Page Synopsis: Until the site is updated to include tms (as it applies specifically to OCD), this page is a repeat of page 31
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page 70 OCD > TRANSCRANIAL STIMULATION
“rTMS can improve fatigue symptom in ME patients regardless of the baseline severity of the fatigue symptoms”
Deep tms is the preferred choice,
TMS and Deep TMS machines can be very pricey
Local clinics in Bay Area and Elk Grove
Mindful Health Solutions - San Rafael
361 E. Third St., Suite A
San Rafael, CA 94901
like many therapies it works for some and not others, also in many cases the effect quickly wears off and must be readministered
A middle-aged man with progressive myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) was referred for neuromodulation.
His condition, likely virally induced decades ago, was characterized by recurring periods of extreme fatigue, lasting months at a time.
Medication trials provided partial benefit. Transcranial direct current stimulation (tDCS) was chosen as a neuromodulation treatment, allowing cumulative, ongoing treatment to target ongoing inflammation .
Patient was trained with tDCS in the office and then treatment was self-administered at home daily.
The protocol was: anode (left dorsolateral prefrontal cortex), cathode (right dorsolateral prefrontal cortex), 2 mA/min, 20 minutes, 40 mA total dose, using 1.5” diameter electrode pads.
Patient reported significant benefit early in the day during the first month of daily tDCS. After four weeks, maintenance tDCS sessions were increased to twice daily.
Over the next few months the patient experienced full clinical recovery. Follow-up quantitative EEG (qEEG) and neurophysiological testing was done 14 months after initial presentation; pre- and post- comparison studies provide insight into possible treatment biomarkers that may help to explain this patient’s full and unexpected recovery
It appears that there have been a couple of recent studies (here and here) which demonstrated that repetitive transcranial magnetic stimulation (rTMS) can reduce the fatigue in ME/CFS.
In one study they found that patients found the benefits were still present 2 weeks after their 6-8 sessions of rTMS.
rTMS is a system which precisely targets specific areas of the brain, so the results of a study will depend on which area of the brain they chose to stimulate.
Unfortunately rTMS machines are relatively complex and expensive, so unlike do-it-yourself at home electrical brain stimulation techniques like transcranial direct current stimulation (tDCS), rTMS sessions will always involve a hospital or clinic visit.
A case study on a single ME/CFS patient found a benefit for home tDCS
A pilot treatment study for mild traumatic brain injury: Neuroimaging changes detected by MEG after low-intensity pulse-based transcranial electrical stimulation
Results: At the baseline MEG exam, all participants had abnormal slow-waves. In the follow-up MEG exam, the participants showed significantly reduced abnormal slow-waves with an average reduction of 53.6 ± 24.6% in slow-wave total score. The participants also showed significant reduction of PCS scores after IASIS treatment, with an average reduction of 52.76 ± 26.4% in PCS total score
Successful application of pulsed electromagnetic fields in a patient with post-COVID-19 fatigue: a case report
Fatigue, work ability, quality of life, and psychological well-being improved clearly over the course of the treatment and showed stable results 6 weeks later.
The use of pulsed electromagnetic field therapy with a device that allows sufficient penetration of the body tissue might be a promising physical modality to manage post-COVID-19 fatigue syndrome
How does Deep TMS compare to standard rTMS?
Transcranial Magnetic Stimulation, or TMS, is a noninvasive treatment that utilizes repeated magnetic pulses to safely and effectively regulate neural activity related to various mental health conditions. Due to the repeated nature of the treatment, TMS is sometimes referred to as repetitive TMS, or rTMS.
There are currently two kinds of TMS publicly available as a form of therapy: the earlier, standard rTMS; and the more advanced Deep TMS™. While they share certain similarities, each holds its own unique attributes, with standard rTMS being the first on the market, and Deep TMS being the only noninvasive therapy FDA-cleared to treat Obsessive-Compulsive Disorder (OCD).
Standard and Deep TMS activate a series of magnetic pulses that safely reaches brain structures shown to be related to a number of mental health conditions. The repeated magnetic pulses they use influence and regulate these brain structures’ neural activity—with Deep TMS managing to directly stimulate deeper structures—thereby reducing adverse symptoms of mental health conditions.
Both standard TMS and Deep TMS have been shown to be safe, noninvasive forms of therapy. In a 2007 randomized controlled study published by Clinical Neurophysiology, the safety of Deep TMS was compared to both the standard TMS treatment and a sham group. The results showed that just like the sham and standard TMS groups, Deep TMS is well tolerated, with no adverse physical or neurological outcomes.
Additionally, both standard and Deep TMS were found to effectively offer greater relief to individuals battling mental health issues. A 2019 study on Major Depressive Disorder (MDD), published in the Journal of Psychiatric Research, elaborates on this point: when examined across all MDD levels of severity, the study found that both standard and Deep TMS treatments resulted in significantly higher remission rates when combined with pharmacotherapy, as opposed to pharmacotherapy alone. Response rates, however, were found to be significantly higher for Deep TMS and pharmacotherapy than both standard rTMS and pharmacotherapy, and pharmacotherapy alone.
Standard rTMS and Deep TMS differ on a number of levels, including their FDA clearance status, the scope of influence, and treatment effectiveness.
Standard TMS received FDA clearance to treat MDD in 2008, and to treat certain migraine headaches in 2013. Deep TMS received an FDA clearance status for treating MDD in 2013, and for treating OCD in 2018. BrainsWay is currently working to expand Deep TMS’s clearance status in treating additional conditions.
In addition to receiving a clearance status from the US’s FDA, Deep TMS has received the European CE certification mark for several other conditions, indicating that Deep TMS was found to conform to the safety, health and environmental standards of products sold within the European Economic Area (EEA).
Deep TMS has received the European CE mark due to its proven ability to alleviate the symptoms of a wide range of mental health conditions. These include MDD, OCD, Alzheimer’s Disease (AD), Autism, Bipolar Disorder, Chronic Pain, Multiple Sclerosis (MS), Parkinson’s Disease, post-stroke rehabilitation, Posttraumatic Stress Disorder (PTSD), the negative symptoms of Schizophrenia, and smoking cessation.
Standard rTMS uses a figure-8 coil, while Deep TMS uses a patented H-coil held inside a padded helmet. While the magnetic pulses activated by standard rTMS only reach a depth of 0.27” (0.7cm), Deep TMS’s technology manages to reach a significant sub-threshold of 1.25” (3.2cm). This as shown in a Brain Stimulation study from 2014. Deep TMS also utilizes a significantly wider field of stimulation compared to that of standard rTMS.
Additionally, since magnetic stimulation caused by standard rTMS is more focal, its pulses are directed at a specific point in the brain, as opposed to the broader stimulation of Deep TMS. Because clinical efficacy relies on activating the correct brain structures, standard rTMS often suffers from targeting issues, resulting in reduced efficacy. While this can be mitigated by pairing standard rTMS with complex and costly neuronavigation equipment, Deep TMS does not require any such equipment.
According to recent studies, Deep TMS’s ability to safely and directly stimulate both deeper and wider ranges of the brain may be crucial in successfully treating mental health conditions, such as MDD. This is due to the fact that several structures are at times involved in the symptoms caused by these conditions, and since the exact location of these structures can greatly vary between individuals.
Due to the two treatments’ use of different equipment, as well as their reliance on different depths and widths of direct stimulation, standard and Deep TMS have been shown to cause different levels of effectiveness in treating a variety of patients and symptoms. Specifically, a 2019 study published in the Journal of Psychiatric Research showed that patients with moderate-to-severe baseline depression achieved significantly higher response rates when treated with Deep TMS and medication, as opposed to standard rTMS and medication, or medication alone.
Deep TMS’s efficacy was also highlighted by the FDA, which found it to be the only noninvasive treatment on the market to significantly alleviate symptoms of OCD.
What mental health conditions is Deep TMS FDA-cleared to treat?
BrainsWay's Deep TMS is currently FDA-cleared to treat both Major Depressive Disorder (MDD) and Obsessive-Compulsive Disorder (OCD). With promising new studies in the pipeline, additional mental health
Who is authorized to administer Deep TMS treatment?
The ability to prescribe and administer Deep TMS therapy varies according to local laws and insurance policies. Psychiatrists are universally able to offer Deep TMS care, with other mental healthcare
Does Deep TMS require any special equipment or facilities?
Deep TMS treatment requires certain amenities to ensure patients receive a comfortable, professional process before, during and after the treatment itself. This includes features such as a treatment s
My biofeedback clinic treats some patients with the NeuroStar, a type of TMS device. They use it mainly to treat depression, but it may have other applications. I see that tDCS is a little different from TMS and will ask the therapist about it the next time I go to the clinic
Yes, tDCS is very different. You put two electrodes on a band around our head, and pass a really small current between them. You can learn to do it at home once you have the kit.
But if you are paying real money, then I wouldn't recommend spending it on this. Those of us who've used tDCS in research are not convinced its effects are real and replicable. Its very likely to be a big placebo.
If you don't have to pay, then sure, give it a try. There are no side effects at the 'safe' levels. But of course, no side effects very probably means no effects at all
Brain stimulation, in particular repetitive transcranial magnetic stimulation (rTMS) is the big winner in FM treatment trials this year. With its non-invasive, generally side-effect free approach (you can drink coffee and read during your rTMS session) rTMS seems like a gift from above.
During an rTMS treatment the patient sits in a chair with a coil pressed against the side of their head. Aside from odd tapping sounds they feel nothing. Sometimes they fall asleep. After about 30 minutes, they get up and resume their day; their pain hopefully much diminished. No drugs are needed. If they do it enough the effects can last. Twenty sessions over one month left FM patients with 60% reductions in FM for the next month as well.
It is costly (about $300 a session I believe) but if it worked and the effects lasted (and you could get insurance to pay for it) – it would be hard to beat. With at least 16 FM studies, rTMS has definitely made the rounds in FM. Unfortunately, two 2016 meta-analyses (somehow) came to strikingly different conclusions regarding the efficacy of rTMS. One suggested rTMS might be “feasible and safe” while the other stated it had minimal clinical effects.
Whatever the correct meta-analytic result, there is a reason not to take the success or failure of past trials too seriously. The rTMS field is moving forward rapidly with newer generation models able to penetrate deeper into the brain without causing little problems like seizures or scalp burns. Since the deeper brain areas may be where the action is in FM and ME/CFS, the effectiveness of rTMS may be increasing over time.
Targeting is getting better as well. Researchers are now able to specifically target areas known to be disturbed in FM such as the anterior cingulate and prefrontal cortex.
Thus far, rTMS has helped Parkinson’s patients move better, people with depression elevate their mood and people with stroke recover better. rTMS machines have been able to restore working memory – a key problem in ME/CFS – to normal levels in bipolar patients.
Even patients with treatment resistant depression can respond well. One study suggested 50% respond well and 1/3rd fully recover. One person with 30 years of depression reported, ”I feel like the person I used to be 30 years ago! I’ve got my brain back”.
Fiur rTMS fibromyalgia trials are under way or will be opening soon. They include one in Limoges, France, a Stanford rTMS/hypnosis trial, another in Limoges, and one in Haifa, Israel.
Direct current stimulation (tDCS) uses electrodes instead of coils, is reportedly cheaper, and also has few side effects. (It may not be as effective as well). If you’re in Egypt or can get to Port Allegre, Brazil, you might want to give this option a try.
Done correctly, cognitive behavioral therapy could be an aid in any chronic disease. This South Carolina tDCS trial will have tDCS, tDCS and CBT and CBT arms.
Other Stimulation Based Treatments
Radial Shockwave Therapy (RST) uses short, intense, very rapidly moving energy waves that can break down scar tissue and increase blood circulation and metabolic activity, causing an inflammatory response that promotes and stimulates healing. An Ontario, Canada study will apply RST to several painful areas and do a brain scan to see if the reduced pain levels affect brain functioning.
USB Ports to the Brain
We’ve seen rTMS, dTDS and now there’s eTNS – external Trigeminal Nerve Stimulation. eTNS is a relatively new stimulation technique which stimulates branches of the big trigeminal nerve which supplies sensations to much of the face. Signals from that nerve travel to the brainstem, thalamus, and cortex where they affect a variety of functions including the parasympathetic and sympathetic nervous systems. The trigeminal nerve, it turns out, is directly connected to the vagus nerve via the brainstem.
