy measure, the Montgomery-Asberg Depression Rating Scale (MADRS) symptom score change at 4 weeks, was statistically significantly superior to placebo (p=0.0006), among NeuroStar-treated patients. Similar results were observed with the Hamilton Depression Rating Scale (HAMD). NeuroStar TMS Therapy-treated patients had statistically significant response and remission rates, which were approximately twice the rate of placebo-treated patients. The response rate is the percentage of patients who had a greater than or equal to 50% improvement in symptoms, and the remission rate is the percentage of patients who achieved virtually complete symptom resolution. NeuroStar TMS Therapy also produced statistically significant improvements on the HAMD factor scores for core depression symptoms, anxiety symptoms, somatization, and psychomotor retardation.

In the future, neuronetics will probably get competition from brainsway, the company making the deep transcranial magnetic stimulation device. This recent Neuronetics TMS trial only targeted the left dorsolateral prefrontal cortex, but researchers may also be able to target the right dorsolateral prefrontal to gain an even greater antidepressant response. So I think this treatment will end up getting better as scientists are able to target more brain areas for activation/deactivation. I suspect Neuronetics had to do a lot of data manipulation to get the right outcome for this recent trial. However, TMS may still become more useful for brain disorders as time goes on.

Non-Invasive Brain Stimulation for Athletes?

Will athletes in the future begin to use non-invasive brain stimulation to get an edge over the competition? Already researchers have used transcranial direct current stimulation tDCS (a non-invasive way to electrically stimulate the brain) to reduce exercise dependent fatigue.

Neuromuscular fatigue is the exercise-dependent decrease in the ability of muscle fibres to generate force. To investigate whether manipulation of brain excitability by transcranial direct current stimulation (tDCS; 1.5 mA, 10 min, 0.026 C/cm(2)) modulates neuromuscular fatigue, we evaluated the effect of brain polarization over the right motor areas of the cerebral cortex of healthy subjects on the endurance time for a submaximal isometric contraction of left elbow flexors.

The researchers found that anodal tDCS (which activates brain areas) was able to decrease fatigue related muscle pain.

Anodal tDCS could improve endurance time by directly modulating motor cortical excitability, modulating premotor areas, decreasing fatigue-related muscle pain, increasing motivation and improving synergist muscle coupling.

I mentioned in the past about using transcranial magnetic stimulation to improve the working memory deficits associated with sleep deprivation. So this technology might be able to improve an athletes concentration from too much fatigue. It may also be able to enhance regular concentration as well. I also discussed about using deep transcranial magnetic stimulation to target the reward areas of the brain with electromagnetism. Doing this may allow researchers to artificially induce a euphoric or stimulant like effect in the subject by selectively stimulating or inhibiting specific brain regions. This would be beneficial for long term endurance where a large boost in mood is necessary for optimal performance. Deep TMS may be able to target several different regions of the brain to improve performance in a variety of tasks.

The banned substance list (pdf) of the recent olympic games does not mention using non-invasive brain stimulation, however both transcranial magnetic stimulation or transcranial direct current stimulation could potentially find increasing use by athletes in the future. It may still be a little early to know how useful these types of technologies would be for athletes. As for cheating, it would be nearly impossible to detect if someone had undergone non-invasive brain stimulation. They wouldn't be able to have any drug tests that could detect this type of treatment. The only plausible method of detection might be a brain scan. So this could be an effective way of brain doping while sidestepping any negative penalties. This is all speculative of course, and it is unclear if these types of brain stimulation would enough of an effect on an athletes performance to be worthwhile.

TMS for Generalized Anxiety Disorder (GAD)

Researchers are continuously coming up with creative new therapies using transcranial magnetic stimulation (TMS) as a treatment modality. Now, they have performed a new study using TMS to improve the symptoms of generalized anxiety disorder (GAD). Generalized anxiety disorder is characterized by chronic worry, tension and anxiety. These symptoms can often occur for no apparent reason and can be quite distressing. For this new study researchers recruited patients who had a diagnosis of GAD. They first performed an fMRI on the subjects to determine which area of the brain to target. This is one of the relatively few fMRI-guided TMS studies I have seen. Basically they take a brain scan, and then target the abnormal area visualized on that scan with TMS.