These devices turn down brain activity (a possibly good thing to do in FM). They’ve been approved for use in epilepsy and migraine, and are being studied in depression, traumatic brain injury, PTSD, fibromyalgia and others. One device manufacturer, Neurostigma, calls them “USB ports to the brain”. Check out how Cephaly works in migraine in the video below.
It looks like they couldn’t be easier to use; simply put the device on over your forehead and turn it on. If you’re in or around Cincinnati, Ohio, you just might want to give this a try. Find out more here
Repetitive TMS is usually done in a doctor's office or clinic. It requires a series of treatment sessions to be effective. Generally, sessions are carried out daily, five times a week for four to six weeks.
Your first treatment
Before treatment begins, your doctor will need to identify the best place to put the magnets on your head and the best dose of magnetic energy for you. Your first appointment typically lasts about 60 minutes.
Most likely, during your first appointment:
⦁ You'll be taken to a treatment room, asked to sit in a reclining chair and given earplugs to wear during the procedure.
⦁ An electromagnetic coil will be placed against your head and switched off and on repeatedly to produce stimulating pulses. This results in a tapping or clicking sound that usually lasts for a few seconds, followed by a pause. You'll also feel a tapping sensation on your forehead. This part of the process is called mapping.
⦁ Your doctor will determine the amount of magnetic energy needed by increasing the magnetic dose until your fingers or hands twitch. Known as your motor threshold, this is used as a reference point in determining the right dose for you. During the course of treatment, the amount of stimulation can be changed, depending on your symptoms and side effects.
During each treatment
Once the coil placement and dose are identified, you're ready to begin. Here's what to expect during each treatment:
⦁ You'll sit in a comfortable chair, wearing ear plugs, with the magnetic coil placed against your head.
⦁ When the machine is turned on, you'll hear clicking sounds and feel tapping on your forehead.
⦁ The procedure will last about 40 minutes, and you'll remain awake and alert. You may feel some scalp discomfort during the treatment and for a short time afterward.
After each treatment
You can return to your normal daily activities after your treatment. Typically, between treatments, you can expect to work and drive.
If rTMS works for you, your depression symptoms may improve or go away completely. Symptom relief may take a few weeks of treatment.
The effectiveness of rTMS may improve as researchers learn more about techniques, the number of stimulations required and the best sites on the brain to stimulate.
After completion of an rTMS treatment series, standard care for depression ― such as medication and psychotherapy ― may be recommended as ongoing treatment.
It's not yet known if maintenance rTMS sessions will benefit your depression. This involves continuing treatment when you are symptom-free with the hope that it will prevent the return of symptoms.
However, if your depression improves with rTMS, and then later you have another episode of symptoms, your rTMS treatment can be repeated. This is called re-induction. Some insurance companies will cover re-induction
High-frequency rTMS for the Treatment of Chronic Fatigue Syndrome: A Case SeriesHigh-frequency rTMS for the Treatment of Chronic Fatigue Syndrome: A Case SeriesWataru Kakuda,1,2 Ryo Momosaki,1 Naoki Yamada,1 and Masahiro Abo1https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5216154 IntroductionChronic fatigue syndrome (CFS) is a chronic, complex pathological condition characterized by extreme fatigue and other non-specific symptoms including pain, sleep disturbance and difficulty in concentration, which do not improve by rest alone (1,2). CFS patients often experience significant disability in their activities of daily living (ADL) and thus may become homebound and bedbound. The etiology and pathogenesis of CFS remain unclear and there are no known effective treatments for this condition at present. However, recent studies identified certain functional and structural abnormalities in the brain of CFS patients (3-6), including lesions in the dorsolateral prefrontal cortex (DLPFC), which seems to be an important part of the neural network involved in the sensation of such fatigue symptoms. Repetitive transcranial magnetic stimulation (rTMS) is a new neuromodulatory therapy used in patients with neurological and psychiatric disorders, such as stroke and depression (7,8). The effect of rTMS on the local neural activity of the cerebral cortex differs depending on the frequency of stimulation. High-frequency rTMS (≥10 Hz) facilitates the cortical neural activity, whereas low-frequency rTMS (≤1 Hz) suppresses the activity (9). To our knowledge, rTMS has not yet been used either therapeutically or for research purposes in CFS patients. Theoretically, the application of rTMS to the DLPFC should improve neural malfunction and thus improve such fatigue symptoms. The purpose of this pilot case-series study was to evaluate the safety and feasibility of high-frequency rTMS applied over the DLPFC in the treatment of CFS. Case ReportThis study was carried out in compliance with the Declaration of Helsinki. The study protocol and intervention were approved by the ethics committee of Jikei University School of Medicine (permitted number: 22-134 6311), and informed consent was obtained from all subjects before the study. Seven CFS patients were enrolled as the subjects of this study. They comprised consecutive patients referred to our hospital as potential candidates for therapeutic high-frequency rTMS between October, 2015 and December, 2015. Each patient was admitted to the Department of Rehabilitation Medicine, Jikei Daisan Hospital, Tokyo, Japan, for five days to receive high-frequency rTMS. Based on the known risks associated with rTMS application (10), the inclusion criteria were applied: 1) Meeting the diagnostic criteria for CFS formulated by the Centers for Disease Control and prevention (CDC) (1); 2) An age of between 15 and 70 years at study entry; 3) A period between disease onset and study entry of more than 6 months; 4) No past history of seizures; 5) No contraindications for rTMS as suggested in the guidelines established by Rossi et al (e.g., cochlear implants, medication pumps, implanted brain electrodes, pregnancy). Each patient was hospitalized for 5 days in order to receive six treatment sessions of 25-minute high-frequency rTMS over three days (two sessions per day, excluding the days of admission and discharge). Throughout the 5-day hospitalization period, all patients were monitored continuously through clinical and neurological examinations by the attending physicians, with special attention paid to the development of adverse events associated with rTMS application, such as headache, nausea, and seizure attacks. Application of high-frequency rTMS: For the delivery of high-frequency rTMS, a MagPro R30 stimulator (MagVenture Company, Farum, Denmark) equipped with a figure-of-eight stimulating coil was used. In the 25-minute high-frequency rTMS session, 10-Hz rTMS was applied in 10-second trains (100 pulses per train) with 50-second intervals between the trains (2,500 pulses per session). In total, high-frequency rTMS was delivered for 50 minutes (5,000 pulses) per day (i.e., 150 minutes or 15,000 pulses, over three days). For this study, the DLPFC of the dominant hemisphere was selected as the target area for high-frequency rTMS. To determine the location of DLPFC, the international 10-20 system for electroencephalograms was used, since the methods for establishing specific cortical areas with this system are relatively widely accepted (11). It has been reported that the F3 and F4 positions identified by the 10-20 system correspond to left and right DLPFC, respectively (12). Therefore, the stimulating coil was placed on the F3 in right-handed and F4 in left-handed patients. To determine the intensity of stimulation, the resting motor threshold was measured for the first dorsal interosseous muscle of the contralateral upper limb of the dominant hemisphere. The intensity of stimulation was set at 90% of the measured resting motor threshold. During rTMS application, the patient was asked to be seated while leaning against a 45-degree reclining chair, with the back of the head in close contact with the head-holding cushion. All patients were monitored carefully throughout the rTMS session by the physician applying rTMS. Clinical evaluation of fatigue: For the evaluation of the fatigue symptoms, two self-assessment scales, including the Visual Analogue Scale (VAS) rate for fatigue and the Brief Fatigue Inventory (BFI) were applied. The VAS rate was evaluated before the first session of rTMS, 1 hour after the first session, 24 hours after the first session, at discharge, and one/two weeks after discharge. At the time of evaluation, the patient was asked to rate the severity of the fatigue symptoms using a 10-cm horizontal line with a “score of 0” meaning “no pain” written on the left end and a “score of 10” meaning the “worst imaginable fatigue” on the other end (13). For this study, we calculated the VAS rate, which was defined as the relative value of fatigue severity at the time after rTMS application in comparison to that before the first rTMS application for each patient. The VAS rate was calculated by the following equation: VAS rate (%) = VAS score at after rTMS application/VAS score before the first rTMS session ×100. The VAS rate before rTMS was considered to be 100, and any decrease in the VAS rate indicated an improvement in fatigue.In addition, the BFI consisting of nine questionnaire items was evaluated before the first session of rTMS, at discharge, and one/two weeks after discharge (14). The first three items of the BFI assess the current, usual and worst fatigue in the past 24 hours. The next six items evaluate the extent to which fatigue interfered with different aspects of life, such as work or social relations, during the preceding 24 hours. Each of the items rates fatigue severity on a 0-to-10 scale, with a score of “0” representing “no fatigue” or “no impact on functioning”, and “10” being the “worst fatigue” or “fatigue that dramatically interferes with normal daily functioning”. The mean score of the nine items was calculated and recorded. For this study, the Japanese version of BFI (BFI-J) was used, since Japanese was the native language of all studied patients. The validity and reliability of this version of BFI has already been confirmed (15). Statistical analysis: Data are expressed as the mean±SD. Differences in BFI and VAS between before rTMS and at the time points after rTMS application were examined for statistical significance using Dunnett's multiple comparison test. A p value of less than 0.05 was considered to be statistically significant. All statistical analyses were performed using The Statistical Package for Social Sciences, v17.0 (SPSS Inc., Chicago, IL, USA). Results: Table summarizes the clinical features of the participating patients. The mean age at admission was 37.0±13.2 years, and the time between the onset of the fatigue symptoms and the commencement of therapeutic rTMS ranged from 3 to 11 years. Six patients were right-handed, thus suggesting a dominant left cerebral hemisphere. No patient had a history of any major depression.Table. Clinical Characteristics of the Patients.Patient number 1 2 3 4 5 6 7Gender Female Female Male Female Female Female MaleAge at admission (years) 57 42 17 41 33 25 44Duration of illness (years) 3 5 3 7 11 3 9Handedness Right Right Right Right Right Right LeftKarnofsky Performance Status at admission (%) 60 80 70 90 80 60 70Comorbidity None Fibromyalgia Irritable bowelsyndrome None None Fibromyalgia NoneNumber of rTMS session provided during hospitalization 6 6 6 6 6 3 2 Among the seven patients, 5 completed the scheduled six rTMS sessions over three days. These 5 patients showed no adverse events during hospitalization. The other two studied patients (Patients 6 and 7) showed certain pathological reactions that could be considered adverse events of rTMS application. One patient experienced nausea, vomiting and headache after two sessions of rTMS. The other patient developed acute hypotension due to vasovagal reflex during the first session of rTMS. However, the symptoms were transient in both patients and disappeared within several hours without any medical intervention. Therefore, after more than 24 hours, one 25-minute session of 10-Hz high frequency rTMS with a stimulation intensity of 80% was administered to both patients. After the session with less intensity, none of the two patients showed any adverse symptoms. None of the seven patients experienced any pathological symptoms during the two-week period after discharge. Fig. 1a shows the effect of rTMS on the VAS rate. One hour after the first rTMS session, two patients showed a more than 30% decrease in the VAS rate. At discharge, five patients showed a more than 30% decrease in the rate. Of these, three patients exhibited a more than 50% decrease in the VAS rate. Furthermore, four patients showed a more than 30% decrease in one week and in three patients two weeks after discharge. The mean VAS rate decreased by 17% at one hour after the first rTMS session (p=0.59, Fig. 1b). The decrease in the rate from the baseline value before the first rTMS was significant not only at discharge, but also at one week after discharge (all ps <0.05). However, the decrease in the VAS rate relative to the baseline at two weeks after discharge was not significant (p=0.21). DiscussionSeveral neuroimaging studies have demonstrated the presence of local functional or structural abnormalities in certain brain areas in CFS patients, and suggested that these local abnormalities in the brain can contribute to the development of fatigue. The initial studies demonstrated the presence of regional SPECT abnormalities in certain cortical areas of CFS patients, including the frontal, parietal and temporal cortex (3). A subsequent study