The goal of this pilot study was to evaluate whether functional magnetic resonance imaging (fMRI)-guided rTMS is effective in reducing symptoms of GAD.

It looks like they got fairly promising preliminary results from this trial.

RESULTS: Overall, rTMS was associated with significant decreases in HAM-A scores (t = 6.044, p = .001) indicative of clinical improvement in GAD symptoms. At endpoint, 6 (60%) of the 10 participants who completed the study showed reductions of 50% or more on the HAM-A and a CGI-I score of 1 or 2; those 6 subjects also had an endpoint HAM-A score.

I think this shows that in the future, researchers will basically be able to look at a real time brain scan to tell which brain areas are overactive or underactive in those with mental illness. If a person is exhibiting a specific symptom associated with a particular brain region being overactive or underactive, they can then increase or decrease activity in that area using TMS or deep TMS. So TMS therapies can be individualized for each person. Researchers have already correlated specific symptoms of mental illness with metabolism in specific brain areas.

"Psychic depression correlated positively with metabolism in the cingulate gyrus (most of the dorsal posterior cingulate and subgenual anterior cingulate), thalamus, ventral striatum, hypothalamus and subgenual basal forebrain. Sleep disturbance correlated positively with metabolism in limbic structures and basal ganglia. Loss of motivated behavior shows a significant negative correlation with an extensive network of dorsal cortical regions, including the dorsolateral prefrontal cortex (PFC), dorsal parietal cortex, and dorsal temporal association cortices."

So in the future, I think there will be a move to diagnosing specific symptoms as opposed to labeling disorders. Usually most mental illnesses are quite heterogenous, as different people may suffer from different symptoms and different brain overactivity or underactivity.

TMS and Migraines

A portable transcranial magnetic stimulation (tms) device has been successfully used to reduce migraine headaches. Migraine headaches are usually pulsating and localized to one side of the brain. They typically can last from 4 to 72 hours. Migraine headaches are often accompanied by nausea, vomiting and sensivity to sight/hearing. Researchers performed a multi-center clinical trial of 164 patients. They found that 39 percent of patients were migraine free two hours after TMS treatment compared to only 22 percent recieving sham/placebo TMS. The adverse reactions from this device were also minimal and similar to the sham/placebo.

The cause of migraines is currently unknown. Migraines have been associated with altered cortical brain excitability. Migraines and epilepsy have been linked to one another, suggesting a common brain disturbance.

"The comorbidity between epilepsy and migraine has been well known for a century, yet it is still not fully understood; the two disorders also share some risk factors, symptoms, and preventive drug therapy. A series of clinical observations and scientific data support the hypothesis of alteration of cortical excitability as a possible mechanism underlying their pathology, with both disorders characterized by transient paroxysmal neurological disturbance. So far, the numerous pathophysiological mechanisms responsible for neuronal hyperexcitability have only been studied in familial hemiplegic migraine (FHM), but they do suggest a link between migraine and epilepsy."

Researchers have used low frequency TMS stimulation to reduce hyperexcitability of the occipital cortex. Low frequency stimulation reduces activity in that specific area of the brain and this resolves migraine symptoms.

"Recent studies showed hyperexcitability of the occipital cortex in subjects affected by migraine with aura. It has been shown that 1 Hz repetitive transcranial magnetic stimulation (rTMS) reduces excitability of visual cortex in normal subjects. The aim of the study was to investigate the effects of low frequency (1 Hz) rTMS on visual cortical excitability by measuring changes in phosphene threshold (PT) in subjects with migraine with aura."

Transcranial direct current stimulation has also been used for migraines and may be a cheaper alternative to TMS.

"If the tDCS treatment makes it through clinical trials, migraine sufferers may end up with a treatment safe enough to use without a physician present and whose only side effect would be a slight tingling sensation. Adding to the good news: “I can’t see it costing more than $10,” Zaghi says."

Currently neither TMS nor tDCS is approved by the FDA for the treatment of migraines. However you may be able to get treatment off label at certain brain stimulation centers around the US.

You can watch a CBS news video about this new technology below.

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.

rTMS and Aspergers

Imagine living your life with no real emotions of any kind. Your mind is analytical and immune to mysticism or emotional attachment to the sensory environment. Now imagine undergoing a treatment that alters your brain, suddenly opening the floodgates of emotion. It would be like having your world transformed from black and white to full color or moving from a 2-dimensional world view, to a 3-dimensional worldview. Apparently researchers using rapid transcranial magnetic stimulation rTMS to affect the brain in patients with Asperger's syndrome have been able to alter consciousness in that way.

Asperger syndrome is a developmental brain disorder. People with disorder often have a poor understanding of nonverbal communication, stereotyped interests and deficits in empathy, Asperger syndrome shares symptoms with negative schizophrenia. Symptoms in both disorders include unchanging facial expression, decreased spontaneous movement, paucity of expressive gesture, poor eye contact, affective nonresponsivity, inappropriate affect and lack of vocal inflections. These two disorders may share functional deficits in common brain regions.

You can read an interesting first hand account of a person with aspergers undergoing an rTMS treatment to stimulate a specific area of the brain. This is the first time I have heard about it being used for this disorder. It looks like it may potentially improve specific symptoms for this syndrome and can have a large impact on a person's perceptual consciousness.

"As we went through the different phases of simulation, I became aware that my reading had been rote initially, and I wasn't getting the full meaning out of what I had been reading. After the brain was stimulated, I started getting more meaning from the sentences. At one point, I was also able to understand the emotional content of sentences, which I had not been aware of previously. It really felt like I had been seeing in two dimensions, and could now see in three dimensions."

People with asperger's syndrome often fail to integrate details in the sensory environment correctly. They lack the emotional coloring of the world that highlights the salient details that are necessary for normal functioning. So they tend to take things literally and don't understand nuances in speech such as sarcasm. They often fail to grasp the larger picture and can get bogged down in the details.

"I also noticed a difference in the way I saw the woman who was reading sentences. Initially, I focused in on the content of her words, and didn't see the larger picture. As I went through the stimulation sessions, I started noticing more of the larger picture, and noticed what was going on besides the exact content of her words. I also started to be able to pick out sentences which I had taken literally when I first read them, and was able to understand meanings of the sentences other than a literal interpretation."

I always find it amazing how rTMS is able to shape consciousness in such profound ways. rTMS may certainly become a treatment modality for those with asperger's who wish to find symptomatic improvement.

Long Term rTMS Treatment

Transcranial Magnetic Stimulation has been used to improve a variety of different disorders as I have already previously mentioned on this blog. This treatment has been successful at altering brain functionality, showing the mind's inherent plasticity in response to electrical stimulation. Not a lot has been done to see how long researchers can maintain a clinically relevant response to rTMS. However, this aspect of rTMS is vitally important to how useful rTMS will be in the future management of brain disorders.

A recent study has come out testing rTMS on treatment resistant depressed patients over a longer period of time to see if they can sustain the antidepressant response. This is one of the few studies I have seen documenting a maintained antidepressant response to rTMS. This is important because it is currently not known how long rTMS can affect brain functioning.

Obviously having rTMS performed on you everyday for the rest of your life is not going to make this method of brain manipulation too popular. If scientists can maintain a response so you would only need rTMS once every couple of months, this would make this treatment option much more desirable for ameliorating mental illness.

RESULTS: Approximately one half of the patients individually sustained a clinically significant response to the repeated courses of rTMS; the mean +/- SD decrease in HAM-D scores was 64.8% +/- 12.6% (p < .0001), and, in BDI scores, 60.4% +/- 20.6% (p < .0001). Despite the lack of adjuvant antidepressant medication, the mean interval between treatment courses was approximately 5 months, and the medication-free period ranged from 26 to 43 months. Transcranial magnetic stimulation was well tolerated, and evaluations regarding the safety of the repeated applications of rTMS revealed no findings of concern. CONCLUSIONS: Repeated rTMS applications have demonstrated a reproducible antidepressant effect in patients with refractory depression who initially showed a clinically significant benefit. The duration of effect varied across patients, but benefits were sustained for a mean of nearly 5 months. Further studies with larger cohorts will be useful in determining the long-term effectiveness of rTMS maintenance therapy.