using 18FDG PET showed a hypometabolism in the mediofrontal cortex and brainstem of CFS patients (4). Furthermore, [2-11C] acetylcarnitine PET studies showed significantly low acetylcarnitine uptake levels in DLPFC, temporal cortex and cingulate cortex in CFS patients, suggesting a possible neural circuitry malfunction in these areas (5). Other MRI-based studies identified a smaller gray-matter volume in the prefrontal cortex in CFS patients (6). Based on the above reports, one can speculate that the fatigue symptom in these patients can be clinically alleviated by modulating the neural activity in these areas.Among these areas showing local abnormalities in CFS patients, the DLPFC has been especially considered to be an important part of the neural network involved in regulating the sense of fatigue. For example, a malfunction of the DLPFC is considered to cause a functional interruption of the striatal-thalamic-frontal cortical loop, resulting in an enhanced fatigability (16). Another study showed that cognitive behavioral therapy improved the fatigue symptoms and that such an improvement correlated with increased grey matter volume of the prefrontal cortex, including the DLPFC (17). Furthermore, unlike other pathological areas in CFS patients, the DLPFC is superficially located on the surface of the brain, which thus makes it easier to target by rTMS. We considered that high-frequency rTMS can stimulate the DLPFC and increase the neural activity in that area, leading to the alleviation of fatigue symptoms. The results of this pilot study showed the safety of high-frequency rTMS (only two patients developed mild adverse events). The fatigue symptoms had improved significantly at discharge, and this beneficial effect was maintained until at least one week after discharge. To our knowledge, this is the first report that describes the safety, feasibility and clinical usefulness of high-frequency rTMS over DLPFC for CFS patients. For stroke patients, it has been reported that interhemispheric inhibition is disrupted. Due to the occurrence of a stroke lesion, the inhibition towards the lesional hemisphere is pathologically increased. To modulate such a disruption of the inhibition, suppressive low-frequency rTMS is applied over the non-lesional hemisphere as a therapeutic tool for stroke patients. However, for CFS patients, no researcher reported the development of such a disruption in the interhemispheric inhibition. Therefore, we determined to apply high-frequency rTMS in order to activate the target area directly for our CFS patients, instead of low-frequency rTMS. While our pilot study did not investigate the underlying mechanisms for the obtained improvement, we speculate that the effect was mediated through the neural activation of the DLPFC in the dominant hemisphere. To determine the mechanism of this improvement, future studies using functional neuroimaging, such as functional MRI or PET, are needed. In this study, the stimulation intensity was set at 90% of the motor threshold of the finger muscle in the contralateral upper limb. This selection was based on previous studies that demonstrated good tolerance of rTMS applied at this intensity in patients with chronic stroke and depression (18,19). Interestingly, the two patients who developed adverse reactions were able to tolerate high-frequency rTMS at a reduced stimulation intensity and thereafter showed an improvement in fatigue symptoms. The optimal intensity of rTMS for CFS patients should be determined for a safe and useful introduction of rTMS for such patients. The treatment protocol included six 25-minute rTMS sessions applied over three days. This was based on previous studies that demonstrated the superiority of several applications of rTMS over several days compared to a single application in stroke patients (20). However, the duration of each rTMS session and the total number of rTMS sessions were determined arbitrarily. It is desired to investigate the optimal treatment duration for CFS patients. Such an investigation could help to elucidate the correlation between the length of treatment and the long-term clinical benefits. The present study has certain limitations. First, this is a case-series pilot study with only a small number of patients that lacked a control group. Comparative studies, such as randomized controlled design studies that include a large number of patients, are needed to confirm the efficacy of rTMS in CFS patients. Second, although all patients met the inclusion criteria for rTMS application, they were a heterogeneous group based on the wide variability of age, duration of illness and severity of the fatigue symptoms. The identification of the clinical factors that correlate with the efficacy of rTMS can help in the selection of patients who will best benefit from the treatment. Third, although it is difficult to stimulate deep brain lesions using the currently available technology, the stimulation of other brain areas with functional or structural abnormalities in CFS, such as the cingulate cortex and brainstem, may produce a better clinical improvement. Furthermore, for one left-handed patient, we applied high-frequency rTMS to the right hemisphere unlike the other six patients. The appropriateness of this therapeutic strategy of rTMS depending on whether patients were right-handed or left-handed should be also confirmed. The present pilot study demonstrated the feasibility and safety of high-frequency rTMS applied over the DLPFC for the treatment of CFS patients. Further large-scale studies are needed to confirm the therapeutic benefits of high-frequency rTMS, determine the optimal cortical target area and find the optimal duration and intensity of treatment for CFS.All procedures performed in this study were in accordance with the ethical standards of the institutional and national research committees
Novel Chronic Fatigue Syndrome (ME/CFS) Brain Stimulation Clinical Trial Begins
by Cort Johnson | Apr 22, 2021 | Homepage, Transcranial magnetic stimulation, Treatment | 83 comments
Solve M.E.’s Chief Scientific Officer, Sadie Whittaker, was on a mission. She wanted to get chronic fatigue syndrome (ME/CFS) embedded in one of the top medical schools in the country.
Solve ME’s chief Scientific Officer, Sadie Whittaker, was on a mission – get ME/CFS embedded in UCLA.
UCLA, located in the tony Westwood neighborhood of Los Angeles, has an immense and impressive campus. US News and World Reports has ranked its medical school 7th in the country.
Whittaker met with some senior administrators who suggested that she talk to the Iris Cantor Women’s Health Center – a Center of Excellence for Women focusing on both research and clinical care.
The Iris Cantor Center didn’t know much about ME/CFS, but when they learned about the high female predominance, the little funding, and the high prevalence, they were enrolled and invited the Solve ME/CFS Initiative to apply for the Center’s Annual Health Pilot Program.
In this program, the Center solicits proposals for UCLA researchers to study a select number of diseases that disproportionately affect women. Five or six studies are typically awarded each year.
Solve M.E. put together a toolkit about ME/CFS and applied to be one of the featured diseases in the program. Their application was accepted – the Center notified UCLA researchers that it was looking for proposals to study ME/CFS – and the proposals rolled in.
Solve M.E. picked the winner. It turned out to be a rarity for this disease – a small clinical trial no less – to assess the effects of repetitive transcranial magnetic stimulation (rTMS) in ME/CFS. Karl Zeile, a Solve M.E. board member, and Dian Zeile stepped up to support it.
I talked with Dr. Juliana Corlier PhD and Dr. Andrew Leuchter MD about their upcoming study. The director of the UCLA Transcranial Magnetic Stimulation (TMS) Clinical and Research Service, Dr. Leuchter has published over 150 scientific papers, including almost 2 dozen studies on rTMS.
For her part, Dr. Juliana Corlier has a PhD in cognitive neuroscience and is currently an Assistant Project Scientist at the UCLA Neuromodulation Division. She has a special interest in treating pain and fatigue with TMS, and leapt at the chance to see if it could be used to reduce the pain and fatigue in ME/CFS.
Repetitive transcranial magnetic stimulation is painless and side-effect free.
I asked Dr. Leuchter how he got interested in magnetic stimulation. Leuchter explained that he was a practicing psychiatrist who was not satisfied with the “serious limitations” of the drugs he was using when he came across magnetic stimulation over a decade ago. The idea of being able to safely rewire the brain to help people feel better intrigued him, and over time he came to specialize in rTMS.
The procedure is remarkably easy on the patients: the participants are awake during the procedure and are able to drive themselves home afterwards. He believes the next generation of small, portable TMS devices that will be able to be used at home will be game-changers for many.
He explained that rTMS has been used for mood disorders for quite some time, but the use of rTMS for pain came about after investigators recognized that it was helping to improve mood problems and reduce pain in some of their subjects.
rTMS mostly stimulates of the surface of the brain cortex but has effects far beyond that. The special 3D cameras they use are able to very precisely target areas.
TMS can also be used to study the brain, and that’s how it’s mostly been used in ME/CFS. Several ME/CFS studies in the early to mid 2000s found reduced motor cortex excitability. That suggested that at least part of the fatigue in ME/CFS was “central”; i.e. it emanated from the brain, and that ME/CFS brains may be having difficulty activating the muscles during exercise.
Except for a small Japanese case series, and a small open label trial, rTMS has been little studied as a treatment option in ME/CFS. The case series, though, concluded that, “In most of the patients, treatment resulted in an improvement of fatigue symptoms”, and the open label trial found that both people with mild/moderate or severe cases of ME/CFS significantly benefitted. It called rTMS “a novel therapeutic intervention for ME patients” and concluded that:
“rTMS can improve fatigue symptom in ME patients regardless of (the )baseline severity of (the) fatigue symptoms”.
I’ve also been in touch with a retired pharmacologist who, after numerous unsuccessful trials (minocycline, Celebrex, Mirapex, SAME, provigil, dextroamphetamine, nexavir, ribose, Dr. Enlander’s protocol, n acetylcysteine, acetyl l-carnitine, vitamin B 12(oral), Trental, Transcranial direct-current stimulation, NADH), found that rTMS twice markedly improved his fatigue, exercise intolerance and mental clarity. (The third attempt, however, failed.)
rTMS has been better assessed in fibromyalgia. With 7/10 studies with positive results, the outcomes have generally been good. Summing up the field is difficult as the degree, target and duration of the stimulation can change from study to study. Researchers are still learning about optimal stimulation rates and optimal stimulation targets for different diseases.
A recent dorsolateral prefrontal cortex study, however, found that the pain levels of FM patients dropped dramatically and stayed reduced for six months
Transcranial Magnetic Stimulation (TMS) Fibromyalgia Study Produces Lasting Relief
The ME/CFS study includes fifteen women with ME/CFS who will receive 20 rTMS sessions.
It also comes with a new and potentially quite significant twist. Past studies have used the rTMS to stimulate one part of the brain, but in a effort to produce a synergistic effect, the study is targeting two parts of the brain. Calling it a new protocol for UCLA, Dr. Leuchter said the ME/CFS study will target both the motor cortex and the prefrontal cortex.
The duo motor cortex/prefrontal cortex approach seeks to damp down the activity of the limbic system and boost the activity of the prefrontal cortex.
Using a process called “inhibitory stimulation”, the motor cortex will be stimulated to turn down activity in the limbic system. The limbic system – which includes the amygdala – adds feelings of “unpleasantness” to the sensations we experience and activates the fight/flight system. (Unpleasantness is a rather mild word for the suffering that the limbic system can impose, but so be it). Suffice it to say that if the stimulation works your unpleasant sensations might still be there but they would be far less intrusive.
Leuchter believes, as others do, that hyperactivated limbic systems may be causing the problems with pain, lights, sounds and odors that often show up in ME/CFS, FM and related disorders.
While the UCLA group attempts to tamp down the activity of the limbic system, they’ll be trying to boost the activity of its antagonist – the dorsolateral prefrontal cortex (dPFC). The prefrontal cortex is tasked with reining in the fear-driven messages coming from the more primitive limbic system. It’s also involved in the “motor planning” that must take place before we can move, as well as cognition, organizing, decision-making, memory, etc. Boosting the dPFC could also result in reduced pain and fatigue, improved cognition, planning, memory, etc.
See the blog below for a fuller explanation of the limbic system/prefrontal cortex interaction
The Ending Suffering Project for ME/CFS, Fibromyalgia, Long COVID, and Allied Disorders
The study doesn’t end there. Electroencephalograms (EEGs) taken before, during, and after the study will also be used to assess if the rTMS changes patterns of activity in the brain.
Corlier and Leuchter reported:
“We anticipate that rTMS treatment will significantly improve many of the symptoms of ME/CFS. Positive results from this study will provide proof-of-concept evidence for a novel rTMS treatment approach for ME/CFS to be validated in a future double-blind, randomized control trial.”
They hope to begin the study soon and are looking for participants. I’m trying to find out the correct contact information the UCLA TMS Clinical and Research Service might work.
That would be a nice step forward for a disease which has had all too few clinical trials.