Brain Manipulation

Technology Review (MIT) has an interesting article entitled "A Gentler Way to Jump-Start the Brain" about the new deep transcranial magnetic stimulation technology by the company Brainsway. They give a good overview of how of this new technology works.

"Instead of a single coil generating a single magnetic field through the brain, Zangen has outfitted a helmet with a number of small coils, each producing a separate magnetic field. As researchers run a standard current through the helmet, the coils, which are connected in a series, produce multiple fields that add up, generating a much stronger magnetic field that goes deeper into the brain before dropping off."

According to the article, it appears that the technology will be approved in Europe fairly soon while the US will have to wait a while longer.

In other news, the Telegraph has a very interesting article and a short video about deactivating brain regions associated with speech using TMS entitled "How a magnet turned off my speech".

"Words failed me. I stuttered as Prof Vincent Walsh turned off the speech centre of my brain for a few thousandths of a second to demonstrate the power of transcranial magnetic stimulation, a popular way to interfere with the most complex known object in the universe."

That site also has another good article about using direct current brain stimulation to prevent migraines (DIY brain therapy could halt migraines)

"These new brain stimulators, called DC machines, introduce very weak electrical currents. But like TMS, DC also has the same effect of changing the "excitability" of brain cells, either damping down their reactivity or boosting it, which can change the way that the brain responds."

Transcranial Magnetic Stimulation TMS rTMS Depression

Transcranial Magnetic Stimulation has been used at a high frequency to stimulate the left dorsolateral prefrontal cortex. By using a high frequency, the brain area being targeted becomes more active than it normally would be. A recent meta-analysis indicates that stimulating this area has mood elevating properties in depressed patients.

Thirty double-blind sham-controlled parallel studies with 1164 patients comparing the percentage change in depression scores from baseline to endpoint of active versus sham treatment were included.

"These findings show that high-frequency rTMS over the left DLPFC is superior to sham in the treatment of depression. The effect size is robust and comparable to at least a subset of commercially available antidepressant drug agents."

Researchers have had considerable difficulty in distinguishing rTMS from sham for many trials, though. Depression is a multifaceted disorder with many different symptoms that are associated with different brain areas. Stimulating the left dorsolateral prefrontal cortex with rTMS is relatively selective and might only be expected to improve a subset of depression symptoms. Left dorsolateral prefrontal dysfunction (LDPFC) is associated with pseudodepressive symptoms. These type of symptoms include apathy, indifference, anergia, poor concentration and psychomotor retardation. Stimulation of this area would be less likely to improve extreme sadness, pleasure and sleep difficulty which may be associated with other brain areas.
Researchers have also found that low frequency stimulation of the right dorsolateral prefrontal cortex which is on the right side of the brain also has a mood elevating effect. Low frequency stimulation does the opposite of high frequency stimulation. It decreases brain activity in the area being targeted. More recently researchers have found a way to squeeze even more of a response out of low frequency rTMS by "priming".

"Recent research has suggested that preceding low-frequency rTMS with a period of low-intensity, 6-Hz stimulation ("priming") enhances the physiological effects of low-frequency stimulation."
"Low-intensity, high-frequency priming stimulation appears to enhance the response to low-frequency, right-sided rTMS treatment in patients with treatment-resistant depression."

So basically this is using a higher frequency to stimulate the target area which is then followed by stimulation with a lower frequency that inhibits brain function. This may allow researchers to decrease brain activity to an even greater degree than with just using regular low frequency rTMS. Exciting the brain with high frequency rTMS has the potential to cause a siezure, so scientists are limited in how high a frequency they can go. Low frequency rTMS on the other hand, inhibits brain functioning and does not have the same risk of causing seizures. It is much easier to decrease brain activity in certain areas than increase brain activity.