User comments (click to open) click again to close 83 CommentsAngela on April 22, 2021 at 4:53 pmAnecdotally, it works. In my case, it did. Unfortunately, the results didn’t last after the treatments ended. I had TMS in 2019. I would go in feeling like I was dying, barely able to hold myself upright, foggy brained. After each appointment, I could think clearly (no brain fog), stand upright and would spend the afternoon like a normal person (ex. Go sit on the beach, meet my sister for lunch). It got me to the point that I was able to travel cross country to see my daughter’s college graduation. I enjoyed every minute of it. That alone was worth the treatment. TMS really needs to be studied for POTS as well. Cort Johnson on April 22, 2021 at 7:02 pmGlad to hear. These techniques are evolving as we speak (hence this new protocol). There’s a lot of learn – the optimal strength, location and duration of the signal needs to be sussed out for each disease. Hopefully they will get more and more powerful and longer lasting.The recent FM study with it’s long lasting effects was encouraging. Nicole Martin on April 23, 2021 at 9:42 amCort:I have had Chronic Lyme/Chronic Fatigue/ME for 6 years. Coincidentally, I am now undergoing Neurostar TMS for treatment-resistant depression. I just received treatment 15 of a total of 36… will post about my progress as far as my debilitating fatigue goes I’ve been an early adopter of technologies, such as Trans cranial Direct Stim ( Fisher-Wallace); vagus nerve stimulation ( CES Ultra), PEMF mats, and photobiomodulation ( Vie Light intranasal) None of these have really helped with generalized fatigue and PEM, so I’m really excited to see if TMS helps. Will post later about this Cort Johnson on April 23, 2021 at 11:54 amYou’ve certainly tried the electrical approach! Let’s hope this duo-brain organ approach works better. Marisa D'Ercole on April 23, 2021 at 4:36 pmIs this just really a form of electro shock therapy for ‘treating’ those deemed ‘mentally ill’ ? Cort Johnson on April 24, 2021 at 7:41 amThis is not electro-shock therapy. There’s no shocking involved. rTMS was developed after ECT and uses magnetic fields instead of electrical shocks. rTMS has been used in anxiety and depression and is now being assessed in a variety of neurological disorders including “Alzheimer’s disease, amyotrophic lateral sclerosis, persistent vegetative states, epilepsy, stroke related disability, tinnitus, multiple sclerosis, and traumatic brain injury.” as well, of course, in fibromyalgia and ME/CFShttps://en.wikipedia.org/wiki/Transcranial_magnetic_stimulation Christina Ward on April 22, 2021 at 4:55 pmI’d love to be in the study but I live in Vancouver, British Columbia, Canada. Any chance someone from here could be included? Cort Johnson on April 22, 2021 at 5:23 pmI’d love to be in the study too but I’m the wrong sex :(. I think LA country residents are probably going to make up most of the participants. You need to be available for 20 sessions which will probably take a month or so to get through. konijn on April 22, 2021 at 6:20 pmI am sorry that if you want to be in this study, you can not because you are the wrong sex. I find it a bit a sexistic study, otherwise you could participate sunie on April 23, 2021 at 12:22 amkonijn, your observation points out an opportunity— perhaps UCLA has a Men’s Research group that could do a balancing leg of the study; or maybe a group that can study both? The study would also be right up the alley of the Institute that Marcia Zinn and Mark Zinn jointly founded— the NCRI. (NeuroCognitive Research Institute)—with their QEEG and eLORETA work. Diane on April 26, 2021 at 5:40 amKonijn, I don’t see this as sexist but rather as an opportunity. The money was available for illnesses that have predominantly women diagnosed with them. We need to apply for all available money and accept the studies gratefully. This is also a slight balancing. Are you aware that in most drug trials only men are targeted? The researchers say that it is too difficult to include women because their changing hormonal cycles affect things too much. Then when the drugs don’t help women, they blame the women for being hysterical rather than looking at the fact that the drugs have not been validated for women. In the light of this, I can see no reason to be concerned about sexism in one small study. Chris Cantor on April 22, 2021 at 5:30 pmWhat has the fear based sympathetic system got to do with CFS? Cort Johnson on April 22, 2021 at 6:45 pmNobody knows how much but potentially a lot. Many studies suggest that the fight/flight or sympathetic nervous system (SNS)has been turned on in ME/CFS while the rest/digest or parasympathetic nervous system is not up to snuff. Here is a smattering. Some researchers believe the SNS activation is tamping down the blood vessels resulting in reduced blood flows to brain (https://pubmed.ncbi.nlm.nih.gov/29855991/) and the muscles (https://pubmed.ncbi.nlm.nih.gov/32247028/). That same SNS activation has linked with poor sleep (https://pubmed.ncbi.nlm.nih.gov/29246267/) and cognition (https://pubmed.ncbi.nlm.nih.gov/23166694/). SNS activation has also been found to be predictive of the fatigue found in ME/CFS – https://pubmed.ncbi.nlm.nih.gov/31906988/). Because ANS controls gut motility increased SNS activity could also be linked to gut motility problems and dysbiosis. Health Rising also recently featured a blog which suggested that SNS problems could be causing increased pain via balky baroreceptors (https://www.healthrising.org/blog/2021/03/25/baroreflex-pain-fatigue-sleep-fibromyalgia-chronic-fatigue-syndrome/)SNS activation also affects the immune system – pushing it in the direction – often found in ME/CFS. Rick on April 27, 2021 at 12:27 pmProbably everything. Elizabeth Edwards on April 28, 2021 at 8:48 amIf I understand correctly, you don’t necessarily have to have experienced fear for the amygdala to get antsy and set off the SNS. It’s a very primitive organ that is simply programmed to react to ANY threat or perceived threat to the preservation of life, etc. and activate the body’s defences, via the SNS to get out of its way, fast, or fight it, or the other response that people forget to mention – the ‘freeze’ response, as when an animal that’s under attack from a predator from which it can’t escape goes still and limp Or in other situations, eg where current environmental factors are not conducive to life, it may be implicated in the dauer response, to send the body into a complete hibernation-like close-down. It’s possible the amygdala could interpret as a threat the sort of events that we know can trigger ME/CFS, such as a viral infection or toxic chemical exposure, or other bodily trauma – especially if there are more than one such triggers in a row, or happening simultaneously. Such repeated or cumulative stressors could be what in some (possibly genetically susceptible) individuals sets off a cascade of complex events (as in the Metabolic Trap hypothesis) or in some other way locks the body’s defence systems into a permanently defensive state producing the array of symptoms of ME/CFS. konijn on April 22, 2021 at 5:46 pmI ask myself with this treatment, what about PEM? PEM is allways a hallmark for ME/CFS. It maybe can help some issues but the whole complex illness that Me/CFS is, I can not imagine it. And the you have the whole heterogenity of this group of ill people. Cort Johnson on April 22, 2021 at 6:54 pmTime will tell but if this technique is able to affect autonomic nervous system functioning – which limbic system activation may be throwing off kilter – and which is regulated by the prefrontal cortex – I would think it could certainly help. Anything that helps with fatigue and pain hopefully would help with PEM. I don’t know how to divorce pain/fatigue/cognitive problems from PEM – since PEM by definition concerns an upsurge in symptoms (like fatigue/ pain/cognitive problems). Until we know how PEM is caused I guess we won’t really know what in advance might affect it. I would not think that this technique could vanquish ME/CFS – I think the disease is probably too complex for that – and that’s a lot of to ask for for any single treatment – but could it help? I think it could. It’s targeting areas of the brain that have shown up on brain imaging studies in ME/CFS (and FM) konijn on April 22, 2021 at 5:49 pmand why would just “a women’s illness” be “cured” with this kind of treatment. Do men have no brain 🙂 Cort Johnson on April 22, 2021 at 6:58 pmSome people think men are a bit short in brains but I hope there’s enough overlap. 🙂Reply konijn on April 23, 2021 at 1:29 pmyes, I would think so although here they say, women are from venus and men are from marsbut i thought, can not remember well, there was a big was it biljon dollar studdy in the US over10 years to map the brain from NIH or so. Do not know what happened or in wich year we are. it was especially because so little is known about the brain. Cort Johnson on April 24, 2021 at 7:47 amThanks for the reminder about the Brain Initiative. It’s a 10 year project that began in 2013. I don’t know specifically what it’s accomplished but one 5-year review thought it was going well. https://www.psychologytoday.com/us/blog/neurophilosophy/201904/five-years-how-fares-the-brain-initiativeSo how does this somewhat risky investment look, five years on? Cautiously, I would say spectacular. On April 11 and 12 I attended the annual meeting of the BRAIN initiative in DC that brought together the people from the funded labs, as well as the scientific administrators at NIH and anyone else who was interested. The drive, dedication, and excitement were clearly evident. A kind of “moon-landing” spirit pervaded the meeting generally. Remy on April 22, 2021 at 6:16 pmI looked into TMS for its effects on resetting the microglial cells, but was really dismayed at the current offerings. I think it’s worth noting that the treatment is really in the early stages and what is offered for depression treatment currently may or may not at all be what works for our population. I can see a future for this kind of treatment, but want to caution people that the centers are of extremely varying quality, in my experience, they can’t answer any questions about the therapy, and are using it like blunt force trauma without fully informing patients of the real risks. Burying them in an already scary document doesn’t count. https://www.madinamerica.com/2020/04/tms-damaged-my-brain Cort Johnson on April 22, 2021 at 7:01 pmI would guess that the UCLA center is of good quality. Other for profit centers – I have no idea – but it sounds like buyer beware with them. Betty I Mekdeci on April 23, 2021 at 6:49 amRemy, thank you for posting this link. I hope that everyone will take the time to read the experience of a patient treated for depression with TMS and the long term and scary side effects he (and others) experienced. From trepanning (drilling holes in the skull) to leeches, desperately ill humans have been willing to try anything to feel better. konijn on April 23, 2021 at 1:34 pmyes, thanks for the link! but even without it i would never be “the first one” , no not me… and would ask those who are doing this treatment to do this treatment first a 10000 times on there own brain. Although I am desperate, I have learned my lessons in 30 years of illness… sunie on April 23, 2021 at 6:47 pmRemy,Thank you for clickable link that discusses, IMO, the extremely unfavourable effects one person experienced. It sounds to me that this is forced exercise for the brain. We know how forced physical exercise worsens cfs/me. Based on that, I do not see this ‘treatment ‘ faring well for cfs/me sufferers. Quote from under section of article titled“TMS – Non-Invasive?” “TMS involves sending multiple strong bursts of magnetic energy into the brain. The pulses are increased in strength until they are actually causing neurons (brain cells) to fire, and are repeated at that intensity about 3,000 times in each session.” Causing neutrons to fire…..about 3,000 times per session?!! How is that not forced exercise for the brain?!? Cort Johnson on April 24, 2021 at 8:00 amI looked it up – each neuron typically fires about 200x’s per second and our brain has 100 billion neurons – https://the phenomenalexperience.com/content/how-fast-is-your-brain Beware of counting too much on one person’s story. We’re always more drawn to individual stories than statistics. That’s how our brains work. We also always think that we’re the ones that are going to have the negative result. Literally hundreds of these studies have been done and the consensus is that rTMS is safe and produces mild side effects. Rarely more serious side effects can occur. Dr. Leuchter said he got into this field in part because it produces less side effects than drugs. Overviewshttps://pubmed.ncbi.nlm.nih.gov/29338288/Overall, rTMS is a well-tolerated treatment with common side effects (such as headache or local pain at the site of stimulation) being mild. Severe adverse effects, such as seizures, hearing impairment or mania, are uncommon. With regard to dementiahttps://pubmed.ncbi.nlm.nih.gov/30246461ith regards to the adverse effects reported, these were mild and not clinically relevant. Fibromyalgiahttps://pubmed.ncbi.nlm.nih.gov/22631436 The most commonly reported side effects were mild, including transient headaches and scalp discomforts at the stimulation site.https://pubmed.ncbi.nlm.nih.gov/27150193 Most of reported adverse effects were minor. Conclusions: Both rTMS and TDCS may be feasible and safe modalities for treating FM. dejurgen on April 24, 2021 at 8:23 am“Literally hundreds of these studies have been done and the consensus is that rTMS is safe and produces mild side effects. Rarely more serious side effects can occur.” Such studdies do not only require blinding towards the patient to exclude placebo effect, but also a research methodology blind to research bias. In such studies, that is a very hard thing to do. How many of those hundreds of studies measured side effects for example by the patient filling out a survey with limited options? If the survey is done at most a few weeks after treatment and the worst option to check is “had significant side effects up to two weeks after treatment”, one can’t expect to catch severe side effects lasting over a year to be reported in this way. I’ve seen such skewed surveys on the “total safety” of GET/CBT before. Well, I missed the second “after treatment” survey as they found a clever way to work me out of it. My terrible worsening due to their “harmless theraphy that improves all who are willing to do the effort” would have sank average outcome below zero and sank their claim no one ever got worse from it. Note: I am NOT saying there are not many far more professional researchers, but saying it is very easy for research bias to skew results even if one not intends. dejurgen on April 24, 2021 at 8:45 amOn a more constructive note:I would love clinical research with fairly subjective outcomes to split the roles of researcher/treatment on one hand and researcher/evaluation on the other hand with both belonging to sufficiently independend groups. Medical schooled people for the first group, statistical schooled people for the second group. AFAIK most medical research with more subjective outcomes sorely lacks this split in roles and independency between both. If independently enough, it would squarely have blocked the PACE trial in its tracks. For the plethora of well meaning researchers, it would improve outcome reliability and reproducability and with it speeding up of successful treatments and quicker weeding out of spending on treatments not surviving removal of unintended research bias. Cort Johnson on April 24, 2021 at 8:46 amI don’t understand this Such studies do not only require blinding towards the patient to exclude placebo effect, but also a research methodology blind to research bias. My understanding is that both placebo and non-placebo participants fill out the same side effect questionnaires. I don’t know if that speaks to anything. The side effect questions have found issues with headaches, pain, sensations, working memory, brief episodes of “monomania”, hearing loss, and in rare cases seizures. etc. It seems like pretty extensive questions are being done. As to duration – yes, most studies assess side-effects during and a couple weeks after the completion of the trial. While it doesn’t capture things that happen after that date I imagine it does capture the great majority of the side effects that occur. dejurgen on April 24, 2021 at 9:57 am“My understanding is that both placebo and non-placebo participants fill out the same side effect questionnaires. I don’t know if that speaks to anything. The side effect questions have found issues with headaches, pain, sensations, working memory, brief episodes of “monomania”, hearing loss, and in rare cases seizures. etc. It seems like pretty extensive questions are being done.” This study for example wont have placebo participants. Many other studies out of those 100 likely did lack at least one of the questions on “headaches, pain, sensations, working memory, brief episodes of “monomania”, hearing loss, and in rare cases seizures. etc.” When it’s not in the questionary, side effects easily gets side tracked. What if someone got trouble to hold urine since treatment? As it is a common symptom in for example ME and that might be brain related, anything changing brain behavior could provoke that. If you don’t specificaly ask that question or specificaly ask to report anything out of the ordinary, it will get side tracked. Many questionaires are either filled out on a computer form (and that’s it) or filled out in a group session where they get the privacy to fill out things on their own but where reviewing the answers at time of filling out the questionairies would break privacy of the individuals. Also, questions like “did you experience increased headaches?” during treatment wont automatically flag a severe problem if it is a yes or no question and no further ellaboration is done. Setting up a high quality clinical research with subjective measures IMO is a rather hard thing to do and quality could be improved in many cases if professional outcome reviewers were hired that are trained to reduce researcher bias. Just my opinion. Cort Johnson on April 24, 2021 at 2:00 pmThese study doesn’t need a placebo arm to assess side effects…Hundreds of other studies have already done that. Yes some studies will not track one or another potential side effect but that will be true for any treatment option. When the number of studies add up you should start to get an accurate picture. Clinical trials indicates that hundreds of rTMS trials are now recruiting or about to recruit for large number of disorders. Besides mood disorders they include vascular neuropathy, post cancer patients (neuropathy), ALS, menstrual cramps (!), Gulf War Illness, neuropathic pain, Parkinson’s, multiple sclerosis, ADHD, headache, traumatic brain injury, low back pain and on. It looks like there are more non mood disorder studies than mood disorder studies. Mary on April 22, 2021 at 7:52 pmIt sounds magical . SO exciting, many thanks Cort for the udate. Fingers crossed for a positive result and lots more studies. Maree on April 22, 2021 at 11:24 pmIt doesn’t sound as though there is any blinding with a control. Which makes it a waste of time and money in terms of telling us if the treatment is useful. If there isn’t blinding, why is Solve ME supporting it? Snow Leopard on April 23, 2021 at 1:04 amI agree with Maree, why bother doing such a study without blinding? TMS studies for depression have previously shown high placebo (or response biases) effects, when sham methodology was used as a control group. Matthias on April 23, 2021 at 2:56 amYes good point. That seems poor. We need to be moving faster and more efficiently than this. dejurgen on April 23, 2021 at 5:33 amGood point indeed. Adding some 20 placebo treatments shouldn’t be high cost. I hope they could still add it to the experiment. Speaking of “rTMS has been better assessed in fibromyalgia. With 7/10 studies with positive results, the outcomes have generally been good.” So 3/10 didn’t? OR is it? In science, few report and publish failures. So it could be just as well 7/20 published positive results, 3/20 published a lack of or negative results and 10/20 chose to not bother publishing or felt ashamed to publish their failure. Combining the above with that sort of thinking doesn’t make me thrilled. Maybe I overthink it and need some rTMS to calm that part of my brain? Cort Johnson on April 23, 2021 at 8:00 amWhy, if it would be so much better to have healthy controls – and it would be – why the researchers wouldn’t just do that? There must be a reason and I imagine that it is cost – 20 more participants = 400 more rTMS sessions. rTMS is also an evolving field. Different targets are being used, different strengths, different study durations. https://pubmed.ncbi.nlm.nih.gov/33473332 The latest FM study – a large (90 person) placebo controlled one – used quite long duration rTMS – similar to that found in this study – 20 sessions over a month – and found the results lasted for 6 months…Other studies have used shorter durations. https://pubmed.ncbi.nlm.nih.gov/32600394 I wouldn’t be surprised if this study does better – that study only stimulated the prefrontral cortex. This study is also going to stimulate the motor cortex. You guys are tough! A waste of time and money? We’d all like things to move faster but this pilot study – is being done in order to provide the data to get the funding for a full blown study. That’s simply how the system works. You can’t get to home without getting to first base first. It’s not a waste if the study works. It’s simply moving more slowly than you want it to. Reminds me of the Doors song “We want the world and we want it NOW”. Of course we do – and yet we have a small field which has attracted little funding, few large donors and very few clinical trials. Hopefully the first phase will have good results and we’ll be able to move onto more substantive studies. Jaci on April 22, 2021 at 11:35 pmI started using a Modius Health Slim device. Vestibular stimulation of the hypothalamus. It connects through pads placed on the mastoid bone behind the ears. The Slim is FDA approved for weight loss, but they found users experienced a wider range of benefits. Within the first two weeks of use I noticed I was enjoying listening to the car radio and actually singing along. Before it was extremely irritating. My sleep has improved. My digestion has improved. My mood is stronger, calmer and no longer triggered easily. I ran out of the pads (shipped from Germany) so I went without it for 4 days. I could feel the things slipping back slightly. I’m not using it on its highest setting, going low and slow. But use it daily. I just redid EEG last week so I’m interested to see if there are any changes. sunie on April 23, 2021 at 12:30 amWith the UCLA study, I would be interested in hearing how before and after each treatment, and serial qeeg’s between treatments and following the last treatment stack up when the data is crunched by someone who is experienced with eLORETA. Hope the NCRI can somehow be drawn onboard with the proposed UCLA study. Emmie on June 9, 2021 at 10:27 pmWhat EEG do you use to measure? I am very happy to find a person who uses an EEG. I’ve been looking at them also. Matthias on April 23, 2021 at 2:55 amWe should always remember that Jay Goldstein was talking about the limbic system and CFS 25-30 years ago. A man way ahead of his time. I have always maintained that the brain / CNS is at the heart of this disease. Promising sounding research. Cort Johnson on April 23, 2021 at 7:51 amThe Limbic Hypothesis 🙂 – https://www.routledge.com/Chronic-Fatigue-Syndromes-The-Limbic-Hypothesis/Goldstein/p/book/9781560249047?utm_source=cjaffiliates&utm_medium=referral&cjevent=837967d9a43f11eb810100f70a1c0e11 Dakota on April 23, 2021 at 3:09 pmDr. Anthony Komaroff believes that the brain is at the heart of it too….. https://www.youtube.com/watch?v=rPW__rAN32w(“Learning from the Past: The Long-Term Consequences of COVID-19 with Dr. Anthony Komaroff”) (from the video) In Dr. K’s words: “ME/CFS often follows an infection illness of some-sort. It’s very similar to what’s seen in long COVID. What causes this? That’s the big question. The big answer is, we don’t know yet. But, we do have theories, theories based on pretty substantial evidence. I think most people in this field think that both ME/CFS & long COVID, the symptoms are caused primarily by brain abnormalities, that include an activation of the immune system in the brain, or neuroinflammation; auto-antibodies or an autoimmune disease that causes auto-antibodies that attack targets in the brain; decreased blood flow to the brain caused by abnormalities of the nervous system; and finally an abnormality in the failure of cells in the brain to produce enough energy molecules to meet the needs of the brain. All of these have been documented in ME/CFS & likely to apply in long COVID as well.” Ann Marie on April 23, 2021 at 10:47 amI spent two months last summer, five days a week getting rTMS treatments both because of treatment resistant depression and ME/CFS. At first it seemed like maybe it was helping with mood and energy. In time, not-so-much, and I stopped after 8 weeks. I guess I was not one of the lucky ones. My main point, however, is that it really, really hurt my head! I don’t know if it was the inexperience of a relatively new technician, or if it was just me, but the supervising doctor just told me I would get accustomed to it. Well, I never did. After 20 years with ME/CFS, I was desperate enough to continue treatment, but it took all I had to tolerate it. Without significant results, not to mention the time and commitment to keep up with it, I decided to discontinue this treatment. I hate to be a wet blanket, but I have a hard time accepting the description that it is pain free. I am absolutely thrilled more research is being done and hopeful it will continue to help a majority of subjects. Cort Johnson on April 23, 2021 at 11:53 amSorry to hear that Ann Marie,I was told it was side-effect free. I wonder if it was done properly (???) sunie on April 23, 2021 at 6:52 pmCort,would you be able to get data that explains how the seizure and adverse events were reported? ( including those reported in link Remy posted) Cort Johnson on April 24, 2021 at 2:05 pmAll I can go by is the study results and meta review of study results. All I can say is that many, many clinical trials of this sort have been done in quite a few conditions and a consensus has emerged around side effects. I just check clinicaltrials.gov and hundreds of rTMS studies in all sorts of conditions are either recruiting or about to recruit patients. Kellie Rawlings on April 23, 2021 at 9:43 pmI have had TMS. I was treatment resistant and required more sessions than normal. Most patients have two sessions daily, but I found it too much, so we went one daily, which extended my hospital stay. Unfortunately I can not say I was one of the successful participants in the program. But at least I tried. I have had more success with ketamine infusions. I believe like with cancer, ME/CFS has many different versions, effecting many parts of our body. Brain, blood, nervous system, bones, gut, liver, ……..you get the idea…… and different treatments will better suit different individuals. Gijs on April 24, 2021 at 3:47 amIt looks like a new type of shock therapy to me. I would never do this. Rachel on April 24, 2021 at 6:03 amThis was already tried in fibromyalgia. It didn’t help. I’m not sure if it was published. This does not address the immune aspects and metablism aspects of CFS and I suspect is a way to psychologise the illness. I would never try it Cort Johnson on April 24, 2021 at 1:36 pmPlease read the blog again (or for the first time) and click on the links for the fibromyalgia studies. rTMS is currently being