I think in the future what is need are better rating scales which correlate depression symptoms with specific brain dysfunctional areas. That way scientists will be better able to measure the response when selectively activating or deactivating a brain area. This would decrease the signal to noise ratio and enable researchers to better distinguish the sham (placebo) TMS from the real TMS.

TMS and Working Memory

Columbia University Medical Center has used conventional transcranial magnetic stimulation (TMS) to reduce the deficits in working memory associated with sleep deprivation. Working memory is the brain's ability to temporarily store and manipulate information. Going without sleep usually causes a decrease in a person's working memory among along with a reduction in other brain functions. This story is a couple months old, but you can watch an interesting new short video below about the use of TMS to improve this aspect of intelligence. The military is currently funding this research in order to create a new method to increase a soldier's performance on the battlefield. In the future this could potentially be used for enhancement type purposes among normal people. Imagine sleeping less without having any of the associated cognitive deficits. It seems like this might be a possibility with the use of TMS or transcranial direct current stimulation targeted to the left dorsolateral prefrontal cortex. In the recent past, TMS has also been used to artificially induce deep sleep. The TMS was able to trigger slow brain waves that contribute to the restorative and beneficial aspect of deep sleep. This technology may allow people to squeeze more out of the hours that they do sleep.

What would life be like if you only needed four or less hours of sleep a day? Are we headed towards a future where people hardly need any sleep at all? I'd imagine a certain percentage of the population wouldn't mind being able to do this. You would have more spare time or more time to work and make money if you were so inclined. I'm sure the Pentagon is drooling over technology that could create a sleepless soldier. I think transcranial magnetic stimulation certainly has the potential to reduce a person's need for sleep. Personally, I'm not sure if I am ready to say goodbye to sleep just yet.

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.

Brain Stimulation With cTMS

Researchers have developed a better way to manipulate a person's brain functioning. They have created a new type of transcranial magnetic stimulation (TMS) device (called controllable pulse width TMS or cTMS for short) that will allow rectangular pulse shapes of the magnetic fields. This device will enable researchers to control the width of the magnetic pulse that passes through the subjects skull. Regular TMS produces a much more unfocused magnetic field that stimulates a larger portion of the brain. It is less selective in its targeting ability and is more likely to stimulate unnecessary or undesirable brain regions. This new TMS on the other hand, may allow more targeted electrical activation or deactivation of specific areas of the brain. Using this new device may lead to fewer side effects and increased efficacy of TMS for disorders such as depression, pain management or schizophrenia. Researchers may also be able to use this technology to get an even better functionality map of the brain to find out what specific brain areas do.

A transcranial magnetic stimulator inducing near-rectangular pulses with controllable pulse width (cTMS).

"A novel transcranial magnetic stimulation (TMS) device with controllable pulse width (PW) and near-rectangular pulse shape (cTMS) is described. The cTMS device uses an insulated gate bipolar transistor (IGBT) with appropriate snubbers to switch coil currents up to 6 kA, enabling PW control from 5 micros to over 100 micros. The near-rectangular induced electric field pulses use 2%-34% less energy and generate 67%-72% less coil heating compared to matched conventional cosine pulses. CTMS is used to stimulate rhesus monkey motor cortex in vivo with PWs of 20 to 100 micros, demonstrating the expected decrease of threshold pulse amplitude with increasing PW. The technological solutions used in the cTMS prototype can expand functionality, and reduce power consumption and coil heating in TMS, enhancing its research and therapeutic applications."

Columbia University Medical Center

"Physiological response to TMS depends on the shape and width of the induced current pulses, however, existing TMS devices allow limited, if any, control over these parameters. The cTMS device induces near rectangular pulses with continuous control over pulse width and shape, allowing the pulses to be physiologically optimized for specific applications."

Angel V. Peterchev, Ph.D.

"These controllable pulse shape TMS (cTMS) devices could enable new methods for mapping neural parameters in vivo, as well as the optimization of stimulation paradigms for improved tolerability and stronger neuromodulatory effect in clinical applications"

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.