assessed in many neurological diseases including Alzheimer’s disease, amyotrophic lateral sclerosis, epilepsy, stroke related disability, tinnitus, multiple sclerosis, schizophrenia, and traumatic brain injury.” as well, of course, in fibromyalgia and ME/CFS https://en.wikipedia.org/wiki/Transcranial_magnetic_stimulation Why would you assume that something that targets the brain would not affect the immune system? The brain, including the sympathetic nervous system, is a huge immune system regulator. Do you believe that neuroinflammation is psychological as well? Animal studies suggest that rTMS is damping down neuroinflammationhttps://www.sciencedirect.com/science/article/abs/pii/S0006899321002845 Cort Johnson on April 24, 2021 at 1:44 pmIt’s not new and it’s not electroshock therapy. It uses magnetic fields not electrical fields and it’s literally been studied hundreds of times in many different conditions.11 studies are underway in Alzheimer’s – https://www.clinicaltrials.gov/ct2/results?recrs=ab&cond=Alzheimer+Disease&term=rTMS&cntry=&state=&city=&dist=, 13 in Parkinson’s,- https://www.clinicaltrials.gov/ct2/results?recrs=ab&cond=Alzheimer+Disease&term=rTMS&cntry=&state=&city=&dist= – and 3 in multiple sclerosis, Issie on April 25, 2021 at 6:46 amFirst thing I thought is it is similar to an MRI, just targeted at one place. Am I right Cort? I’m having all my MRI this Monday, to look at the brain meningioma. I’ll let you know if my brain gets better. Its been 3 years since we looked at things. So I will pay close attention. Cort Johnson on April 25, 2021 at 2:34 pmThat’s a good question. Both involve magnets. I don’t know. I do know that TMS is also used for research purposes. issie on April 26, 2021 at 4:00 pmOkay, back from MRIs and it gave me a massive headache. I’m sensitive to energy and you could sure feel it. Its pulsating and spins around your body. Not thinking I’d want it concentrated in one area. (But it may not even be the same. Could be different.) But it gave me a headache. Jaci on May 4, 2021 at 6:11 pmIn response to Issie comment on the MRI. I had a different experience. An MRI of the brain, no contrast. The minute I got into the car afterwards, the radio on…WOW. The sounds seemed brighter, lighter. Like someone hit a switch that intensified the experience. I felt good. But was tired later on as the day went on. A temporary experience. I’ve been using daily the Modius Health vestibular stimulation of the hypothalamus device with great results. Previous EEGs always showed slow left prefrontal cortex and possible seizure activity. This last EEG was all normal. Emmie on June 9, 2021 at 10:38 pmPulsed electro magnetic field devices also already approved for Alzheimer’s and urinary / bladder and some other things. I’ve used pemf and thousands throughout the world do. There’s a small pemf device– it goes by two names, omnipemf and NeoRhythm. It lets users choose their settings which is remarkable in this pemf category of devices. Indeed many pwme are sensitive and these waves do work. It’s not likely a CURE… but can be of great assistance. What’s missing in the emerging frequency medicine industry are blood tests and EEG. Someone here in these comments, Jaci, is using an EEG. It would be great if more of us could use one and standardize some of the things we test. Nikki Paul Knoll on April 24, 2021 at 7:26 amThis is super interesting to me. I have chronic migraine along with the diagnoses that come with CFS/ME and since I’m so sensitive to pharmaceuticals, my neuro prescribed Cefaly. It’s a small device that stimulates and tones the trigeminal nerve. It has two settings – one for daily use and the other for acute relief during a migraine. It has helped decrease severity and frequency by half! Another device prescribed is cost prohibitive but does the same with the vagus nerve – gammacore Sapphire. Thanks so much for reporting this, it gives me great hope after 28 years. Waiting on April 24, 2021 at 1:52 pmI agree that neurological research could hold the key for ME – I welcome it, especially the involvement of Solve ME & UCLA!Regarding treatment, *all* ME treatment needs to be carried out very carefully, very slowly (the start low, go slow maxim) and by qualified people. ME patients are just too sensitive, physiologically, for anything less. sunie on April 24, 2021 at 11:18 pmCort,this has been an especially difficult one, would you know how much of the brain—do they have any way of knowing? or measurin? how many neurons fire ( per minute or per ? ) snd how many times? Is there a way to measure how many neurons are firing, and how often, in the moments before treatment is started? and how nany neurons are firing, and how often, at the end — in moments — or days (some set period of time) after a treatment session?? or is there no way of quantifying and measuriing the rate and number of neurons affected by each impulse from machine? thank you, Cort, for firing up your brain to make this difficult subject more understandable. how is the firing of the neurons physically or electrically different than how a brain neuron fires on its own? or how is the neuron’s pulse stimulated firing physically different from how electric (shock?) fires them up? would it be like a wave pattern in brain for a person’s neurons firing without machine stimulation? vs all of the neurons being stimulated to fire all at the same time by the machine? or in phase or in timing all neurons made to fire at once from the pulses from the machine?? Tracey Anne (Burgess) on April 25, 2021 at 1:59 amI haven’t had TMS but I do think calming my chronically triggered sympathetic nervous system – fight/flight/freeze has been central to the improvements I have made. However, it’s been a long, slow process, including everything that I felt might help. I considered myself to be in an extended convalescence and still do. I’m currently attempting to live in the equivalent of fifth gear – trying to avoid power surges. Being constantly wired and hardly sleeping was increasing my food intolerances and used more energy than I had available. I could hardly think and had zero memory. From my current vantage point, I can see that for me, managing my stress response continues to be crucial. And I would add that this is different to being stressed about something – it’s about my response to that perceived stress. So, if TMS or something else, helps to calm the triggered hypervigilant, survival oriented parts of the brain, then I think that is a really useful thing to do. But then I think unhurried time is needed for the exhausted brain/body/mind/spirit etc to gently start to repair itself, as much as possible. That has been my experience anyway. ElsannaV on April 25, 2021 at 3:28 amMmm … as much as I applaud any study done on ME, I have doubts popping up immediately. – you can not compare Fibro to ME brains (enough studies about the differences) – I had extensive qEEG LORETA (which was then sent to the Zinn’s for a second opinion). I have so many zones in ‘red’ (over activated already) and general conclusion (two seperate reports) : Brain connectivity is off. How could rTMS fix brain Connectivity I wonder. – my brain (neurons) is ‘firing’ too hard already. So adding more ‘fire’ scares me. And I don’t scare easily. – If anything, I need things to temper my brain. Only meds that work a bit on over-excitability (noise, smells, …) are ‘tempering meds’. Not healthy but without them it’s hell. – the fact that Whitney Dafoe can finally engage a bit online since taking Ativan on and off … I get where that’s coming from. Tempering the brain/CNS/ANS I guess. – rTMS … don’t know about the details so I’m speaking with two words, but it seems to do the opposite? “Adding more fuel to the brain?” Hoping they can pinpoint the exact spot (if it exists) that can “counteract” the mainly over-excited poorly connected ME brain. Because if they target the wrong area? And with poor connection issues? Wondering how 1 spot (if found) will be able to influence the rest of the brain. Just a few thoughts. Hoping it works of course. But I’m in limbo here. Don’t compare Fibro to ME. Praying the researchers get that part. Do their homework very very well. Overlap yes, but totally not the same. Remember Sophia? Inflammation basal root ganglia in autopsy report? Same as Lynn? rTMS in ME cases (without knowing about possible inflammation going on) sounds … dangerous. Cort Johnson on April 25, 2021 at 2:28 pmThanks Elsanna, Agree FM and ME/CFS have differences. Not totally comparing ME/CFS to FM – two small papers on rTMS on ME/CFS have been published. We shall see. I think its worth a try. sunie on April 25, 2021 at 9:16 pmElsannav,thank you for describing much better than i did concerns re: firing up brain cells. your point re: inflammation seems wise. cfs me is so unusual in so many ways, maybe something anout this study will inform researchers on how to design their next studies. sunie on April 25, 2021 at 9:17 pm*about* this study Cort Johnson on April 26, 2021 at 6:52 pmIf this study can calm down the limbic system – which is putting everything on edge and likely triggering inflammation – I would bet it will damp down neuroinflammation. ME/CFS is unusual but the patterns of brain wave activity don’t appear to be that unusual so far as I can tell. I think the big question for me is how is the brain stem involved. If it’s pounding the rest of the brain with too much stimuli this study could help with that by calming things down. ManShadow on April 25, 2021 at 7:15 pmAre we able to find out the studies that lost out to rTMS? Also, I wonder how late my until psilocybin is trialled for ME… ManShadow on April 25, 2021 at 7:16 pm*how long until psilocybin Nikos on April 26, 2021 at 8:00 amHello Cort, Nice update, thanks! Do your remember last year’s discover by Petter Brodin, who had used an intranasal device to stimulate the vagus nerve, and this resulted to a 30% improvement on symptoms? It was a blinded study and I remember the whole mecfs community being ecstatic. Some months back I asked him about progress on this treatment, and he told me to stay tuned for more (exciting?) updates:https://twitter.com/xNikos/status/1267403239558914048 This year I asked him again and he never replied, so I am not sure how to interpret that. Cameron on April 26, 2021 at 5:29 pmCort, I agree – pretty tough bunch of customers here! Kudos on this very smart and interesting discussion. Cort Johnson on April 26, 2021 at 6:53 pmSomething about brain stimulation I think. Anyway I learned more by participating in the discussion and doing so made me more interested in this approach. Rick on April 27, 2021 at 12:38 pmI’ll tell you already what the EEG will show: decreased relative and possibly absolute SMR across the central strip (i.e., motor cortex); decreased slow wave activity occipitally and parietally; decreased fast wave left frontal and front central region; and most likely increased very high frequency (23-38Hz) temporally, locking in all the dysfunction. If TMS can reorganize the EEG so that it sticks, that would be great progress. But it sounds from people’s experience so far that the effects aren’t lasting. I think it will take more than just TMS to reverse neuro ME/CFS; I think the brain will actually have to learn to readjust itself out of the dysfunctional patterns through operant EEG training and whatever cognitive/emotional therapies are needed to alleviate underlying trauma. Otherwise, the limbic dysfunction will remain and just keep reactivating as soon as the TMR stimulus is removed, or the effects “wear off,” which is what seems to be happening so far. Rick on April 27, 2021 at 12:52 pmJust to add – don’t get me wrong, I’m very glad they’re doing this research. I hope something therapeutic or at least informative comes out of it. sunie on April 27, 2021 at 8:43 pmHi Rick, it sounds like you possibly know thrun either research or personal experience, or both. is the limbic dydfunction the original injury, in your opinion? or is it one of the many side effects? Jaci on May 4, 2021 at 6:29 pmYes, I think you’re right. It takes a village. I started using the Modius Health Slim device in December. It operates by vestibular stimulation of the hypothalamus through the mastoid bone behind the ears. I also did weekly somatic therapy with a therapist, and of course diet and supplements. I use the Modius daily and on a low and slow setting. My last EEG came back normal. Previous EEGs for the last 11 years always said the same thing, slow left prefrontal cortex and possible seizure activity. (Sorry, don’t have paperwork for past EEGs, only by memory of it saying same thing year after year and doctors wanting to do a 24 hour to catch seizure, which I never did). Besides the normal EEG, I fall asleep easily and sleep through the night peacefully, my digestion has improved so no more alka seltzer or GERD, I enjoy singing to music in the car again (this was big improvement), I feel emotionally stronger and less triggered by my environment. I still have weak legs and a mild adrenaline type surge, but hey… it’s getting better. Marco on April 29, 2021 at 7:52 amVery interesting! Is it possible to know more about the “inhibitory stimulation” of the motor cortex, i.e. the exact location of the magnet? I’d like to replicate the experiment on myself. Thank you very much! SP on May 23, 2021 at 5:54 pmIam a realist aling withbeing a hardworking single mom of a college student. I have only had CFS/ME for two years but undoubtedly the worst and scariest experience my life. Before the crash I was at the height of success very active and full of life. Now I spend $1500-2k a month on weekly acupuncture, energy healing, fitness coach and.chinese herbs to stay functional enough to work roughly 30 hours per week from my once 60. I have seen at least 2 doctors in fields of endocrinology, neurology, rheumatology. Psychology, etc. I meditate at least 2-4 per day. I have spend countless weekends going deeper into my mind body connection. When I can focus on this, it is amazing however I do not have 7 hrs a day to do this. Once I get back into my “envirnoment” it is challenging. I do know it works. We can rewire our brains to get back to a parasympathetic state but it takes a lot of work and focus. I have researched for countless hours, calling doctors from all parts of the world. The truth is no one really has the answer. Amazing how behind western medicine is. I signed up for this trial to help me piggy back off the work iam doing on my own. I have lost a lot of living in two years along with a lot of $$$. Iam thankful and grateful to have help and support to improve. Iam willing to take the risk. This is an investment in my future and of those in my shoes.I will be traveling from oregon to live in LA for a month all on faith that what is meant to be will be. Life is a gamble and this opportunity at the 7th best medical schools in the country brings me hope! Hope that one day this disease will be treatable at the least and one day curable. I do appreciate everyones concerns and skepticism, everyone’s views are valid. Marco on June 26, 2021 at 2:39 pmGood luck sp from the bottom of my heart! Clyde on November 17, 2021 at 10:53 amHow did it go? Clyde on November 14, 2021 at 5:37 pmDoes anyone know when we will have results from this study? Cort Johnson on November 15, 2021 at 8:01 amThey hoped to have it done fairly quickly. Maybe early next year? Deep Brain Stimulation And Depression http://www.everydayhealth.com/health-report/major-depression-resource-center/sanjay-gupta-targeting-depression-deep-inside-brain.aspx?xid=aol_eh-emo_9_20141110_&aolcat=hlt&icid=maing-grid7|main5|dl19|sec1_lnk3&plid=561818 "Helen Mayberg, MD, a researcher at Emory University in Atlanta, takes the patients no one else can help. The severely depressed people who enroll in her trials have not responded to medication, to talk therapy, or even to electroconvulsive therapy (ECT), in which voltage is applied to the temples of a sedated patient to induce a seizure. She is achieving astonishing results: 75% of her patients get better and stay better. Dr. Mayberg is achieving these results by permanently implanting electrodes deep inside the brain. The electrodes are powered by a battery pack implanted under the skin below the collarbone. . . ."(Click the link above to read the full article. Nov 12, 2014barbc56There's another alternative to this which doesn't involve any invasive techniques. It's called Transcranial magnetic stimulation (TMS). Mayo Clinic offers this treatment. http://www.mayo.edu/research/depart...timulation?_ga=1.21403896.23340665.1407807349t A YouTube presentation about TMS. BarbWhere there is much desire to learn, there of necessity will be much arguing, much writing, many opinions; for opinions in good men is but knowledge in the making. JOHN MILTONI urge readers to explore both a deeper and a greater context for TMS and neurosurgery. For example - Close readings of actual studies, as media may include spin/bias. Consider conflict of interests, harms, and other negative study info that media may have ignored: http://www.madinamerica.com/2014/02/transcranial-magnetic-stimulation (Is TMS truly non-invasive?) Please also consider patient consent. So long as psychiatry is involved, individuals may be subjected to "treatments" which they and/or their family do not want and to which they do not consent. Notes on neurosurgery were recently shared here: http://forums.phoenixrising.me/index.php?threads/psycho-neuro-limbic-surgery-questions-notes.33593 Please consider if you want to be a guinea pig if/when the biopsychosocialists advocate TMS or neurosurgery for ME/CFS patients who are treatment-refractory, i.e. do not respond to CBT/GET/antidepressants. I also don't know/understand how device patents work with FDA, but my impression is that if a current design is FDA approved, then physicians can manufacture similar devices for use without FDA approval. Perhaps someone knows/understands more about this? I believe patients/consumers have to ask then what conflicts of interests a psychiatrist/neurosurgeon might have. For example: http://www.fbi.gov/stlouis/press-re...ies-indicted-on-federal-anti-kickback-charges and this, "Surgeons Eyed Over Deals with Medical-Device Makers" http://online.wsj.com/articles/SB10001424127887324263404578615971483271856 Another area of concern - NIMH and Insel have warned that pharma isn't developing new drugs for mental illness, and so NIMH has to consider how best to invest its funding without pharma assistance as before (as I understand it). These events then seem as though they could facilitate a move toward a possible neuromodulation / neurosurgery trajectory. http://www.cnsspectrums.com/aspx/articledetail.aspx?articleid=2625 http://www.nimh.nih.gov/about/director/2012/experimental-medicine.shtml I'm not saying that some kind of neuro procedure can never be part of the solution or the solution to some/all ME/CFS dysfunction. I am concerned that patient consent will not be honored; I'm concerned that research underfunding means there isn't enough knowledge to find the best solution(s); I'm concerned about political/economic pressure to repurpose "treatments", even when it's not appropriate to do so; I'm concerned about government manipulation of media; And I'm concerned about psychiatry as a political and totalitarian tool used to violate patient consent and civil liberties. Nov 12, 2014adrenoTMS is very safe. I haven't heard of any serious side effects. Deep brain stimulation carries risk during the implantation, but has been very effective for Parkinson's, epilepsy, and perhaps it seems for treatment-resistant depression. TMS and deep brain stimulation cannot be compared to cutting out pieces of the brain. Of course, we agree that patient consent is required. It seems you (and several others) are against any therapy that exists, including psychotherapy, drugs, TMS, deep brain stimulation. Depression is serious, people are killing themselves, or leading very miserable lives. So what do you propose for treating depression? GhostGumThe statements written in post #4 do not accurately reflect my beliefs/opinions/concerns or the research which has influenced my beliefs/opinions/concerns. From what I understand, TMS has to be done in a hospital setting. Some biofeedback clinics offer Neurofield, similar to rTMS, but with lower magnitude. http://www.neurofield.org/ ArtemisiaRen said:I urge readers to explore both a deeper and a greater context for TMS and neurosurgery. For example - Close readings of actual studies, as media may include spin/bias. Consider conflict of interests, harms, and other negative study info that media may have ignored: http://www.madinamerica.com/2014/02/transcranial-magnetic-stimulation/(Is TMS truly non-invasive?) Please also consider patient consent. So long as psychiatry is involved, individuals may be subjected to "treatments" which they and/or their family do not want and to which they do not consent. Notes on neurosurgery were recently shared here:http://forums.phoenixrising.me/index.php?threads/psycho-neuro-limbic-surgery-questions-notes.33593/ Please consider if you want to be a guinea pig if/when the biopsychosocialists advocate TMS or neurosurgery for ME/CFS patients who are treatment-refractory, i.e. do not respond to CBT/GET/antidepressants. I also don't know/understand how device patents work with FDA, but my impression is that if a current design is FDA approved, then physicians can manufacture similar devices for use without FDA approval. Perhaps someone knows/understands more about this? I believe patients/consumers have to ask then what conflicts of interests a psychiatrist/neurosurgeon might have. For example:http://www.fbi.gov/stlouis/press-re...ies-indicted-on-federal-anti-kickback-chargesand this, "Surgeons Eyed Over Deals with Medical-Device Makers" http://online.wsj.com/articles/SB10001424127887324263404578615971483271856 Another area of concern - NIMH and Insel have warned that pharma isn't developing new drugs for mental illness, and so NIMH has to consider how best to invest its funding without pharma assistance as before (as I understand it). These events then seem as though they could facilitate a move toward a possible neuromodulation / neurosurgery trajectory.http://www.cnsspectrums.com/aspx/articledetail.aspx?articleid=2625http://www.nimh.nih.gov/about/director/2012/experimental-medicine.shtml I'm not saying that some kind of neuro procedure can never be part of the solution or the solution to some/all ME/CFS dysfunction. I am concerned that patient consent will not be honored; I'm concerned that research underfunding means there isn't enough knowledge to find the best solution(s); I'm concerned about political/economic pressure to repurpose "treatments", even when it's not appropriate to do so; I'm concerned about government manipulation of media; And I'm concerned about psychiatry as a political and totalitarian tool used to violate patient consent and civil liberties.Ren, thank you for this. I read the Hickey piece about the dubious science. I'm considering TMS and I'm very hesitant. I know how studies can be manipulated and presented in a misleading way, and this article shows quite a lot of evidence in this case. Maintenance tDCS: A Case of Full and Durable Recovery from Myalgic Encephalomyelitis/Chronic FatigueJul 13, 2017Jesse2233A middle-aged man with progressive myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) was referred for neuromodulation. His condition, likely virally induced decades ago, was characterized by recurring periods of extreme fatigue, lasting months at a time. Over the next few months, he experienced full recovery with improved exercise tolerance and a return to physical exercise several times each week. During this period, we stopped modafinil, but he felt less well, so it was resumed at 100 mg daily. Maintenance treatment with daily tDCS and modafinil led to full recovery from ME/CFS, likely exerting synergistic effects on the brain and immune system. The patient’s recovery was documented through sequential biomarkers including behavioral measures, ERPs, heart metrics and qEEG. Post-treatment improvements in HRV and cardiac power reflect improved cardiac as well as cerebral perfusion. Treatment: Photopheresis, mHBOT, LDN, B-complex, methylfolate, NAG, IVIGLabs: Coxsackie B4, Mycoplasma Pneumoniae, Bartonella (henselae and quintana)Autoantibodies (D1, D2, Lysoganglioside, Tubulin, A1 Adrenergic, SMA, ACA), Speckled ANA, PGF2a, TNFa, IL-6, IFNy ljimbo423Medication trials provided partial benefit. Transcranial direct current stimulation (tDCS) was chosen as a neuromodulation treatment, allowing cumulative, ongoing treatment to target ongoing inflammation . It sounds like decreasing the neuro-inflammation, greatly improved his cfs. I think neuro-inflammation, caused by immune system dysfunction, is a huge cause of symptoms and I am becoming more and more convinced of it all the time. It's always nice to hear success stories!Jim Mary@Jesse2233 - this looks potentially very interesting. I have a lot of questions - are they sure the man had ME/CFS? It's not the same thing as extreme fatigue, though he might have had ME/CFS. I'm very surprised that psychiatrists actually came up with something useful! I have such a low opinion of them and generally run the other way at the first whiff of them. Although, maybe they're right - it has been all in our heads all this time, neuroinflammation-wise. I wish the paper was open access. Have they tried this with other patients? Has anyone else done this? I know you don't have these answers. And I'm wondering if they would be willing to share their protocol with other researchers. I guess there's one way to find out --- Thanks for posting -- testingInteresting, but they don't say enough to be convincing on their diagnosis. He was working, he slept normally, no mention of PEM, and he had a childhood history of neurological illness. We need more information to even attempt to evaluate this. WoolieIts good that they collected some objective measures of improvement. Otherwise, with this being an open label study, the patient-reported improvements would be pretty uninterpretable. But tDCS is a worry. Its involves placing electrodes at different points on the skull, and passing a very small current across them. Its super small. You can place the two electrodes at different points to sort of "target" the electrical potential to different parts of the brain. In a loose kind of way. I have worked with tDCS in my research, and have not been able to obtain any reliable behavioural effects using it. Lots of other researchers I've spoken to have had the same experience. tDCS was really hyped for a while, but now we're all starting to question whether it really does anything, short or long term. Could just be a huge placebo pill. One also wonders why this is a single case study. Case studies have a place in science, but to be useful, we need to know something about the reasons the case was selected for report. Was it because he's the only person they've seen with such intractable CFS? If so, they don't get about much. Or is it - as seems more likely - that he was the only person to respond? If so, it could be a random effect - the paper notes that this patient's condition is relapsing-remitting, so its entirely possible that one of his remissions just coincided with the treatment. I hate to put a downer on everyone by being so sceptical. But I do worry that false claims about "neuro" type treatments could be heading us in the wrong direction. The claim that ME is all in the brain isn't very different from the claim that it is all in the mind, especially in the minds of some of the numpties working in our area. And we've already seen where things like "central sensitization syndrome" lead us, and its not good. And besides, a neuro explanation just doesn't seem to meet the minimum requirements for me. There isn't a plausible brain mechanism that can explain all the ins and outs of MECFS. But there are plausible immune mechanisms that fit the whole picture. So that seems to me a much better place to look for answers. WooliePS I'm pretty sure this guy had MECFS. His viral history is a really strong indicator, I reckon. Seven7Stimulant! Not such a good idea for some. CFS/ME Videos https://www.youtube.com/channel/UCGuQZPHK85FADUlnLiR-_uA ++ MAO-A R297R, BHMT-02, BHMT-08 +- VDR Bsm, VDR Taq, MTRR K350A, AHCY-01, AHCY-19, MTHFR A1298CProtocol: OI = BetaBlocker, Midodrine, Florinef, Antiviral: Famvir. Sleep: Trazadone. Supp: FishOil,C, CQ10, All in One Multi. Oxford Peptides Once a Month ljimbo423Woolie said:And besides, a neuro explanation just doesn't seem to meet the minimum requirements for me. There isn't a plausible brain mechanism that can explain all the ins and outs of MECFS. But there are plausible immune mechanisms that fit the whole picture. So that seems to me a much better place to look for answers. I don't think it has to be either or, neuro or immune. Why can't it be both?Image Immune system dysfunction can cause glial cell (immune cells in the brain) activation, and neuro-inflammtion. Immune system dysfunction can also cause mito. dysfunction by increasing oxidative stress.Jim Woolieljimbo423 said:Why can't it be both?It could be. Or it could just be that the brain, being part of the body, is affected by MECFS too. I find it odd that people are surprised when a systemic illness affects the brain. Of course it does, the brain is a body part. And probably the most vulnerable of them all. But if you're looking for a causal explanation, good explanations start simple - with one primary cause - and you only add on complexity if you need it. The brain isn't the place to start, I don't think. ljimbo423Woolie said:But if you're looking for a causal explanation, good explanations start simple - with one primary cause - and you only add on complexity if you need it. The brain isn't the place to start, I don't think. I agree that the brain isn't the place to start. I think it's the immune system and whatever it is reacting to, that is causing the problems, everything else is down stream of those 2 events, including neuro-inflammation.Jim HipI tried a home-made version transcranial direct current stimulation (tDCS) myself, by passing a battery-powered low voltage current through my bathwater while I was in the bath (this is called a galvanic bath, although galvanic baths usually pass current through the body rather than the head). This bath approach has the advantage of not needing any electrodes, since the water itself evenly delivers the current to your skin, and therefore avoids the creation of hotspots and skin irritation where the electrodes are attached. Although you don't have the ability to target specific areas of the brain without using electrodes. I did these galvanic baths daily for one week, but did not notice much, except that I found on the days I did these baths, I did not need my usual midday 45 minute nap, possibly as a result of the mild stimulating effect that the electric current produced. In my galvanic baths, I used electric currents of comparable strength to those used in tDCS (Wikipedia says for tDCS, up to 60 min and up to 4 mA daily is safe, so I based my galvanic bath current on that). In the study on tDCS for ME/CFS, they used 2 mA for 20 minutes, placing the anode (+) electrode pad on the left dorsolateral prefrontal cortex, and the cathode (-) electrode pad on the right dorsolateral prefrontal cortex. The location of the dorsolateral prefrontal cortexes is shown in this blog article. But looking at the full paper here on Sci Hub, it says:Patient reported significant benefit early in the day during the first month of daily tDCS. We increased tDCS sessions to twice daily (6 AM and 12 Noon). Over the next few months, he experienced full recovery with improved exercise tolerance and a return to physical exercise several times each week. So it looks like the full benefits of this treatment only appear after a few months. Thus I may have stopped my tDCS experiments too soon, as I stopped after one week. After reading this, though, I am tempted to try it again for longer. It's interesting how the study measured various physiological parameters both before treatment, when the patient had ME/CFS, and after treatment, when he was in remission:Evoked Reaction Potentials: Pre-treatment visual ERP findings (156 ms, -12.6 mV) improved substantially at post-treatment (180 ms, -13.2 mV). Heart Metrics: Heart-rate variability (25 ms) and total power (287 ms²) were both low at pre-treatment. Post-treatment heart-rate variability improved significantly (35 ms); total power improved substantially (511 ms²). We performed qEEG analysis to assess brain wave states that might explain his full and unexpected recovery (see Fig. 1 showing Pre vs. Post qEEG after one year of maintenance tDCS). Before treatment, qEEG showed higher than normal incidence of alpha in the right frontal lobe (7-9 Hz), higher than normal incidence of alpha in both temporal lobes (7-9 Hz, left greater than right) and lower than normal inci- dence of frontal Beta (22-30 Hz). At follow-up, in full recovery, the qEEG showed more normalized incidence of alpha in these ranges at these locations, as well as normalized frontal Beta frequencies (22-30 Hz). The authors note that:The most notable change in the qEEG is reduced alpha (8 Hz) in the left temporal lobe, consistent with previous findings that implicate the left temporal lobe in ME/CFS pathophysiology. This normalization of temporal alpha likely reflects improved thalamic gating. The study says that:Maintenance treatment with daily tDCS and modafinil led to full recovery from ME/CFS, likely exerting synergistic effects on the brain and immune system. So if I understood this correctly, it appears that he requires daily tDCS to keep his ME/CFS at bay; thus in this case tDCS is not a cure, but keeps his ME/CFS in remission. Sounds like this man had mild ME/CFS though, as he was still able to work in teaching (those with moderate or severe ME/CFS are not able to work):Presenting complaints: For the prior two years his life was severely circumscribed due to severe, persistent fatigue, with inability to exercise. He social life was curtailed as he focused his limited energy on teaching and his family. Also, his ME/CFS was a little unusual in that he seemed to have intermittent fatigue, rather than the more continual fatigue symptoms that most of us here are used to:His condition, likely virally induced decades ago, was characterized by recurring periods of extreme fatigue, lasting months at a time. edited: Jul 15, 2017 #11This has more holes in it then Swiss cheese We know nothing about him and can't confirm he had ME/CFS at all. If he slept normally and had no PEM then it sounds likely he had something else. Modafinil keeps you awake, its not a wonder drug that cures inflammation, fixes pyruvate dehydrogenase, modulates the immune system/microbiome/whatever is causing ME/CFS and kills viruses. If it did all these things we would not only all be better, it would be in the product label, these uses would greatly expand their market and they would be happy to extend the patent. It would be nice if this was a universal ME/CFS fix it drug, but its more likely he spontaneously recovered or didn't have ME/CFS at all. If they want to run a double blind placebo controlled crossover study they can add more evidence to their results but i would be very unsurprised if the study did not pan out the way they expect. What's old Doc Washburn prescribe? Do you have Dropsy? The Grippe? Scrofula? The Vapors? Jungle Rot? Dandy Fever? Poor Man's Gout? Housemaid's Knee? Climatic Bubo? The Staggers? Dum-Dum fever? barbc56Hip said:I tried a home-made version transcranial direct current stimulation (tDCS) myself, by passing a battery-powered low voltage current through my bathwater while I was in the bath (this is called a galvanic bath, although galvanic baths usually pass current through the body rather than the head You have to be kidding! Water and electricity do not mix. If you do any little thing wrong you might as well take a bath with your plugged in hair dryer while eating your swiss cheese. It's a tragedy waiting to happen! Plus what @Alvin2 said.Last edited: Jul 16, 2017Where there is much desire to learn, there of necessity will be much arguing, much writing, many opinions; for opinions in good men is but knowledge in the making.JOHN MILTON lansbergenWoolie said:Or it could just be that the brain, being part of the body, is affected by MECFS too. I find it odd that people are surprised when a systemic illness affects the brain. Of course it does, the brain is a body part. And probably the most vulnerable of them all. Hipbarbc56 said:You have to be kidding! Water and electricity do not mix. That sounds like the sort of comment an over-anxious auntie might make. It's completely safe if you use low battery voltages. Although I wouldn't suggest anyone without a scientific or technical background attempt it, ie, those who don't understand basic equations such as Ohm's law. Alvin2 said:its more likely he spontaneously recovered or didn't have ME/CFS at all. The progress he made is very common in ME/CFS patients: on the scale of severe, moderate, mild and remission, he merely moved up one level on the scale, from mild to remission. We see these types of improvements in ME/CFS patients all the time, from various therapies, eg LDN or oxymatrine. Why do you find it so hard to believe that this combined therapy of tDCS and modafinil moved him up the relatively small jump from mild to remission? Hip said:The progress he made is very common in ME/CFS patients: on the scale of severe, moderate, mild and remission, he merely mode up one level, from mild to remission. We see these types of improvement in ME/CFS patients all the time, from various therapies, eg LDN or oxymatrine. Why do you find it so hard to believe that this combined therapy of tDCS and modafinil moved him up from mild to remission?Because its likely it was spontaneous remission and i know a great deal about Modafinil, its an atypical wakefulness promoting agent, used in people deficient in Orexin or to prevent sleep. If ME/CFS was another name for narcolepsy then Modafinil (or better yet Armodafinil) would be the first line therapy. I'm glad to hear this person got better but i am not at all convinced Modafinil is an ME/CFS treatment of choice, especially given its been tried elsewhere to rather poor effect. However if all those observations were wrong then Dr Davis should be made aware of it and after Rituximab Modafinil can be the subject of a double blind placebo controlled study HipAlvin2 said:i know a great deal about Modafinil, its an atypical wakefulness promoting agent, not a mitochondrial booster by design.I don't know where you got this assumption that a drug must boost mitochondria in order to be helpful for ME/CFS. There are dozens of drugs that are helpful for ME/CFS, but whose mechanism is nothing to do with mitochondrial function. Several ME/CFS doctors find modafinil helpful for some ME/CFS patient's fatigue and brain fog: see this article. But improvement of this guy in the study is more attributable to the tDCS, because if you read the paper, you will notice that he was already taking modafinil even before he started using tDCS. In fact after starting tDCS, he actually lowered his modafinil dose. But I'd be more interested in reports of other ME/CFS patients who try tDCS, and post their results. Alvin2Hip said:I don't know where you got this assumption that a drug must boost mitochondria in order to be helpful for ME/CFS. There are dozens of drugs that are helpful for ME/CFS, but whose mechanism is nothing to do with mitochondrial function. Several ME/CFS doctors find modafinil helpful for some ME/CFS patient's fatigue and brain fog: see this article. But improvement of this guy in the study is more attributable to the tDCS, because if you read the paper, you will notice that he was already taking modafinil even before he started using tDCS. In fact after starting tDCS, he actually lowered his modafinil dose. But I'd be more interested in reports of other ME/CFS patients who try tDCS, and post their results. Fair enough that it does not have to boost mitochondria. However i don't have the energy to argue this, so if you wish to try Modafinil then go ahead, and if it does not work i won't be at all surprised. Its safety profile is quite good so thats a bonus HipI don't do well on stimulants myself: they work for me, but I tend to feel quite mentally depleted the next day, almost like a hangover. So I personally don't have much interest in modafinil. But I am interested in the tDCS, and whether this might have benefits for ME/CFS. This study of 41 fibromyalgia patients found that tDCS was useful for reducing pain after 10 daily sessions. Interestingly, the patients who had tDCS applied the to left primary motor cortex got longer lasting results (lasting for two months) than those who had tDCS applied to the dorsolateral prefrontal cortex. Alvin2Electrocute your brain to treat something that may be caused by a lack of pyruvate dehydrogenase activity. mert
Oxford Textbook of Neurorehabilitation (2 edition 'Enhancement of neuroplasticity by cortical stimulation'
Together with other branches of restorative neuroscience this approach provides the opportunity to reduce neurological impairment, and hence disability, in patients undergoing rehabilitation. Applying such techniques correctly to appropriate patients has the potential to produce clinical benefits whose magnitude equals or exceeds that observed in other branches of clinical neuroscience
Experimental depression treatment is nearly 80% effective in controlled study
Successful Treatment of Post-COVID Symptoms With Transcranial Direct Current Stimulation | Psychiatrist.com
Testing Laboratories, Treatment Centers, Specialists and Clinics
Testing for amount and kind of brain cells by evaluating R2t* signal from MRI scan
Hormone Replacement Therapy (HRT)
Disruption in Blood Brain Barrier and (mast cell or astrocyte) production cytokine